Pharmacodynamics of Drugs PDF

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dk oenmim.a asa Inhibition of Enzymes Pharmacodynamics of Drugs Enzymes are substances that speed up many chemical reactions and control a number of metabolic processes. Some drugs have the property of inhibiting the “What the DRUG does to the BODY” activity of some enzymes. Pharmacodynamics In the patient (ACE inhibitors; NSAIDs) The action of a drug on the body, including the study of: In microbes (sulfas, penicillins) Mechanisms of drug actions In cancer cells (5-FU, 6-MP) I. The pharmacological actions of drugs; dose- Action on cell membrane; Action on Ion Channel response phenomena. Dr. Mohannad A. Almikhlafi Local anesthetics block Sodium (Na+) channels. Assistant Professor of Pharmacology and Toxicology II. The mechanisms of therapeutic and toxic actions of Calcium channel blockers (CCB) e.g. Verapamil block L-type of voltage gated Faculty of Pharmacy Taibah University drugs. as ask.ms calcium channels of heart & blood vessels. heart i sina.suiaimi imon Block c PCont. The drug-receptor theory Interference with Metabolic Pathway (Antimetabolites). Drug-receptor interaction (receptor theory) Drug-Receptor Theory B) Blockers: The drug may be similar in structure to a substance (metabolite) which is A Receptor is a chemo-sensitive & chemo-selective cellular Types of Ligands Blocking receptors to prevent its activation. used by the cells for their function. macromolecule that reacts specifically with a Ligand (drug, Blockers can be: Thus, in the presence of the drug, the cell cannot use its endogenous transmitter or hormone) to produce a biological response. metabolites and fails to multiply. A) Stimulants = Agonists: 1- Antagonists: They are able to bind to target receptors The drug is thought to fit onto a receptor rather as a key fits a lock (Key & Lock Theory). A drug binds to a receptor and produces a biologic response that because they possess strong affinity. They occupy the Example: The anticancer agent. mimics the response to the endogenous ligand. receptor without producing any effect and should have: ❑ 6-mercaptopurine (6-MP) which competes with purine bases in the Example: Adrenaline actions on  &  adrenergic receptors a- Affinity. synthesis of DNA, interferes with cell division. ❑ Sulfonamide antibiotics compete with PABA in bacteria →  Synthesis of folic acid (Agonist = affinity + efficacy). c- Slow dissociation from receptors. ex b- No = Zero efficacy “no intrinsic activity”→ No dose/response curve s.im They block the action of agonists. (Antagonist = affinity, no efficacy). Examples: Prazosin, propranolol in twicaaid an Types of Antagonism it i Types of Antagonism t.is Cont. The drug-receptor theory  Antagonism could be chemical, physiological or pharmacological. 2- Partial Agonists = Dualists: Interaction of an agonist and antagonist with the receptors  Antagonism could be chemical, physiological or pharmacological. 1. Pharmacological: They should have: Molecule of A) Competitive Block: Antagonists bind REVERSIBLY with the receptors. Antagonists Less maximum response (Emax) than agonists ; have efficacies Ac etylcholine Molecule of can be DISPLACED by excess agonists. 2. Chemical antagonist: Ac etylcholine (intrinsic activities) greater than zero, but less than that of a full By combining with another drug and rendering it inactive. agonist. B) Non-Competitive Block: If the antagonist binds to a site other than where the agonist (e.g. Protamine neutralizes the anticoagulant effects of heparin by forming an inactive binds, the interaction is noncompetitive or allosteric. Antagonist is NOT displaced by complex). They produce initial stimulation then block of the receptor. agonist. Muscarinic rec eptors Rec eptors are occupied by the in smmoth musc le ag onist and the musc el is Types of Non-Competitive Block : 3. Physiologic antagonism: Example: Nicotine (NN). stimulated a- REVERSIBLE : The antagonist binds REVERSIBLY to the receptor. Usually of Short duration of action. An antagonist may act at a completely separate receptor, initiating effects that are functionally opposite to those of the Fts Molecule of Ac etylcholine b- IRREVERSIBLE : agonist. This antagonism is also known as functional antagonist. (e.g. epinephrine antagonize the effect of histamine). The antagonist binds IRREVERSIBLY to the receptor. Usually of Long duration of action. we Atropine Rec eptors are bloc ked by atropine; acetylcholine has no effect  Airmoreasective Dose-Response Relationships The magnitude of the drug effect depends on the drug concentration at the The effect of dose on The effect of dose on the receptor site. the magnitude of drug magnitude of pharmacologic binding. response. e As the concentration of a drug increases, the magnitude of its pharmacologic effect also increases. The relationship between dose and response is a Panel A is a linear graph. continuous one. Infected effect Dose-Response Relationships Drug + Receptor Drug-Receptor Complex Panel B is a semilogarithmic plot of the same data. The response is a graded effect, meaning that the response is continuous EC50 = drug dose that shows fifty b and gradual. percent of maximal response. itiacurve So A graph of this relationship is known as a graded response curve. Plotting the magnitude of the response against increasing doses of a drug produces a graph that has the general shape shown in the following figure. Drug A is more potent than Drug B because less Drug A is needed to obtain 50 percent effect. to effect I MN nmmsn i at titanium a gamma Potists Potency Efficacy (intrinsic activity) Tolerance gg Potency is a measure of the amount of drug necessary to produce an effect of a given magnitude. Typical dose-response curve for 3 drugs showing differences in potency and efficacy. say Kashiwagi This is the ability of a drug to produce a physiologic response when it  Tolerance can be described as a decreased response to interacts with a receptor. (EC50 = drug dose that shows the usual dose of a drug after repeated administration. fI fifty percent of maximal I EC50: The concentration producing an effect that is fifty percent response.) of the maximum is used to determine potency. Efficacy is dependent on the number of drug-receptor complexes  Patient may need to increase dose to obtain the same formed and the resulting cellular responses. effect. An important contributing factor to the dimension of the EC50 is the affinity of the drug for the receptor. make The following Figure shows the response to drugs of differing  It is sometimes described as desensitization or potency and efficacy. By plotting the log of the concentration, the curves become tachyphylaxis. sigmoid in shape. It is also easier to estimate the EC50. responcittraction Phissoligcal receptors meats.dk.ba bsivw Log www.wsigmoidshape gdmitgida.ua s nine if in Drug-Drugone p Interactions Cont. Drug-Drug Interactions Dependence c) Potentiation: wasDoses of Drugs When two drugs are administered together, one of the following phenomena could be observed:  It occurs when a drug which has no effect, by itself, We1- Therapeutic Dose: Average dose calculated for an Adult, Male, 20-60 year old & 70 Kg body weight.  This describes an aspect of drug abuse, which means that the increases the effect of another active drug, i.e., 0+1>1. 2- Maximal Tolerated Dose; Highest dose without toxic effects. individual is dependent on a certain drug. a) Additive effect:  Example: Barbiturates potentiate the analgesic activity of 3- Lethal or Fatal Dose: Dose that kill the patient or an experimental animal  When the drug is stopped, withdrawal symptoms occur. This occurs if the two drugs have similar effects. In this salicylates although they have no analgesic action on 4-Therapeutic Index: Ratio = LD50 / ED50 their own. p case, the effect produced due to the combined LD50 = Lethal dose in 50% of animals ED50 = Effective dose in 50% of animals Dependence may be: administration is equal to that produced by a double dose a. Psychological dependence, e.g. tobacco smoking. of an individual drug, i.e., 1+1=2. d) Antagonism: Discussed before. A good guide to determine & compare SAFETY of drugs. The b. Physical dependence, e.g. morphine, ethyl alcohol or Higher the therapeutic index → The Safer the drug barbiturates. b) Synergism: e'dshe Both drugs are biologically active, and when combined, the net effect is greater than the sum of their individual effects, i.e., 1+1>2. a stave Iit aan  Pharmodynamic mechanisms of a drug qq.gg inhi eintfhacemeta.ba Drug receptor Antematbolise Enzyme 111191 Jail III k iisa wi.mx mmol nell sw mchanellch g.ns insignia is.LI agonists E.am anastathia cardie t.sii.si sings fÉ dualists chemical combining2drugs making it nutritize Pharmacogical mat I competitive non Phisyological Reifton Mahman Short Long she Ii will L