GCU NUR-635 Mid-Term Study Guide – Dr. Don Marsh
- Pharmacology (from the Greek word ‘pharmakon,’meaning drug): the study of drugs and their
... [Show More] structure, targets of action, mechanisms of action (MOA), distribution (how the body disburses them throughout the body), desired physiologic effects (efficacy) and undesirable side effects (toxicity).
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Pharmacokinetics includes ADME (absorption, distribution, metabolism and elimination).
- Absorption: absorption from the administration site either directly or indirectly into the blood/plasma.
- Distribution: reversibly/irreversibly movement of drug from the bloodstream into the interstitial and intracellular fluid.
- Metabolism: drug biotransformation via metabolic pathways, primarily the liver, or by other tissues.
- Elimination: how parent drug & its metabolites are eliminated from the body
Absorption Factors:
- Gastrointestinal pH changes
- Gastric emptying
- Gastric/intestinal enzymes
- Bile acids & biliary function
- Gastrointestinal flora (type and quantity of bacteria)
- Food & nutrient interactions (most common interaction influencing GI drug absorption)
- Lipid solubility of the drug
Distribution:
- Membrane permeability: Cross membranes to site of action
- Blood brain barrier reduces the speed of drug passage into and out of brain tissue
- Plasma protein binding: drugs bound to plasma proteins do not cross membranes (Note: Malnutrition = albumin = free drug = greater pharmacologic response)
- Aging cause a reduction in production of plasma proteins
- Lipophilicity of drug: lipophilic drugs concentrate in adipose tissue; remain in the body for a longer period of time
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Volume of distribution
• Body Composition
• Total body water and extracellular fluid
• Adipose tissue and skeletal muscle
• Protein Binding (changes with aging)
• Albumin, bilirubin, 1-acid glycoprotein
• Albumin affected by nutrition
• Low albumin (hypoalbuminemia) can cause less protein-bound drug reaching the tissue site of action.
• Tissue Binding
• Compositional changes
Metabolism:
• Drugs can undergo metabolism in the lungs, blood, liver, intestines and kidney
• Volatile drugs are primarily excreted by the lungs
• The body changes drugs to more or less active forms (metabolites), increases water solubility to increase elimination.
Phase I Metabolism:
• Cytochrome P450 system
• Located within the endoplasmic reticulum of hepatocytes.
• Through electron transport chain, a drug bound to the CYP450 system undergoes oxidation or reduction.
• Drug metabolism in the liver is also affected by:
• Enzyme induction
• Drug interactions
CYP450:
• CYP: a set of isozymes primarily found in the liver and GI tract
• Convert lipophilic drugs into more polar (and soluble) molecules
• Four isozymes are responsible for the majority of Phase I reactions
1. CYP3A4/5
2. CYP2D6
3. CYP2C8/9
4. CYP1A2
• Considerable genetic variability exists across race and gender
• Results in CYP450 polymorphisms which have a direct effect on drug metabolism.
• If you have a patient experiencing a pharmacokinetic drug interaction, consider [Show Less]