Basic Principles of Pharmacology II

Question 1

Agonist

Answer 1

A drug that activates a receptor by binding to the receptor (a protein)– the combination is usually reversible and when the receptor is bound to the agonist ligand, the effect of the drug is produced.

Question 2

Antagonist

Answer 2

A drug that binds to the receptor without activating the receptor.
Antagonists block the action of agonists by merely getting in the way of the agonist and preventing it’s binding to the receptor to produce the drug effect.
Competitive vs. Noncompetitive

Question 3

Competitive antagonism

Answer 3

Increasing concentrations of the antagonist progressively inhibit the response to the agonist

Question 4

Noncompetitive antagonism

Answer 4

After administration of an antagonist, even high concentrations of an agonist cannot completely overcome the antagonism.

Question 5

Contributes to variability in response to drugs

Answer 5

changing receptor numbers

Question 6

When a drug binds to a receptor, it changes the activity of the machine by…

Answer 6

• Enhancing its activity: propofol increases the sensitivity of the y-aminobutyric acid receptor [GABAa] to GABA
• Decreases its activity: ketamine decreases the activity of N-methyl-D-aspartate [NMDA] receptor
• Triggers a chain reaction: opioid binding to the mu opioid receptor activates an inhibitory G protein that decreases adenylyl cyclase activity

Question 7

Pharmacokinetics

Answer 7

The quantitative study of the absorption, distribution, metabolism, and excretion of injected and inhaled drugs and their metabolites (what the body does to the drug).

Question 8

Anesthetic solubility

Answer 8

Highly lipid soluble (poorly water soluble)

Question 9

High fat solubility

Answer 9

means that the molecule will have large volume of distribution because it will be preferentially taken up by fat, diluting the concentration in the plasma

Question 10

Vessel Rich Group (VRG)

Answer 10

Following bolus injection, the drug primarily goes to tissues that receive the bulk of arterial blood flow: the brain, heart, kidneys, and liver.

Question 11

Protein binding

Answer 11

Only free or unbound drug can readily cross cell membranes and bind to receptors. Age, hepatic and renal disease and pregnancy can all result in decreased plasma protein concentrations.

Question 12

Metabolism

Answer 12

Convers pharmacologically active, lipid-soluble drugs into water-soluble and usually inactive metabolites; exceptions are metabolism to active compounds as for diazepam and opioids (M6G is more potent than morphine; codeine is the prodrug metabolized to morphine).

Question 13

Four basic pathways of metabolism

Answer 13

Oxidation, reduction, hydrolysis, and conjugation

Question 14

Phase I reactions

Answer 14

Oxidation, reduction, and hydrolysis

Increase the drugs.’ polarity and prepare it for phase II reactions

Question 15

Oxidation

Answer 15

Cytochrome P450 enzymes are crucial for oxidation reactions. Examples of oxidation metabolism of drugs catalyzed by cytochrome p450 include hydroxylation, deamination, desulfuration, dealkylation, and dehalogenation.

Question 16

Reduction

Answer 16

Cytochrome P450 enzymes are also responsible for reduction. Under conditions of low oxygen partial pressures, cytochrome P450 enzymes transfer electrons directly to a substrate such as halothane rather than oxygen.

Question 17

Conjugation

Answer 17

With glucuronic acid involves cytochrome p450 enzymes. The resulting water-soluble glucuronide conjugates and then excreted in bile and urine.

Question 18

Hydrolysis

Answer 18

Enzymes responsible for hydrolysis of drugs, usually at an ester bond, do not involve the cytochrome p450 enzyme system. Hydrolysis often occurs outside of the liver (Remi, succ, esmolol, and ester local anesthetics are cleared in the plasma and tissues via ester hydrolysis.