Section 2 - Pharmacology: Autonomic Drugs

Question 1

Enzyme Inhibition

Answer 1

Reversible competitive inhibitors cross each other competitively, whereas noncompetitive inhibitors do not.

Question 2

Pharmacokinetics Bioavailability

Answer 2

Fraction of administered drug reaching systemic circulation unchanged. For an IV dose F=100% orally: F typically

Question 3

Volume of distribution

Answer 3

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.

Question 4

Clearance

Answer 4

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

Question 5

Half-Life

Answer 5

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.

Question 6

Dosage calculations

Answer 6

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.

Question 7

Zero-order eliminations

Answer 7

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)

Question 8

First-order elimination

Answer 8

Rate of elimination is directly proportional to the drug concentration (ie constant fraction of drug eliminated per unit time)

Question 9

Urine pH and drug elimination

Answer 9

Ionized species are trapped in urine and cleared quickly Neutral forms can be reabsorbed.

Question 10

Weak acids

Answer 10

Examples: Phenobarbital, methotrexate, aspirin, TCA’s. Trapped in basic environments. Treat overdose with bicarbonate.

Question 11

Weak Bases

Answer 11

Example: Amphetamines, trapped in acidic environments. Treat overdose with ammonium chloride

Question 12

Drug metabolism

Phase 1

Answer 12

Reduction, oxidation, hydrolysis with with cytochrome P-450 usually yield slightly polar water-soluble metabolites

Question 13

Michaelis-Menten Kinetics

Answer 13

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.

Question 14

Drug Metabolism

Phase 2

Answer 14

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.

Question 15

Efficacy

Answer 15

Maximal effect a drug can produce. Partial agonists have less efficacy than full agonists.

Question 16

Potency

Answer 16

Amount of drug needed for a given effect. Potent drugs can have high or low efficacy.

Question 17

Competitive Antagonist

Answer 17

Shifts curve right (Downward arrow) potency. No change in efficacy. Can be overcome by (upward arrow) the concentration of agonist substrate.

Diazepam (agonist) + flumazenil (competitive antagonist) on GABA receptor.

Question 18

Noncompetitive antagonist

Answer 18

Shifts curve down (downward arrow) efficacy. Cannot be overcome by (upward arrow) agonist substrate concentration.

Norepinephrine (agonist) + phenoxybenzamine (noncompetitive antagonist) on a-receptors

Question 19

Partial agonist (alone)

Answer 19

Acts the same site as full agonist, but with lower maximal effect (downward arrow) efficacy. Potency is an independent variable.

Morphine (full agonist) vs buprenorphine (partial agonist) at opioid u-receptors

Question 20

Therapeutic index

Answer 20

Measurement of drug safety. Therapeutic window - measure of clinical drug effectiveness for a patient. Safer drugs have higher TI values. Drugs with lower TI values include digoxin, lithium, theophylline, and warfarin.

Question 21

Central and peripheral Nervous system

Answer 21

Note that the adrenal medulla and sweat glands are part of the sympathetic nervous system but are innervated by cholinergic fibers.
Botulinum toxin prevents release of acetylcholine at cholinergic terminals.

Question 22

ACh receptors

Answer 22

Nicotinic ACh receptors are ligand-gated channels; (found in autonomic ganglia) and (found in neuromuscular junction) subtypes.
Muscarinic ACh receptors are G-protein-coupled receptors that usually act through 2nd messengers; 5 subtypes

Question 23

See page 248

Answer 23

See page 248

Question 24

See page 249

Answer 24

See page 249