PHARMACOLOGY AND PHARMACOVIGILANCE-STUDSAVER

PHARMACOLOGY AND PHARMACOVIGILANCE-STUDSAVER

      CONCEPT OF PHARMACOLOGY AND THERAPEUTICS

The term pharmacology is derived from the Greek word; ‘Pharmakon’ meaning drug in modern Greek or poison in classic Greek and ‘Logos or Logia’ meaning study of or knowledge of. Therefore, ‘Pharmacology’ is a scientific study of drugs and how it can be used to modify the normal living functions of organism. Specifically, pharmacology is the study of the interactions that occur between a living organism and chemicals or substances that affect normal or abnormal biochemical function.

Thus, the main tasks of pharmacology in the search and development of new medicines involves;

1. Screening for desired activity.

2. Determining mode of action, and

3. Quantifying the drug activity when chemical methods are not available.

Branches of pharmacology

·         Therapeutics-is defined as scientific study of disease state of living tissues and how drug (medicine) can be used to treat them.

·         Toxicology -is a branch of pharmacology that deals with the study of undesirable effect of chemicals or substances on living systems from individual cells to complex ecosystems.

·         Pharmacognosy-the study of medicine derived from natural sources such as plants and animals (study of physical, chemical, biochemical and biological properties of drugs derived from plants, animals and minerals).

·         Pharmacotherapy-the use of drugs to treat conditions, especially psychiatric disorders.

·         Clinical pharmacology-study of pharmacologic effects of drugs in men or evaluation of drugs in humans.

·         Chemotherapy-the use of chemical agents to treat diseases, infections or other disorders especially cancer.

·         Pharmacotherapeutics-study of drugs used purposely to treat diseases.

·         Pharmacogenetics-study of genetically determined variations in drugs response (variations of drugs response as a result of genetic differences in populations).

·         Ethnopharmacology-study of herbal medicines in cultural practices.

·         Medical pharmacology- the science of substances used to prevent, diagnose and treat disease or science of substances that interact with human body.

·         Pharmacy-The art or knowledge that deals with preparation, storage, dispensing and sale of drugs.

1.2         DIFFERENCE BETWEEN PHARMACOLOGY AND PHARMACY

Although pharmacology and pharmacy deal with drugs or pharmaceutics, pharmacology is not synonymous with pharmacy and the two terms are frequently confused. Hence, some of the distinguishing features between the two terms.

1.      Pharmacology is a study whiles pharmacy is an art or a skill or knowledge acquired by somebody.

2.      Pharmacology deals with the theoretical aspect of pharmaceutics whiles pharmacy deals the practical aspect of pharmaceutics.

3.      Pharmacology is research –oriented while pharmacy is a business oriented.

4.      Pharmacology is a second degree programme while pharmacy is a first degree programme.

5.      Pharmacology is biomedical science whiles pharmacy is health sciences profession.

6.      Pharmacology is concerned with discovery of chemicals or drugs whiles pharmacy deals with the application of principles learned from pharmacology in its clinical settings, etc.

 

1.3         Some basic terminologies as used in the study of pharmacology.

·         Effects (therapeutics effect) - the desired result of administration of medication.

·         Side effects- any unintended effect of a pharmaceutical product occurring at normal dosage which is related to the pharmacological properties of the drug. Side effect may be harmful or beneficial. Often “side effects” refers to mild, common, and nontoxic reactions; “adverse reactions” refers to more severe or life-threatening reactions.

·         Adverse Drug Reactions-Adverse reactions are undesirable drug effects. They may be mild, severe, or life threatening.

·         Indication or therapeutic use- The reason for administering a medication or performing a treatment.

·         Contraindications- Factors that prevent the use of a medication or treatment or a condition for which the use of a medication is not recommended.

·         Onset- The time it takes for the drug to elicit a therapeutic response.

·         Duration –the time a drug concentration is sufficient to elicit a therapeutic response.

·         Drug action- This involves mechanism by which the drug act to produce effect.

·         Potency- Refers to the relative amount of a drug required to produce the desired response, or drug’s strength or its power to produce the desired effect.

·         Efficacy- relates to the maximal response or effect achieved when dose-response curve reaches its plateau, or effectiveness of a drug used in treatment.

·         Drug Tolerance - A decreased response to a drug, requiring an increase in dosage to achieve the desired effect. Drug tolerance may develop when a patient takes a certain drug, such as a opioid or tranquilizer, for a long time.

·         Therapeutic index (margin of safety)- It is relationship between a drug’s desired effects and its adverse effects.

·         Idiosyncratic reaction- it is sensitivity-related adverse reaction that do not result from known pharmacologic properties of a drug or from patient allergy or an unexpected reaction to a drug that occurs the first it is given. Or It is any reaction that is different from the one normally expected from a specific drug and dose. E.g, a patient may be given a drug to promote sleep (e.g., a hypnotic), but instead of falling asleep the patient remains wide awake and shows signs of nervousness or excitement.

·         Iatrogenic effect-unfavourable response induced by a therapeutic effort.

·         Drug allergy (hypersensitivity)- antigens/antibody reaction that occurs in susceptible client which results from call damage and release of histamine and other intracellular substances. It may manifest as skin rash, itching, asthma, anaphylactic shock, etc.

·         Purity- refers to the uncontaminated state of a drug containing only one active component.

 

SOURCES AND NOMENCLATURE OF DRUGS (MEDICATION)

 

The term ‘drug’ is derived from the French word ‘drogue’ meaning ‘a dry herb’. The term ‘drug’ has several definitions, and can be broadly defined as: “any man-made, natural or endogenous (within the body) molecule which exert a biochemical and /or physiologic effect on the cell, tissue, organ or organism”. However, a drug may be contextually or operational defined based on the subject matter, and examples such as definitions are as follows:

·         A drug is any chemical or non-infectious biological compound which is administered to or for patient either human or animal as an aid in diagnosis, treatment, or prevent of diseases or abnormal conditions.

·         A drug is a substance used recreationally for its effect on the central nervous system.

·         A drug is any substance other than food which when administered alters the physiological process of the biological being.

·         A drug is any substance that can affect living processes.

Other names of Drugs

Medicine – A plant or animal substance used to treat disease (ancient name)

Agent – Collective name for drugs e.g. Antihypertensive agents, antimicrobial agents

Compound – any chemical used for pharmacological process but not as a therapeutic agent

Pharmacological tool – Drug used to control process or state in living tissue or organelles

Some characteristics of a drug

·         A drug may be administered for local or systemic effect. Drugs with local effects, such as lotions and local anaesthetics, act mainly at the site of application. Those with systemic effects are taken into the body, circulated through the bloodstream to their sites of action in various body tissues, and eventually eliminated from the body.

·         A drug may also be given for relatively immediate effect (e.g. in acute problems such as pain or infection) or long-term effect (e,g, to relieve signs and symptoms of chronic disorders).

Note that the term ‘drug’ is a general term used for both legal and illegal substances which alter physiological processes. However, drugs administered for therapeutics purposes are usually referred to as medication or medicine.

FORMS OF DRUGS

Drugs exist in all three states of matter,

1. Solid (e.g. tablets),

2. Liquid (e.g. syrups)

3. Gas (e.g. inhalations)

 

1.4         SOURCES OF DRUGS

Historically, drugs were mainly derived from plants, animals and minerals but today, most drugs are synthetic chemical compounds manufactured in laboratories, by altering the chemical structure of an existing drug. Such techniques and other technologies advances have enabled the production of new drugs as well as synthetic versions of many drugs originally derived from plants and animals. Therefore, drugs are derived from four main sources namely natural, synthetic, semisynthetic and genetic engineered sources.

1.5         Natural 

(1). Biological –plants, animals and micro-organisms

(a). Plant sources-roots, leaves and barks of plants were used to treat diseases. Later the active ingredients were extracted and used in modern medicine e.g. morphine, quinine, ephedrine, artemether and digoxin.

(b). Micro-organism e.g. antibiotics.

(c). Animal source-some of the animal products used for the treatment of diseases are Insulin, Anti-snake serum, thyroid powder, and heparin.

 

(2). Non-biological-Minerals

Minerals or chemical sources-minerals as simple elements or their salts are used as drugs e.g. Ferrous Sulphate, Magnesium trisilicate, and radioactive Iodine.

2. Synthetic Source-Majority of drugs in used today are synthetically prepared or manufactured in various forms of chemotherapeutic agents e.g. aspirin, barbiturates, sulphonamides, procaine, corticosteroids, benzodiazepines and antihypertensive.

3. Semisynthetic Source- Produced by combining natural and synthetic products e.g. clavulanic acid (synthetic) ÷ amoxicillin (partly natural), Amoksiclav.

4. Genetic engineered or DNA Recombinant or Biotechnology source- E.g. insulin production, gene codes for insulin in humans are taken from the human genome and inserted into an animal genome, the animal will then produce human insulin which is harvested and used (Transgenic animals)

DRUGS NOMENCLATURE/ NAMING

 

The individual drug may have as much as three (3) different names;

1. Chemical name- is the scientific name based on the compound chemical structure. It also describes the constituents of the drug. Usually gives precise chemical composition of the compound. Example, diazepam is chemically known as; 7-chloro-1, 3dihydro-1-methyl-5-phenyl-2H-11, 4-benzodiazepine-2-one, Paracetamol is p-acetamidophenol

2. Generic name (approved, official, non-proprietary name)- It is the name by which the drug will be known throughout the world no matter how many companies manufacture the drug. It is the approval name by the national committees and documented in pharmacopoeias. A drug can have only one generic name in a country.

Advantages

·         Have common roots or endings providing clues to their use or pharmacological action.

·         Used in prescription writing.

3. Trade name or Proprietary or Brand name- The name given to the drug and legally own by the manufacturing company. Thus, single generic name can be sold under five different trade names e.g. Brand names of diazepam = valium, sedapam ,  Kinaquine by Kinapharma Company, and Efpac by Effah Pharmacy. It appears in literature with this sign ® or ™ at the upper right.

Advantage of brand/trade names

·         The quality of the drug is ensured.

·         They are easy to remember and have ‘catchy’ names for commence.

·         They are also cheaper

Disadvantages:

·         Very expensive

·         Several manufacturing companies → several brand names in same country

 

1.6         Classification of drugs

Complex exercise. No standardized procedure because a drug may belong to many classes

Medications may be classified according to;

·         The body system that they interact with e.g. cardiovascular medications, nervous system drugs, digestive system drugs.

·         Their therapeutic uses-this usually reflects the conditions for which the drugs are used for. e.g antihypertensive, analgesics, antacids, anti-malarial.

·         The disease they used they are used for. E.g. anticancer drugs, antimalarial drugs.

·         Their chemical structure/activity e.g. beta-adrenergic blocking agents, anticholinergics.

·         Their overall effect on the body. E.g. sedatives, hypnotics.

However, most of these classifications lacks exactness because some drugs act on the several systems of the body and may be used for different purposes for different people. But, nurses are much more concerned about the therapeutic classification.

1.7         Drug information sources

The term ‘pharmacopoeia’ is derived from the Greek word ‘pharmakon’ meaning ‘drug’ and ‘poien’ meaning ‘make’. The pharmacopoeias are a class of drug compendia (book) which are periodically revised, and serve as the main source of drug information all over the world, and there are several of them based on the country of origin. The pharmacopoeias contains monographs on drugs and ancillary information, description, identification, purity data, directions for storage and dosage.  Drugs included in the current edition of a pharmacopoeia are designated as ‘official’. The other source of drug information is the National Formulary which is comparatively smaller than the pharmacopoeia, and much handier book containing formulations of therapeutic value. Example of the pharmacopoeia are;

        I.            International pharmacopoeia (IP)-WHO

     II.            Pharmacopoeia of India (PI)- India

  III.            British Pharmacopoeia (BP)-British

  IV.            British Pharmaceutical Codex (BPC)-British

    V.            United states Pharmacopoeia (USA)- USA   

Examples of formulary and others (compendia, pharmaceutical firms, journals).

1. British National Formulary (BNF).

2. National formulary of USA

3. Physicians’ Desk Reference-USA

4. National Drug Handbook-USA

5. Nursing Drug Handbook-USA

6. Standard Treatment Handbook-USA

7. Medical Journals

8. Leaflets (inserts).

 

 

 

1.7.1        Use of drugs

Drugs (medicines) are useful in promoting health, preventing and managing disease but can be harmful when used inappropriately. Specific use of drugs includes:

·         Prevention-used as prophylaxis to prevent disease e.g. vaccines, fluoride prevent tooth decay.

·         Diagnosis –establishing the patient’s disease or problem. E.g. Radio-contrast dye, edrophonium.

·         Suppression –suppresses the signs and symptoms and prevents the disease process from progressing e.g. anticancer, antiretroviral.

·         Treatment-alleviate the symptoms for patients with chronic disease e.g. anti-asthmatics, antihypertensive, antidiabetics.

·         Enhancement of aspect of health- to achieve the best state of health e.g. vitamins, minerals.

·         Cure –complete eradication of diseases. E.g. antibiotic

·         Socio-economic expediency e.g. antifertility drugs for birth control

·         Recreational purpose. E.g. marijuana, alcohol.

1.7.2        Effect of inappropriate use of drugs

The inappropriate use of drugs (medicines) has medical, social and economic implications:

·         Mental disorders. e.g. Schizophrenia, mania

·         Drug induced medical conditions e.g. Parkinson’s disease, liver cirrhosis, hypertension, diabetes mellitus.

·         Social stress as a result of financial burden.

·         High government budget on the health sector.

·         High rate of social vices. E.g. arm-robbery, delinquency.

·         Low productivity.

 

PRINCIPLES OF PHARMACOLOGY

General drug metabolism

Medicines (drugs) that produce systemic effect may be injected, absorbed from the gastro-intestinal tract after oral or rectal administration or applied topically. However. Irrespective of the route of administration, the drug molecule has to reach the bloodstream or the target tissue in order to produce effect. Thus, the process by which the administered drug molecule moves through the tissue and enter the bloodstream is referred to as absorption. The term bioavailability is used to donate that proportion of administered dose of a drug which reaches the circulation for effect. There, to improve bioavailability, the drug molecule is modified to form a better absorbed compound which liberates the active drug readily after absorption. Such modified drugs are known as prodrugs. As such bioavailability is expected to be 100% for intravenous medications but if given by other routes only a proportion may reach the circulation. Therefore, the bioavailability of oral medications is always less than 100%, because absorption of oral medicine may be modified by several factors like;

·         The rate at which the stomach empties

·         The presence or absence of food in the stomach.

·         Interactions with other medicines

·         Disease of the gastro-intestinal tract.

·         Frist past effect

·         Dosage form.

Most drugs are not absorbed from the gastro-intestinal tract directly, in the course of absorption, the medicines has to pass via portal vein to the liver before reaching the general circulation. In the liver, medicines are metabolized (broken down) by hepatic microsomal enzymes as they pass through it so that only a proportion of the absorbed actually reaches circulation. This removal of medicines as it pass through the liver is called First-Pass Effect. Thus, medicines which show large first-pass effect are almost inactive if swallowed. E.g. Lidocaine. A term that sound similar to bioavailability but with different meaning is bioequivalent. Two drug products are said to be bioequivalent and many be used interchangeably if both are absorbed in the bloodstream at the same rate and to the same extent. In other words, bioequivalence is said to exist when the bioavailability of a drug from the different formulations are the same. 

Therefore, generally drug metabolism involves the processes occurring between administration of drug (medicine) and the production of its effect. The processes may be conveniently divided into three phases as pharmaceutical, pharmacokinetic and pharmacodynamics properties.

Pharmaceutical phase

This relate to the physical and chemical properties of the medicine that are capable of influencing the desired effects of the drug. The pharmaceutical phase of the drug could influence;

·         the rate of absorption

·         the amount to absorb

·         the proportion reaching circulation for desired effect.

1.8         PHARMACOKINETIC

This relate to what the body does to the medicine or how the body handles the medicine. Pharmacokinetic involves drug movement through the body to reach sites of action, and involves processes like absorption, distribution, metabolism (biotransformation) and excretion. These processes largely determine serum drug levels, onset, peak and duration of drug actions. Drug half-life, therapeutic and adverse drug effects, and other aspects of drug therapy.

Absorption = movement of drug from site of administration into circulation

Distribution = reversible movement of drug from the blood to the tissues

Metabolism = chemical conversion of the drug to active or inactive compounds

Excretion = elimination of drug from the body via renal, biliary or other processes 

ADME

Absorption

Absorption is the process by which administered dose of drug moves from the site of administration or absorption site into the blood stream or target tissues. It also refers to the processes that occur from the time a drug enters the body till the time it enters the bloodstream to be circulated. Numerous factors affect the rate and extent of drug absorption, these include;

·         dosage formulation

·         route and site of administration

·         blood flow to the site of administration

·         gastro-intestinal tract function

·         presence of food and other drugs

·         chemical stability of the drug

·         lipid solubility

·         age of the patient.

These factors have significant effects on the other pharmacokinetic and pharmacodynamics properties of the drug.

Distribution

Distribution refers to the transfer of drug from systemic circulation to tissues or site of action. Distribution describes the processes which transport a drug to it site of action, to other storage site in the body, and to organs of metabolism and excretion. Lipid-soluble drugs tend to distribute more widely in the body compared to lipid-insoluble drugs.

  Factors affecting distribution include;

·         route of administration

·         organ or tissue perfusion/ the amount of blood reaching the tissue

·         protein binding

·         regional blood

·         availability of active transport system

·         lipid solubility

·         Underlying disease condition. e.g. in heart failure or cardiogenic shock tissue perfusion is reduced.

Highly perfuse organ

Heart, liver, kidney, brain, lungs and spleen

Less perfuse organs

Skeletal muscles, skin, fatty tissues in the body.

Metabolism

Metabolism is the process by which an active drug is change into inactive metabolite and excreted. Most often, an active drug is changed into one or more inactive metabolites but some active drug yield metabolites that are also active. Others are initially inactive and exert no pharmacological effects until they are metabolized. Thus, the function of metabolism is to convert fat-soluble drugs into water soluble metabolites for easy excretion. Drug metabolism occurs predominantly in the liver by way of hepatic microsomal enzyme system. Lipid-soluble drugs easily gain access to these metabolizing enzymes in the liver cells.

Metabolism occurs by two reactions namely;

·         Non-synthetic reaction-in these processes, the drug molecules are either oxidized or hydrolysed, and occur in the liver or other tissues like the kidneys, lungs, plasma or intestinal mucosa.

·         Synthetic reactions-these occur in the liver, where hepatic enzymes conjugate or join the drug to other substances like glucuronic acid to make the transformed drug molecules water soluble and thereby more excretable.

Metabolism or transformation is likely to be influenced by such factors as;

·         Hepatic disease

·         Renal disease

·         Cardiovascular disease

Therefore, abnormal functions of these systems can alter the rate and extent of biotransformation.

Excretion

A drug remains active until it is metabolized into an inactive substance and excreted. Thus, excretion is the process by which a parent compound or its metabolite is transferred from the internal environment to external environment.

Major excretory organs

Kidneys-the kidney handle most excretion by expelling both the drug and its metabolites in urine.

Spleen, Lung, Liver

Gastrointestinal tract- some drugs are excreted in the bile and eliminated in faeces.

Skin -through sweat

Mouth-saliva, tears

Breast –through the breast milk. That is why it is adviceable for nursing mothers not to take certain medications.

Excretion rate and efficiency depend on;

Ø  the adequacy of cardiovascular system

Ø  hepatic functions

Ø  renal functions

 Thus, factors impairing excretion, especially severe renal disease, leads to accumulation of numerous drugs and may cause severe adverse effect if dosage is nor reduced. The pharmacokinetics phase is of great practical importance in the choice and route of administration of a particular drug medicine for a particular patient.

1.9         Pharmacodynamics

Pharmacodynamics simple refers to what the medicine does to the body and concern with the actions, interactions and the mechanism (mode) of action of the drugs. Drugs do not create new functions but can only modified inherent functions of the tissues or cells concerned and in terms of drug action there are two (2) main divisions:

a)      Drugs acting on pharmacological receptors situated on or within the cells. e.g. Acetylcholine, adrenaline, and histamines with the following characteristics;

Ø  act at low concentration

Ø  react with specific receptors

Ø  show structure-activity relationship

Ø  can be antagonized by specific antagonists.

b)      Drugs that act without interacting with pharmacological receptors. e.g. Halothane. As such they have opposite characteristics to those that act on receptors.

The receptor theory of drug action

Drug-receptor interaction-like hormones and neurotransmitters that normally regulate cell functions, most drugs exert their effect by chemical binding with receptors at the cellular level. Receptor are mainly protein substances located on the surfaces of cell membranes or within cells. When drug molecules bind with receptor molecules the resulting drug-receptor complex initiates physiochemical reactions that stimulate or inhibit normal cellular functions. E.g Lidocaine actions on the neurone or atropine antagonist acetylcholine.

When drug molecules chemically bind with cell receptors, the pharmacologic effect are those due to either agonism or antagonism. Agonist are drugs that produce effect similar to those produce naturally occurring hormones or substances. On the other hand, antagonist are drugs that inhibit cell function by occupying receptors sites. This prevent natural body functions. E.g. the blocking of acetylcholine by Atropine. Once drug action occurs, the drug molecule may detach from receptor molecules, return to the blood stream, and circulate to the liver for metabolism and the kidney for excretion.

Factors influencing dosage and actions

        i.            A dose-many factors affect drug action qualitatively and quantitatively, and one of such factors is a dose of the medicine as predetermined by age and body weight. A dose of drug (medicine) is the amount of medicament to be administered to the patient as directed by the physician. It is expressed in terms of weight (g, mg, mcg), volume (ml) or in standard units. Generally, the official doses mentioned in the pharmacopoeias are doses for adults, unless mentioned otherwise.

      ii.            Presence of previous pathologic conditions may alter pharmacokinetic processes. In general, pharmacokinetics processes are decrease in cardiovascular disorders as a result of decrease blood flow to the tissue.

    iii.            Psychological considerations- Attitudes and expectations related to drug in general, a particular drug, or a placebo influence client response. They also influence compliance or willingness to carry out the prescribed drug regimen, especially with long term therapy.

    iv.            Genetic-A person’s genetic characteristic may influence drug action in several ways. For instance, genes determine the type and amount of proteins produce in the body. When most drugs enter the body, they interact with the proteins to reach their sites of action, and with other proteins to be transformed and eliminated from the body. E.g. people with G6PD deficiency may have haemolytic anaemia when given antimalarial and Sulphonamides.

      v.            Ethnicity –Inter-ethnic variations become evident when drugs and dosage developed for white people produced unexpected responses, including toxicity when given to other ethnic groups

    vi.            Gender –some gender differences in response to drugs may stern from hormonal fluctuations in women during menstrual cycle.

  vii.            Route of administration-Routes of administration affects drug actions and response largely by influencing absorption and distribution.

viii.            Drug –diet interactions-food may slows the absorption of oral drugs by slowing gastric empting time and altering GIT secretions and motility, especially when taken with or soon after food.

    ix.            Drug-drug interactions- the action of a drug may increase or decrease by interaction with other drugs in the body.

 

WEIGHTS AND MEASURES

Dosage calculation is necessary when the patients is a child and when the drug is dispensed in large doses or strength or unit other than prescribed. The dosage is determine by multiplying the dose (quantity to be taken at a time) while the dosage by the frequency (how many times per day) of the specific drug (medicine) while dosage regimen is also determined by multiplying the dosage by the period of time (number of days) for which the drug is to be taken for its therapeutic effect.

Determination of dose is base on age, weight and at times on the body-surface estimates of the patient.

Weights

The strength of drugs is usually stated in the metric system, using kilogram (kg), gram (g), milligram (mg) and microgram (mg or mcg). It is safer not to use the abbreviated form of microgram because when hand written they may mistakenly read as milligram. Similarly it is safer to avoid using decimal point when stating drug strengths to avoid mistakes in dispensing, e.g. 500 mg instead of 0.5g, 100 microgram and not 0.1 mg.

·         1 kg   =  1000 g

·         1  g      =  1000 mg

·         1   mg  =  1000 microgram

VOLUMES

The metric measures for liquids are:

•                    1 litres (L) =1000 (ml)

•                    1 millilitres (ml) = 1000 microliter

•                    1 millilitre (ml) = 1 cubic centimeter (cc)

The strength or concentration of a liquid preparation is normally stated as weight per volume, e.g. syrup Ampicillin 125 mg/5ml, Injection Chloroquine 40 mg/ml.

Liquid injections usually state the strength as “per ml” but the total amount in the ampoule or vial can vary. E.g. Ampoules of injection chloroquine 40 mg/ml usually contain a total of 5 ml (a total of 200 mg of chloroquine). Therefore, always check both the strength and total volume on any injection label.

 Oral mixtures and syrups are usually prepared so that a normal dose of the drug is contained in 5 ml quantities.

•           One teaspoonful          = 5 ml

•           One dessertspoonful   = 10 ml

•           One tablespoonful       = 15ml

 

1.10     DOSAGE FORMS, METHODS AND ROUTE OF ADMINISTRATION OF DRUGS

 

Drug formulation is the process of combining various chemical substances with the active drug to form a final medicinal product. Drug formulation vary according to the drug’s chemical characteristics, reasons for use, and route of administration. Some drugs are available in only one dosage form e.g. insulin while others are available in several dosage formulations e.g. Paracetamol. Some formulations are for internal administration like tablet and syrups whiles others are for external administration like lotions and ointment.

Various drug formulations

Tablet: Disc-shaped and rough skin. Contain active drug plus other substances like binders and preservatives. Most dissolve in the acid fluid of the stomach and absorbed in the alkaline fluids of the upper small intestine.

Capsule- Contain active drug in a gelatin capsule. It be hard or soft. Hard capsules contain the drug in solid form and soft capsule have the drug in liquid or semi-solid form. Some enteric coated capsules are coated with a substance that is insoluble in the stomach acid. This delays dissolution until the medications reaches the intestine, usually to avoid gastric irritation or keep the drug from being destroyed by gastric acid.

Pills-smaller, smooth and coated

Suppositories –use for anal insertion. Useful for unconscious patients.

Syrup-it has high concentration of sugar and basically used by children.

Mixture/suspension-

Pessaries-intravaginal administration

Bitters

Ointment

Cream

Liniment

The absorption is more efficient and rapid with liquid formulation than solid formulation. Solid forms need to be liberated before going into solution for effective absorption.

1.11     ROUTES OF ADMINISTRATION

The route is the pathway through which a drug (medicine) in appropriate dosage form is introduced into the human or animal body. The route of administration has a tremendous influence on the therapeutic activity of the medicine because different absorption membranes are involved. The choice of routes of administration depends on drug characteristics, client characteristics, and desired response.

There are two major route of administration; Enteral and Parenteral

1.11.1    Enteral route of drug administration

Drugs introduced into the gastrointestinal tract.

Types of enteral

Oral: in the mouth with some amount of water

Sublingual : Mostly antihypertensive drugs

Rectal

Buccal

Oral route

It involves ingestion of the medicine through the mouth into the body. The medicine is swallowed with fluid or given through Nasogastric tube but is contraindicated in patients with nil per os (NPO), who is unconscious and patients with fresh gastro-intestinal tract surgery.  When possible, it is the first choice for the administration of drugs, since it is both convenient and economical. Drugs administered orally are placed in the mouth and swallowed.

Most drugs that are given orally are absorbed into the circulation from the gastrointestinal tract very efficiently within the limits of the physicochemical properties of the drug concerned. Certain drugs are taken orally for their local effects within the bowel e.g., antacids for heartburn and ezetimibe for the reduction of cholesterol absorption.

Advantages of oral route of drug administration

Ø  It is the simplest, most convenient, and safest means of drug administration.

Ø  It can be self-administered and pain-free.

Ø  It is economical since it does not involve the patient in extra cost. Where the drug is a solid.

Ø  If the drug is in liquid form, nothing is needed except a measuring tool that comes with the drug in most cases.

Ø  No sterile precautions needed.

Ø  Danger of acute drug reaction is minimal.

Ø  Neither special knowledge nor special supplies (syringes, needles) is required for its use.

Ø  It is suitable treating disease of the gastro-intestinal tract.

Disadvantage of oral route

Ø  It is not suitable for emergency as onset of action of orally administered drugs is relatively slow.

Ø  It can only be used in conscious patients and those patients who can swallow.

Ø  It requires patient’s cooperation or compliance, especially outpatients.

Ø  It is not suitable for:

·         unpalatable and highly irritant drugs

·         drugs that are destroyed by gastric acid and digestive juices (e.g., insulin)

·         drugs with extensive first-pass metabolism (e.g. lignocaine, imipramine)

·         patients with severe vomiting and diarrhea.

Ø  Oral route of drug administration is sometimes inefficient as absorption is in most cases irregular and incomplete.

Sublingual/ Buccal route

In this route of administration, the drug is placed under the tongue (sublingual route) or between gums and inner lining of the cheek (buccal route). In both cases, the drug is allowed to dissolve, avoiding swallowing as far as possible. The drug is rapidly absorbed through the mucosa into circulation, thereby bypassing the portal circulation and, thus, the first-pass metabolism in the liver.

Sublingual and buccal routes are of value when the medication concerned is destroyed or partially inactivated in the stomach if swallowed and when a more rapid action is required. These routes however are not suitable for bitter preparations.

Examples of drugs administered through sublingual and buccal routes are Nitroglycerine (glyceryl trinitrate), buprenorphine, and desamino-oxytocin.

 

Rectal route

Medications are sometimes ordered to be administered by rectal route. The rectal mucosa is capable of absorbing many soluble drugs into the circulation. Rectal medication may be in suppository form or in liquid form to be administered as a retention enema.

Unlike the oral route, drugs with irritant or unpalatable nature can be administered through the rectum. Rectal route can also be preferred when the patient has persistent vomiting or is unable to swallow. Also, this route can be used for systemic drug administration in addition to the local administration.

Topical route

This involves local application of the drug to have intimate contact with the target tissue. By this method, medicines are applied locally as lotions, liniments, drops, ointments or creams to the skin, wound surfaces and mucous membrane of the eye, ear, nose, mouth, vagina, etc., mainly for local action. This route provides a high local concentration of the drug without affecting the general circulation. However, drugs that are absorbed into the circulation after local administration may then have systemic effects.

Advantages of Topical route

·         It is suitable for unconscious patients.

·         It provide intimate contact between the medicine and the target or disease tissues.

·         Mode of administration is easy.

Inhalation route

Drug delivery by inhalation is a common route, both for local and for systemic actions. This delivery route is particularly useful for the direct treatment of asthmatic problems, using both powder aerosols (e.g. salmeterol xinafoate) and pressurize metered-dose aerosols containing the drug in liquefied inert propellant (e.g. salbutamol sulphate inhaler).

Instillation

Drug in liquid form is put into the body cavity by this methods. E.g. an orifice of ear, eye, nose.

Pessary

Medicine administered through the vagina.

 

PARENTERAL ROUTE OF DRUG ADMINISTRATION

Is drug administration outside the gastrointestinal tract of the patient. It involves the introduction of medicine into the blood stream or body tissue by injection, and all medications given by parenteral route must be sterilized and free from micro-organism. Parental drug administration can be taken literally to mean any non-oral means of drug administration, but it is generally interpreted as relating to injection directly into the body, by-passing the skin and mucous membranes.

Vials and ampoules

The vials are closed glass or plastic container with rubber stoppers through which sterile needle can be inserted for withdrawing medications. Single-dose is vials usually do not contain a preservative and must be discarded after a dose is withdrawn while multiple-dose vials contain a preservative and may be re-used if aseptic technique is maintained.

Ampoules on the other hand are sealed glass containers the tops of which must be broken off to allow insertion of a needle and withdrawal of the medication. Broken ampoules and any remaining medication are discarded because they are no longer sterile. When vials or ampoules contain a powder form of the drug, a sterile solution of water or 0.9% sodium chloride must be added and the drug dissolved before withdrawal.

Types of Parenteral Routes of Drug Administration

1.  Injection routes

2.  Non-injection routes

Injection Routes

 

INTRAMUSCULAR INJECTION

It is the introduction of the medicine deep into the muscles. They mainly involve introducing the drug in form of solution or suspension into the body at various sites and to varying depths using syringe and needle.

Common site IM injection

Four muscle sites are recommended for IM administration

·         Vastus lateralis;

·         Rectus femoris

·         Deltoid

·         Ventrogluteal.

Rate of absorption = 30 minutes after injection. Rate tend to differ from muscle to muscle

Rate of absorption deltoid > gluteus maximus (especially in women where gluteus maximus muscle is endowed with much fatty tissue)

Complications of poorly performed IM injection include:

·         Pain, bleeding, abscess formation, cellulitis

·         Injuries to nerves and blood vessels

·         Inadvertent intravenous (IV) access

 

 

 Subcutaneous (SC)- route

·         Route is for drugs that are meant for slower and more continuous absorption

·         Blood flow to these areas are low and absorption is therefore slower than IM

·         Vasoconstrictors are sometimes added to further slowdown absorption

Intraarterial route

Definition. Injecting drug directly into an artery

Rarely used (dangers associated with it)

Uses

·         Administer diagnostic agents

·         Cancer chemotherapeutic agents.

Common sites for injections

The common sites of injection for the various sub-divisions may include:

·         Subcutaneous- Upper arms, abdomen, back, and thighs

·         Intramuscular- deltoid, dorsogluteal, ventrogluteal, rectus femories and vastus lateralis muscles.

·         Intravenous- Veins on the back of the hands and the forearms, subclavian and jugular veins are also used, mainly in critically ill patients.

·         Intradermal- the area of scapula, upper chest, dorsal upper arm, or ventral forearm.

 

Advantages of parental administration

·         Drugs that are poorly absorbed, inactive or ineffective if given orally can be given by this route

·         The intravenous route provides immediate onset of action

·         The intramuscular and subcutaneous routes can be used to achieve slow or delayed onset of action

·         Patient compliance problems are largely avoided.

·         It is suitable for unconscious patient.

·         It is suitable for medicines that can cause GIT irritation.

Disadvantages of parenteral administration

·         Once drug injected, you can’t get out

·         Precise computation of dose should be done to avoid toxicity

·         Sterile formulations and equipment needed to avoid introduction of infections.

·         Need highly trained experts 

·         Quite expensive

·         Not suitable for drugs with oily vehicles

·         Not suitable for drugs that lyse red blood cells

·         Painful

·         Emboli contamination

·         Patient compliance can be a problem

·         Anaphylactic reactions in hypersensitive individuals is increase

Special note:

·         Sterile needles and syringes are used to measure and administer parenteral medications; they may be packed together or separated.

·         Many injectables are available in prefilled syringes with attached needles which are inserted into special designed holders and administered. E.g Heparin

·         Syringes are available in various sizes and types, and calibrated so that drug doses can be measured accurately. E.g. 1ml, 2 ml, 3ml, 10ml, 5ml,

·         Choice of needle gauge and length depends on the sub-route of administration, viscosity of the drug solution to be given, and the size of the client.

1.12     DRUG POLICIES IN GHANA

National Drug Policy (NDP)

Introduction

Pharmaceuticals are essential to the delivery of health care in any given population or country. Drugs (including vaccines) cut across all major areas of health care delivery. The absence or inadequate supply of drugs has always led to a loss of confidence in the health care system. Drugs are useful in promoting health, preventing and managing diseases but can be harmful when used inappropriately.

The inappropriate use of drugs has medical and social implications and may exert undue financial burden on the health care system as well as on patients. For example, drugs are estimated to constitute 60 - 80 % of the cost of health care in Ghana. It is the responsibility of the state to ensure that certain functions in the pharmaceutical sector are clearly defined and implemented. A national drug policy forms the basis of government’s responsibility to ensure access of its citizens to good quality drugs at affordable prices, enacting drug regulations, developing professional standards, and promoting the rational use of drugs. In view of this, first edition of the National Drug Policy has been documented and approved by the government in 1999 and subsequently revised in 2004 to form the basis for planning and implementation, monitoring and evaluation of interventions in the pharmaceutical sector.

Functions of the National Drug Policy (NDP)

1.      Provision of guidelines for procurement, storage and distribution of essential drugs.

2.      Promotion of drug research, local drug production and rational drug use.

3.      Determining legal and regulatory framework for effective and efficient control of drugs and pharmaceuticals e.g. drug selection and registration, procurement, local manufacture of drugs, storage, distribution.

4.      Addressing concerns regarding access to medicines for managing existing and emerging disease of public health importance such as HIV/AIDS, TB, malaria.

5.      Addressing issues involving human resource development as well as drug financing, quality assurance, and traditional herbal medicines among others.

GOAL

The overall goal of the policy is to improve and sustain the health of the population of Ghana by ensuring the rational use and access to safe, effective, good quality and affordable pharmaceutical products

OBJECTIVES OF THE NATIONAL DRUG POLICY

The objectives of the policy are to:

􀀹 Promote the rational use of drugs by prescribers, dispensers and consumers;

􀀹 Strengthen quality assurance by ensuring that only safe and effective drugs are sold or supplied to consumers by both the public and private sector;

􀀹 Establish financing mechanisms which ensure access and equity to essential drugs;

􀀹 Improve the system of supply and management of drugs by rationalizing the procurement system and improving the drug distribution and management systems at all levels of health care delivery; and

􀀹 Increase the quantity and quality of health human resources involved in pharmaceuticals at all levels of the health sector.

In its efforts to achieve this, the Ministry of Health and other related ministries and agencies have faced a number of problems including the following:

• An under-developed machinery to ensure enforcement of existing laws and regulations resulting in poor compliance;

• Lack of qualified and experienced management and technical personnel, inadequate drug supply management procedures, unsuitable and insufficient distribution and storage facilities, often resulting in increased procurement costs and losses;

• Lack of systematic and continuing education coupled with inadequate reference and learning materials for various sectors of the healthcare delivery system have contributed to poor patient care practices (including inappropriate use of drugs) and efficiency;

• The increasing cost of drugs and medical supplies with the expanding provision of health services and its effect on the national health budget; and

• The dramatic increase in the number of drug outlets in both the public and private sectors. In addition the number of drugs currently registered by the drug regulatory agency stands at 680 generics and 2100 specialities.

Recognizing these problems, the Ministry of Health has taken a number of steps directed at addressing some of the problems. These include:

• The promulgation of the Food and Drugs Law 1992 (PNDCL 305B) and the Pharmacy Act, 1994 (Act 489), which have provided the legal framework for the control of pharmaceutical activities in the country;

• Development of Traditional Medical Practice Act 2000 (Act 575) and efforts to constitute TMP council;

• The establishment of the Ghana National Drugs Programme;

• Government’s approval of the first edition of the National Drug Policy in August 1999;

• The publication and distribution of a National Essential Drugs List, Standard Treatment Guidelines; and

• The establishment of regional focal persons responsible for promoting the rational use of drugs and the training and deployment of clinical pharmacists.

 

 

 

1.13     Classification of drugs NDP

 

The National Drug Policy classified drugs according to levels at which they are prescribed and dispensed into two (2) main groups.

1.      Non-prescription drugs which are sold “over-the-counter” (OTC) as they are judged to be safe for use without medical supervision. Hence, over-the-counter medicines are simple or compound preparations that can be purchased without a medical prescription. They are normally supplied at the customer’s request or on the advice of the seller.

2.      Prescription drugs which are considered to be unsafe for use except under medical supervision and are dispensed only on a physician’s prescription.

Therefore, in terms of safe prescribing and dispensing, the two main classifications of drugs are;

PART 1: May be dispensed by a registered pharmacist only.

a)      Schedule 1: Are prescription only medicines (PoM).

·         Prescription from a registered doctor, veterinary or dental surgeon.

·         May be dispensed in limited quantities without prescription (emergency or where a registered practitioner is not available) by registered pharmacist. 

b)     Schedule 11: Pharmacy Only Medicine (P): Prescription from authorized prescriber required.

Examples: Narcotics, analgesic, morphine, pethidine, codeine, Amphetamine.

PART 11: May be dispensed by pharmacist and other authorized persons.

a)      Schedule 111: Dispensed by registered pharmacist without a prescription or by pharmaceutical technologist on prescription from an authorized prescriber

Dispensary requirement: These have less potential for abuse than schedule 1 and 11 drugs but may lead to psychological and physical abuse. A written prescription lasts for six months. E.g. HPT or Diabetic patients who have the prescription can go with the same within the six months.

Example: Mixture containing small amount of codeine.

b)      Schedule IV: Over the counter (OTC) medicines, sold in authorized outlet without prescription.

1.13.1    PRESCRIPTION 

Prescription is written order or an instruction or direction for making up or use of medicine, duly signed by medical practitioner, Dentist or veterinary surgeon. Prescription may also be referred to as medication order. The prescriber may however give a verbal order (directly or via a telephone) at times. These are written on client’s order sheet, signed by the message recipient, and later countersigned by the prescriber. The recipient must make sure that the order is clear by repeating the order to the prescriber. If verbal order is given, it must be documented or entered into the medical records, and the information must includes;

·         Name of prescriber

·         Name of medication with dose, dosage form, frequency and the period

·         Route of administration

·         Message recipient’s name and rank, and other relevant information.

·         Part of prescription

Traditionally, prescription consist of the following parts;

1.      Name and address of the physician, and telephone number-this is usually printed on a prepared pad of blanks.

2.      Patient’s name, address, age, and the date of prescription

3.      Superscription-this consist of the symbol Rx, the abbreviation for ‘recipe’ which means ‘take thou’.

4.      Inscription- this part forms the body of the prescription order and contains the name and the amount of each ingredient or medicine expressed in metric system of weights and measures.

5.      Subscription-this part consist of the direction to the pharmacist regarding the compounding and dispensing of the prescription.

6.      Signature or signatura- this part includes the directions for the patient. It may also be referred to as the label, as these directions are written by the pharmacist on the container in which the preparation is dispensed.

7.      Prescriber’s signature and registration number-this is required by law.

Legal validity of prescription or characteristic of valid prescription

A prescription may be valid or invalid depending upon the nature or features present. Therefore, the Pharmacy and Drug Act 1961 (act 64^th) obliges the pharmacist to ascertain that the prescription is valid on criteria below;

·         It must be in indelible ink, legible and must be dated.

·         It must bear the usual signature of the prescriber.

·         It must bear the name, qualification and address of the prescriber

·         It must state who (pregnant, elderly, infant etc), the name, age, or weight and address of the person for whom treatment is given.

·         If coming from the hospital, it must bear the hospital registration number.

·         It indicates, except in the case of ointments, the total amount of the drug (medicine) to be supplied and the dose to be used, express in the metric system only i.e. gram, milligram, microgram or millilitres.

·         It must indicate the name (generic or official) and the form of the medicine.

 

Some Latin abbreviations used on prescriptions

Abbreviation	Latin meaning	English meaning
b.i.d or bd o.d.      o.m.     o.n. o.c p.a.      p.c.                  p.r.n.   PR       pulv. PV q.d or Q.i.d q.d.s. stat or St tab	Bis in die Die or omni die Mane or omni die Nocte Occulentum Parti affectae Post cibum Pro re nata   Pulvis   Quater in die Quater in die Statim Tabletta	Two times daily Every day Every morning Every night eye ointment to the affected part after food when required per rectum Powder Per vagina Four times daily To be taken four times daily Immediately A tablet

 

Types of medication orders

a)      Standard written orders-apply indefinitely until the prescriber writes another order to alter or discontinue the first one. There are two forms namely;

·         Schedule Order- these have no specific period after which the medication should be stopped e.g. Insulin 20 IU daily.

·         Self-terminating Order- it specify number of days or dose of the drug patient is to receive e.g. Tab Paracetamol 1gm t.i.d × 5.

b)      Stat Order- an order for a single dose of drug to be given immediately.

c)      PRN Order- in the judgement of the nurse or client’s condition demands it.

d)      Single Orders –for medications that are given only once e.g. Tetanus Toxoid

e)      Standing Order (Protocols)-they are established guideline for treating a particular disease or set of symptoms.

f)       Verbal Orders-medications given orally rather than in writing

g)      Telephone Order- verbal orders given to a nurse via telephone.

1.13.2    MEDICATION ERRORS

These are daily occurrence in health care facilities resulting in fatal or near fatal consequences. It should be the goal of every health care professional to be aware of potential errors and strive to prevent them. These errors can occur during prescription, Dispensory, administration or documentation phase of medication administration.

Prescription phase:

There may be a wrong prescription to the right patients or vice versa. There could also be an over dosage or under dosage prescription for a patient.

Dispensory phase:

The tendency of not getting the actual drug but a drug that is kind of similar to the actual prescribed drug.

Administration phase:

Taking drugs together or separately. Some drugs are meant to be taken alone whiles others are to be taken together with other drugs.

Documentation phase:

When drugs are served but not documented in the notes. At times drugs are given but patient have not taken then meanwhile it will be documented that it has been served.  Failure to label infusions into which supplements have been added.

 

DANGEROUS DRUGS ACT (DDA)

Forensic pharmacy is an aspect of the pharmaceutics that deals with pharmaceutical legislation. Therefore, ‘Dangerous Drug Act’ (DDA) is an act of the parliament that governs the procurement and use of drugs. It main objective is to exercise regulatory control over the sale and use of drugs (medicine) and poisons in the country.

 

2           THERAPEUTIC FOODS AND PREPARATIONS

 

Therapeutic foods are designed for specific, usually nutritional, therapeutic purposes as a form of dietary supplement. They are primarily used for emergency feeding of malnourished children or to supplement the diets of persons with special nutrition requirement such as the elderly. The therapeutic foods are usually made of a mixture of protein, carbohydrate, lipids, vitamin and mineral’s. They are usually produced by grinding all ingredients together and mixing them in a dry state to prevent spoilage. The process of mixing allows for proteins and carbohydrate components of the food to be embedded in the lipids matrix. Some therapeutic foods requires the addition of water before administrating, while other can be consumed at it is. The world health organization’s standards for treating of malnutrition in children specify the use of two formulas during initial treatment, Formula 100 (F-100) and Formula 75 (F-75). These formulas contain a mixture of powdered milk, sugar, and other ingredients designed to provide an easily absorbed mix of carbohydrates and essential micronutrients. They are generally provided as powdered mixes which are reconstituted with water. These formulas are used with gradual introduction of other food until the child approaches a normal weight. The standard treatment of childhood malnutrition is administered in two phases.

·         The phase one usually deals with children who are severely malnourished and very ill as a result and the recommended formula in this phase is F-15 with parenteral antibiotics until there is improvement in the child’s appetite and clinical condition. After this, the child is entered into phase two

·          Phase two of the treatment using F-100 until he/she is no longer wasted. The phase two start while the child is on admission but usually completed after the child goes home. The parents then feed the child with flour supplement made of cereals and legumes as a replacement for milk-based foods used in phase one and two.

 

Students presentation

Ready-to-use therapeutic food (RUTF)

Formular-100

Formular-75

Rehydration solution for malnutrition (ReSoMal)

Combined mineral and vitamin mix (CMV) mix

 

3            

 

DRUGS AFFECTING THE NERVOUS SYSTEM

 

## Read on the physiology of the central nervous system.

Assignment 2: list the various neurotransmitters and their functions

Introduction

 Antipyretics

Antipyretics are drugs that lowers’ the body temperature when it is raised. They are mainly effective in pain originating from muscles and joints, in headache resulting from distension of blood vessels and meninges and in pains originating from nerve trunks. Examples are aspirin and paracetamol.

 Anti-inflammatory analgesics

These reduce inflammation in addition to their analgesic action. They are useful in the treatment of patients with chronic disease accompanied by pain and inflammation e.g. rheumatic diseases. Examples are aspirin, ibuprofen, indomethacin

Analgesics

Analgesics are drugs administered to relieve pain without producing general anaesthesia. Pain is the sensation of discomfort, hurt, or distress which may occur with tissue injury and inflammation. Pain involves both physical and emotional experiences, and can be classified as acute e.g. injuries like cut or tear of ligaments, chronic non-malignant e.g. arthritis, chronic malignant e.g. cancer or kidney disease. Headache are the most common cause of pain and can be considered a separate class of pain. In terms of source or tissue involved, it may be categorized as peripheral, central neural and visceral pains. The visceral pain is primarily conducted by sympathetic nerves, and is dull, aching and vaguely localized. Pain of visceral origin is sometimes felt on certain cutaneous areas of the body surface at the same distance from the involved visceral. Additional, pain may be classified into two as superficial (intergumental) and deep pain.

## Read on Painful pathway and pain perception (pathophysiology of pain)

Analgesic may be classified as;

1.      Narcotic or Opiate Analgesics

2.      Non-narcotic analgesics

3.      Non-Steroidal Anti-inflammatory drugs (NSAIDs)

In addition to the analgesics property, an analgesic may equally have antipyretic or anti-inflammatory properties or both.

Narcotic or Opiate Analgesics

The term ‘narcotic’ refers to any analgesic derived from opium poppy alkaloids as well as to compound chemically similar to the alkaloids as a result of their habit-forming nature as described by the Harrison Narcotic Act of 1914. Therefore, the narcotics are a group of naturally occurring and synthetic agents which interact with specific opioid receptor sites in the nervous system to relieve moderate to severe pains, particularly those of visceral origin.  The narcotics agonist alter pain perception by inhibiting the transmission of pain impulses in sensory pathways in the spinal cord, reducing cortical response to painful  stimuli in the brain stem, thalamus and limbic system, and by altering behavioral response to pain as they are mediated in the frontal lobe. Narcotics analgesic are absorbed well from the GIT and rectal mucosa and are distributed to most body tissues. Parenteral administration produces the most rapid onset of action, but duration of action varies depending on the drug and route of administration. They do not have any anti-inflammatory and antipyretic action. Chemically, narcotics analgesics may be classifies as;

A. Narcotics agonist analgesics

        1.  Phenanthrenes

                                i.            Naturally occurring opium alkaloids e.g. Morphine, Codeine

                              ii.            Semisynthetic derivatives of Morphine e.g. Hydromorphone, Oxymorphone

                            iii.            Semisynthetic derivatives of codeine e.g. Hydrocodone

2. Methadones e.g. Methadone, Propoxyphene

3. Morphinan e.g. Levorphanol

4. Phenylpiperidine e.g. Pethidine

B. Narcotic Agonist-Antagonist Analgesics

1.      Phennanthrene e.g. Buprenorphine, Nalbuphine

2.      Morphinan e.g. Butorphanol

3.      Benzomorphans e.g. Phenazocine, Pentazocine

MORPHINE SULPHATE

Indications: Morphine interacts with opioid receptors in the central nervous system to reduce pain perception and produce analgesia. Morphine is irregularly absorbed from the gastro-intestinal tract and is rarely administered orally for pain. The oral route is useful in the management of cancer pain. Morphine and its congeners are well absorbed by diffusion from parenteral sites, and can be given by SC, IM or IV injections. Morphine is mostly excreted through urine.

Side effect; nausea, vomiting, constipation, respiratory depression, hypotension, bradycardia, urinary retention, bronchial spasm, urinary retention.

Contraindications-bronchial asthma, emphysema, head injury, delirium.

Presentation: by injection, 5-15 mg every 4 hours.

 

PETHIDINE HYDROCHLORIDE

Indications: Pethidine has a quicker on set of action but short lasting and less potent that morphine. It is used principally for analgesia in labour but equally used for relief of pain of coronary occlusion, biliary or renal colic. It is also used pre-operatively as an adjunct to anaesthesia. It produces analgesia by interacting with opiate receptors in the nervous system through reduction of pain impulse perception.

Side effect; dizziness, tachycardia, nausea, vomiting, orthostatic hypotension

Contra-indication: like morphine but should be avoided in severe renal impairment

Dosage; by, 50-150 mg every 4 hours,

 

NON-STEROIDAL ANTI-INFLAMMATORY DRUGS (NSAIDS)

They reduce both pain and inflammation of chronic inflammatory disorders such as rheumatoid arthritis, nut they do not alter or modify the disease process itself. There are several groups of NSAIDs, these include;

1.      Indole derivatives e.g. Indomethacin

2.      Propionic acid derivatives e.g. Ibuprofen, Naproxen, Ketoprofen

3.      Fenamate e.g. Mefenamic acid

4.      Phenylacetic acid derivatives e.g. Diclofenac

IBUPROFEN (Brufen)

Analgesic, anti-inflammatory and antipyretic. It is used for mild to moderate pain in conditions such as dysmenorrhoea, migraine, postoperative pain, rheumatic disorders such as ankylosing spondylitis, osteoarthritis, rheumatoid arthritis and in other musculoskeletal and joint disorders like sprains and strains.

Dose:  By mouth 1.2 – 1.8 g daily, although a maintenance dose of 0.6 – 1.2 g daily may be effective in some patients.

Children: 20 – 40 mg per kilogram body weight in divided doses daily.

Adverse effects: G.I. disturbances, peptic ulceration, G.I. bleeding, headache, dizziness, nervousness, skin rashes, pruritus, tinnitus, oedema, depression, drowsiness, insomnia, blurred vision and other ocular reactions, agranulocytosis and thrombocytopenia, etc.

 Caution: Asthmatics, bronchospasm, bleeding disorders, cardiovascular disease, peptic ulceration, renal failure.

Contraindication: patients generally sensitive to aspirin.

Presentation: tablets 200 mg, 400 mg, 600 mg; syrup 100 mg/ml

NOTE: The administration of NSAIDs to pregnant patients can lead to ductal (ductus arteriosus) constriction in utero and may lead to problems in establishing pulmonary blood flow after birth.

PARACETAMOL

Paracetamol has analgesic and antipyretic properties with no useful anti-inflammatory action.

Indications: It is used for mild to moderate pain and pyrexia.

Dose: 0.5 – 1g every 4 – 6 hours; the maximum daily dose is 4 g.

Children: 3 months – 1 yr.  60 – 120 mg

                1 yr. – 5 yrs.   120 –250 mg

                6 yrs – 12 yrs 500 mg to be taken 3 –4 times daily or as required.

Adverse effects: these are usually mild though haematological reactions, skin reactions and other allergic reactions may occasionally occur. Liver damage may occur from overdose or prolonged use.

Caution: hepatic impairment, alcoholism.

 Presentation: tablet 500 mg, elixir/syrup 120 mg/5ml.

 

3.1         SEDATIVES-HYPNOTICS

Hypnotics are drugs administered to induce sleep.

 Sedatives are drugs administered to cause sedation (they relax the patient without producing sleep).

Tranquilizers are those that are administered to quieten or calm down disturbed or excited patient.

Anxiolytics are drugs administered to lessen anxiety.

In many cases the same drug can be used to produce all or many of these effects depending on the dose used for instance, most anxiolytics will induce sleep when given in large doses at night. Similarly, for most hypnotics, if given in small divided doses during the day will cause sedation (act as sedatives).

Cautions; Ideally hypnotics and sedatives should be used for short courses of treatment in people who are acutely disturbed. Tolerance to their effects occurs within 3 to 14 days of continuous use. The use of hypnotics should be avoided in children except for occasional use in night-terms and sleep-walking syndromes. Their use in the elderly who are at risk of being unable to control their movement and confused should be avoided because they might fall and injury themselves.

3.1.1        Tranquilizers

Sedatives/minor tranquilizer

Anxiolytic sedatives or minor tranquillisers are used in the management of psychoneurosis to reduce pathological anxiety, agitation and tension. They may also be employed in anaesthetic premedication. Examples are the benzodiazepines – diazepam, chlordiazepoxide (librium), lorazepam (Ativan) and Nitrazepam (mogadon). Benzodiazepines are preferred because of their low incidence  of adverse effects for instance, absence of enzymes induction, little effect on REM sleep and low incidence of interactions as well as small record of abuse.

Benzodiazepines used as sedatives-hypnotics can be divided in two groups depending on their length of action.

a.       Long acting Benzodiazepines-the effect of evening dose may well last into the next day leaving the patient drowsy, uncoordinated and very susceptible to effect of alcohol. The drugs include Nitrazepam, Flurazepam, and Diazepam.

b.      Short acting Benzodiazepines-these have usually been sufficiently cleared or excreted by the body after an evening dose to leave little or no hangover effect the next day. This include Temazepam, Triazolam and Lorazepam.

 

 

Diazepam

A benzodiazepine with anticonvulsant, anxiolytic, sedative, muscle relaxant and amenestic properties.

Indications:  It is used in the treatment of anxiety and tension states; as a sedative and premedication; in the control of muscle spasm as in tetanus and in the management of alcohol withdrawal symptoms. It may also be used in epilepsy and as premedication before surgery

Dose: 5 – 15 mg, increasing to 30 mg in severe anxiety daily in divided doses.

Diazepam may also be used in febrile convulsions in a dose of 250 micrograms per kilogram body weight by slow I.V or rectally in a dose of 200 - 500 micrograms per kilogram body weight which may be repeated if necessary. The dose may be repeated in 2 –5 hours if necessary.

Contra-indications: Patients with respiratory depression and hepatic impairment.

Adverse effects: These include dizziness, vertigo, light headedness, and headache. Others are confusion, mental depression, changes in libido, ataxia and tremor. There may also be gastrointestinal disturbances, urinary retention or incontinence; it may also produce paradoxical excitement.

Presentation:

                    Diazepam tablet 2 mg, 5 mg, 10 mg.

                     Injection 5 mg/ml in 2 ml ampoules;

                     Diazepam rectal solution, 2 mg/ml, 4 mg/ml.

Intramuscular injection of diazepam is slow and erratic, depending on the site of administration. When diazepam is injected into the deltoid muscle, absorption is usually rapid and complete.

 

Neuroleptics or major tranquillisers (Antipsychotics)

They are also referred to as antipsychotic agents and are used in the management of psychosis. Examples are the

a.       Phenothiazenes e.g. chlorpromazine, thioridazine and trifluoperazine

b.      Butyrophenones e.g. Benperidol and Haloperidol, etc.

Other atypical antipsychotic drugs include Olanzapine and clozapine.

 

3.1.2        CHLORPROMAZINE

Indications: A phenothiazine used for schizophrenia and other psychoses, mania, psychomotor agitation and violent or dangerously impulsive behaviour. It is also used in palliative care in treating nausea and vomiting in terminal diseases.

Dose: initially 25mg three times daily (or 75mg at night) orally, adjusted according to response, to usual maintenance dose of 75-300mg daily.

By deep IM injection, 25-50mg every 6-8 hours. Child 1-5 years, 500 micrograms/kg every 6-8 hours, max 40mg daily. Child 6-12 years, 500 micrograms/kg every 6-8 hours (max 75mg daily).

By rectum as suppository, 100 mg every 6-8 hours, as chlorpromazine base.

Presentation: Chlorpromazine hydrochloride tablets 10mg, 50mg, 100mg

Chlorpromazine hydrochloride oral solution 25mg/5ml, 100mg/5ml

Chlorpromazine hydrochloride injection 25mg/ml.

Chlorpromazine suppository 100mg as chlorpromazine base.

 

3.2         ANAESTHETIC AGENTS

 

Anaesthesia:  Reversible state of central nervous system depression resulting in loss of response to and perception of external stimuli. These are agents that cause loss of sensation in producing analgesic effects. Various agents are used for the purpose and are applied per different routes (IV, IM, Topical or Inhalational).

·         General anaesthetics

·         Local anaesthetics

 

LOCAL ANAESTHETICS AGENTS

Local anaesthetics agents act by causing reversible block to conduction along nerve fibres. The local effects exerted by these drugs include loss of pain, decrease in temperature, and loss of touch, vasodilation, and loss of motor power. They also offer a safe alternative to general anaesthesia for elderly or debilitated patients.

Compound use as local anaesthetic fall into two chemical types;

·         Esters of Para-amino Benzoic Acid (PABA) e.g Amethocaine, Benzocaine, Cocaine, Procaine

·         Amides- e.g.  Bubivacine, Cinchocaine, Lignocaine, Prilocaine

 

Use and application of Local Anaesthetics

Local anaesthetics can be administered in a variety of ways because some compounds are more suitable than others for a particular method of administration. These are;

·         Topical Anaesthesia-application of the drug directly to an external surface or site which is to be anaesthetized. This type is useful for anaesthesia of the mucus membrane of the eye, nose mouth, ear and perineal region.

·         Infiltration or field (block) Anaesthesia- this is the injection of the drug around the site of irritation or operation. To prevent quick absorption of the anaesthesia into the blood stream, blood vessel constrictors such as Adrenaline is often injected at the same time in small quantity. The suitable drugs include Cocaine, Procaine, Lignocaine.

·         Regional Anaesthesia-This is reserve for specific surgical procedures such as hand or foot. The anaesthetics in injected intravenously into an exsanguinated limb to cause loss of sensation and motor activity in the localized area.

·         Nerve Block Anaesthesia-In this procedure, the local anaesthesia is either injected around a nerve trunk (e.g. radial, ulnar, pudendal) or into the spinal column.

 

LIDOCAINE (LIGNOCAINE)

Indications: It is effectively absorbed from mucous membranes and is a useful surface anaesthetic in concentrations of 2% to 4%. Except for surface anaesthesia, solutions should not usually exceed 1% in strength.

Duration of action (with adrenaline) is about 90 minutes.

Caution: It should be used with caution in epilepsy, hepatic or respiratory impairment, impaired cardiac conduction and bradycardia. Reduce dose in the elderly or debilitated. 

Contra-indication – hypovolaemia, complete heart block; do not use solutions containing adrenaline for anaesthesia in appendages.

Dose – Infiltration anaesthesia, by injection, according to patient’s weight and procedure, maximum 200mg (or 500mg if given in solution containing adrenaline. Surface anaesthesia, usual strength 2-4%.

 

3.2.1        GENERAL ANAESTHETICS

General anaesthetics agents depress the central nervous system (CNS) to produce reversible loss of consciousness, loss of responsiveness to sensory stimulation including pain, and muscle relaxation. The anaesthetics action is exerted at the synapses where they depress both transmitter and excitability of the post-sympathetic membrane. Therefore, goals of general anaesthesia are to achieve:

        i.            Analgesia

      ii.            Loss of consciousness

    iii.            Loss of reflexes to minimize (laryngo-spasm, cardiac arrhythmias, salivation, vomiting, and postoperative abdominal distension)

    iv.            Skeletal muscle relaxation which is desirable during abdominal surgery.

However, general anaesthesia may result from one or a combination of drugs. But except for short procedures, it is common to use a combination of several drugs, each with different action to produce anaesthesia.

The choice of a particular anaesthetic agent for a patient involves several considerations such as:

a.       Patients physiological state

b.      Patient medical history

c.       Types of surgical procedure, and

d.      Anticipated postoperative course

Types of General Anaesthetics Agents

There are various varieties of general anaesthetics depending upon their physical and chemical properties, and duration of action. Thus, general anaesthetics agents are;

1.      Volatile liquids or gases vaporized in oxygen and administered by inhalation

2.      Non-volatile solutions administered by injections.

Therefore, they are grouped into two groups as intravenous and inhalation anaesthetics.

1. Intravenous Anaesthetics- they are used in situations requiring a short duration of anaesthesia. They are also use to promote rapid induction of anaesthesia or to supplement inhalation anaesthesia. They are categorized into three (3) depending on their chemical characteristics like mechanism of action. They include

        i.            Ultra-short acting barbiturates- they are use short procedure. E.g. Methohexital, Thiopental.

      ii.            Rapid-acting non-barbiturates hypnotic-use for induction, and for supplementing other anaesthetics e.g. Etomidate

    iii.            Dissociative anaesthetic-induce a neuroleptic-like state without loss of consciousness e.g. Ketamine.

Thiopental Sodium

Indications: it produces hypnosis and anaesthesia without analgesia within 30-60 seconds, and last for few minutes. However, when consciousness returns, the patient is left dazed and not fully in control of mental capacities. Complete recovery takes up to 6-8 hours.

Side effects: apnoea, hypotension, coughing, yawning, laryngospasm.

Contra-indications; tumours in the pharynx or larynx, acute cardiovascular failure.

Dose; 100 to 150mg over 10-15 seconds, repeated if necessary according to the patient’s response after 20-30 seconds.

 

Ketamine

Indications- On administration, it produces anaesthesia-like state where patient feels totally dissociated from the surroundings. Ketamine is a rapid-acting anaesthetic producing a state of dissociation with profound analgesia. The patient appears to be awake but does not response to pain and does not recall the experience on recovery.

Side effects: hallucination, psychotic sequelae

Contra-indications: hypertensive patient’s, history of mental illness, etc.

Dose: 1 to 2 mg/kg IV over 60 seconds, repeated according to patient’s response.

 

2. Inhalation anaesthetics.

These are gaseous and volatile drugs which are mainly used to maintain the anaesthesia once it has been induced by intravenous drugs. However, some have rapid onset of action and can be used for induction. To prevent hypoxia, gaseous agents must be given with adequate concentration of Oxygen. Inhalation anaesthetics are used for surgery because they offer more precise and rapid control of depth of anaesthesia than injections anaesthesia. Inhalation anaesthetics agents are administered as gases, so the quantity of anaesthetics agents needed can be determine by a measurement called the minimum alveolar concentration (MAC). The agents includes; Nitrous oxide, Enflurane, Isoflurane, Ethylene, Cyclopropane, and Halothane.

Nitrous oxide (gas)

Indications- It is used for induction and maintenance of anaesthesia or commonly used as a component of ‘balanced anaesthesia’. It is a weak anaesthetic but has analgesic properties and it is relatively non-toxic. It is combined with oxygen that is 20% of oxygen on induction and 30% of oxygen during maintenance. It may be given 50:50 mixed with oxygen when it is used as analgesic during painful procedures such as wound dressing and labour.

Side effect: Megaloblastic anaemia, depression of white blood cell formation.

Halothane (volatile liquid).

Indications; It is a volatile colourless non-inflammable liquids with a chloroform-like odour. Concentrations up to 5% are given mixed with at least 25% oxygen. This may be given or with Nitrous oxide/oxygen mixtures in a balanced anaesthesia. Halothane will produce moderate muscle relaxation, but a specific muscle relaxant may be added if necessary. Recovery is rapid if used more than once in 4-6 months.

Side effects: Liver damage, cardiorespiratory depression.

 

 

 

 

4           DRUGS AFFECTING THE CARDIO-VASCULAR SYSTEM

Brief physiology of the myocardium and the key concepts of the cardio-vascular system

The cardio-vascular or circulatory system consist of the heart, blood vessels and blood. The main functions of the system is to carry oxygen, nutrients, hormones and antibodies to all body cells, and to remove waste products of cell metabolism. Blood flow results from pressure differences in the circulatory (forces of blood flow-force of resistances) while blood pressure refers to the force exerted by the blood against the blood vessels. The cardiac output is a function of the stroke volume and the heart rate.

Mathematically, Cardiac output= Stroke volume (amount of blood ejected when the left ventricle contracts/ per beat) × the rate (the number of beats/minute).

The stroke volume (60-90ml) is affected by myocardial contractility, preload and afterload.

Thus, cardiac output is the amount of blood pumped out of the heart per minute i.e. approximately 5.5 litres/minute.

The peripheral circulation refers to the amount of blood ejected from the left side of the heart ( blood to all body tissues and organs except the lungs)

Pulmonary circulation refers to the blood ejected from the right side (blood to the lungs via the lungs via the pulmonary arteries). On the other hand,

Venous return is the amount of blood returned to the right atrium (usually equals to the cardiac output, but differences may occur).

 Afterload refers to the amount of resistance in the aorta and peripheral blood vessels that the heart must overcome to pump effectively/ pressure against which the heart must work to eject blood during systole

Preload refers to the blood volume in the ventricle at end of diastole or amount of resistance venous blood returning to the heart. The preload helps to determine the force of the ventricular contractions. According to the Starling’s law, increased ventricular stretch usually leads to increase in stroke volume and arterial pressure.

 

4.1         ANTIHYPERTENSIVES

Antihypertensive are drugs used to treat hypertension. The term hypertension literally means an abnormally raised arterial pressure, usually above 140/90 mmHg. Hypertension is denoted primary or essential when no specific cause is evident, and it is secondary hypertension when it is due to other underlying clinical conditions e.g. renal disease. Thus, primary or secondary hypertension occurs when homeostatic mechanisms fail to regulate blood pressure. Hypertension increases risks of myocardial infarction, congestive heart failure, cerebral infarction and haemorrhage, and renal disease among others. However, in order to understand how antihypertensive drugs act, it would be useful to review the factors which regulate blood pressure. The four main factors which are directly under the control of the sympathetic nervous system are suspected to be defective in a hypertensive patient.

The factors include:

i.          Total peripheral resistance (TPR)

ii.         Heart rate

iii.        Myocardial contractility, and

iv.        Venous returns

 

Additionally, there is strong evidence that in hypertensives, the Renin-Angiotensin-Aldosterone system is also faulty. Renin as a kidney enzyme is derived from the granules of the juxtaglomerular apparatus. On renal ischemia, renin is released which acts on a substrate in the blood called angiotensinogen which is converted into angioten-1(a decapiptide). This is further converted into angiotensin-II ( an octapeptide) by the angiotensin converting enzymes located in the lungs. The angiotensin-II (angiotensin) stimulates the adrenal cortex to release aldosterone. The aldosterone acts on the sodium pumps of the cells in the distal tubule and collecting duct to increase the sodium re-absorption mechanism. This leads to water retention and blood volume is increased resulting to increase in blood pressure. Angiotensin II is a potent vasopressor than noradrenaline which causes strong arteriolar constriction and a rise in both diastolic and systolic blood pressures. Thus, secretion of catecholamine from adrenal medulla and aldosterone from adrenal cortex results to hypertension. Additionally, vasopressin (ADH) is also released from posterior pituitary in response to hypotension. Therefore, the antihypertensives influence arterial blood pressure at four effector sites namely arterioles, veins, heart and the kidneys. Specifically, blood pressure is directly influenced by Total Peripheral Resistance and Cardiac output which is also dependent on the stroke volume and heart rate. The stroke volume is dependent on the myocardial contractibility and venous return which in turn depends on the venous tone and blood volume. Thus, the

1. The Beta-blockers  - They act by competing with epinephrine for beta-adrenergic receptor sites thereby inhibiting or blocking sympathetic stimulation to decrease heart rate and cardiac output, and reduce blood pressure. The release of adrenaline or epinephrine occurs at points near to the beta- receptor sites in the heart. This release mechanism is greatly increased during stress or motion and the beta-blockers interfere or block the mechanism of stimulation of the adrenaline.

The beta-blockers are grouped into two as

1. Non-selective (blocking beta I or cardiac receptors and beta2 non-cardiac receptors). Examples include: Carteolol, Nadolol, Pentbutolo, Pindolol, Propranolol, Timolol

2. Selective (blocking primarily beta I receptors.

Examples: Acebtolol, Atenolol, Betaxolol, Bisoprolol, and Metoprolol.

By blocking beta I receptors in the heart, these drugs decrease heart rate and myocardial contractility and ultimately lower cardiac output. Since renin release is mediated through beta I receptors in the kidneys, beta blockers also decrease the effect of the renin-agiotensin-aldosterone system.

 

a.         Propranolol hydrochloride

Contra-indications: asthma, heart failure cardiogenic shock, etc

Side effects: bradycardia, heart failure, bronchospasm, peripheral vasoconstriction, depression, lethargy, impotence, headache, vertigo, etc.

Dose; 40 mg 2-3 times daily

 

b. Atenolol

Contra-indications and side effects same as Propranolol

Dose. Peripheral vasoconstriction 100 mg daily in 1 or 2 doses.

 

2. Alpha - blockers - The alpha-adrenergic blocking agents selectively block alpha I receptors to interfere with sympathetic stimulation and directly relax arteriolar smooth muscle. This interference reduces peripheral vascular resistance and produces vasodilation without tachycardia or reducing cardiac output. This action also increases gastric secretions, and may result in nausea, vomiting and diarrhoea. Additionally, this action produces reflex tachycardia as a result of direct cardiac stimulation and orthostatic hypotension from vasodilation.

Example: Doxazosin, Prazosin, Phenoxybenzamine and Terazosin

Prazosin

Side effects; postural hypotension, paroxysmal tachycardia, etc

Dose: 2 mg tid for 4 to 6 weeks.

 

3. Alpha + Beta-blockers - Is a mixed alpha- and beta-adrenergic blocking agent with an alpha, blocking action and nonspecific beta I &2 adrenoceptor blocking action. It lowers blood pressure primarily by blocking alpha receptor in the peripheral arterioles, reducing the TPR, reduces renin and aldosterone levels as well as renal vascular resistance and may produce cardiac output. Labetalol lowers both systolic and diastolic pressures without postural or exercise induced hypotension.

Examples of drugs; Labetalol, and Carvedilol.

Side effects: nasal stuffiness, vivid dreams, epigastric pain etc.

Dose:  100 mg t.i.d orally, increased to 200 mg 3 to 4 times daily for 1 or 2 weeks.

 

4. Centrally Acting Agents or Central-acting Sympathetic Nervous System Inhibitor

These are drugs that act on the mechanism within the brain which decreases sympathetic tone and resistance in peripherals arterioles, peripheral vasodilation, lowering the standing and supine blood pressure and decreasing the heart rate and cardiac output.

Examples of drugs: The drugs include Clonidine hydrochloride, Guanabenz acetate, Guanfacine, and Methyldopa.

Methyldopa

In the central neurones, methyldopa is converted to alpha-methylnoradrenahne which is an alpha2-receptor agonist by the enzyme dopa-decarboxylate. This interaction with the receptor leads to a decreased sympathetic outflow from the brain and causes peripheral vasodilatation and reduction of TPR.

Dose: 250 mg twice daily or increased to 500 mg four times per day.

Side effects: depression, nightmares, fluid retention, haemolytic, anaemia, enlargement of breast, drug fever, etc.

Contra-indication: Can led to erectile dysfunctioning

5.         Ganglionic blocking agents - They compete with acetylcholine to occupy cholinergic receptors on the autonomic ganglia and thereby interrupt transmission of parasympathetic and sympathetic impulses. The resulting reduction in sympathetic tone and cairdiac output increases vasodilation and lowers the blood pressure. The drugs include Mecamylamine, and Trimethaphan.

Mecamylamine hydrochloride

It is used to treat moderate to severe hypertension but considered as an adjunct rather than a primary agent.

Dosage: initially, 2.5 mg by mouth twice daily, increased by 2.5 mg every 2 or more days until the desired response is achieved. The average maintenance dosage is 25mg/day given in three divided doses.

Side effects: shortness of breath, respiratory depression, tachycardia, etc.

6. Direct Vasodilators - The direct vasodilators act on arteries, veins, or both to cause dilation and relaxation and as well promote an increase in cardiac output. Vasodilators are potent drugs, especially when used in combination with a beta-blocker and a thiazide in the management of hypertension. Some are usually used to treat resistant or refractory hypertension, and also reserved for use in hypertensive crisis. The drugs are

Examples of drugs: Minoxidil, Diazoxide, Nitroprusside sodium, and Hydralazine hydrocloride.

Hydralazine hydrochloride

Indication: It is used with beta-blockers and thiazide in severe hypertensive crisis. Hydralazine is direct relaxant of vascular smooth muscle and reduces both systolic and diastolic blood pressures. It also increases renal blood flow and is useful in hypertension with renal dysfunction.

Contra-indications: Porphyria and others.

Side effects- Tachycardia, fluid retention, nausea, and vomiting, headache, palpitation, nasal congestion, bone marrow suppression, peripheral neuropathy, etc.

Dose: 25 mg twice daily, increased to a maximum of 50 mg twice daily. For IV, 10mg st.

 

7. Calcium Channel Blockers - The calcium channel blockers interfere with the inward displacement of calcium ions through the slow channels of active membranes thus reducing mechanical activity of vascular smooth muscle. This inhibition reduces peripheral vascular resistance, decreasing the blood pressure. The same action dilates the coronary arteries, improving myocardial perfusion.

Examples of drugs; Verapamil hydrochloride, Nifedipine, Lidoflazine, Nicardipine hydrochloride, Nimodipine, Amlodipine, Diltiazem hydrochloride, Isradipine, and Felodipine.

Nifedipine

It relaxes vascular smooth muscle and dilates coronary and peripheral arteries. Nifedipine has more influence on vessels and less on the myocardium than Verapamil, and unlike verapamil has no anti-arrhythmic activity.

Contra-indications: Cardio-genic shock, pregnancy, porphyria, etc.

Side effects: headache, palpitation/tachycardia flushing, lethargy, peripheral oedema, eye pain, gum hyperplasia, etc.

Dose: 10mg 3 times daily increased to 20mg 3 time daily with or without food or after food’ Doses of 20 to 40mg of the sustained release preparation may be used daily or twice daily for management or prophylaxis of hypertension and angina.

 

7. Angiotensin-Converting Enzyme Inhibitors (ACE Inhibitors)

Indications: The ACE inhibitors act by interfering with the renin-angiotensin-aldosterone system by inhibiting the enzyme that converts angiotensin I to angiotensin II. This action decrease aldosterone release by the adrenal cortex, preventing sodium and water retention and reduces peripheral arterial resistance resulting in decrease high blood pressure without affecting the heart and cardiac output.

Examples of drugs; Lisinopril, Ramipril, Benazepril hydrochloride, Captopril, Enalapril, Fosinopril sodium, Quinopril hydrochloride.

Captopril

Contra-indications: Pregnancy, porphyria.

Side effects: dry cough, loss of taste, sore mouth, abdominal pain, rash, angioedema, hypotension, proteinuria, agranulocytosis, neutropenia, hyperkalemia, etc.

 

8.         Angiotensin II Receptor Blockers- there are two types of receptor subtypes. AT1receptor is located predominately in the vascular and myocardial tissue, brain, kidneys, and adrenal glomerulosa which secrete aldosterone. The AT2 receptors are located in the adrenal medulla and possibly in the brain.

Examples of drugs: Losartan, Candesartan, Valsartan and Saralasin.

Side effects: Similar to ACE inhibitors except dry cough and angioedema.

Dose: usually, 50-100mg daily but consult medicine leaflet

 

ANTI-ANGINA DRUGS

 

Angina pectoris is a clinical syndrome characterised mainly by chest pain or pressure. It occurs when there is a deficit in myocardial oxygen supply (myocardial ischemia) in relation to myocardial oxygen demand. Angina pectoris manifest itself in the form of a dramatic and terrorizing retrosternal pain often of a ‘crushing’ nature. This ischaemic pain may last for several seconds and terminate on rest (angina of effort). At a cellular level it is the result of deficient myocardial perfusion. This oxygen-demand imbalance is the basis for the pathophysiology of angina. The only way for the heart muscle to get more oxygen is to increase the coronary flow which is done by dilation of the coronary arteries. In Angina pectoris, the coronary arteries are constricted and unable to dilate leading to lessening of blood flow and oxygen supply to the heart muscle. The result is typical pain behind the sternum especially during stressful efforts or motion when the oxygen need is greater and cannot be met. Angina pectoris is described as a dull, heavy substernal pain that radiates into the left shoulder and down the arm. The pain may also radiate to the back, neck, or lower jaw. Initially, symptoms of angina may be mild and patient may confuse the angina with indigestion, heartburn, chest muscle strain or pain referred from other organs. The typical pain and failure to deliver enough oxygen to the heart muscle may be caused spasm, atherosclerosis, complete or partial thrombosis of the coronary arteries as well as causes such as anaemia. Angina may be classified as:

i.          Stable angina (also called predictable or chronic angina)- it is termed as exertional  angina or angina of effort. It is characterised by typical chest pain that is usually precipitated by exercise, stress, anxiety, smoking, or cold weather which reaches maximum intensity quickly and relief by rest or Nitroglycerin.

ii.         Unstable angina (also called pre-infarction or crescendo angina, acute coronary insufficiency, or impending myocardial infarction)-it results from progressive atherosclerosis and produces frequency, intensity and duration of symptoms. Unstable angina takes unpredictable course is less responsive to rest and other medical therapy. The ischemia is severe in this case and the person is at high risk of myocardial infarction .

iii.        Prinzmetal’s angina (also called variant or vasopastic angina) –myocardial ischemia is the result of coronary vasospasm; pain is prolonged. It usually occurs while the patient is at rest but may develop during activity as well. Occasionally, a patient may have stable and Prinzmetal’s angina.

The drugs may be classified as:

i.          Nitrates and nitrites

a. Relief of pain - e.g. Nitroglycerin (Glyceryl trinitate)       

b.         Prevention of angina attacks-e.g. Pentaerythriyl tetranitrate, Erythrityl tetranitrate, Isosorbide dinitrate, Isosorbide mononitrate, Amyl nitrite, and Mannitol hexanitrate.

Treatment of cyanide poisoning —  e.g. Sodium nitrite, and Sodium thiosulphate.

ii.         Agents for prevention of angina attacks

a. Beta blockers - Propanolol, Nadolol, Atenolol, and Metoprolol.

b- Calcium channel blockers - Amlodipine, Bepridil, Nicardipine, Verapamil, Nifedipine, and Diltiazem.

c- Antiplatelet agents - Dipyridamole, Aspirin, and Clopidogrel

iii.        Other measures            &         '

a.         Antianxiety drugs - Diazepam

b.         Induction of myxoedema with radioiodine or antithyroid drugs

 

The Nitrates and Nitrites

The action of these drugs is to dilate the peripheral blood vessels thus lessening resistance making the flow of blood easier and reducing the amount of work the heart to perform. All types of blood are dilated, and the coronary arteries share this generalized vasodilation. Nitrate dilate the veins, considerably  leading to less blood returning to the heart and decreasing blood volume in the ventricles at the end of diastole. By decreasing preload, nitrates reduce ventricular size and wall tension which reduces the myocardial demand for oxygen needed to pump blood out of the ventricles. Nitrates also dilate arteries by direct action or arterial smooth muscles, independent of autonomic nervous system intervention. Nitrates thereby decrease preload and energy required for the heart to pump blood and reduce myocardial oxygen demand. Though there is a moderate reflex tachycardia the end result is reduced cardiac work. These agents also cause the musculature of the bronchi: the gall bladder, and the biliary tract, uterus, the stomach and the intestines.

Glyceryl trinitrate

Indications; is dissolved under the tongue tor quicker absorption (sublingual administration).

Contra-indications: anaemia, closed-angle glaucoma, cerebral haemorrhage, etc.

Side effects: flushing, dizziness, postural hypertension, tachycardia, etc.

Dose: 0.3-1 mg, repeated as required; by mouth 2.6-6.4 mg 2-3 times daily.

Beta-blockers, Calcium channel blockers and Antiplatelet agents

The drugs in this group are mainly used for prevention of angina attacks. The beta-blockers include Propranolol, Nadolol, Atenolol, and Metoprolol. The calcium channel blockers are Verapamil. Nifedipine, and Diltiazem while the antiplatelet agents are Dipyridamole, Clopidogrel and Aspirin. Other drugs like anti-anxiety agents e.g. diazepam may also be useful for the prevention of anginal attacks.

 

 

VASOCONSTRICTORS

 

The vasoconstrictors raise blood pressure transiently by occupying the adrenergic receptors to constrict peripheral blood vessels. They are sometimes used as an emergency method of elevating blood pressure, and also used in general and spinal anaesthesia to control blood pressure. The danger of vasoconstrictors is that although they raise blood pressure they do so at the expense of perfusion of vital organs such as the kidney. Further, in many patients with shock the peripheral resistance is already high, and to raise it further is unhelpful. Thus, the use of vasoconstrictors in the treatment of shock is to be generally deprecated.

Examples of drugs: Noradrenaline, Phenylephrine hydrochloride, Adrenaline, Metaraminol, and Methoxamine hydrochloride.

 Noradrenaline acid tartrate

Contra-indications: myocardial infarction, pregnancy, etc.

Side effects: headache, palpitations, bradycardia, etc.

Dose: 0.5 to 0.75 ml of a solution containing noradrenaline 200 mcg/ml.

 

ANTICOAGULANTS

The body maintains a delicate balance between clot formation (coagulation) and clot destruction (fibrinolysis). Therefore, anticoagulants are drugs used to prevent the formation of clot or speed up the breakdown of blood clot.  They are therefore used to treat and prevent conditions in which the formation of blood clot within the circulatory system may be a dangerous factor. Anticoagulants are employed in the prevention and treatment of deep venous thrombosis, myocardial infarction pulmonary embolism, coronary thrombosis and other thromboembolic disorders.

Examples of drugs: Heparin, Warfarin and Phenindione.

Therefore, anticoagulants may be classified into three (3) groups as:

 

1.         Intravenous anticoagulant or Heparin and Its derivative (directly acting) e.g., Heparin

2.         Oral anticoagulants (indirectly acting).

Examples      

·         Coumarin derivatives – Warfarin (Counmadin), Acenocoumarin (Sinitrom)

·         Indanedione derivative - Phenindione (Dindevan)

3.         Antiplatelet drugs e.g. Aspirin

 

Heparin and its derivative.

Heparin is a natural anticoagulant found in body tissues and also prepared artificially from animal tissue for use in preventing clot formation and treating thromboembolism. It is extracted from animal tissue and made available in 5 ml vials in strength of 1000, 5000 and 25000 units per ml, but it also can be extracted from sheep and whales. Heparin is ineffective by mouth and usually given intravenously but it also can be given intramuscularly. Heparin is non-toxic, non-cumulative and is often used to prevent coagulation outside the body (in vitro) as in test tube or apparatus used in connection with blood and inside the body (in vivo) but does not affect the synthesis of clotting factors. Thus, it cannot dissolve clots, an action performed by the body's own fibrinolytic system or hastened by thrombolytic agents.

Enoxaparin, the newest form of heparin, is a low-molecular-weight heparin that is made by reducing unfractionated porcine heparin to its simpler compound is used to prevent deep-vein thrombosis after hip replacement surgery.

Mode of Action- It combines with antithrombin III (a natural anticoagulant in the blood) to inactivate clotting factors IX, X, XI and XII, inhibit the conversion of prothrombin to thrombin, and prevent thrombus formation. Thus, it inhibits clot formation (not to dissolve existing ones). After thrombosis has developed heparin can inhibit addition coagulation by inactivating thrombin, preventing the conversion of fibrinogen to fibrin and inhibiting factor III. (fibrin-stabilizing  factor). Heparin action is immediate but of very short duration since is constantly being released into the blood from the liver.

Contra-indications:  haemophilia, peptic ulcer, cerebral aneurysm, severe hypertension, severe liver disease, etc.

Side effects: haemorrhage, thrombocytopenia, hypersensitivity reactions, osteoporosis after prolong use, alopecia, etc.

2. Oral anticoagulants

The Coumarin compounds Warferin sodium. Acenocoumarin, and Dicumarol are the oral anticoagulants widely used. Warfarin is similar to vitamin K in structure and therefore acts as a competitive antagonist to hepatic use of vitamin K. Warfarin has no effect on circulating clotting factors or on platelet function thus when administered anticoagulant effects do not occur for 3 to 5 days after warfarin is started, it is most useful in long-term prevention or management of venous thromboembolic disorders.

Mode of Action; it acts in the liver to prevent synthesis of vitamin K-dependent clotting factors (i.e. factors II, VII, IX and X) thereby reducing the formation of prothrombin by the liver and subsequent reduction of prothrombin in the blood.

Contra-indications: pregnancy, peptic ulcer, severe hypertension, bacterial endocarditis, etc.

Side effects: haemorrhage, etc.

Dose: Warfarin 10 mg daily for maximum of 3 days.

Antiplatelet Drugs

Antiplatelet drugs have shown some potential in preventing arterial thromboembolism, especially in patients at risk for myocardial infarction (MI) and cerebrovascular accidents (CVA) from arteriosclerosis. The drugs interfere with platelet activity aggregation in different drug-specific and dose-related ways. The drugs may include Ticlopidine, Aspirin, Dipyridamone, Sulfinpyrazone, and Clopidogrel.

 

HAEMOSTATICS

Haemostatics are preparations used to control haemorrhage or bleeding. Most act directly by application to the bleeding point but some can be described as indirect haemostatics because they prevent or lessen haemorrhage by acting indirectly in various ways.

Examples of indirect haemostatics include: Ascorbic acid, Phetomenadione, Oxytocin, Ergometrine, Natural Oestrogen, Ethamcylate, and Tranexamic acid.

Direct haemostatics are mostly used by local or topical application.

Examples of drugs : Adrenaline, Thrombin, Russell’s viper Venom, Gelatin sponge, Oxidised cellulose, Human fibrinogen, and Fibrin foam.

 

i. Adrenaline

It is used in strength of I in 1,000 to 1 in 10,000 during surgery for its rapid vasoconstriction effect, that is, it closes up the blood vessels.

Contra-indications: hyperthyroidism, hypertension, diabetes mellitus, etc.

Side effects: anxiety, tremor, tachycardia, arrhythmias, dry mouth, etc.

ii. Thrombin (powdered cattle thrombin)

It acts by speeding up the natural process of clotting. The method of application is to dissolve it in normal saline and soak a piece of gauze or cotton wool in the solution to be applied to the bleeding point.

 

5           HAEMATINICS

 

Haematinics are anti-anaemics or preparations used in the prevention and treatment of anaemia. In anaemia there are some deficiency in the quality, or in the quantity of blood leading to diminished tissue oxygenation. Anaemia can divided into;

a.         Microcytic hypochromic or iron deficiency anaemia

b.         Megaloblastic or macrocytic hyperchromic –folic acid deficiency.

c.         Pernicious anaemia- Vitamin B12 (Cynobalamin) deficiency

d.         Aplastic-deficiency of stem cells

e.         Haemolytic-abnormal breakdown of RBCs

f.          Normocytic anaemia-erythropoietin deficiency

 

1.         Iron deficiency Anaemia (microcytic hypochromic)-Iron is an essential factor for normal RBC’s production, and about 66% of total body-iron is found in the haemoglobin in RBCs. A deficiency may occur if either insufficient iron is absorbed or if too much iron is lost resulting in hypochromic anaemia, that is the RBCs are pale hence the patient is pale and usually and faints frequently. In this, case, the RBCs are usually smaller than normal, that is microcytic. With this, the cause should be identified and removed if possible, and patient is put on iron.

Causes of Iron deficiency anaemia-

a)         Chronic nutritional hypochromic anaemia

b)         Hypochromic anaemia of pregnancy, infancy or childhood. In these cases the RBC count may be normal but their haemoglobin content is low. Cells may be smaller than normal and are described as microcytic

c)         Posthaemorrhagic anaemia.

IRON THERAPY

This is justifiable only when there is the presence of a demonstrable iron deficiency state e.g. in situations where there is inadequate dietary iron intake, malabsorption, and loss of blood as in ulcers, menorrhagia, and trauma.

However prophylasis is justifiable in pregnancy and menorrhagia.

Dose:

The therapeutic dose of iron is 120 – 180 mg daily and the prophylactic dose is 60 mg daily.

Children (therapeutic dose):

                    Under 1 year –              36 mg

                               1 – 5 years         72 mg

                                6 – 12 years      120 mg

ORAL PREPARATIONS

a)  Ferrous sulphate tablet:

       This is available as a 200 mg tablet containing 60 mg of elemental iron.

       Dose – 1 tablet 3 times daily with food

b)         Ferrous gluconate tablet:

A 300 mg tablet containing 35 mg of elemental iron.

Dose :–    2 – 6 tablets in divided doses daily.

c)         Ferrous fumarate tablet:

A 200 mg tablet containing 60 mg of elemental iron.

Dose: - 1 tablet 3 times daily

d)         Ferric ammonium citrate (FAC)

This contains approximately 21.5% of iron.

Dose is 15 ml 3 times daily.

Adverse drug interactions

Oral preparations are prone to producing gastric irritation. This effect may be minimised if the drug is taken after food (iron is best absorbed in the fasting state though); liquid preparations may be taken after dilution. Other side effects are nausea, epigastric pain, and constipation (mostly in the elderly) or diarrhoea. Liquid preparations may stain the teeth. This can be minimised by taking it well diluted or with a straw. Oral iron may also stain the faeces black.

Parenteral preparations

These can be used where there is failure of oral therapy, gastrointestinal side effects, continuing blood loss or resistant malabsorption.

There are two main preparations – iron dextran 50 mg/ml of 2 ml and 5 ml ampoules and iron sorbitol.

Iron dextran is given by slow intravenous infusion over 6 to 8 hours. It is patient who cannot tolerate the oral therapy.

Contra-indications-Cardiac abnormalities, liver disease, kidney infection

 

Adverse drug interactions:

Staining of the skin, transient nausea and vomiting, flushing and rarely severe anaphylaxis - fatalities have been reported. Others are circulatory collapse, headache and dizziness.

Drug interactions:

Oral iron forms insoluble complexes with magnesium trisilicate and the tetracyclines, thus reducing their absorption.

FOLIC ACID

Folic acid deficiency may result in megaloblastic anaemia. Certain drugs, among other factors may cause folic acid deficiency, among which are pyrimethamine, fansidar, trimethoprim and the sulphonamides.

Indications; Folic acid is widely used in pregnancy to prevent megaloblastic anaemia. It is also used prophylactically in chronic haemolytic states such as thalassaemia, sickle cell anaemia.

Dose:  10 – 20 mg daily by mouth for 14 days or until a haematopoitic response has been achieved. Maintenance dose is 2.5 – 10 mg daily. Prophylactic dose in pregnancy is 200 – 500 micrograms daily.

 

 

Adverse drug reactions:

Folic acid is generally well tolerated. However gastrointestinal disturbances and allergic reactions may occasionally occur.

Presentation:

Folic acid tablet 5 mg; 100 micrograms;

Folic acid syrup 2.5 mg/5ml.

 

Hydroxocobalamine/cyanocobalamine(Vitamin B12)

Indications: Megaloblastic anaemia due to vitamin B12 deficiency and pernicious anaemia (megaloblastic anaemia due to lack of gastric intrinsic factor leading to malabsorption of vitamin B12 from the G.I.T.)

Dose: 250 – 1000 micrograms on alternate days for 7 – 14 days, then 250 micrograms weekly till blood count normalises.

Presentation:

Vitamin B12 injection 1 mg/ml;

Vitamin B12 tablets 50 micrograms.

 

DRUGS AFFECTING THE RESPIRATORY SYSTEM.

 

 ## Read on the physiology of the respiratory system

5.1         Bronchodilators

The bronchodilators are agents used in the treatment of respiratory disorders characterized by bronchoconstriction and bronchospasm, inflammation, mucosal oedema, and excessive mucous production. Bronchoconstriction involves narrowing of the airways which is aggravated by the inflammation, mucosal oedema, and excessive mucous production as a result of asthma, bronchitis, and emphysema. The resultant symptoms include dyspnoea, wheezing, coughing, and other signs of respiratory distress. Bronchodilators are drugs used in the management of such conditions especially asthma. Bronchodilators are classified as follows:

1.      Sympathomimetics (Adrenoreceptors stimulants)

2.      Anti-cholinergics bronchodilators

3.      Xanthines bronchodilators

4.      Corticosteroids

5.      Cromolyn sodium (anaplylatic).

5.2         Sympathomimetics (Adrenoreceptors stimulants)

Adrenoreceptors stimulants have a similar action to that caused by the stimulation of post-ganglionic sympathetic or adrenergic nerves. The types of effect a sympathomimetic agent will depends on the types of receptor at which it act. The two main groups of adrenoreceptors are alpha (@) and beta (Ɓ) receptors. When alpha receptors are stimulated, the result is vasoconstriction in the blood vessels in the skin and abdomen. It also leads to rise in the blood pressure, dilatation of the pupils and relaxation of the gut. The beta receptors are important in the treatment of asthma. But, stimulation of beta receptors leads to increase in contraction rate and force of the heart. It leads to blood flow to the skeletal muscles and relaxation of the uterus, intestines and bronchial muscles. The beta receptors can be separated two groups as β1 and β2 receptors in which β2 is much of importance in the treatment of bronchial asthma. The sympathomimetics or adrenoreceptors are further grouped into three as:

a)      Non-selective Adrenoreceptors Stimulants

These drugs act on both the alpha (α) and beta (β) receptors. Although there is a relaxation of the bronchioles, they also stimulate the heart. This side effect is the main reason for their limited use in the treatment of asthma. The drugs includes Adrenaline, Ephedrine, and Isoprenaline. However, Adrenaline is given parenterally in emergency treatment of severe asthma (status asthmaticus).

Ephedrine

Ephedrine stimulates both alpha and beta receptors. It is readily and completely absorbed after oral or parenteral administration. Ephedrine is used for mild or moderate severe bronchial asthma.

Side effect: CNS stimulation, vomiting, sweating, tremors, nervousness, insomnia and cardiac irregularities.

Dose: 30 to 60 mg orally 3 0r 4 times daily.

 

b)      Selective β2 Adrenoreceptor stimulants

These act only at β2 receptors and therefore avoid stimulation of the heart. The most common route of administration is by inhalation. This limit absorption in to the blood streams because the drug applied directly to the affected tissues, the bronchioles, and therefore the result is a speedier effect. The drugs are Salbutamol, Terbutaline sulphate, Isoetharine, and Rimiterol.

Salbutamol

Cautions:  hyperthyroidism, ischeamic heart disease, hypertension, pregnancy. Elderly patients.

Nursing implication: intravenous administration to diabetics, monitor blood glucose.

Side effect: fine tremors (usually hands), nervous tension, headache, peripheral vasodilation, tachycardia, hypokalaemia.

Dose: by mouth 4 mg 3-4 times daily; by SC or IM 500 mcg, repeated every 4 hours if necessary; by IV initially, 5 mcg per minute adjusted according to response; by aerosol or inhalation, 5mg, st., repeated according to patients response.

 

c)      The beta (β1) and beta (β2) adrenoreceptor stimulants

These drugs act on both β1 and  β2 receptors. Although there is a relaxation of the bronchioles, they also stimulate the heart, and it is this side effect which is the main reason for their limited use for the treatment of asthma.

Orciprenaline

It is a long-act ing derivative of Isoprenaline. It stimulate both beta1 and beta2 receptors, although it is claimed that it has little effect on the heart muscle. It is given orally to reduce frequency and severity of asthmatic attacks, when inhaled as aerosol, it act acts promptly.

Dose: orally 20 mg every 6 hours. The metered aerosol produces 0.75 mg per dose, and adult may take up to 12 doses in 24hrs.

5.2.1        Anti-cholinergics bronchodilators (Antimuscarinic bronchodilators)

These drugs have traditionally been regarded as more effective in relieving bronchoconstriction associated with chronic bronchitis. As their name suggest, they block the action of acetylcholine in the bronchial smooth muscles when given by inhalation. This action reduces intracellular c-GMP. This Atropine-like action results in the relaxation of the bronchiole muscle, and also leads to reduction of the bronchial secretion. Typical examples are Ipratropium, Atropine, and Tiotropium.

Ipratropium bromide

Cautions: glaucoma, prostatic hypertrophy

Nursing implications; they should be avoided in children, because although they reduce bronchial secretions, sputum viscosity may be increase and this can lead blockage of the smaller airways.

Side effects; dry mouth, constipation

Dose: by aerosol inhalation, 20-40 mcg in early treatment up to 80 mcg by inhalation of nebulized solution.

5.2.2        Xanthines bronchodilators

This includes Theophylline, choline, theophyllinate, Diprophylline, Caffeine, and Theobromine. Theophylline is clinically employed as Aminophylline as its water-soluble form.

Aminophyline

Aminophylline is theophylline combined with ethylenediamine. Theophylline directly relaxes the smooth muscles of the bronchial airway and pulmonary blood vessels thus acting mainly as a bronchodilator and smooth muscle relaxant

Indications: Treatment of symptoms of reversible airway obstruction associated with chronic asthma and other lung diseases such as emphysema and chronic bronchitis.

Contraindication: Active peptic ulcer, seizure disorders, hypersensitivity to the components.

Dose: IV 250 mg over at least 20 minutes; repeat in 30 minutes if no improvement and subsequently, 1000 – 1500 mg should be infused in 24 hours or 250 mg every 6 hours.

Children may be given the equivalent of 3-5 mg/kg body weight

Side effects: Tachycardia, palpitations, GI disturbances, CNS stimulation, convulsions especially if given by rapid IV, urticaria, etc.

Presentation: Aminophylline inj. 25 mg/ml in 10 ml ampoule.

Cautions: epilepsy, liver disease, breast-feeding, cardiac diseases.

Nursing implications: IM injection is painful and therefore not used.

5.2.3        Corticosteroids

Corticosteroids are life-saving in acute attack or status asthmaticus. Probably they function as non-specific anti-inflammatory agents to provide relief from congestion and exudation. Specifically, steroids reduces inflammation and mucous secretion while increasing sensitivity of beta adrenergic receptors. Example, Prednisolone, Hydrocortisone, Beclomethasone dipropionate which is chlorinated analogue of betamethasone acts locally on the respiratory mucosa, and the metered dose inhaler delivers 42 or 50 mcg/puff.

5.2.4        Anti-anaphylactic e.g. Cromolyn sodium

Cromolyn prevent mast cell breakdown and subsequent release of histamine and other bronchoconstrictive substances when mast cells are confronted with allergens and other stimuli. Cromolyn sodium is used primarily as prophylactic treatment of bronchial asthma, but not useful in treating acute asthmatic attacks. It is given by inhalation because it is absorbed poorly after oral administration.

 

5.3         ANALEPTIC OR RESPIRATORY STIMULANTS

These are preparation used to produce stimulation of failing respiration and peripheral circulation. They are also used to antagonize the central depressant effect of poisoning by hypnotic drugs. Essentially analeptics are CNS stimulation and some of them stimulate respiratory centre in the medulla. They do not have specific action on this area and stimulate the cerebrospinal axis at all levels causing general arousal and in larger doses produces convulsions. Hence, their use in this way is been abandoned because of convulsions caused by such drugs. The drugs are Nikethamide, Ethamivan, Picrotoxin, Leptazol, Sodium benzoate, and Doxapram.

Nikethamide

Contra-indications; Respiratory failure due to neurological disease or drug overdose, status asthmaticus, coronary artery disease, thyrotoxicosis.

Side effects: nausea, restlessness, convulsions, dizziness, tremors, vasoconstriction

Dose; slow IV 0.5-1 g repeated at intervals of 15-30 minutes.

 

5.4         Cough preparations

Cough as a symptom of respiratory disorder, is a forceful expulsion of air from the lung. It is normally a protective reflex for removing foreign bodies, environmental irritants, or accumulated secretions from the respiratory tract. The cough is triggered by stimulating nerve receptors that are sensitive to chemical and other irritants. The cough receptors are located throughout the respiratory tract as well as in the stomach, pleural, and diaphragm. Once the receptors are stimulated, impulses are transmitted through the vagus nerve and the glossopharyngeal nerve to the cough centre in the medulla. The cough reflex is processed and coordinated in the brain stem. The cough serves as an important protective mechanism when the cilia prove ineffective against abnormal quantities or types of materials in the respiratory tract.

Numerous causes of cough include congenital abnormalities, disease such as cystic fibrosis, foreign body aspiration, reactive airway disease, irritants, and psychogenic reactions. Although coughing is useful, protective, and beneficial, it can be irritating and exhausting. Treatment of cough depend on its cause for example cessation of smoking usually improves the cough associated with chronic bronchitis.

Preparation for cough are classified into Expectorants and compound cough preparation for wet coughs, and cough suppressants (Antitussives) and Demulcents for dry cough.

Expectorants and compound cough preparation

Expectorants facilitate mucokenesis, hence they are cough preparations used to stimulate and ease expulsion of bronchial secretions. Usually when sputum is thick and sticky, and cough is not able to bring it up, expectorants are believed to provide relief in such conditions. As expectorant mixture is expected to liquefy the bronchial secretion and enable it to disengage more easily. As a result the sputum is brought out with less difficulty and breathing is made more comfortable. Example include Benylin expectorant, and Tolu linctus.

5.5         Mucolytics

These are preparations used to reduce the viscosity of the sputum, making it easier to expectorants. Bronchial secretions can be occasionally obstruct in the tubes of the trachea. Mucolytic can be administered by mouth and inhalation. Examples includes Menthol eucalyptus, Tincture of benzoic compound (TBC), Acetylcysteine, and Sodium chloride.

Cough suppressants

Antitussive agents cough by depression of the cough centre in the brain (medulla oblongata) or the cough receptors in the throat, trachea, or lungs. It is often not advisable to completely suppress cough in cases of chronic bronchitis as it may result in the retention of secretions in the tracheobronchial tree. Antitussive may be classified as:

1.      Centrally-acting antitussive-these include:

·         Narcotic antitussive such as Codeine, Ethylmorphine, Morphine, Diamorphine, and Methadone.

·         Non-narcotic antitussive like Dextromethorpharn, Noscapine, Propoxyphene, and Isoaminile citrate.

2.      Peripherally-acting antitussives-these include;

·         Mucosal anaesthetics like Benzonatate, Chlophedianol

·         Bronchodilators like Ephedrine

·         Hydrating agents like steam, aerosols

·         Miscellaneous like Bromhexine

Side effect: constipation, sputum retention, sedation

Contra-indication: liver disease, ventilator failure

Dosage: it varies according to composition of the preparation.

 

5.5.1        Demulcents

They are soothing preparations which are relatively harmful but very acceptable by patients. To relieve a dry irritating cough, the official preparation called Simple linctus is the medicine of choice. Despite its harmlessness, care must be taken not to abuse as an overdose particularly in children will disturb the blood electrolyte balance. A simple home remedy of this is honey and lemon juice in warm water.

5.5.2        Cough sedatives

These are used to prevent cough or lessen cough. Cough sedative of mild action are used to treat cough which is caused by irritation of throat or larynx. Cough sedatives are usually in the form of thick syrup or linctus form to be neatly sipped slowly. The main effect is to soothe locally as it passes down e.g. simple linctus. The squill opiate linctus of the BNF contains a small amount of morphine and has a more sedatives action. It is well known by its old name Gee’s linctus.

 

6           DRUGS ACTING ON THE DIGESTIVE SYSTEM

## Read on the physiology of the digestive system

1 ANTACIDS:

These are agents that are used to counteract hyperacidity in the stomach thus relieving the gastric pain associated with the excess acid.  They are usually weak base administered to neutralize gastric acid. They are used to anticipate and relieve pain in the symptomatic management of gastric and duodenal ulcers and reflux oesophagitis by neutralizing hydrochloric acid in the gastric secretion.  They relieve symptoms on both ulcer and non-ulcer dyspepsia. They promote ulcer healing. Antacids are best given between meals and at bedtime when symptoms occur or are expected. The liquid preparations are more effective than solid preparations.

Aluminium and Magnesium containing Anatacids

Generally, magnesium and aluminium containing antacids are longer in action. Magnesium containing antacids tend to be laxative whereas aluminium-containing antacids may be constipating. Sodium bicarbonate and antacids with high sodium content e.g. magnesium trisilicate should be avoided in patients on salt restricted diet.

Antacids should not be taken at the same time as other drugs. This is because gastrointestinal absorption can be reduced by adsorption on insoluble antacids or changes in gastric emptying time and the effects of a drug may be diminished or enhanced by alterations in the intestinal pH or by the formation of complexes.     

6.1.1        Aluminium hydroxide (Aludrox)

Dose: 1-2 tablets to be chewed when required (10ml of the gel). Mixture;5-10mls 4 times daily between meal and bedtime or as required.

Presentation: Tablet: 500mg, Gel: 4% w/w

Side effect: constipation

Contra-indication: hypophosphataemia

 

Magnesium Hydroxide (Milk of Magnesia)

Indications: dyspepsia, mild laxative in children.

Dose: 5-10ml

MAGNESIUM TRISILICATE

DOSE: 10-20 ml or 1-2 tablets to be taken when necessary.

Presentation: Tablet: 250mg, 500mg

Magnisium trisilicate mixture.

 

6.2         ANTISPASMODIC AGENTS

The smooth muscle relaxant properties of these drugs are employed in the adjunctive treatment of non-ulcer dyspepsia. They are indicated for gastrointestinal disorders characterised by smooth muscle spasm.  They are use to reduce spasm or contraction of the stomach and intestinal muscle which appear as painful cramps and colic.

Examples are atropine sulphate, hyoscine butyl bromide and propantheline bromide.

Side effects include dry mouth, thirst, and dilatation of the pupils with difficulty of accommodation, difficulty with mituration and constipation.

Caution: the elderly, urinary retention, prostate enlargement and breast-feeding.

Hyoscine butyl bromide (Buscopan):

Dose: 20 mg 4 times daily;

            Children 6 – 12 years 10 mg 3 times daily;

By IM or IV ( in acute spasm) 20 mg to be repeated after 30 minutes if necessary.

Presentation: Tablets 10 mg,

                   Ampoules: 20 mg/ml.

Propantheline bromide

Indications: Adjunct in gastrointestinal disorders characterised by smooth muscle spasm; nocturnal enuresis; urinary frequency and incontinence.

Dose: 15 mg 3 times daily one hour before meals and 30 mg at night, maximum of 120 mg daily.

Enuresis: 7 – 12 years 15 mg at night, maximum 2 mg/kg of body weight daily in divided doses.

Presentation: tablets 15 mg.

 

PEPTIC ULCER HEALING DRUGS

       I.            H-2 RECEPTOR ANTAGONISTS

Histamine released from the parietal cells excites acid secretion. This action is mediated through the histamine –2 (H-2) receptors, which are blocked by H-2 receptor antagonists. This blockade is effective in antagonising the effect of histamine and gastrin in evoking gastric acid secretion and reducing gastric acid output. They may also relieve heartburns in peptic oesoghatis. Examples of drugs: Cimetidine (tagamet), Ranitidine (zantac), Famotidine, and Nizatidine (axid). These are competitive inhibitors and have no action on H-1 receptors.

Adverse effects:

These include gastrointestinal disturbances, headache, dizziness, rash and tiredness. Other side effects are depression, hallucinations, hypersensitivity reactions, blood disorders and occasionally impotence, gynaecomastia and alopecia.

Ranitidine:

Indications: duodenal and gastric ulcers, hypersecretary conditions e.g. the Zollinger – Ellison syndrome, acute gastro-oesophageal reflux.

Dose: 150mg twice daily or 300mg at night for 4 – 8 weeks. Maintenance dose is 150mg at night.

Child: 2- 4mg/ kilogram body weight twice daily to a maximum of 300mg

Presentation: Ranitidine tablets 150mg, 300mg,

                  Syrup: 75mg/5ml,

                   Injection 25mg/ml in 2ml ampoules.

 

 

 

    II.            PROTON PUMP INHIBITORS

These drugs act by inhibiting the ‘proton pump’. They therefore inhibit the final transport of hydrogen ions into the gastric lumen. They are used to treat gastric and duodenal ulcers and erosive oesophagitis. It can also be used to treat Zollinger-Ellison syndrome

Examples of drugs: Omeprazole (losec), Oesomeprazole, Lansoprazole, Pentoprazole. etc.

 

Omeprazole

Uses: They are used for the short term treatment of duodenal as well as gastric ulcer, hyper secretory conditions etc.

Dose: 20mg once daily for 4 – 8 weeks which may be increased to 40mg daily in severe recurrent cases.

Side effects: Haematological abnormalities (anaemia), abdominal pain, anaphylaxis, insomnia, alopecia and hallucinations. Other side effects are liver enzyme changes, steven Johnsons syndrome, and rarely impotence, etc.

Presentation: Dispersible tablets - 10mg, 20mg.

Capsules enclosing enteric coated granules – 10mg, 20mg,

IV infusion – 40 mg/vial; injection – 40mgt/ vial.

 

Helicobacter Pylori Eradication Regimen

Nearly all ulcers and most gastric ulcers are caused by Helicobacter pylori. Acid inhibition with antibiotic treatment is highly effective in the eradication of H. pylori leading to long-term ulcer remission. Triple therapy (a proton pump inhibitor + a macrodile + either amoxicillin or metronidazole) given for 1 week is recommended and provides high eradication rates.

 

 

 

 

 

 

 

LAXATIVES AND PURGATIVES

Laxatives are preparations used to induce or help in bowels evacuation. A laxative can be termed purgative if the action is powerful and drastic. A mild dose of SennaCo will have a laxative effect whereas a heavy dose may work as purgative. As a group, the purgatives are used in the treatment of constipation which is a functional disturbance of the GIT, and a symptom of many underlying disease.

The drugs may be classified as;

1.      Lubricating laxatives

They act by increasing water retention in the stool by creating barrier between the colon wall and faeces. This barrier prevents colonic reabsorption of faecal water and eases the passage of faeces through the large bowels. E.g. liquid paraffin

                  Liquid paraffin

Indication: It is a thick clear mineral oil which is not digested when absorbed, thus it softens the bowel contents, lubricates the intestinal channel and encourage smooth and painless movement of the faeces.

Cautions: avoid prolong use because this way can cause cancer

Side effect: anal seepage of paraffin and subsequent irritation

Dose: 10-30 ml when necessary

2.      Bulk-producing laxatives

These preparation by their filling effect in the intestines exert pressure on the bowel wall. Examples: Methylcellulose, Agar, and Psyllium, Bran

Bran

Cautions: adequate fluid intake should be maintained to avoid intestinal obstruction

Contra-indications: intestinal obstruction, colonic atony, faecal impactation

Side effect: flatulence, abdominal distension.

 

3.      Saline (osmotic) laxatives

They relieve constipation by keeping water in the bowel by their osmotic effect. Distension of the bowel leads to increase peristalsis and decrease intestinal transit time, and the result is a very watery stool. So, sufficient water should be taken to keep up with the amount lost. The preparation may include Magnesium Sulphate, Magnesium hydroxide, sodium phosphate, Glycerin, Lactulose and magnesium citrate.

 

Magnesium Sulphate (Epson salt)

Contra-indications: intestinal obstruction

Side effect; colic

Dose: 5-10 g in a tumblerful of water preferably before breakfast.

 

4.      Irritant purgatives and synthetic laxatives

Irritant laxatives, also known as stimulants cathartics may irritate the intestinal mucosa directly or stimulating nerve endings of the intestinal smooth muscles and pulling water into the bowel lumen. As a result, faeces are move through the bowel too rapidly to allow colonic absorption of faecal water, and so watery stool is eliminated.  Examples: Senna, Cascara sagrada and aloes, Castor oil, Phenolphthalein, Bisacodyl, Sodium picosulphate.

 

DRUGS USED IN DIARRHOEA.

Oral Rehydration Therapy

The basic principle in the control of diarrhoea is the replacement of lost fluids and electrolytes. The use of antibacterial agents should be with some amount of circumspection. Some antibacterial agents may in fact prolong the period of diarrhoea. Infections may resolve on their own in most cases, while others may be viral and need no antibacterial treatment.

In infants the essential treatment is to restore the electrolyte balance and rehydrate the patient. In severe cases intravenous fluids are given but in milder cases oral rehydration salt (O.R.S) or a home prepared sugar salt solution may be given for one or two days.

·         ORS is preferred because home solutions are not adequate to replace potassium and bicarbonates, which may also be depleted.

·         In the early stages of some diarrhoea appropriate chemotherapy may prevent deterioration of infection. Agents such as chloramphenicol and cotrimoxazole have been used.

·         Occasionally antispasmodic agents may be used to treat abdominal cramps associated with diarrhoea.

·         For chronic diarrhoea, motility reducing drugs like codeine, morphine, diphenoxylate (Lomotil) and loperamide (Imodium) may be used to provide symptomatic relief.

ORS

Intestinal absorption of sodium and water is enhanced by glucose, therefore replacement of fluids and electrolytes lost through diarrhoea can be achieved by giving solutions containing sodium potassium and glucose.

An oral rehydration solution should:

1)         enhance optimally the absorption of water and electrolytes

2)         replace electrolyte deficit adequately and safely

3)         contain an alkalising agent to counter acidosis

4)         be simple to use in hospital and at home

5)         be palatable and acceptable, especially to children and

6)         be readily available.

A sample composition of an oral rehydration solution

Sodium chloride              3.5g        2.1g

Potassium chloride          1.5g        0.9g

Trisodium citrate dihydrate           

(sodium citrate)               2.9g        1.74g

Anhydrous glucose       20.0g      12.0g

Sufficient water to            1 L          600ml

 

NB: Sodium bicarbonate 2.5g may be substituted for sodium citrate in some formulas

Dose:

Infants: 1 litre over a 24-hour period;

Children: 1 litre over an 8 – 24 hour period according to age;

Adults: drink freely as required.

 

EMETICS AND ANTI-EMETICS

 

EMETICS

Nausea and vomiting may be symptoms of serious organic disturbances involving any of the viscera of the chest or abdomen, or produced by drugs, radiation, movement, infections, metabolic and emotional disturbances, neoplasms or painful stimuli. However, emesis/vomitting may be induced in certain clinical conditions, and drugs used for such purposes are referred to emetics. This include Apomorphine hydrochloride, and Ipecac syrup.

Ipecac syrup

Mostly preferred in young patients because it produces less CNS depression.

Dose: 20 ml orally, followed by 200 t0 300 ml of water.

ANTI-EMETICS

Anti-emetics are drugs which are used to reduce nausea and vomiting by depressing the vomiting centre in the brain. Vomiting is common with post-operative patients, pregnancy, and deep x-ray therapy and travel sickness. Vomiting in excess causes weakness in the patient and cause loss of fluid and electrolyte especially chloride ions from the stomach, blood and eventually tissues in protracted vomiting and the result is exhaustion and weakness. The main groups of agents used as anti-emetics are;

a.       Anticholinergics e.g. Scopolamine (Hyoscine)

b.      Antihistamines like the Ethanolamine (e.g. Diphenhydramine, Dimenhydrinate), the Piperazines (e.g. Cyclinzine, Meclozine, Buclizine), and the Promethazine (Promethazine Hydrochloride).

c.       Phenothiazines e.g. Chlorpomazine

d.      Miscellaneous drugs e.g. Metoclopramide

Promethazine hydrochloride (Phenergan)

Indications: It acts by depressing the vomiting centre in the brain. It is recommended for treating vomiting during pregnancy and in pre-operative patients.

Side effect and cautions: drowsiness impairs ability to operate machinery, dry mouth, and blurred vision.

Contra-indication: alcohol

Dose; adult 25-75 mg daily in divided doses; children 5-25 mg daily.