Pharmacokinetics and Pharmacodynamics

Question 1

Pharmacokinetics

Answer 1

• Time-course of drugs and their metabolites in various tissues of the body.
• What the body does to the drug.
• Study of the absorption, distribution, metabolism, and excretion (ADME).
• Deals with the dose-concentration part of the drug dose-effect relationship

Question 2

o Pharmacodynamics

Answer 2

• Linked to pharmacokinetics by the drug-receptor complex theory: intensity of pharmacologic effect is related to the concentration of drug gaining access to drug receptor
• Time-course of drug concentration at receptor strongly influence the time-course of drug action (therapeutic and toxic action)

Question 3

Therapeutic range

Answer 3

• Between minimum effective concentration and maximum safe concentration
• Averages so use as initial guide to therapy
• Some narrow, some wide, narrow may require precise dosing

Question 4

Absorption

Answer 4

DIRECT: IV, intrathecal into CSF
INDIRECT: oral tract (via GI), transdermal, IM, inhalation
• Physical formulation of drug is important
• Biophysical properties of the drug are also important determinants of rate/extend of absorption

Question 5

Bioavailability

Answer 5

• Extent of drug entry into system circulation
• Max is 100% via IV
• Rate of bioavailability: speed with which drug is avail to system circulation

Question 6

Metabolism/biotransformation

Answer 6

Alteration of a drug by the body to one or more metabolites. Effects: Bioavailability: First-pass effect: liver has first go at drug, reduces bioavailability
Clinical effects of metabolites: Some are active, some are not; In some cases, the metabolite is the goal of the drug

Question 7

Metabolite

Answer 7

Product of alteration of a drug, usually by the liver

Question 8

Distribution

Answer 8

Drug gains access to various tissues by movement across vascular and cellular membranes

Question 9

First-pass effect

Answer 9

Liver is located b/w the gut and systemic circulation; Lose bioavailability as drug is metabolized by the liver

Question 10

Elimination half-life

Answer 10

• t ½
• Time required for the drug level to decline by 50%
• Important in decions about proper dosing intervals
• Greater the half life, the more likely med will have a longer dosing interval

Question 11

Steady state concentration

Answer 11

• With chronic use of drug
• Rate of drug entry equals rate of drug elimination
• Blood level will fluctuate between an average max level and an average min level

Question 12

Cytochrome P-450

Answer 12

• Generic name for group of enzymes that are responsible for most drug metabolism reactions
• Largest is CYP3A4
• Most drugs are substrates for these enzymes

Question 13

Induction

Answer 13

Increases metabolism of drugs

Question 14

Inhibition

Answer 14

Decreases metabolism of drugs

Question 15

Pro-drug

Answer 15

• Drug form that remains inactive until reaches the site of action
• Inactive precursor to a drug
• Reconversion to active form occurs inside a specific organ, tissue, cell
• Increase solubility or absorption, increase chemical and metabolic stability, mask irritation or taste

Question 16

identify the properties of a drug that affect indirect absorption of a drug into the body

Answer 16

o Drug formulation: tab, solution (faster), etc.
o Biophysical properties: determine permeability across membranes
o Bioavailability

Question 17

factors that determine the distributional properties of a drug

Answer 17

o Molecular size
o Lipophilicity
o Acid/base properties
o Bond affinity to circulating and tissue proteins

Question 18

what is the effect of the first pass effect on bioavailability

Answer 18

If liver has high affinity and high metabolizing capacity for drug, may greatly reduce the drug’s bioavailability

Question 19

State two ways that drug biotransformation may contribute to drug elimination

Answer 19

1. May convert lipophilic substance into water soluble form, easily excreted in urine or bile
   • Phase 1 or Phase 2 reaction (1 only, 1 & 2, 2 only)
2. If transformed to inactive metabolite, effectively eliminates from the system

Question 20

Select the effect of CYP 450 enzyme induction or inhibition on the metabolism and pharmacologic effect of a drug

Answer 20

o Induction: increases metabolism of drugs (reduction of pharmacologic action)
o Inhibition: decreases metabolism of drugs (increased drug availability, greater action)

Question 21

What is the primary organ where drug biotransformation takes place?

Answer 21

liver

Question 22

Given a drug’s elimination half life, est the time it takes for a drug to reach a steady state concentration, when given the drug’s half life and est the time it takes for a drug to be eliminated from the body when the drug is discontinued

Answer 22

Review this concept.
Reach steady state after approx. 5 half lives.
• If t ½ = 7 days
• Steady state = 7 days (4 half lives) = 28 days to get to steady state
• If t ½ = 7 days
• Elimination from body = 7(4) = 28 days

Question 23

ID factors affecting drug metabolism

Answer 23

1. Patient factors:
   • Body size and composition
   • Sex
   • Age
   • Habits such as smoking, alcohol consumption (increase metabolism of some drugs)
2. Disease and Concurrent Therapy
   • Diseases that affect organ function (esp liver and kidney) affect clinical response to a drug
   • Drug:drug interaction: some drugs inhibit metabolism of other drugs, some stimulate metabolism of other drugs

Question 24

Linear pharmacokinetics

Answer 24

(Most drugs)
• Steady state serum concentrations change proportionately with long-term daily dosing
• Double dose, double the steady-state serum concentration

Question 25

non-linear pharmacokinetics

Answer 25

• Serum concentration change more or less than linear with each increase in dose
• Ex: double dose, quadruple effect (therapeutic and toxic)
• Sometimes harder to dose, have to monitor serum levels
• Not common but important to do right!

Question 26

Select the dosage forms that bypass first pass elimination

Answer 26

IV and intrathecal

Question 27

Given a dosage form, match its route of administration

Answer 27

o Oral: Tablet, capsule, lozenge, oral liquid
o Topical: ointment, cream, gel, paste, transdermal, patch, dusting powder
o Topical Eye: solution, suspension, ointment
o Vaginal, Intrauterine, rectal: Film, cream, ring, tablet, suppository, IUD
o Parenteral: IV, IM, Subcutaneous, intradermal
o Inhalation: inhaler, spray