ADME Processes: Absorption, Distribution, Metabolism, and Excretion, Exams of Pharmacokinetics

Download ADME Processes: Absorption, Distribution, Metabolism, and Excretion and more Exams Pharmacokinetics in PDF only on Docsity! Pharmacokinetics Pharmacokinetics - the study of what happens to the drug(s) in the patients body after administered. Includes absorption, distribution, metabolism and excretion. (ADME) - Absorption, Distribution, Metabolism, Excretion What does ADME influence? - -the drug levels -kinetics of drug exposure to tissue -Therefore the performance and pharmacological activity of the drug Absorption - the process by which a drug crosses various barriers to reach the bloodstream Which route of administration is absorption not considered a factor? - Intravenous Bioavailability - the degree to which a drug is absorbed and becomes available via the general circulation The two main methods of absorption: - 1. Passive Processes 2. Active Process Passive Processes (3) - (All require no energy)1. Simple diffusion 2. Facilitated Diffusion: H2O soluble drugs through pores or channels 3. Pinocytosis/Phagocytosis: cells engulfing particles or droplets (less common) Active Process - Active Transport: requires energy to move substances against the concentration gradient Seven Factors that Affect Drug Absorption - 1. Blood Supply 2. Route of Administration 3. Ionization 4. Size of Drug Molecule 5. Drug Solubility 6. Formulation of the Drug 7. Concentration of the Drug Factors Affecting the Absorption of Oral Drugs - 1. GIT disease may reduce the number of viili or cause diarrhea 2. Gut fill and pyloric empting rate may delay transit of drugs into the small intestine where most of the absorption occurs 3. Drugs may bind to GIT contents which may delay or prevent absorption 4. Low gastric pH may destroy or inactivate some drugs What are the Four Problems Ruminants Can Have WIth the Oral Route? - 1. Dilution of drugs in the large rumen 2. Basic pH of the rumen may trap acidic drugs 3. Microbial activity in rumen can affect the stability of many drugs 4. Variability in the rate of passage for feed through the rumen (amount and digestible level of feed are factors) Factors Affecting the Absorption of Parenteral Drugs (2): - 1. Blood Supply to Injection Site 2. Number of sites used Parenteral Drugs Must be Formulated to Be (4): - 1. Pyrogen free 2. Sterile 3. Adjusted to body pH 4. Adjusted to body osmolality Factors affecting the Absorption of Topical Drugs: - 1. Slow absorption if on skin due to sebaceous secretions and keratinized epithelium (only lipid soluble molecules pass thru) 2. Increased absorption if the skin is broken, has increased circulation, or if a drug such as DMSO is first applied Factors Affecting the Absorption of Inhaled Drugs: - Very rapid absorption due to the large surface area and excellent blood supply of the lungs Drug Metabolism - the body's ability to chemically change a drug from the form it was administered in to a form where it may be eliminated from the body What is another word for Drug Metabolism? - Biotransformation What is a drug that has been metabolied called? - a metabolite Are all drugs metabolized? - No. Some are excreted in their original forms What are the three enzymatically mediated changes that can occur when a drug is metabolized? - 1. It's activity/toxicity can be reduced (most common) 2. It's activity/toxicity can be increased (uncommon) 3. It can be changed into a form that is readily excreted Some drugs require metabolism to achieve their ______ _____, but most drug metabolites are __________. - -active form -inactive What is the number one organ for drug metabolism? - Liver Where are other locations drug metabolism occurs? - -kidney -lung -blood -nervous tissue -gut wall -gut content (bacteria) _________ are proteins which metabolize drugs - Enzymes The amount of enzymes available and so the capability of metabolizing drugs depends on: (7) - 1. Species 2. Age 3. Sex 4. Stress 5. Nutritional Status 6. Disease 7. Enzyme Induction Affect of stress on enzyme availability/metabolism of drugs: - -may have decreased matabolism in a stressed animal Affect of species on enzyme availability/metabolism of drugs: - -e.g. cats have a limited ability to metabolie barbiturates, narcotics, acetaminophen and aspirin Affect of sex on enzyme availability/metabolism of drugs: - -anabolic steroids of the male sex promote increased metabolic enzyme production Affect of age on enzyme availability/metabolism of drugs: - -young animals have underdeveloped liver enzyme systems -old animals have decreased ability to synthesize enzymes When is the first pass effect a concern? - -only when considering the effect of oral administration of drugs What is the first pass effect? - -When drugs are absorbed from the gut they enter portal circulation, the blood in these portal veins is filtered by the liver before entering the systemic circulation -These drugs are therefore exposed to metabolic enzymes some may be metabolized before reaching the systemic circulation and their various target sites beyond the GIT Affect of nutritional status on enzyme availability/metabolism of drugs: - -might not have enough raw material to produce the needed enzymes Affect of disease on enzyme availability/metabolism of drugs: - -liver disease = decreased enzymes Affect of enzyme induction on enzyme availability/metabolism of drugs: - -the continual administration of certain drugs will cause an increase in the enzymes that metabolize that drug How does the first pass effect make the oral administration of certain drugs ineffective? - -For some drugs the amount of drug that is metabolied before reaching the systemic circulation is so large they are rendered ineffective and so must be given by a route other than oral The Five Routes of Drug Elimination: - 1. Renal 2. Biliary 3. Intestinal 4. Glandular Secretions 5. Lungs What is the number one organ of drug excretion? - kidney Renal Route of Elimination (3): - -The drug must be water soluble to be passed in the urine (liver metabolism usually makes drugs water soluble) -The kidneys must be healthy and have normal blood flow -The lower urinary tract must be functioning normally Biliary Route of Elimination: - -The liver secretes the drugs into bile which is then secreted into the GIT -The drug may then either be eliminated in the feces or may be reabsorbed and enter the enterohepatic cycle Intestinal Route of Elimination: - -Can be excreted in gut secretions especially ruminant saliva (alkaline saliva traps acidic drugs which are excreted in feces) -Some drugs are secreted by active transport across the GIT mucosa Glandular Secretion Route of Elimination -