Pharmacology 1 - Lab 2 PDF

PHARMACOKINETICS 1- Absorption 2- Distribution 3- Metabolism 4- Excretion Fate of administered drug 1- Absorption How the drug is moved from the...

PHARMACOKINETICS 1- Absorption 2- Distribution 3- Metabolism 4- Excretion Fate of administered drug 1- Absorption How the drug is moved from the site of administration into blood stream 2- Distribution How much drug is moved to different body tissues. 3- Metabolism 4- Excretion This will depend on blood flow How the drug is used, through the tissue How much of the drug is altered, and broken down removed from the body Bioavailability Is fraction (F%) of the administered drug dose that reaches the systemic circulation in an unchanged form (active form) then reaches the target cell  Plasma protein binding & drug availability Many drugs become bound to circulating plasma proteins such as albumin, globulins, lipoproteins, glycoproteins… This can limit the bioavailability of active compounds by controlling their passage through biological membranes. However, binding to plasma proteins allows hydrophobic drugs to be transported in the aqueous environment of the human organism. Therefore, the drug could be in: Bound form Free form Drug half-life (t ½) Half-life is the time required for the plasma concentration of the drug to reach 50% of its original administered concentration value This value help in determining: Dosing requirements How long a drug remains in the body Determining the dosing interval Determining time to plateau Absorption  Intravenous administration (IV) IV Route advantages Rapid onset Control Use of large fluid volume Use of irritant drugs (e.g., stomach ulcers) IV Route disadvantages High cost Difficulty Inconvenient Irreversibility : once a drug has been injected, there is no turning back, can be dangerous Q: what is the bioavailability of IV administered drug? Oral drug administration Oral Drug Administration is the process of delivering medication through the mouth in solid form, such as tablets or capsules, or liquid form such as syrups. They come as solid tablets, capsules, chewable tablets to be either orally disintegrating tablets, to be swallowed whole, or sucked. Or as a liquid in the form of drops, syrups or solutions. In most cases, the ingredients in oral medication don't enter the bloodstream until they reach the stomach or intestines where they get absorbed. Q: Is this step part of pharmacodynamics or pharmacokinetics?  All substances absorbed from the intestines go to the portal vein. This vein delivers these substances to the liver prior to distribution to other organs. Most drugs must pass through the liver, which is the primary site for drug metabolism. Once in the liver, enzymes convert prodrugs to active metabolites or convert active drugs to inactive forms. Therefore, the first crucial factor after oral absorption is the efficient first pass uptake and metabolism of compounds by the liver What is first pass? Blood coming from the liver not from the circulation Bioavailability of orally administered drugs Oral bioavailability (F%) is the fraction of an oral administered drug that reaches systemic circulation. Orally administered drugs achieve a bioavailability level substantially lower than 100% due to incomplete absorption and/or elimination during the first pass through the liver. Excretion Drugs and/or its metabolites are eventually eliminated from the body - Unchanged (original form) Elimination of the drugs - Metabolites Kidney (Urine), GIT (Stool), Skin (Perspiration) Routes of excretion Lungs (Expiration), Eyes (Tears) Pharmacodynamics The study of what the drug does to the body. Onset : The time for a drug to start a therapeutic response Peak : The time for a drug to reach its maximum therapeutic effect Duration : The time a drug concentration is sufficient to therapeutic response Receptors “Sites on the organism that bind the drug to initiate its effect” Mechanism of drug action Action on cell membrane Action on metabolic processes within the cell, e.g. enzyme activation/inhibition Action outside the cell, e.g. osmotic diuretics, antacid Characters of the drug at the receptor site Affinity: ability of the drug to bind with the receptor Efficacy: ability of the drug to induce a desired (therapeutic) response Potency: is how much drug must be administered to induce a desired response Agonist : a molecule that activates a receptor to produce an effect similar to that of a physiological molecule. Antagonist : a molecule that prevents the action an agonist on a receptor but does not have an effect of its own. Partial agonist : molecules that activate receptors to produce sub-maximal effect but antagonizes the action of full agonists. Effects of administering combination of drugs Addition : 1 + 1 = 2 The overall effect of two chemicals acting together equals sum of the effects of the chemicals acting independently. Example, co-administration of midazolam and propofol at the induction of anaesthesia reduces the amount of propofol necessary for the same anaesthetic effect. Synergism : 1 + 1 = 3 Two drugs with the same effect are given together and produce a response greater than the sum of their individual responses  Potentiation : 0 + 1 = 2 A drug what has no effect but enhances the effect of a second drug Antagonism : 1 + 1 = 0 A drug that inhibits the effect of another drug, but usually has no inherent activity Drug tolerance How response to the same amount of drug (usually decrease) after repeated administration. Drug intolerance: Side effects of a drug in an individual at therapeutic doses e.g: Vomiting with a single dose of salicylate