Pharmacokinetics and Pharmacodynamics Flashcards
Pharmacokinetics
- 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
o Pharmacodynamics
- 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)
Therapeutic range
- 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
Absorption
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
Bioavailability
- Extent of drug entry into system circulation
- Max is 100% via IV
- Rate of bioavailability: speed with which drug is avail to system circulation
Metabolism/biotransformation
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
Metabolite
Product of alteration of a drug, usually by the liver
Distribution
Drug gains access to various tissues by movement across vascular and cellular membranes
First-pass effect
Liver is located b/w the gut and systemic circulation; Lose bioavailability as drug is metabolized by the liver
Elimination half-life
- 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
Steady state concentration
- 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
Cytochrome P-450
- Generic name for group of enzymes that are responsible for most drug metabolism reactions
- Largest is CYP3A4
- Most drugs are substrates for these enzymes
Induction
Increases metabolism of drugs
Inhibition
Decreases metabolism of drugs
Pro-drug
- 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
identify the properties of a drug that affect indirect absorption of a drug into the body
o Drug formulation: tab, solution (faster), etc.
o Biophysical properties: determine permeability across membranes
o Bioavailability
factors that determine the distributional properties of a drug
o Molecular size
o Lipophilicity
o Acid/base properties
o Bond affinity to circulating and tissue proteins
what is the effect of the first pass effect on bioavailability
If liver has high affinity and high metabolizing capacity for drug, may greatly reduce the drug’s bioavailability
State two ways that drug biotransformation may contribute to drug elimination
- 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) - If transformed to inactive metabolite, effectively eliminates from the system
Select the effect of CYP 450 enzyme induction or inhibition on the metabolism and pharmacologic effect of a drug
o Induction: increases metabolism of drugs (reduction of pharmacologic action)
o Inhibition: decreases metabolism of drugs (increased drug availability, greater action)
What is the primary organ where drug biotransformation takes place?
liver
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
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
ID factors affecting drug metabolism
- Patient factors:
• Body size and composition
• Sex
• Age
• Habits such as smoking, alcohol consumption (increase metabolism of some drugs) - 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
Linear pharmacokinetics
(Most drugs)
• Steady state serum concentrations change proportionately with long-term daily dosing
• Double dose, double the steady-state serum concentration
non-linear pharmacokinetics
- 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!
Select the dosage forms that bypass first pass elimination
IV and intrathecal
Given a dosage form, match its route of administration
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
