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Toxicology & TDM

Pharmcokinetics

QuestionAnswer
Pharmacokinetics dynamics associated w/ the movement of drugs across the cell membrane --What the body does to the drug--
Pharmacodynamics what the drug does to the body, the effects on man, the reason the drug is used
Pharmacokinetics includes (CLADME) Compliance Liberation Absorption Distribution Metabolism/Bio-transformation Excretion
What is the main reason why drugs do not work? Compliance
The release of the drug from whatever form in which is has been administered is called....? Liberation -drugs are formulated to be released at differing rates
6 Routes of Drug Administration Intravenous-injected directly into circulation [does not need to be absorbed] Intramuscular: injected into muscle Subcutaneous: injected just under skin Transcutaneous: inhaled or absorbed through skin Suppository: rectal delivery Oral: by mouth
Absorption-Bioavailability -Indicates the fractional extent to which... a dose of drug reaches its site of action
Absorption-Bioavailability -Takes into account what 3 factors? [making if more useful to clinicans than absoprtion] anatomical, physiological & pathological factors
Absorption-Orally Administered drugs -Efficiency from GI tract depends on what factors? 1. formulation of drug 2. uptake by transport mechanism intended for dietary vonsitutents vs passive diffusion 3. changes in intestinal motility, pH, inflammation, food, other drugs 4. variation among pop 5. age, pregnancy, pathological conditions
First Pass Metabolism: --Route, Results, How they are given orally ingested drugs are absorbed, enter portal vien and pass directly to the liver. Results in very little part drug exiting after metabolism Types are usually given IV
Gastric Absorption: -Limited by -Facilitated by Limited by: gastric-emptying time Facilitated by: pH (basic), bile (solubilize), active transport system, high blood perfusion
Distribution: -Bound to....(acid drugs & basic drugs) Bound to proteins Albumin (acid drug) alpha 1-acid glycoprotein (basic drug)
Distribution: -The more widely the drug is distributed, the more likely the drug will be... slowly eliminated
Distribution: -Free vs Bound Free/unbound can interact w/ site of action & cause biological response %free depends on physiological/biochemical parameters
Fractional Protein Binding--Bound/Free Ratio -Normal circumstances -Factors that alter BF Ratio bound/free drug ratio is relatively constant Altered by low albumin, abnormal pH, uremia, multiple drug displacements
Fractional Protein Binding--Bound/Free Ratio -Net effect of factors altering BF ratio heightened pharmacological response due to the increased free drug while the total serum drug levels may be in therapeutic range
Fractional Protein Binding--Bound/Free Ratio -Net effect of factors altering BF ratio example pH of blood shifts causing more of drug to be released from the protein--free drug concentration rises; represents a threefold increases in the pharmacological active free drug fraction w/out any change in total serum concentration--could cause toxicity
Unbound Drugs: -Total drug (bound & unbound) are usually measured due to sensitivity of the tests & ease in methodology
Only (bound or unbound) drugs are metabolically active? Unbound
If over ___% bound, ____ drug should be tested if over 85% bound, free drug should be tested
Metabolism: -Primary metabolism occurs in -Secondary metabolism occurs in Primary: liver Secondary: kidney, muscle & intestinal mucosa
Two types of metabolism 1. first pass metabolism (directly to liver, little parent drug exiting) 2. hepatic metabolism: purpose of liver is to transform nonpolar parent drug into a more polar (H2O soluble metabolite).
Metabolites of hepatic metabolism are usually less active
Body's capacity to metabolize drug is dependent on ___? Age -Increases from neonate to adult -Decreases w/ aging
Elimination: -First Order rate of change of concentration of proportional to the concentration of the drug. --constant % is removed over time
Elimination: -Zero Order constant amt is removed over time
Elimination: which order will you see at -low concentrations -high concentrations -low concentration--first order -high concentration--zero order (overdose)
Elimination: -Routes tears, saliva, bile, feces, expired air, sweat, breast milk
Elimination: -drug testing of urine requires knowledge of metabolite structures
Bile may be ____ & the drug may be ____ bile may be reabsorbed and drug recycled
Drug clearance is affected by what 2 organs? Kidney & Liver or conditions that affect profusion of theses organs (CHF or shock)
Created by: haley.gooch