6 Flashcards
(45 cards)
what are the 4 pharmokinetic properties that determine the onset, intensity, and duration of drug action
- Absorption 1st
- Distribution 2nd
- Metabolism 3rd
- Elimination 4th
what pharmokinetic properties explain drug clearance
metabolism and elimination
hepatic metabolism leads to production of products with _____ which allows what to occur?
increase polarity which allows the drug to be eliminated
what is the principle site of drug metabolism
the liver
although the enzyme involved in metabolism are present in many tissues
what structure of the GI tract contribute to drug metabolism and how?
intestines, endoplasmic reticulum of gastric mucosa
-contributes to first pass effect
an inactive or weakly active substance that has an active metabolite is called a:
prodrug
what is the definition of active drug
the drug/medication is in its active form upon administration and does not require any metabolic conversion
example of an ocular prodrug (inactive drug)
nepafenac (Nevanac) which is an NSAID for pain and inflammation post cataract surgery (hydrolyzed to amefenac active drug in ocular tissue
2 other examples of prodrugs
- clopidrogel -> active thiol medicine, an anti platelet med
- enalapril -> enalaprilat (vasotec), an ACEI for hypertension
what is the black box warning for clopidrogel (plavix)?
diminished effectiveness in poor metabolizers, the effectiveness of clopidrogel is dependent on its activation to an active metabolite by CYP2C19
what is the goal of metabolizing a drug chemically?
to make the drug easier to excrete which means non-pole drug molecules are chemically changes into more polar molecules
explain phases of drug metabolism (& do all drugs go through the phases?)
many have Phase I followed by Phase II metabolism, but phases are functional rather than sequential and some drugs undergo only phase I or II
what occurs with the kidney and lipophilic drugs?
the kidney cannot efficiently eliminate lipophilic drugs that readily cross cell membranes and are reabsorbed in the distal convoluted tubules
what phases do lipid soluble agents metabolize in?
first metabolized into more polar or hydrophilic substances in the liver via 2 general sets of reactions (phase I and phase II)
most drugs are ____ soluble and require chemical modification to minimize ___ ___ ____
lipid soluble
-to minimize distal tubular reabsorption
are polar or ionized conjugates able to back diffuse out of the kidney lumen?
no, they are unable
most common Phase I (functionalization)
- oxidation
- hydrolytic
- reduction
functionaliztion =
formation of new/modified functional group or cleavage
most common Phase II (conjugation)
- glucuronic acid conjugation
- sulfate conjugation
- glutathione or mercapturic acid
conjugation =
addition of an endogenous substance
involves the search for genetic variations that lead to inter-individual differences in drug response
pharmacogenetics
the study of the entire spectrum of genes that interact to determine drug efficacy and toxicity
pharmacogenomics
the study of heritable variability in drug response or gene-drug interactions
pharmacogenetics
the study of how drugs interact with total genome to influence biological pathways and processes
pharmacogenomics
