Pharm - Pharmacokinetics/-dynamics (Elimination & Metabolism)

Question 1

Define zero-order elimination.

Answer 1

Rate of elimination is constant regardless of Cp (i.e., constant AMOUNT of drug eliminated per unit time)

Question 2

In zero-order elimination, how does Cp act/change over time?

Answer 2

Cp decreases linearly with time

Question 3

What are 3 examples of zero-order elimination drugs?

Answer 3

Examples of drugs - (1) Phenytoin (2) Ethanol (3) Aspirin (at high or toxic concentration); Think: “PEA (a pea is round, shaped like the “0” in ZERO-order)”

Question 4

What is the limitation/dependency of zero-order versus first-order elimination?

Answer 4

Zero-order: Capacity-limited elimination; First-order: Flow-dependent elimination

Question 5

Define first-order elimination.

Answer 5

Rate of elimination is directly proportional to the drug concentration (i.e., constant FRACTION of drug eliminated per unit time).

Question 6

In first-order elimination, how does Cp act/change over time?

Answer 6

Cp decreases exponentially with time

Question 7

Draw graphs of time (x-axis) versus plasma concentration (y-axis) depicting zero-order versus first-order elimination.

Answer 7

See p. 240 in First Aid 2014 for graphs

Question 8

Describe the treatment of ionized species versus neutral forms in terms of elimination.

Answer 8

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

Question 9

What are 3 examples of drugs that are weak acids?

Answer 9

Examples: phenobarbital, methotrexate, aspirin.

Question 10

In what kind of environments are weak acids trapped? Draw an equation depicting this.

Answer 10

Trapped in basic environments; RCOOH (lipid soluble) RCOO- + H+ (trapped)

Question 11

What is used to treat an overdose of weak acids?

Answer 11

Treat overdose with bicarbonate

Question 12

What is an example of a drug that is a weak base?

Answer 12

Example: amphetamines

Question 13

In what kind of environments are weak bases trapped? Draw an equation depicting this.

Answer 13

Trapped in acidic environments; RNH3+ (trapped) RNH2 + H+ (lipid soluble)

Question 14

What is used to treat an overdose of weak bases?

Answer 14

Treat overdose with ammonium chloride

Question 15

What are the 2 types of drug metabolism?

Answer 15

(1) Phase I (2) Phase II

Question 16

What is the mechanism of Phase I metabolism? What kind of products usually result?

Answer 16

Reduction, oxidation, hydrolysis with cytochrome P-450 usually yield slightly polar, water-soluble metabolites (often still active)

Question 17

What is the mechanism of Phase II metabolism? What kind of products usually result? What is usually their fate?

Answer 17

Conjugation (Glucorinidation, Acetylation, Sulfation) usually yields very polar, inactive metabolites (renally excreted); Think: “GAS”

Question 18

Describe drug metabolism in geriatric patients.

Answer 18

Geriatric patients lose phase I first. Geriatric patients have “GAS” (Phase II).

Question 19

In Phase II metabolism, what does acetylation rate affect, and why?

Answer 19

Patients who are slow acetylators have greater side effects from certain drugs because of decreased rate of metabolism