General Pharmacology PDF

University of Al-Ameed College of Medicine Department of pharmacology Practical Pharmacology /1 Introduction to clinical Pharmacology Dr. Haider Elmoosawy M.B.Ch.B MSc. Clinical Pharmacology  Clinical pharmacology comprises all aspects of sc...

University of Al-Ameed College of Medicine Department of pharmacology Practical Pharmacology /1 Introduction to clinical Pharmacology Dr. Haider Elmoosawy M.B.Ch.B MSc. Clinical Pharmacology  Clinical pharmacology comprises all aspects of scientific study of drugs in human. Its objective is TO: to optimize drug therapy Minimizing adverse effects as possible.  Nearly 500 years ago, Swiss physician and chemist Paracelsus expressed the basic principle of toxicology: “ All things are poisons, and nothing is without poison; only the dose makes a thing not a poison.  It means that a substance that contains toxic properties can cause harm only if it occurs in a high enough concentration. Pharmacology is the base of Pharmacotherapeutics (the treatment of diseases with drugs). It overlaps extensively with pharmacy - the science of drug production.  Molecular pharmacology Population pharmacology: randomized clinical trials and observational studies (such as case–control studies); pharmacoepidemiology. Aspects of pharmacovigilance; pharmacology Pharmacoeconomics; social factors that affect therapy; medicines policy. Role of *the general aspects for safe and clinical effective therapy. pharmacolo *drug therapy for individual gy diseases. *safe introduction of new medicines. More detailed aspects of clinical pharmacology include: *Pharmacodynamics, how the drugs affect our body. *Pharmacokinetics, how the body handles a drug.  Therapeutic evaluation o Whether a drug is of value? o How it may best be used? o Formal therapeutic trials o Surveillance studies for both efficacy and safety (adverse effects) - pharmacoepidemiology and pharmacovigilance.  Control:  Rational prescribing and formularies.  Official regulation of medicines. Social aspects of the use and misuse of medicines.  Pharmacoeconomics.  1/ Intermittent use; to cure a disease. E.g.: bacterial and parasitic infections, anesthesia…. etc Uses of 2/ to suppress (or control) a disease e.g: Drugs hypertension, DM, asthma , joint diseases ….etc 3/ to prevent a disease; or a condition ; primary prevention like in malaria, use of a contraceptive pill.In secondary prevention; like preventing HF in MI pateints. Reduction *better knowledge of the disease. of Drug *site specific effects. Risks *site specific delivery. *informed, careful and responsible prescribing.  Unacceptable risk Grades of Acceptable risk Drug Risks Negligible risk Risk assessment is different in life threatening from mild diseases. Pharmacological terms  Affinity: the ability of a drug to bind to a receptor. Selectivity: the property for a drug to bind to a target rather than to another one. Agonist: A ligand that binds to a receptor and alters the receptor state resulting in a biological response. Full agonist: This is an agonist that produces the largest maximal response of any known agonist that acts on the same receptor.  Partial agonist: A partial agonist is an agonist that produces a response that is less than the maximal response produced by another agonist acting at the same receptors on the same tissue, as a result of lower intrinsic activity.  Bioavailability The percent of dose entering the systemic circulation after administration of a given dosage form. Frequently, the “standard formulation” used in assessing bioavailability is the aqueous solution of the drug, given intravenously.  Therapeutic efficacy describes the effect of the drug on a desired Efficacy: efficacy refers to biological endpoint and can be the capacity of a drug to used to compare drugs that act via produce an alteration in a different pharmacological target cell/organ after mechanisms (e.g. loop diuretics binding to its receptor. induce a greater diuresis than thiazide diuretics and therefore have greater therapeutic efficacy).  First-pass effect: The biotransformation and/or excretion of a drug by intestinal and hepatic, including biliary, mechanisms following absorption of the drug from the GI tract, before drug gains access to the systemic circulation.  Half-life: The period required for the concentration or amount of drug in the body to be reduced to exactly one- half of a given concentration or amount. Example of potency Potency: An expression of the activity of a drug, in terms of the concentration or amount needed to produce a defined effect.(a comparative measure of different doses of two drugs that are needed to produce the same pharmacological effect) Bumetanide ( diuretic) dose is 1 mg Furosemide (diuretic) dose for example is 20 mg Bumetanide produce a response that is greater than furosemide , which in this case is considered more potent.  Synergy: mutually reinforcing drug interaction such that the joint effect of two drugs administered simultaneously is greater than the sum of their individual effects. Syner gy  Desensitization refers to the common situation in which the biological response to a drug diminishes when it is given continuously or repeatedly. It may be possible to restore the response by increasing the dose of the drug but, in some cases, the tissues may become completely refractory to its effect. Tachyphylaxis  a rapid decrease in response to repeated doses over a short time period. Or Decrease in response to a drug due to previous exposure…. It is not DOSE-DEPENDANT. This rapid loss of response is due to depletion of chemicals that may be necessary for the pharmacological actions of the drug (e.g. a stored neurotransmitter released from a nerve terminal). After a relatively short period of withholding the drug, its effect is restored (i.e tachyphylaxis resolves rapidly) examples : Nitroglycerines, Sodium nitropresside  A condition characterized by a reduced effect of a drug upon repeated administration. Tolerance In some cases, it may be necessary to increase the dose of (dependence) the drug to attain the same effect, or the original level of effect may be unattainable. This slower change implies changes in receptor numbers or the development of counter-regulatory physiological changes that offset the actions of the drug.  Therapeutic Index: is a measure of the approximate “safety factor” for a drug;. Drugs have multiple potential adverse effects, but the concept of therapeutic index is usually reserved for those  Drugs with low therapeutic index: Warfarin Digoxin Lithium Contraceptive Theophylline Gentamicin Cytotoxic drugs Tacrolimus Antiarrhymic drugs