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A comprehensive overview of key pharmacological concepts, including drug administration routes, pharmacokinetics (absorption, distribution, metabolism, and excretion), and pharmacodynamics. It delves into the mechanisms of drug action, the influence of factors like body composition and enzyme systems on drug efficacy, and the importance of dosage adjustments based on individual patient characteristics. The document also includes examples and explanations of important concepts like first-pass metabolism, cytochrome p450 system, and drug clearance.
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What routes of med admin are parenteral - All Injections ( IM Sub Q IV, Intrathecal), AND Inhaled , transdermal (patches) , transmucosal (sublingual, nasal, rectal). All PO meds = enteral; Topical is all ointments placed on the skin PO meds absorption pattern - Varies greatly due to: »»Stability and solubility of the medication »»Gastrointestinal pH and emptying time »»Presence of food in the stomach or intestines »»Other medications currently being administered »»Forms of medications (enteric-coated pills, liquids) Rectal medication admin is? - Unreliable/ inconsistent absorption/ good for unconscious, vomiting pts or small children parenteral = - any route of administration other than oral or rectal ; injections, irrigation solutions, dialysis solutions Pharmacokinetics - What the body does to drug/ how it processes it. The process by which drugs are absorbed, distributed within the body, metabolized, and excreted. factors that impact drug absorption - Body Factors: Area of absorptive surface i.e. in GI the microfolds increase surface area, gut pH level, GI motility, presence of other substances. other diseases; In elderly less acidic stomach ph and less blood flow to GI. Drug Factors: Formulation , molecular size , lipid water solubility, concentration etc. Pharmacodynamics - = study of what a drug does to body relationship between drug concentration @ site of action and resulting effect, including time course and intensity of therapeutic and adverse effects. The effect of a drug present at site of action is determined by that drug's binding with a receptor. Receptors may be present on neurons in central nervous system (i.e., opiate receptors) to depress pain sensation, on cardiac muscle to affect intensity of contraction, or even within bacteria to disrupt maintenance of bacterial cell wall Pharmacology - distribution - = process by which drug passes from bloodstream to body tissues and organs .The following factors influence drug distribution: · Lipophilicity: Lipophilic drugs pass through cell membrane/dissolves much easier vs hydrophilic. · Drugs are redistributed in organs according to their fat and protein content. · Most psychotropic medications are lipophilic and highly protein-bound.
barrier prevents fetal exposure to some drugs but allows passage of others. Brain has stronger barrier- no slit junctions in brain cell membrane. · Plasma protein binding=binding of drugs to plasma proteins, i.e. albumin, reduces amount of "free" drug in blood. "Free" drug molecules, but not protein+bound molecules, reach an equilibrium between blood and tissues. only free drug is active. Drugs w/ high molecular weight tend to be extensively protein bound · Depot storage: Lipophilic drugs, i.e. sedative thiopental, accumulate in fat. These agents are released slowly from fat stores. Thus, an obese person might be sedated for a greater period of time than a lean person to whom same dose of thiopen The apparent volume of distribution (Vd) - =· a calculated value that describes nature of drug distribution. Vd is volume that would be required to contain adminstered dose if that dose was evenly distributed at concentration measured in plasma. You could predict that a drug with Vd "" 3 liters is distributed in plasma only (plasma volume"" 3 liters), whereas a drug with Vd 16 liters is likely distributed in extraceliuJar water (extracellular water"" 3 liters plasma plus tD-13liters interstitial fluid). A drug with Vd > 46 liters is Likely sequestered in a depot because body only contains 40-46 liters of fluid. Define Metabolism in terms of pharmacology - : Drugs, chemicals, and toxins are all foreign to our bodies thus body attempts get rid of foreign chemicals, regardless of whether they are therapeutic or harmful. Most drugs must be biotransformed/ metabolized, before they can be excreted. In pharmacology "metabolism" =process of making a drug more polar and water soluble; often results in drug inactivation and excretion, it is INCORRECT to assume that a metabolite will be less active or more easily excreted than parent drug. Metabolic reactions can make active drug into less-active or inactive forms. OR make a PRODRUG (inactive or less-active drug) into a more active drug. Discuss P450 system - P450 system = group of enzyme families in the liver which metabolize drugs and endogenous compounds; The liver microsomal drug oxidation/reduction system (The P450 system) is responsible for metabolism of many drugs. Cytochrome P450 (so named because it maximally absorbs light at 450 run) is a family of isoenzymes located in endoplasmic reticulum of hepatocytes. Through an electron transport chain which uses NADPH as a proton carrier, a drug bound to cytochrome P45Q can be oxidized or reduced (Phase I Reaction). Cytochrome P450 can be induced (increased in activity) by a number of drugs or chemicals. Induction occurs in response to presence of a chemical which is metabolized by P450 (more enzyme is produced to handle chemical load). Once enzyme is induced,it will metabolize "inducing agent" more rapidly. Because cytochrome P450 is not specific for inducer, however, other drugs metabolized by induced enzyme will also be biotransformed more rapidly. What are CYTOCHROME P450 INHIBITORS - Buproprion Clomipramine Cimetidine Clarithromycin Fluoroquinolones Grapefruit and grapefruit juice Ketoconazole Nefazodone SSRIs
Clearance determines maintenance dose required to achieve desired steady-state concentration. AND is a function of blood flow to clearing organs and efficiency of organ in extracting drug. Clinicians should begin considering dosage adjustment of renally eliminated drugs at what creatinine clearance value? - 60ml/min Volume of distribution - =loading dose required to achieve desired steady-state concentration AND is a function of physiologic volume of blood and tissues and how drug binds in blood and tissues. Hydrophilic (ie plasma) or lipophilic drug (adipose issue) Half-life determines: time to reach steady state AND dosage interval AND is dependent on value of volume of distribution and dependent on value of clearance .Factors to be considered when prescribing best drug dose of a patient include age,gender, weight, other concurrent disease states and drug therapies. Beers Criteria - originally developed by a group headed by Dr. Mark H. Beers, listing of drugs that carry high risks for older adults and criteria for potentially inappropriate medication use in older adults; 3categories: Potentially inappropriate medications and classes to avoid; Potentially inappropriate medications and classes to avoid in certain diseases and syndromes that listed drugs could exacerbate; Medications to be used with caution.