Section 2 - Pharmacology: Autonomic Drugs Flashcards
Enzyme Inhibition
Reversible competitive inhibitors cross each other competitively, whereas noncompetitive inhibitors do not.
Pharmacokinetics Bioavailability
Fraction of administered drug reaching systemic circulation unchanged. For an IV dose F=100% orally: F typically
Volume of distribution
Theoretical volume occupied by the total amount of drug in the body relative to its plasma concentration. Apparent Vd of plasma protein - bonded drugs can be altered by liver and kidney disease. Drugs may distribute in more than one compartment.
Clearance
The volume of plasma cleared of drug per unit time. Clearance may be impaired with defects in cardiac, hepatic, or renal function.
CL = Rate of elimination of drug/plasma drug concentration = Vd x Kf
Half-Life
The time required to change the amount of drug in the body by 1/2 during elimination (or constant infusion) Property of first order elimination. A drug infused at a constant rate takes 4-5 half-lives to reach steady state level.
Dosage calculations
In renal or liver disease, maintenance dose and loading dose is unusually unchanged. Time to steady state depends primarily on and is independent of dosing frequency.
Zero-order eliminations
Rate of elimination is constant regardless of constant amount of drug eliminated per unit time. Examples of drugs - Phenytoin, Ethanol, and Aspirin (at high or toxic concentrations)
First-order elimination
Rate of elimination is directly proportional to the drug concentration (ie constant fraction of drug eliminated per unit time)
Urine pH and drug elimination
Ionized species are trapped in urine and cleared quickly Neutral forms can be reabsorbed.
Weak acids
Examples: Phenobarbital, methotrexate, aspirin, TCA’s. Trapped in basic environments. Treat overdose with bicarbonate.
Weak Bases
Example: Amphetamines, trapped in acidic environments. Treat overdose with ammonium chloride
Drug metabolism
Phase 1
Reduction, oxidation, hydrolysis with with cytochrome P-450 usually yield slightly polar water-soluble metabolites
Michaelis-Menten Kinetics
Is inversely related to the affinity of the enzyme for its substrate.
Is directly proportional to the enzyme concentration.
Most enzymatic reactions follow a hyperbolic curve, however enzymatic reactions that exhibit a sigmoid curve usually indicate cooperative kinetics.
Drug Metabolism
Phase 2
Conjugation (Glucuronidation, Acetylation, sulfation) Usually yields very polar, inactive metabolites (renally excreted)
Geriatric patients have GAS(phase 2) patients who are slow acetylators have + side effects from certain drugs because of - rate of metabolism.
Efficacy
Maximal effect a drug can produce. Partial agonists have less efficacy than full agonists.
