Chapter 1.5 Pharmacodynamics (Mode of Action of Drugs)
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Section 1/ General Principles of Pharmacology 38 Plasma concentration (µg/ml) Plasma concentration (µg/ml) MTC MEC - Second dose - First dose 10 12 Time (hr.) MTC MEC 14 - IInd dose - First dose Fig 1.4.5: Shows the administration of 2nd dose between the 7-8 hours interval which maintains the drug plasma levels above minimum effective concentration Plasma concentration (µg/ml) 10 12 14 Time (hr.) Fig 1.4.6: Shows the administration of 2nd dose after 7-8 hours interval which does not maintain the drug plasma concentration at MEC level MTC MEC — 2nd dose —Ist dose 10 12 14 Time (hr.) Fig 1.4.7: Shows the administration of 2nd dose before 7-8 hours interval which crosses the MTC which may produce toxic effects of drugs tterer p p a h CCh 1.5 1.4 Pharmacodynamics Pharmacodynamics (Mode of Action of Drugs) (Mode of Action of Drugs) Pharmacodynamics is the study of drug effects (biochemical and physiological) and their mechanism of action When the drug reaches its site of action it has a pharmacological effect which may be responsible for an eventual therapeutic effect and also responsible for the adverse effects as well as some other effects which may be of no clinical importance SITE AND MECHANISM OF DRUG ACTION The site of drug action means where a drug acts and mechanism means how the drug acts Drug which act only at the site of application (i.e localized region) are termed as local or topical action for example, ointments, paste, creams and certain other local preparations used externally produce only local effect The local anaesthetics like lignocaine, procaine produce anaesthesia (local) in a localized region only The second type of action is systemic or general action which produce their action after absorption, for example, general anaesthetics act centrally after absorption, and often drugs like antibiotics, antacids, and so many other drugs acts systemically The proper localization of the site of drug action can be determined pharmacologically When a new drug is introduced its screening gives an idea about the site and mechanism of drug action, for example, if any drug is said to be antihypertensive in nature and by blocking this action by prior administration of an antihistaminic, it will gives an idea that the drug may act in the same place and same mechanism as histamine The use of certain blocking agents also help in suggesting the probable site of action of drugs TYPES OF DRUG ACTION The drug may produce their effects by: i ii iii iv v Stimulation Depression Irritation Replacement Bactericidal and cytotoxic action Stimulation 40 Section 1/ General Principles of Pharmacology STIMULATION Stimulation is an increase in the selective activity of specialized cells, which increases the secretion from a gland, for example, morphine stimulates vagus, acetylcholine stimulates exocrine glandular secretions, high dose of CNS stimulant picrotoxin produces convulsions production of endogenous components is reduced e.g thyroxine is used to replace natural thyroid hormone secretion in hypothyroidism, insulin in diabetes mellitus, levodopa in parkinsonism, hydroxycobalamin (vitamin B12) and ferrous salts in the treatment of conditions associated with their deficiency DEPRESSION It is a reduction/decrease in the activity of specialized cells For example barbiturates depress central nervous system, quinidine depresses myocardium Certain drugs stimulate one type of cells but depress others e.g morphine stimulates the vagus and chemoreceptor trigger zone but depresses the vomiting and cough centres Similarly acetylcholine stimulates intestinal smooth muscle but depresses SA node in the heart IRRITATION It is the effect of drugs on the growth, nutrition and morphology of living tissues which induce a gross change in cellular function Such drugs produce a nonselective, often noxious effects and is particularly applied to less specialized cells and causing a mild inflammation or irritation, corrosion and necrosis of cells The other cellular changes produced by irritation are precipitation of protein (astringent effect) and when these agents as applied locally to the skin to relieve deep seated pain by increasing the blood flow to the site (counter irritant action) e.g liniments to relieve muscular pain (turpentine oil liniment) REPLACEMENT It includes certain drugs, which are used to replace some missing endogenous component of the body or when the BACTERICIDAL AND CYTOTOXIC ACTION The bacteriostatic activity which is inhibition of growth and multiplication of bacteria and bactericidal activity, which is bacterial death, is induced by certain types of antibiotics Cytotoxic action is selective for invading cancer cells and altering them without affecting the host cells FACTORS MODIFYING DRUG ACTION The drug action can be modified either quantitatively (in which the action of drug is increased or decreased) or qualitatively (in which the type of response is altered) The factors are: Age: In newborn infants, the glomerular filtration rate and tubular transport is immature, which takes to months to mature Also, the hepatic drug metabolism capacity is also inadequate (that is why chloramphenicol can produce ‘grey baby syndrome’), and due to the higher permeability of blood brain barrier, certain drugs attain high concentration in the CNS The dose of a drug for children is often calculated from adult dose Child dose = #IG × #FWNV FQUG #IG Section 1/ General Principles of Pharmacology 42 drugs like morphine, barbiturates, phenothiazines, benzodiazepine can produce more CNS depression In gastrointestinal disease: • The absorption of orally administered drug is altered e.g achlorhydria reduces aspirin absorption • Absorption of amoxycillin is reduced in coeliac disease Other important diseases in which the drug action is altered are: • The hyperthyroid patients are relatively resistant to inotropic action but more prone to arrhythmic action of digoxin • In congestive heart failure the drug elimination is retarded due to decreased perfusion and congestion of liver, also reduced glomerular filtration and increased tubular reabsorption • In head injury, morphine (in normal dose) can cause respiratory failure In severe pain, hypnotics may cause mental confusion Tolerance: Tolerance is a condition when there is a requirement of higher dose of a drug to produce a given response Drug resistance: It is tolerance of micro-organisms to inhibitory action of antimicrobials e.g staphylococci to penicillin 10 Other drugs: Drugs may modify the response to each other by pharmacokinetic or pharmaco-dynamic interaction between them Tachyphylaxis is the rapid development of tolerance in which there is a marked reduction in response even after repeated doses of a drug It is not necessary that tolerance develop equally to all the action of the drug, e.g tolerance of morphine occurs to its analgesic and euphoric action and not to its constipating and miotic actions Likewise in phenobarbitone, tolerance occurs to its sedative action and not to its anti-epileptic action Cross tolerance is development of tolerance to pharmacologically related drugs e.g morphine and barbiturates CHEMICAL CHARACTER OF DRUGS STRUCTURE ACTIVITY RELATIONSHIP (SAR) The effect of certain structural compounds in relation to its activity, duration of action and mechanism can be altered by changing the structure of drugs of known activity A new product can show different reactions, different relation between the drugs and cell constituents and perhaps even new mechanism of action The structure activity relationship is useful in synthesis of new active compounds with more specific actions with lesser unwanted effect, and to know about their mechanism of action DRUG RECEPTORS The drug receptors are macromolecular sites which are situated on the surface or inside the effector cells with which specific agonist combines to produce its response Antago- ... of action it has a pharmacological effect which may be responsible for an eventual therapeutic effect and also responsible for the adverse effects as well as some other effects which may be of... 1/ General Principles of Pharmacology STIMULATION Stimulation is an increase in the selective activity of specialized cells, which increases the secretion from a gland, for example, morphine stimulates... concentration in the CNS The dose of a drug for children is often calculated from adult dose Child dose = #IG × #FWNV FQUG #IG Section 1/ General Principles of Pharmacology 42 drugs like morphine,