Exam1Lec3Pharmacokinetics Flashcards
The phase 2 reactions are mainly involved in ____ of drug
coupling
What is coupling of drug?
Takes drug and conjugates to an enfogenous drug by the use of transferases
ex: glucuronic acid (the most common conjugation rxm, e.g morphine)
What groups can be added to drug for conjugation reaction?
- Sulfate
- Acetyl
- Methyl
- Glutathione, glycine
most conjugates are ____ and unable to cross plasma membrane making them ____
highly polar/water soluble
pharmacologically inactive
What are the names of the different types of conjufation (phase 2) rxns?
glucoronidation
methylation
acetylation
sulfation
GSH (reduced glutathione)
Amino acids
The word “transferase” is associated with what?
Conjugation/phase 2 rxns
What are the factors influencing Drug Metabolism?
“DPAGEER”
Drug dosage
Physiologic/disease state
Age
Genetic variation
Enzyme induction
Enzyme Inhibition
Route of Drug Administration
Explain how physiologic/disease state can influence drug metabolism
- Any disease that affects liver fxn influences a drug’s hepatic clearance.
- Congestive heart failure can decr hepatic blood flow and distribution of drugs ( if blood flow is reduced to liver, then % of biotransf is effected)
- Liver is the center of serum albumin, so alteration
in albumin production can alter the ratio of bound to unbound drug
remeber albumin binds drugs
Explain how genetic variation can influence drug metabolism.
There is a great variation in the activity of N-acetyl transferase enzyme among different population.
the proportion of drugs metabolized by the major cytochrome P450 enzyme (know about CP450 CYP2D6 is a polymorphic drug-metabolizing enzyme)
If you are a fast acetylator, do you have more or less drug concentration in blood? Do you have more or less tranferase?
Less drug
less transferase
If you are a slow acetylator, do you have more or less drug concentration in blood? Do you have more or less tranferase?
more drug
more transferase
How does dosage influence drug metabolism?
as drug dosage increases = drug [ ] may saturate metabolic enzyme
ex: high dosage of acetaminophen causing hepatic cell death
How does age influence drug metabolism?
In young children, drugs may be more active. This is b/c the lack complete development of Phase 1 and II enzymes.
older children: some drugs less active than in adult (liver larger=more biotransf=less drugs active bc undergoes biotrans faster)
In older ppl, metabolizing enzymes decline.
How can the route of drug administration influence drug metabolism?
First pass effect: combined action of bacterial enzyme w/ intestine and liver on the drug taken orally.
Think: there are lots of enzymes in the intestine and liver, and this can destroy drug
Explain how enzyme induction can influence drug administration
Phenobarbital and Rifampin act as enzyme inducers
wil be on exam
How does Phenobarbital and Rifampin act as enzyme inducers
increase synthesis or decrease degradation of drug metabolizing enzymes
will be on exam
with enzyme induction, the second drug you take can. be metababolized at much faster rate (reduce, half life)
In cigarette smokers, polycyclic aromatic hydrocarbon appear to induce ____
N-demethylation (Phase I oxidation rxn)
so cig smokers have lower plasma lvs of drugs than non-smokers
Enzyme induction can produce a condition known as ____
pharmacokinetic tolerance
drugs can block certain enzymes that are involved in metabolizing other drugs
Explain how enzyme inhibition can influence drug metabolism.
some drugs can. decr the metabolism of other drugs. This inhibition can occur by destruction of drug-metabolizing enzymes by inhibitiin of enzyme synthesis
phenytoin is increased by co-admin of chloramphenicol (enzyme inhibitor)
What are the three Renal excretion processes?
excretion of drugs and metabolites in the urine involve:
Glomerular filtration (+) (GFR)
Active tubular seceretion (+) (fixed capacity)
Passive tubular reabsorption (-) (pH effect)
What is Glomerular filtration
Free drug enters glomerular fltration to enter urine
note: when drug is bound to plasma protein, it doesn’t enter filtration
you see free drug in urine because when its bound, it doest not go through glumerular filtration
What is Active tubular secretion?
some drugs get actively secreted into urine
on exam: fixed capacity: you have many transporters that can do many things, but it will reach vmax
What is Passive tubular reabsorption?
unionized form of drug can get readily reabsorbed in systemic circulation
take blood from urine and put back into systemic circulation
What is biliary excetion?
Enterohepatic recirculation (biliary cycling)
Transport system analagous to those found in kidney actively secrete drugs into bile
transport drug into bile through active transport, then get reabsopbed from GI tract.
Biliary excretion favors compounds with molecular weight ____
greater than 300
Conjugated drugs can be ____ to the free drug by _____ and ____ into circulation
hydrolyzed
intestinal bacteria
reabsorbed
enterohepatic recirculation ____ elimination of drugs and ____ duration of action
reduces
prolongs
keeps drug in body for long time
know this
milk is ___ and ___ drug will get trapped
acidic
basic
impt for nursing infant and as a residue in dairy products
True or false, Drugs can be excreted from the lungs?
True (anesthetic gases, alcohol)
breath analyzer ex
What is clinical pharmacokinetics?
process of using drug [ ], pharmacodynamics principles to optimize drug therapy in individuals
What is bioavailability?
percentage of the dose which reaches systemic circulation
IV drugs have a bioavailability of ___
1
Apparent volume of distribution
amount of drug in the body to the serum [ ] (L or ml)
If the volume distributiion is large, that tells us that the drug is in the body but not the plasma
Clearance & half-life
C= rate of drug removal (how much of the drug is removed per unit time ml/min)
H= time it takes for [ ] of drug in plasma to decrease by 50% (unit of time)
