Pharmacology Lecture 2: Pharmaco-dynamics PDF

Pharmacology Pharmaco-dynamics LECTURE (2) Pharmaco-dynamics (2) DR. El-Sawy 0  Pharmacology...

Pharmacology Pharmaco-dynamics LECTURE (2) Pharmaco-dynamics (2) DR. El-Sawy 0  Pharmacology Pharmaco-dynamics  Ability of a drug to produce response (effect) after binding to the receptor.  Measured by Emax (the maximal response that a drug can elicit at full concentration): Full agonist Partial agonist The drug that gives maximal The drug that gives response at full concentration submaximal response even Efficacy (at full occupancy). at full concentration i.e. never gives Emax  ED50 (Effective Dose) Dose of the drug that gives 50% of the Emax. Dose that gives the desired effect in 50% of a test Potency population of subjects.  A drug that gives ED50 by smaller doses  "potent" drug.  Potency of drugs is generally less clinically important than efficacy because you can increase the dose of a less potent drug to obtain the effect of a more potent one (provided that it is not toxic). DR. El-Sawy 1  Pharmacology Pharmaco-dynamics  TD50 (Toxic Dose): Dose needed to cause a harmful effect in 50% of a test population of subjects.  LD50 (Lethal Dose) : Dose needed to cause death in 50% of a test group of animals. Safety It is experimental term that can be determined in animals.  Ratio between the LD50 and the ED50.  Measure of safety: If there is a large difference between the dose of drug that produces the desired effect and the dose that produces a toxic effect  the drug has a large TI. Drugs with high TI are more safe for clinical use, and vice versa (e.g. warfarin has a narrow TI and requires careful therapeutic monitoring). DR. El-Sawy 2  Pharmacology Pharmaco-dynamics Definition:  The ligand that combines with the receptor and does not activate it.  Cause a pharmacological response by inhibiting the actions of endogenous substances or other drugs. DR. El-Sawy 3  Pharmacology Pharmaco-dynamics Types:  If the antagonist binds to the same site of the agonist on the receptor , It may be:  Makes weak bond with receptor so as you can overcome the block by giving high doses of the agonist, and even you can get the Reversible maximal response in presence of the antagonist antagonist (i.e. surmountable effect).  Duration of block is short because antagonist competitive can be easily washed off receptors.  Makes covalent bond with the receptor so as you cannot overcome the block or get the maximal response by increasing the dose of Irreversible agonist (i.e. non-surmountable effect). antagonist  The occupied receptors are permanently blocked, so the duration of block is long, and the body has to synthesize new receptors to regain the original state.  If the antagonist binds to another site on the receptor, and non- competitive prevented the action of the agonist. DR. El-Sawy 4  Pharmacology Pharmaco-dynamics Other types of drug antagonism  One acidic drug when added to a basic drug can cause precipitation of each other’s  The addition of gentamycin (basic drug) to carpenicillin (acidic drug) in same syringe causes chemical complex. Chemical antagonism  Antagonism between two drugs producing opposite effects by activation of different receptors.  Adrenaline is the physiological antagonist of histamine because:  Histamine causes hypotension & bronchoconstriction through activation of histamine H1 receptors  Adrenaline causes hypertension & bronchodilatation through activation of adrenergic a & ẞ receptors Physiological respectively. antagonism DR. El-Sawy 5  Pharmacology Pharmaco-dynamics  Antagonism between two drugs carrying opposite charges  Protamine is used for ttt of heparin overdose because protamine carries +ve charge while heparin carries -ve charge. Physical antagonism  One mg of protamine can neutralize 100 units of heparin.  One drug may prevent absorption of another drug: e.g. antacids ↓ absorption of iron & aspirin.  One drug may increase metabolism of another drug : Pharmacokinetic e.g. rifampicin induces hepatic enzymes and ↑ antagonism metabolism of oral contraceptive pills.  One drug may ↑ excretion of another drug : e.g. NaHCO3 cause alkalinization of urine and ↑ excretion of acidic drugs like aspirin. DR. El-Sawy 6  Pharmacology Pharmaco-dynamics How drugs could modulate ion channels? 1. Physical block: e.g. blocking of Na+ channels by local anesthetics. 2. The ion channel may be part of receptor e.g. ion channel-linked receptors. 3. The ion channel may be modulated by G- protein linked receptors. 4. Ion channels may be modulated by intracellular ATP e.g. ATPase sensitive K+ channels in the pancreatic beta cells, rise of intracellular ATP causes closure of pancreatic K+ channels. How drugs could affect enzymes? The drug may act as 1. Competitive inhibitor of enzyme e.g. neostigmine on cholinesterase enzyme. 2. Irreversible inhibitor of enzyme e.g. organophosphates on cholinesterase enzyme. 3. False substrate for enzyme e.g. α-methyldopa is a false substrate for dopa decarboxylase. 4. Induction or inhibition of hepatic microsomal enzymes activity DR. El-Sawy 7  Pharmacology Pharmaco-dynamics  Small protein molecules that carry organic molecules across Definition the cell membrane when they are too large or too polar.  Drugs could affect carrier molecules by blocking their Effect of drug recognition site. DR. El-Sawy 8