Pharma Slide 01

processes. It modifies an already existing function, and does not create a new function. Pharmacology: The science of drugs. It is the knowledge of history, source, physical and chemical properties, absorption, distribution, biotransformation, excretion, actions and therapeutic uses of drugs (or toxic effects on microbes),

Definitions Medical (or Clinical) Pharmacology: Is the science that deals with the use of drugs for diagnosis, prevention and treatment of human disease. • Toxicology: Is that aspect of pharmacology which deals with adverse effects of drugs and the toxic effects produced by household, envb,nmental and industrial chemicals. [poisons are also drugs, why?)

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Definitions Two aeneral principlesttt ev~ry student should always r Jmember: 1. All substances can u~def certain conditions be toxic. ' ' 2. All dietary supplements and all substances promoted as healthenhancing should meet the same standards of efficacy and safety.

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Definitions

Definitions

• Pharmacotherapeutics: Is the use of drugs in the prevention and treatment of disease ( or the medical uses of drugs). • Chemotherapeutics: Is the use of drugs to stop the growth or kill microorganisms or cancer cells

• Ph?rmacogenomics: The relation between the individual's genetic makeup to his/her response to specific drugs (entire genome). • Pharmacogenetics: Interindividual variation in drug response that is due to genetic influences (specific gene).

Definitions

Areas of Pharmacology

Idiosyncratic drug response: Unusual response, infrequently observed in most patients. Usually caused by genetic differences in metabolism of drug, or by immunologic mechanisms including allergic reactions. • Tolerance: Is a decrease in the responsiveness to the drug with continued drug administration. • Tachyphylaxis: Similar to tolerance but m9!e rapid.

• Pharmacodynamics:

Is what the drug does to the body, which includes the biochemical and physiological effects of the drug, including the mechanism of action, interaction with receptors as well as the adverse effects.

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Areas of Pharmacology

Areas of Pharmacology

Pharmacokinetics:

2. Distribution: Is the movement of drug molecules from the circulation to tissues and between different parts of the body. 3. Biotransformation: Is conversion of the drug from one chemical structure into another by the action of metabolic enzymes (metabolism) 4. Excretion: Is the movement of drug molecules out of the body.

Is what the body does to the drug. Deals with absorption, distribution, biotransformation and excretion of drugs. 1. Absorption: Is the movement of drug molecules from the site of administration into the circulation.

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Pharmacokinetics & Pharmacodynamics

Pharmacokinetics & Pharmacodynamics

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Drug Receptors

Drug Receptors

A receptor is a component of the cell that interacts with a drug and initiates a chain of events leading to drug's action. Receptors are responsible for selectivity of drug action. Receptors determine the quantitative relationship between drug concentration and pharmacological effect. Receptor function can be modified by agomsts and antagonists. Antagonists int'lrfere with the ability of the agonist to activate the receptor.

Most receptors are 'protelns: 1. The best characterized drug receptors are regulatory proteins, which mediate the actions of endogenous chemical signals such as neurotransmitters, autacoids and hormones. 2. Some receptors Include enzymes that could be Inhibited by drugs. (dihydrofolate reductase and trimethoprim). 3. Some receptors are transport proteins (Na' I K' ATPase and digitalis). 4. Some receptors are structural proteins (tubulin and colchicine).

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Signaling Mechanisms Five basic transmembrane signaling mechanisms are well understood: 1. A lipid-soluble chemical signal crosses the plasma membrane and acts on an intracellular receptor. 2. The signal binds to the extracellular domain of a transmembrane protein, thereby activating an enzymatic actiVity of its cytoplasmic domain. 3. The signal binds to the extracellular domain of a transmembrane receptor bound to a protein tyrosine kinase, which it activates. 4. The signal binds to and directly regUlates the opening of an ion channel. " 5. The signal binds to a cell-surface receptor linked to an effector enzyme by a G protein. • J""

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Drug Receptcr Interaction Definitions: Agonist: A d"ug that binds to and activates the receptor to bring about the pharmacological effect. 1. A full agonist produces maximal pharmacological response with full receptor occupancy. 2. A partial agonist produces less than maximal (lower) pharmacological response with full receptor occupancy. It is also calleq partial antagonist.

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Drug Receptor Interaction

• Antagonist: A drug that binds to the receptor but does not activate it. It prevents the agonist from binding to the receptor and prevents its activation and the generation of pharmacological effect It can be either reversible or irreversible, competitive or noncompetitive. Some antagonists are called "inverse agonists". They reduce receptor activity below basal levels observed in the absence bound ligand (drug).

Drug Receptor Interaction

Drug Receptor Interaction

• Competitive Antagonist In the presence of a fixed concentration of agonist, increasing the concentrations of a reversible competitive antagonist progressively inhibit the agonist response; high antagonist concentrations prevent response completely.

• Conversely, suffic::ilntly high concentrations of agonist can completely overcome the effect of a given concentration of the antagonist. • Because the antagonism is competitive, the presence of antagonis increases the a~onist concentration required for a given degree of response, and so the agonist concentration effect curve is shifted to the right.

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• Irreversible Antagonist: Some anta~onists bind to the receptor in an irreversible fashion either by forming covalent bond with the receptor or binding tightly to it, so that the receptor not available for a~onist binding. Th) remaining unoccupied receptors bind agonist normally, but might not be enough to elicit an adequateresponse. The duration of action of the irreversible antagonist is more dependent on recepto turnover than antagonist elimination.

FIGURE 2.5 Id~aliled dosc-rcsoonse cun'li:s of an agonist in tfIE. absence Ie) and lhc presence (b. c. d} of incrt:a~in6 oose-s of ilr'l cquilibnum-eonll'Ctil,\,C antacofllst.

Drug Receptor Interaction

Drug Receptor Interaction B

• Another way of noncompetitive antagonism is binding to the receptor on a different site that binds the agonist, thereby preventing receptor activation by the agonist without blocking agonist binding. This is also called

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Drug Receptor Interaction Other mechanisms of drug antagonism: 1. Chemical antagonism: heparin & protamine. 2. Physiologic antagonism: Insulin and glucocorticoids effects on blood glucose.

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• Occupation of a receptor by an agonis is only the first of many steps required to bring about the pharmacologic effect. The transduction process that links drug occupancy of receptors and pharmacologic response is termed coupling.

Spare Receptors Sometirr,es the effect of the drug is linearly related to the number of receptor bound. In other cases, the effect increases disproportionately to the number of receptors occupied by drug. Receptors are said to be "spare" for a given pharmacolo£ic response if a maximal response is elicited at an agonist concentration that does not result in full occupancy of receptors.-

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