Pharm 1 - Enzymes Flashcards
CYP1A2 affected by….
inhibited by fluvoxamine
CYP2C9 affected by….
inhib by fluconazole, amiodarone
CYP2C19 affected by…
inhib by Lans+omeprazole
CYP2D6 affected by…
inhib fluoxetine, paroxetine, quinidine, ketoconazole
CYP3A4 affected by…
inhib by Clarithro, grapefruit, ketoconazole, verapamil
Significant drug interactions + effects: verapamil + \_\_\_\_--> \_\_\_\_\_\_\_ amiodarone + \_\_\_\_ --> \_\_\_\_\_\_\_\_ diltiazem + \_\_\_\_ --> \_\_\_ Grapefruit juice + \_\_\_\_ --> \_\_\_ Paroxetine + \_\_\_\_\_ --> \_\_\_\_ clarithromycin + \_\_\_ --> \_\_ ketoconazole + \_\_\_ --> \_\_\_\_
verapamil + beta blockers –> sev bradycardia, asystole, hypotension
Amiod + warfarin → haemorrhage
diltiazem + bb → AV block, bradycardia
grapefruit juice + ciclosporin → toxicity ciclosporin
paroxetine + nsaids → risk bleeding
clarithro + terfenidine → torsades
ketoconazole + buprenorphine → incr buprenorph levels
CYP2D6 function
responsible for codeine conversion to morphine
10% caucasians are poor metabolisers
CYP2C9 function
metabolises S- warfarin
Oral bioavailability of: aspirin paracetamol oramorph diclofenac ibuprofen
Oral bioavailability of: aspirin ~65% paracetamol ~90% oramorph~25% diclofenac~50% ibuprofen~>80%
Routes of elimination: sevoflurane benzylpencillin esmolol remifentanil mivacurium cisatracurium
Routes of elimination:
sevoflurane - lungs>95% excreted unchanged
benzylpencillin - rapid excr by tubular secretion
esmolol - red cell esterases
remifentanil - tissue esterases + plasma esterases but tissure more important
mivacurium - butyrylcholinesterase
cisatracurium - hofmann process
In one compartment model for kinetics of drug:
- Vol of distribution at steady state can be calculated by how much drug?
- if volume of distribution stays the same, clearance increases if the time constant ____
- context sensitive half time is ____ and ___ to half-life
- after an iv bolus dose the rate of elimination at a particular time is proportional to ___ (___ is constant)
- behaviour of drug depends on vol of distribution and ___ ( or ___). clearance gives ratio of these two values
In one compartment model for kinetics of drug:
- Vol of distribution at steady state can be calculated by a single bolus of drug
- if volume of distribution stays the same, clearance increases if the time constant DECREASES
- context sensitive half time is ALWAYS CONSTANT and EQUAL to half-life
- after an iv bolus dose the rate of elimination at a particular time is proportional to PLASMA CONCENTRATION - an exponential relationship (CLEARANCE is constant)
- behaviour of drug depends on vol of distribution and TIME CONSTANT( or RATE CONSTANT FOR ELIMINATION). clearance gives ratio of these two values
If a drug given by continues IV behaves according to three-compartment model:
a) most important determinant of variability of contest sensitive half time are ___
b) elimination only occurs from __
c) if plasma level reached steady state then clearance out of the body can be calulated from infusion __ and __
d) catenary or mamilary model?
e) effect compartment equilibrates with ___
If a drug given by continues IV behaves according to three-compartment model:
a) most important determinant of variability of contest sensitive half time are DURATION OF INFUSION + RATIO OF ELIMINATION TO REDISTRIBUTION rather than VDss. If elimination is very rapid and redistribution from compartments 2+3 is slow then CSHT will not vary as much as if elimination were rapid and redistribution also rapid
b) elimination only occurs from central/first compartment
c) if plasma level reached steady state then clearance out of the body can be calulated from infusion RATE and CONCENTRATION
d) mamilary model where elimination will be from central compartment
e) effect compartment equilibrates with central compartment
Considering elimination of drug from body:
a) rate of elimination = clearance x ___
b) urinary elimination depends on GFR + ___
c) CYP450 found in ___ cells
d) hepatic enzymes involved in xenobiotic metabolism are assoc with____
e) more than 99% of drug will be eliminated after __ half-lives of __ time constants
Considering elimination of drug from body:
a) rate of elimination = clearance x DRUG CONC
b) urinary elimination depends on GFR + RENAL TUBULAR SECRETION
c) CYP450 found in MANY cells
d) hepatic enzymes involved in xenobiotic metabolism are assoc with CYP in the SER, metabolic enzymes in cytoplasm (alcohol dehydrogenase) and mitochondria (MAO)
e) more than 99% of drug will be eliminated after 5 half-lives of 3 time constants
For one compartment model:
a) half life is __ than time constant
b) slope of graph that plots log(conc) against time = ?
c) clearance = ?
d) rate of elimination = ?
e) shape of curve describes rise of drug conc with time on starting a constant rate infusion is ?
For one compartment model:
a) half life is ALWAYS SHORTER than time constant
b) slope of graph that plots log(conc) against time = RATE CONSTANT FOR ELIMINATION
c) clearance = Vd/tau = Vd x k ( tau is time constant, k is rate constant for elimination)
d) rate of elimination = vol of distribtion x rate constant for elimination divided by plasma conc
e) shape of curve describes rise of drug conc with time on starting a constant rate infusion is wash in curve = negative exponentional
In hepatic failure + ascites:
a) Vd is increased/decreased
b) metabolism of all drugs is incr/decreased
c) bioavailability of drugs with moderate hepatic extraction ratio is incr/decreased
d) terminal elimination half life for remifentanil is inc/decreased/not affected
e) dose of NDMR for intubation is incr/decreased
In hepatic failure + ascites:
a) Vd is increased
b) metabolism of most are decreased but not all
c) bioavailability of drugs with moderate hepatic extraction ratio is increased - metabolic capacity will be reduced as may hepatic flow so it is likely that bioavailability will be increased
d) terminal elimination half life for remifentanil is not affected
e) dose of NDMR for intubation is increased as initial increased Vd means larger initial dose needed but maintenance doses need reducing
