Pharmacology Flashcards
Drugs with high hepatic extraction ratio
Drugs with high hepatic extraction ratio – clearance determined by hepatic blood flow
GTN
Verapamil
Propranolol, Metoprolol
Lignocaine, Ketamine, Morphine, Propofol
Drugs with low hepatic extraction ratio
Low hepatic extraction ratio – clearance determined by intrinsic clearance and fraction unbound
Diazepam, lorazepam Warfarin Phenytoin Theophyline Methadone Carbamazepine
ABC proteins
ABC proteins use energy derived from hydrolysis of ATP to ADP to actively extrude compounds from cells
P-glycoprotein (P-gp), Multidrug resistance associated protein 1-8 (MRP) and breast cancer resistance protein (BCRP) are all ABC proteins
SLC proteins
SLC proteins are ATP-independent - function either by facilitated diffusion or secondary active transport processes
OATP PEPT1 OCT 1-3 OCTN2 OAT 1-3
are all SLC proteins
Substrates of OATP
Substrates of OATP are:
- Pravastatin
- Rosuvastatin
- Thyroxine
Substrates of PEPT1 (Oligopeptide transporter):
Ampicillin
Captopril
Valacyclovir
Substrates of organic cation transporter (OCT) 1-3
Amantadine
Cimetidine
Substrates of carnitine transporter
Carnitine
Quinidine
Verapamil
Substrates of OAT (organic anion transporter) 1-3
Acyclovir
Adefovir
Methotrexate
OAT inhibitorsP
Probenecid
OATs are extremely important in facilitating the secretion of penicillins and cephalosporin antibiotics into the urine
Probenecid (an OAT inhibitor) prevents secretion, leading to enhanced penicillin/cephalosporin concentrations.
Probenecid also inhibits URAT – this is the predominant mechanism for probenecid’s uricosuric effect
What is the mechanism for probenecid’s uricosuric effect?
Probenecid inhibits URAT at the renal Proximal tubule – this causes increased urinary uric acid excretion
Combined strong P-gp and strong CYP3A4 inducers? (x4)
Carbamazepine
Phenytoin
Rifampicin
St John’s wort
What is clearance? How is it measured?
Irreversible elimination:
- Excretion in urine (unchanged), gut
- Liver (Metabolic conversion)
Measured as:
- Volume of blood cleared of drug per unit time
Clearance is constant for a particular drug and a particular patient.
What are first order kinetics?
A constant PROPORTION of drug eliminated per unit time.
Ie. Elimination rate is proportional to drug concentration.
What is zero order elimination?
Which drugs are eliminated by zero order elimination?
In zero order elimination, drug clearance is constant and not proportional to concentration.
The following drugs follow zero-order kinetics:
- Aspirin
- Ethanol
- Phenytoin
