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Pharmacology Introduction to Pharmacology. Drugs should be used to prevent, to cure and to diagnose diseases. Pharmacology is the study of the actions, uses, mechanisms, and adverse effects of drugs. Pharmacodynamics, Pharmacokinetics Toxicology.
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Drugs should be used to prevent, to cure and to diagnose diseases. Pharmacology is the study of the actions, uses, mechanisms, and adverse effects of drugs. Pharmacodynamics, Pharmacokinetics Toxicology
Pharmacodynamics is the study of the biochemical and physiological effects of drugs and their mechanism of action
A. Excitation is an increase or enhancement of mental activity by a drug. For example, stimulation of mental activity by caffeine. Inhibition is a decrease of the function produced by a drug. For example, barbiturates induced sedative-hypnotic effect.
B. Direct Action refers to the action produced directly by a drug at the site of contact with drug. A direct action at one part can at times elicit effects on remote organs or tissues, which are designated as indirect action.
For example, norepinephrine constricts the blood vessels directly, increases blood pressure, It is the direct action. It reflexively decreases heart rate. That is the indirect action.
C. Selectivity: A drug is usually described by its most prominent effect or by the action thought to be the basis of that effect. Cardiac glycosides mainly stimulate myocardium; diazepam inhibits central nervous system; streptomycin suppresses tubercle bacilli.
D. Therapeutic effect is the effect affecting the physiological and biochemical functions of the organisms and pathogenic processes. It is used to prevent and treat diseases.
Etiological treatment means that the drug may eliminate the primary pathogenic factor and cure disease. Such as, antibiotics eliminate pathogenic organisms within body.
Symptomatic treatment means that the drug may improve the symptoms of disease, such as, use aspirin to treat high fever. In some critical condition, shock, convulsion, congestive heart failure, high fever, severe pain, symptomatic treatment is more urgent than etiological treatment.
E. adverse effect: Any response to drug that is noxious and unintended and that occurs at doses used in man for prevention, diagnosis and therapy of a disease, or for the modification of physiological function.
Side effects of drugs are the effects which we do not want to have , but are nondeleterious, such as dry mouth with atropine which treat the spasm of intestine .
Toxic effects mean noxious effects induced by over dosage of drugs or accumulation of large amount of drugs.
They include acute toxicity which may damage the functions of circulatory system, respiratory system and nervous system, and chronic toxicity which may damage hepatic, renal, bone marrow and endocrine function.
Carcinogenesis, teratogenesis and mutagenesis belong to chronic toxicity. Toxic effect are necessary prelude to avoidance of them or, if they occur, to rational and successful management of them.
Allergy is an adverse reaction that result from previous sensitization to a particular chemical or to one that is structurally similar. Such reactions are mediated by the immune system. The terms hypersensitivity and drug allergy are often used to describe the allergic state.
After effect: The effect still exists , after withdrawal of the drug, the drug concentration is below the threshold, such as, the patient feels hangover next morning, after taking barbiturates.
Secondary reaction: After long term of using broad spectrum antibiotics, due to the change of intestinal normal flora, the sensitive bacteria are abolished, then it appears the overgrowth of non-sensitivity bacteria such as staphylococcus and fungi, staphylococcus enteritis or candida infection (candidiasis) appears, This called secondary reaction.
Graded Dose- Response curve As the dose administered to a single subject or isolated tissue is increased, the pharmacologic effect will also increase. At a certain dose, the effect will reach a maximum level.
Efficacy: The maximum effect of drug, Emax is a measure of drug efficacy. Efficacy is also called intrinsic activity.
Potency: A comparative measure, refers to the different doses of two drugs that are needed to produced the same degree of effect. These two drugs have similar chemical structure and mechanisms of action. The lower the dose of drug effect, the higher the potency of drug.
Graded dose-response curve for three drugs Efficacy and potency
B. Quantal Dose – Response Curve 1. A quantal response is an all –or – none response to a drug and relates to the frequency with which a specified dose of a drug produces a specified response in a population.
2. The quantal dose-response curve is a cumulative graph of the frequency distribution curve . The dose of drug required to produce a specified magnitude of effect in a large number of individual patients or experimental animals are plotted the cumulative frequency distribution of responses versus the log dose.
The specific quantal effect may be chosen on the basis of the clinic relevance (e.g. relief of headache or it may be in experimental animal). When these responses are summated, the resulting cumulative frequency distribution constitutes a quantal- dose-effect curve of the proportion or percentage of individuals who exhibit the effect plotted as a function of log dose.
Quantal dose – effect curve may also be used to generate information regarding the margin of safety to be expected from a particular drug used to produced a specified effect
ED50: The dose at which 50% of the individuals exhibit the specified quantal effect. LD50: The dose at which 50% of the animals exhibit death.
Dose-response curve of effect and toxicity of A,B equal ED50 and LD50, toxicity B>A
Receptor. Macromolecular structure to which a drug binds in such a way as to initiate or modify a biological function.
K1 D+R DR ……E K2 Note: D: drug; R: receptor; DR: drug receptor complex; E: effect; K: rate constant.
When the receptors are occupied, the pharmacological effects will occur. The effects of drug are directly proportional to the numbers of receptors occupied. Stephenson revised the opinion; it is not necessary to occupy all the receptors, when the maximal effect occurs.
Affinity: It is the tendency of a drug to form a combination with the receptors Affinity = 1/KD; KD = dissociation constant
Intrinsic activity: Its inherent ability to produce an effect
Dissociation constant, KD is a characteristic of the drug and of the receptor, it has the dimensions of concentration and is numerically equal to the concentration of drug required to occupy 50% of the sites of equilibrium (50% of the maximal effect. Minus log KD is pD2= -log KD), which is called affinity index. The higher the affinity of the drug for the receptor, the lower will be KD, at the same time, the higher pD2, the stronger will be the effect of the drug.
A B A: a, b, c (equal pD2 , difference Emax) B: a, b, c (equal Emax , difference pD2) Intrinsic activity and affinity of a drug
2. Rate Theory: The response of a drug is the function of the rate of dissociation of drug receptor complex.
3. Two model theory: Receptors have to different conformation, activated conformation (R* ) and resting conformation (R ). They may change to the other one. Activated form may combine with agonists, then may show its effect; resting conformation may combine with antagonist, which has no effect.
Ligand: chemical substances which can combine with receptors are called ligands, ligands include drug, hormones and neurotransmitters.
Spare receptors: For a highly active agonist with a high efficacy, the maximal response will be produced by a concentration that dose not occupy all receptors. The receptors remain unoccupied are termed spare receptors.
1. An agonist has high affinity to receptors and high intrinsic activity. An agonist is a drug that produces a pharmacological effect when it combine with receptors
