Drug Metabolism Flashcards
Drug metabolism/Biotransformation is the (physical or chemical?) modification of drugs in the body which transforms relatively lipo___ agents into products more ____, hydro_____ products which can easily be excreted.
Chemical
philic; polar
philic
Drug metabolism can Sometimes lead to chemical activation of inactive drugs to their active substrates
T/F
With examples
T
Enalapril to enalaprilat, Codeine to morphine
Inactive to active
Enalapril to _______, Codeine to _____
enalaprilat
morphine
Drug metabolism occurs Mainly in the _____, involves both ________ and ________ enzymes.
liver
microsomal and non microsomal
Drug metabolism Occur in almost all organs of the body
T/F
T
other relatively common sites for drug metabolism besides liver include the ____,_____,_____, and _____
lungs, kidney, GIT and the skin
Drug metabolism is categorized MAINLY into 2 main reactions - ______ and ______ metabolism.
Phase I and Phase II
Phase 1 of drug metabolism must occur before phase 2 of drug metabolism
T/F
F
Could occur in any order.
Phase 3 reaction has also been described – Mainly involved in the removal of drugs that _________________ by _______ (_________)
have undergone phase 1 and or 2 reactions
transporters
P-glycoprotein
Phase I Reactions/__________ reaction / ________ reaction
functionalization
nonsynthetic
Phase 1 reaction
Convert parent compound into a more __________ metabolite by adding or unmasking ________ (-OH, -SH, -NH2, -COOH, etc.) eg._____
polar (=hydrophilic)
functional groups
oxidation
Phase 1 reactions include _____,________, and _________ reactions. Others ________,______
Oxidative, reductive and hydrolytic
cyclization and decyclization
Main function of phase I reactions is to prepare chemicals for ________ and _____
phase II metabolism and subsequent excretion.
The drug May be sufficiently polar after phase 1 to be excreted readily
T/F
T
phase 2 metabolism involves,
________ with ________ to further increase aqueous solubility
Include ____,_____,_______,______,_____etc
Conjugation
endogenous substrate
glucoronide, sulfate, acetate, amino acid, glycine
Phase ____ is the true “detoxification” step in the metabolism process
II
Microsomal enzymes
Located on ____ in the ____,_____,_____,_____
sER
liver, kidney, lungs , intestinal mucosa
Example of microsomal enzymes include
____,________,______,_______
Monooxygynases, cytochrome P450, UGT, epoxide hydroxylases
Microsomal enzymes are only involved in phase 2 reactions
T/F
F
Involved in phase 1 and 2 reactions
Non-microsomal enzymes
Can be found in _______,______,______
examples include ____,______
Cytoplasm, mitochondria, plasma
Esterases, amidases,
Microsomal cytochrome P450
Act on only structurally related drugs
T/F
F
They act on structurally unrelated drugs
Microsomal cytochrome P450
which _____ drugs
oxidize
Microsomal cytochrome P450 ,__________ family of enzymes
monooxygenase
_______ enzyme Metabolizes the widest range of drugs.
Microsomal cytochrome P450
_______ enzyme metabolizes the widest range of drugs
Microsomal cytochrome P450
Cytochrome P450 system
These enzymes are _____-bound, _______-containing protein.
membrane; heme
The human CYP family consists of ___ genes, with ___ families and _____ subfamilies.
57
18
44
Examples of human CYP enzymes include
_____,____,____,_____,_______
CYP2D6,CYP2C19,CYP2C9,CYP3A4andCYP3A5.
The enzymes are named based on the _____ -
Eg
CYP3A4 belongs to ______ — , ______ —, and ________ —-
family
family 3
subfamily A
gene number 4.
CYP ______ is involved in a significantly higher number of drug metabolism compared to the other enzymes.
CYP3A4
Inhibition of CYP enzymes - ___eased degradation of co-medicated drugs, ____eased drug plasma concentrations,
Risk of ___________. Inhibitors: _______,______, MAO Inhibitor (_________)
Decr
Incre
severe adverse events
cimetidine
Isoniazid
Phenelzine
Induction of CYP enzymes - ___eased degradation of co-medicated drugs , ____eased drug plasma concentrations , Loss of ________ , Risk of _________.
Inducers: _______,________,______, cyclophosphamide
Incr
Decr
pharmacological effect
therapeutic failure
barbiturates; rifampicin, carbamazepine
Who is a more efficient metabolized between human and rats?
Rats
Diseases affecting the liver will (reduce or increase ?) rate of drug metabolism.
reduce
Testosterone is an enzyme (inducer or inhibitor?)
inducer
felodipine inhibited by _____
grape juice
Progesterone in an enzyme (inducer or inhibitor ?) .
inducer
Placenta contains metabolizing enzymes
T/F
T
Drugs with extensive first pass effect include – _______,______,______,______
lidocaine, propranolol, nitroglycerin, morphine
Puritane (hinders or enhances?) sleep
Enhances
List all the inhibitors of cyp450
Cimetidine
Isoniazid
Grapejuice fruit
Phenelzine
Omeprazole
Ketoconazole
Erythromycin
Refonavir
List the inducers of cyp450
Carbamazepine
Rifampicin
Barbiturates
Cyclophosphamide
St John’s wort
Diazapam (hinders or enhances?) sleep
Enhances
Diazepam taken with ______ would make you sleep longer
Why?
Cimetidine
Cimetidine inhibits cyp450 that would metabolize diazepam
Why don’t you give insulin orally?
Because of the first pass effect
First pass effect is _____ proportional to bioavailability
Inversely
L-dopa is given orally
T/F
With reason
F
Sue to the presence of dopa decarboxylase
Propranolol has (high or low?) bioavailability
Low
Determining bioavailability is important for calculating ________ for nonintravenous routes of administration.
drug dosages
Bioavailability is the rate and extent to which an ___________.
For example, if 100 mg of a drug
is administered orally and 70 mg is absorbed unchanged, the bioavailability is _____ or ____%%
administered drug reaches the systemic circulation
0.7 or 70
Bioavailability of a drug given
orally is the ratio of the __________ to the
__________________
AUC following oral administration
AUC following IV administration
First-pass hepatic metabolism:
When a drug is absorbed
from the _______, it enters the ______ before entering the ______.
If the drug is rapidly metabolized in the _______ or ______ during this initial
passage, the amount of unchanged drug entering the systemic circulation is ____eased.
GI tract; portal circulation; systemic circulation
liver or gut wall
Decr
First-pass metabolism by the ______ or ______ limits the _______ of many oral medications.
intestine or liver
efficacy
For example, more than __% of nitroglycerin is cleared during
first-pass metabolism. Hence, it is primarily administered via the _______ or _______ route.
90
sublingual or transdermal
Drugs with high first-pass metabolism should be given in doses sufficient to
ensure that enough active drug reaches the desired site of action.
T/F
T
Very hydrophilic drugs are (poorly or well?) absorbed
Why?
drugs that are extremely lipophilic are
(poorly or well?) absorbed
Why?
Poorly
because of their inability to cross lipid-rich cell membranes.
Poorly
because they are totally insoluble in
aqueous body fluids and, therefore, cannot gain access to the
surface of cells.
For a drug to be readily absorbed, it must be largely _____, yet have some solubility in ______
This is one reason why many drugs are either _______ or ______
lipophilic
aqueous solutions.
weak acids or weak bases.
penicillin G, are stable in the pH of the gastric contents.
T/F
F
unstable
insulin, are destroyed in the ______ by degradative enzymes.
GI tract
Two drug formulations are bioequivalent if they show comparable _____ and similar times to __________
bioavailability
achieve peak blood concentrations.
UGT-_____________
Uridine diphosphate-glucuronyltransferase (UGT)
UGT converts the (toxic or non-toxic?) form of ____ ( ___________ ) to its (toxic or nontoxic?) form (________), making it able to be dissolved and removed from the body.
Toxic ; bilirubin
unconjugated bilirubin
Non toxic; conjugated bilirubin
List 4 microsomal enzymes
Monooxygynases, cytochrome P450, UGT, epoxide hydroxylases
List 2 Non microsomal enzymes
Esterases, amidases,
Progesterone in an enzyme ( inducer or inhibitors?)
Inducer
Drugs with extensive first pass effect include – ________,________,______,______
lidocaine, propranolol, nitroglycerin, morphine
