3. Distribution Flashcards
2 key areas involved in Drug metabolism and CLEARANCE/ELIMINATION
LIVER & KIDNEYS
- HEPATIC and RENAL CLEARANCE
total CLEARANCE = CLEARANCE (H) + CLEARANCE (R)
HEPATIC CLEARANCE is divided into 2 main elements:
- METABOLISM
- TRANSPORT
(proteins mediating movement of drugs from blood to Liver and then for clearance)
RENAL CLEARANCE involves:
- FILTRATION
- ACTIVE TRANSPORT
2 types of TRANSPORT in HEPATIC CLEARANCE
- UPTAKE
- BILIARY CLEARANCE
HEPATIC CLEARANCE: METABOLISM PHASE I uses which key enzyme
CYPs - CYTOCHROME P450
HEPATIC CLEARANCE: METABOLISM PHASE II uses which key enzymes
UGT - GLUCURONYL TRANSFERASE
ST - SULPHOTRANSFERASE
DRUG METABOLISM ALTERS…
DRUG CONCENTRATION
INTERACTIONS between drugs often involve METABOLISM and can lead to..
- TOXICITY
- ALTERED PHARMACOLOGICAL EFFECT
DRUG TOXICITY is often a RESULT of
METABOLISM to a TOXIC METABOLITE
CLEARANCE/METABOLISM can also influence SELECTION of..
Appropriate DOSING
DRUG METABOLISM can be DEFINED as..
the ENZYME-CATALYSED CONVERSION of a DRUG into a CHEMICALLY-DISTINCT Product (METABOLITE)
how should DRUGS be CONVERTED to allow for EASIER EXCRETION (in METABOLISM)
MOST DRUGS are LIPOPHILIC / NON-POLAR
-> must be made MORE HYDROPHILIC/POLAR
where is the MAIN SITE of DRUG METABOLISM
LIVER
What happens in PHASES I and II of METABOLISM
CHEMICAL GROUPS ADDED
small chemical changes
to INCREASE POLARITY / WATER SOLUBILITY
(for EXCRETION)
most IMPORTANT ENZYMES in DRUG METABOLISM - CYTOCHROME P450 are also involved in..
Steroid Biosynthesis
Vitamin A & D Metabolism
over 1200 individual P450 ENZYMES are described in: animals, …
Plants, Yeast, Bacteria
very few organisms don’t have P450
CYTOCHROME P450 ENZYMES are a superfamily of enzymes with..
OVERLAPPING SUBSTRATE SPECIFICITIES
P450 is the TERMINAL OXIDASE COMPONENT of an ELECTRON TRANSFER SYSTEM where?
SMOOTH ER
CLEARANCE DEFINITION
VOLUME of PLASMA from which DRUG IS REMOVED PER UNIT TIME
CLEARANCE EQUATION
RATE of DRUG ELIMINATION / CONC.
or
VOLUME of DISTRIBUTION X RATE CONSTANT of ELIMINATION (K)
or
VOLUME of DISTRIBUTION (Vd) x 0.693
/ HALF LIFE (t1/2)
INHIBITED CYTOCHROME P450 ENZYME activity results in
REDUCED CLEARANCE of DRUG SUBSTRATES from body
(whereas enzyme induction, increases)
what drugs can INDUCE and INHIBIT several CYP450 ENZYMES
MULTIFACTORIAL DDIS
- ANTIRETROVIRAL DRUGS
What can AFFECT HEPATIC CLEARANCE
LIVER DISEASE
