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
