Pharmacology- Pharmacokinetics and Pharmacodynamics Flashcards Preview

USMLE 1 > Pharmacology- Pharmacokinetics and Pharmacodynamics > Flashcards

Flashcards in Pharmacology- Pharmacokinetics and Pharmacodynamics Deck (21)
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1
Q

Michaelis-Menten kinetics

A

Km is inversely related to the affinity of the enzyme for its substrate.

Vmax 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 (eg, hemoglobin).

2
Q

Effects of enzyme inhibition

A

¨Pag 228

3
Q

Lineweaver-Burk plot

A

The higher the y-intercept, the lower the Vmax.

The further to the right the x-intercept, the greater the Km and the lower the affinity.

Kompetitive inhibitors increase Km.

4
Q

Bioavailability (F)

A

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

5
Q

Volume of distribution (Vd)

A

Theoretical volume occupied by the total amount of drug in the body relative to its plasma concentration.

Vd = amount of drug in the body / plasma drug concentration

Low Vd: Intravascular
Medium Vd: ECF
High Vd: All tissues

6
Q

Clearance (CL)

A

The volume of plasma cleared of drug per unit time.

CL = rate of elimination of drug / plasma drug concentration = Vd × Ke (elimination constant)

7
Q

Half-life (t1/2)

A

The time required to change the amount of drug in the body by 1⁄2 during elimination.

In first-order kinetics, a drug infused at a constant rate takes 4–5 half-lives to reach steady state. It takes 3.3 half-lives to reach 90% of the steady-state level.

t1/2 = 0.7 × Vd / CL
*in first-order elimination

8
Q

Loading dose =

Maintenance dose=

A

Cp × Vd / F

Cp × CL × τ / F

Cp = target plasma concentration at steady state
τ = dosage interval (time between doses), if not
administered continuously

9
Q

Types of drug interactions

  • Additive
  • Permissive
A

Effect of substance A and B together is equal to the sum of their individual effects (Aspirin and acetaminophen).

Presence of substance A is required for the full effects of substance B (Cortisol on catecholamine responsiveness).

10
Q

Types of drug interactions

  • Synergistic
  • Tachyphylactic
A

Effect of substance A and B together is greater than the sum of their individual effects (Clopidogrel with aspirin)

Acute decrease in response to a drug after initial/repeated administration (Nitrates, niacin, phenylephrine, LSD, MDMA)

11
Q

Competitive antagonist (pag. 230)

A

Shifts curve right (Low potency), no change in efficacy. Can be overcome by increasing the concentration of agonist substrate.

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

12
Q

Noncompetitive antagonist (pag. 230)

A

Shifts curve down (Low efficacy). Cannot be
overcome by Increasing agonist substrate concentration.

Norepinephrine (agonist) + phenoxybenzamine
(noncompetitive antagonist) on α-receptors.

13
Q

Partial agonist (alone) (pag. 230)

A

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

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

14
Q

Zero-order elimination

A

Rate of elimination is constant regardless of Cp (ie, constant amount of drug eliminated per unit time). Cp decrease linearly with time.

PEA: Phenytoin, Ethanol, and Aspirin (at high or toxic concentrations). *Capacity-limited elimination

15
Q

First-order elimination

A

directly proportional to the drug concentration (ie, constant Fraction of drug eliminated per unit time). Cp Decrease exponentially with time. Applies to most drugs.

*Flow-dependent elimination.

16
Q

Urine pH and drug elimination

  • Weak Acids
  • Weak Bases
A

Examples: phenobarbital, methotrexate, aspirin (salicylates). Trapped in basic environments. Treat overdose with sodium bicarbonate to alkalinize urine.

Example: TCAs, amphetamines. Trapped in acidic environments. Treat overdose with ammonium chloride to acidify urine.
* TCA toxicity is generally treated with sodium bicarbonate to overcome the sodium channelblocking
activity of TCAs, but not for accelerating drug elimination.

17
Q

Drug metabolism

  • I phase
  • II phase
A

Reduction, Oxidation, Hydrolysis with cytochrome P-450. *Geriatric patients lose phase I first.

Conjugation (Methylation, Glucuronidation, Acetylation, Sulfation). *Patients who are slow acetylators have higher side effects from certain drugs

18
Q

Efficacy

A

Maximal effect a drug can produce. Represented by the y-value (Vmax). High y-value = high Vmax = high efficacy.

19
Q

Potency

A

Amount of drug needed for a given effect. Represented by the x-value (EC50).

Left shifting = Low EC50 = High potency = Low drug needed.

20
Q

Therapeutic index

A

Measurement of drug safety. TD50/ED50

TD50 median toxic dose
ED50 median effective dose

Drugs with lower TI values frequently require monitoring
(eg, Warfarin, Theophylline, Digoxin, Lithium;
Warning! These Drugs are Lethal!)

21
Q

Therapeutic window

A

dosage range that can safely and effectively treat disease

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