Model questions and answers Pharmacodynamics [Dr.Rathnakar U.P.

]
Q.1. Explain mechanism of action of drugs 5 Answer: Various biochemical physiological processes by which a drug produces a response in living organisms are the mechanism of actions of the drug. The mechanisms include1. Physical property- e.g. Mannitol [osmotic], chelation [EDTA]. 2. Chemical property- KMNO4 [oxidizes alkaloids] 3. Enzymes-stimulation [microzomal enzymes]or inhibition [Anticholinesterases] 4. Ion channels [local anesthetics and Na channel] 5. Receptors- G protein coupled, Intrinsic ion channel, Enzyme linked and nuclear receptors By these various mechanisms a drug brings about both beneficial and adverse effects.

Q.2.

Define a receptor. Classify super family of receptors with examples

1+2

Protein macromolecules present on cell wall or inside the cell to which drug binds, interacts, and produces action. Super family: 1. 2. 3. 4. G-protein coupled receptors- Eg. Muscarinic receptors Intrinsic ion channel receptors- Eg. Nicotinic receptors Enzyme-linked receptors-Eg. Insulin receptors Nuclear receptors- Eg. Glucocorticoid receptors Q.3. Write briefly on 1. Therapeutic index Therapeutic index is the ratio between median lethal dose [dose required to kill 50% of experimental animals] and median effective dose. T.I= Median lethal dose [LD50]/Median effective dose [ED50]. T.I. Defines the safety margin of the drug. Drugs with high safety margin like penicillins have high T.I. and those with low safety margin like Digoxin have low T.I. 5 each

2. Combined effect of drugs A. What is drug synergism?

When two drugs are administered together, if the action of one drug is facilitated or increased by the other, they are said to be synergistic. Synergism can be additive or supraadditive [potentiation] Additive: Eg. Aspirin + Paracetamol, Nitrous oxide + Halothane. When two drugs are combined with additive properties the combination helps to reduce adverse effects without compromising efficacy Supraadditive [potentiation]: both can be active or one can be inactive Trimithoprim + Sulfamethaxozole [both active] = effect is more than the sum of effects of individual drugs-1 Levodopa [active] + carbidopa [inactive] = effect more than that of Levodopa B. Explain antagonism. Enumerate the differences between competitive/non-competitive antagonism 5+2 When two drugs are administered [combined] together one drug decreases or abolishes the action of the other.
(a) Physical antagonlsm: eg. Charcoal adsorbs alkaloids. This physical property of charcoal is used to treat alkaloid poisoning. (b) Chemical antagonism: eg. [1] KMnO4+ oxidizes alkaloids. [2] Chelating agents (BAL, Cal. disod. edetate). The two drugs react chemically and form an inactive product. (c) Physiological/functional antagonism: Eg. [1] Histamine [Bronchconstriction] + adrenaline ++ ++ [Bronchodilatation]. [2] Hydrochlorothiazide [increases K excretion] + triamterene [decreases K excretion]

Here two drugs produce opposing physiological actions (d) Receptor antagonism: [1] Competitive [surmountable]: Eg. Acetylcholine and atropine on muscarinic receptors Eg. Morphine and naloxone on opioid receptors Antagonist [atropine and naloxone] have affinity but no intrinsic activity on the receptors. Antagonist binds to the same site as agonist on the receptor and prevents the effect of agonist [Ach of morphine]. Their effect can be overcome by increasing the concentration of agonists [2] Non competitive: Eg. Diazepam and biccuculine on GABA receptors Here antagonist [Biccuculine] to a different site on the receptor and alters the receptor so that it can not combine with agonists. Effect is not surmountable. Have affinity but no intrinsic activity. Not clinically used

Differences - competitive and non-competitive antagonists Competitive Non-competitive Antagonist bind to same site as agonists Bind to another site Chemically resemble agonists Do not resemble Surmountable Non surmountable Eg. Ach & Atropine Eg. Diazepam & Biccuculine Q. 4. Name four factors modifying drug action. Explain any one with examples 5 1. Body size. 2. Age. 3. Sex. 4. Species and race. 5. Route of administration 6. Pathological states 7. Psychological factors. 8. Genetics. 8. Environment. 9. Other drugs. 10. Tolerance. 11. Drug resistance Route of drug administration: Route administration decides the speed and intensity of response to drugs. Parenteral routes are faster acting than oral routes. Intravenous route effects immediate response. Sometimes change in route can change the action of drugs. Eg. MgSo4 orally-Causes purgation, topically anti-inflammatory, administered and intravenously acts as CNS depressant. Age: Various formulae are used to calculate the children dose of the drug [Youngs and Dillings]. However there are physiological difference in infants and children compared to adults. g.f.r. is low, Drug metabolizing capacity is less than adults, and BBB is deficient in new born. These factors should be remembered in deciding dose in children. Elderly can have compromised renal function, reduced motility of intestine, incidence of adverse effects are more in aged people. Q.5. Write briefly on 1. Placebo. 2. Tolerance 3. Tachyphylaxis 2x3

Placebo: Is a factor which can modify action of a drug. It is defined as an inert substance given as a medicine. It usually does not have any physiological effects. It is used in clinical trials as a control with an experimental drug. Some times used to satisfy the patient who does not need active pharmacological agents. Placebos can induce endorphins in brain hence said to be effective as analgesics, but effect is variable. Injection and capsules are more effective as placebo compared to tablets. Lactose tablet is usually used as placebo. Tolerance: It refers to the requirement of higher dose, than earlier, of a drug to produce a given response. It can be
natural or acquired

Natural- Some species/individual is born less sensitive to the drug, e.g. rabbits are tolerant to atropine; black races are tolerant to mydriatics. Acquired-This occurs by repeated use of a drug in an individual who was initially responsive now becomes resistant to the effects of the drug. Eg. Tolerance develops to sedative action of chlorpromazine but not to its antipsychotic action. Tolerance occurs to the sedative action of phenobarbitone but not as much to its antiepileptic action. Tolerance occurs to analgesic and euphoric action of morphine, but not as much to its constipating and miotic actions. Cross tolerance: It is the development of tolerance to pharmacologically related drugs, e.g. alcoholics are relatively tolerant to barbiturates and general anesthetics. Mechanism of tolerance: PK [Disposition] Drug excretion is increased on repeated administration. Eg. Barbiturates PD [cellular] - Cells become less responsive due to down regulation of receptors. Eg. Morphine Tachyphylaxis: Tachyphylaxis (Tachy- fast, phylaxis-protection. rapid development of tolerance when doses of a drug repeated in quick succession. This is usually seen with indirectly acting drugs, such as ephedrine, tyramine, nicotine. Other mechanisms like slow dissociation of the drug from its receptor, desensitization / internalization or down regulation of receptor.

Q.6. Write briefly on 1. Therapeutic window 2. Drug induced diseases 3. Drug allergy 4. Terratogenic diseases 5. Down regulation of receptors 6. Idiosyncrasy

2 2 4 2 2 2

Therapeutic window [therapeutic range]: The range bounded by the dose which produces minimum therapeutic effect And the dose which produces maximal acceptable adverse effects.[see Tripathi 7th ed. Page 56 for figure] Drug induced diseases: These are also called iatrogenic (physician induced) diseases. They are diseases caused by drugs. The symptoms and signs can be present even after the drug is completely stopped. e.g.: Peptic ulcer by salicylates and corticosteroid-. Parkinsonism by phenothiazines Hepatitis by isoniazid. Drug allergy: It is an immunomodulated response to a drug which is not related to pharmacological action of the drug. Prior sensitized patients, reexposure leads allergic reaction There are four types, Type I [Anaphylactic], II [Cytolytic], III [Arthus], IV [Delayed hypersensitivity]

Treatment: The drug causing allergy is immediately stopped. Antihistaminic may be required. Treatment of anaphylactic shock; 1. Raise the foot end. 2. Administer oxygen 3. Adrenaline 1:1000, 0.5ml i.m. 4. Antihstaminic i.m. 5. i.v.hydrocortisone
Terratogenic diseases: Capacity of a drug to produced abnormalities in fetus when administered to

pregnant mother. Eg.Valproic acid may cause spinabifida, thalidomide may cause phocomelia. Drugs may affect in three stages Fertilization and implantation [up to 17 days of pregnancy]: Failure of pregnancy Organogenesis [18-55 days]: Deformities of organs Growth & development [after 55 days] Terratogenic drugs are classified into five risk categories [A, B, C, D, X] by WHO.

Down regulation of receptors: Prolonged use of agonists leads reduction in the no. of receptors or decrease in their sensitivity. For example prolonged use of clonidine leads to down regulation of 2 receptors and leads to sudden rise in blood pressure.

Idiosyncrasy: Is a genetically determined reaction to a drug. It is an unusual individual reaction to food or a drug. Eg. Barbiturates cause excitement and mental confusion in some persons. Chloramphenicol causes aplastic anemia

Q.7. What is a dose response curve? Explain with a figure

Dose is plotted on X axis and the response to a dose is plotted in Y axis. Dose-response curves determine how much of a drug (X-axis) causes a particular effect, or a side effect, in the body (Y-axis). Types of DRCs: Simple dose response curve, Log-dose response curve and quantal dose response curve

Uses of DRC: 1.To compare efficacy and potency 2.To find out antagonism and Synergism. Advantages of Log-dose curve: 1. Large no. of doses can be plotted on a small graph paper. Comparison of two or more drugs is easier as middle portion is in a straight line.