Grand Canyon University NUR-635 Mid-Term Study Guide – Dr. Don Marsh

GCU NUR-635 Mid-Term Study Guide – Dr. Don Marsh
- Pharmacology (from the Greek word ‘pharmakon,’meaning drug): the study of drugs and
their 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).
-
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
-
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
CYP450.
• Some drugs or exogenous substances can induce CYP isozymes (less effect)
• Example: St. John’s wort (CYP3A4) and hormonal birth control
• Some drugs can inhibit CYP isozymes (causes greater effect of substrate drugs)
• CYP450-related drug interactions can make predicting blood plasma levels/steady
state levels difficult.
• If a drug inhibits enzymatic activity, a substrate drug for that enzyme system will
have a greater concentration in the blood.
Phase II Metabolism:
• Polar group is conjugated to the drug
• Results in increased polarity of the drug
• Types of reactions

, • Glycine conjugation
• Glucuronide conjugation
• Sulfate conjugation

Competitive antagonism is where one drug displaces another on cell receptors.
Different ethnic groups may have different hepatic metabolism rates
Excretion/Elimination:
• Routes of elimination:
1. Pulmonary = expired in the air (volatile substances)
2. Bile = excreted in feces
3. Renal
• glomerular filtration
• tubular reabsorption
• tubular secretion
Glomerular Filtration Rate (GFR) 90-125L/min
Elimination of drugs most often involves renal function (renal blood flow, creatinine clearance
[CrCl]).
• Linear = Rate of elimination is proportional to amount of drug present.
• Dosage increases result in proportional increase in plasma drug levels.
• Unbinding of nonvolatile drugs from plasma protein binding sites
• Volatile drugs are excreted by the lungs
Bioavailability:
Prescribing decisions are affected by the drug’s pharmacokinetic properties.
Bioavailability is a very important concept with narrow therapeutic index or sustained-release
medications
The route of administration with the highest bioavailability is intravenous; putting entire dose
into a patient’s vein and bypassing absorption.
Intravenous route avoids first-pass metabolism in the liver.
Rectal administration has variable and erratic absorption.
Half-life = The time required for serum plasma concentrations to decrease by one-half (50%).
Steady state (SS) is usually reached within 4-5 half-lives of a drug
Biological half-life of a drug is how long it takes for half the drug to be excreted from the body.
- Determines how frequently the drug must be administered
- Predicts how long toxic effects can last (when the drug is over the minimum toxic level)
- Half-life is constant with first-order pharmacokinetics of a drug