Pharmacokinetics Principles 3 (metabolism and excretion)

Question 1

chemical alteration of the drug in the body

Answer 1

biotransformation (metabolism).

Question 2

transformation in biological system

Answer 2

biotransformation

Question 3

in which order of kinetics the rate of elimination depends on dose

Answer 3

first order

Question 4

in which order of kinetics the rate of elimination does not depends on dose

Answer 4

zero order kinetics

Question 5

list the 4 steps of metabolism

Answer 5

1- converts non polar (lipid soluble) substances.
2- to polar (lipid insoluble) substances.
3- no reabsorption in renal tubules.
4- excretion in urine.

Question 6

if drug A is active, and the product B is inactive.
metabolism in this case ___________

Answer 6

stops drug action

Question 7

if drug A is active, and the product B is active.
metabolism in this case ___________, and name an example of a drug.

Answer 7

action is prolonged.
eg, diazepam.

Question 8

if drug A is inactive, and the product B is active.
metabolism in this case ___________

Answer 8

activates the drug after we reach the action site.

Question 9

few drugs are inactive and need conversion in the body to one or more active metabolites, such drugs are called _________

Answer 9

prodrug.

Question 10

give an example of a prodrug?

Answer 10

like in parkinson’s, dopamine cannot cross the BBB so we give Levodopa

Question 11

what are the 2 reactions of biotransformation

Answer 11

1- phase 1, non-synthetic, functionalization reactions.
2- phase 2, synthetic, conjugation.

Question 12

what happens to lipophilic drugs in phase one of biotransformation?

Answer 12

gets converted to polar molecules.

Question 13

metabolites in phase one of biotransformation are ________ (active, inactive)?

Answer 13

may be active or inactive.

Question 14

what is conjugated to drug metabolites in phase 2?

Answer 14

endogenous radical

Question 15

metabolites in phase two of biotransformation are ________ (active, inactive)?

Answer 15

mostly inactive.

Question 16

what are the 5 reaction in phase 1?

Answer 16

1- oxidation.
2- reduction.
3- hydrolysis.
4- cyclization.
5- decyclization.

Question 17

what is the most common reaction in phase 1?

Answer 17

oxidations.

Question 18

the oxidation reaction in phase 1 is mostly carried out by _____ in the ________

Answer 18

monooxygenases (cytochrome P450),
in the liver.

Question 19

in oxidation reactions of phase one we either add ________ or remove ________ ?

Answer 19

add oxygen/ negatively charged molecules.
or
remove hydrogen/ positively charged molecules.

Question 20

name 3 examples of oxidation reactions?

Answer 20

1- hydroxylation.
2- dealkylation.
3- oxidative deamination.

Question 21

name 2 examples of a monooxygenases in the liver?

Answer 21

1- cytochrome P450
2- CYP3A4

Question 22

_________ carries out metabolism of largest number of drugs.

Answer 22

CYP3A4

Question 23

In reduction reactions of phase one we either add______ or remove______?

Answer 23

add hydrogen or remove oxygen.

Question 24

give an example of reduction reactions

Answer 24

levodopa reduced to dopamine in the brain.

Question 25

what enzyme reduces levodopa to dopamine?

Answer 25

dopa decarboxylase.

Question 26

in hydrolysis reactions of phase one we add ______ in the presence of ______ such as, ______

Answer 26

add water molecules in the presence of enzymes such as esterase and amidase.

Question 27

list the 4 drugs that undergo hydrolysis?

Answer 27

1- procaine. 2- aspirin. 3- pethidine. 4- succinylcholine.

Question 28

what is the most important synthetic reaction?

Answer 28

glucuronide conjugation.

Question 29

glucuronide conjugation is carried out by which enzyme?

Answer 29

UDP-glucuronosyl transferase (UGTs).

Question 30

gray baby syndrome is caused by a deficiency of which enzyme?

Answer 30

glucuronyl transferase enzyme.

Question 31

gray baby syndrome is caused by the usage of which drug?

Answer 31

chloramphenicol use.

Question 32

list the 7 drugs that undergo glucuronide conjugation?

Answer 32

1- chloramphenicol. 2- aspirin. 3- paracetamol. 4- morphine. 5- PABA. 6- diazepam. 7- digoxin.

Question 33

list the 3 endogenous substances that undergo glucuronide conjugation?

Answer 33

1- bilirubin. 2- sex steroids. 3- thyroxine.

Question 34

when _____ combines with paracetamol it turns it into harmless products

Answer 34

glutathione

Question 35

in the case of paracetamol poisoning, ________ supply falls short and is unable to convert it to harmless products.

Answer 35

glutathione.

Question 36

give examples of microsomal enzymes?

Answer 36

monooxygenases, cytochrome P450, UGTs

Question 37

where are microsomal enzymes located?

Answer 37

smooth endoplasmic reticulum, in the liver, kidney and intestines.

Question 38

drugs that increase activity of microsomal enzymes and increase the metabolism of other drugs or the same drug itself

Answer 38

liver microsomal enzymes inducers.

Question 39

drugs that decrease activity of microsomal enzymes and decrease the metabolism of other drugs or the same drug itself

Answer 39

liver microsomal enzymes inhibitors.

Question 40

list 6 examples of microsomal enzyme inhibitors?

Answer 40

1- allopurinol. 2- erythromycin. 3- ketoconazole. 4- cimetidine. 5- HIV protease inhibitors. 6- grape juice.

Question 41

list 3 examples of microsomal enzyme inducers?

Answer 41

1- anticonvulsants, rifampin induce CYP3A4. 2- isoniazid and alcohol induce CYP2E1. 3- polycyclic hydrocarbons in cigarette smoke, charcoal broiled meat induce CYP1A.

Question 42

the irreversible removal of drug from the body

Answer 42

elimination.

Question 43

what does elimination involve?

Answer 43

1- biotransformation (drug metabolism). 2- excretion.

Question 44

what are the 3 major routes of elimination?

Answer 44

1- hepatic metabolism. 2- biliary metabolism. 3- urinary metabolism.

Question 45

the volume of blood from which the drug id cleared per unit time?

Answer 45

clearance

Question 46

what are the 2 main routes of excretion?

Answer 46

1- renal excretion. 2- biliary excretion.

Question 47

what are the 5 minor routes of excretion?

Answer 47

1- pulmonary excretion. 2- salivary excretion 3- mammary excretion via milk. 4- skin / dermal excretion via sweet. 5- tears.

Question 48

what is the most important channel of excretion for majority of drugs?

Answer 48

renal elimination.

Question 49

what organ is responsible for excreting all water soluble substances?

Answer 49

the kidneys

Question 50

net renal exertion is expressed by?

Answer 50

(glomerular filtration + tubular secretion) - tubular reabsorption

Question 51

what are the 3 processes involved in renal elimination?

Answer 51

1- glomerular filtration. 2- tubular reabsorption. 3- tubular secretion.

Question 52

where are drugs and their metabolites can be excreted?

Answer 52

1- faeces. 2- exhaled air. 3- saliva and sweat. 4- milk.

Question 53

most of the drug in faeces is derived from what?

Answer 53

bile.

Question 54

the rate of elimination is directly proportional to drug concentration

Answer 54

first order kinetics.

Question 55

constant _______ of drug is eliminated per unit time in 1st order kinetics?

Answer 55

fraction

Question 56

in first order kinetics increase in does, ________ t1/2.

Answer 56

unalter

Question 57

what is the most common order of kinetics?

Answer 57

1st

Question 58

rate of elimination is not dependant on drug concentration

Answer 58

zero order kinetics.

Question 59

constant ________ of drug is eliminated per unit time in zero order kinetics?

Answer 59

amount

Question 60

increase in dose, ______ elimination in zero order kinetics.

Answer 60

does not increase.

Question 61

increase in dose, ______ t1/2 in zero order kinetics.

Answer 61

increases

Question 62

there is risk of toxicity in which order of kinetics?

Answer 62

zero order

Question 63

give examples of drugs that undergo zero order kinetics

Answer 63

ethanol, high doses of phenytoin.

Question 64

give examples of drugs that change from 1st order to zero order kinetics?

Answer 64

- phenytoin. - tolbutamide. - theophylline. - warfarin.

Question 65

T 1/2 is ____ ______ to volume of distribution and ______ _______ to clearance.

Answer 65

directly proportional. inversely proportional.

Question 66

rate of drug elimination equals rate of drug administration

Answer 66

steady state.

Question 67

how many half lives does it take to reach steady state?

Answer 67

4-5 T1/2

Question 68

Dosing rate is expressed by

Answer 68

DR = (C)(CL) / F F = bioavailability CL = clearance C = target plasma concentration

Question 69

loading rate is expressed by

Answer 69

LD = Vd (C) / F Vd = volume of distribution C = clearance. F = bioavailability.

Question 70

dose required to maintain Css

Answer 70

dosing rate

Question 71

administered to achieve the desired plasma level rapidly.

Answer 71

loading dose

Question 72

the measurement of plasma concentration of drugs

Answer 72

therapeutic drug monitoring (TDM)

Question 73

what are the 6 uses of TDM?

Answer 73

1- drugs with low safety margin. 2- if individual variations are large. 3- potentially toxic drugs used in the presence of renal failure. 4- in cases of poisoning. 5- in cases of failure of response without any apparent reason. 6- check patient compliance.

Question 74

give example of drugs with low safety margin?

Answer 74

- digoxin. - anticonvulsants. - antiarrhythmics. - theophylline. - aminoglycoside ABx. - lithium.

Question 75

give example of drugs with individual variation are large?

Answer 75

- antidepressants. - lithium.

Question 76

give example of drugs with potentially toxic drugs used in the presence of renal failure?

Answer 76

- aminoglycoside antibiotics. - vancomycin.

Question 77

give example of drugs with failure of response without any apparent reason?

Answer 77

antimicrobials.

Question 78

give example of drugs that need to be check for patient compliance?

Answer 78

- psychopharmacological agents.

Question 79

what are the 3 cases where TDM is of no value?

Answer 79

1- drugs whose response is easily measurable. 2- drugs that get activated in the body. 3- drugs with irreversible action.

Question 80

give example of drugs whose response is easily measurable?

Answer 80

antihypertensives

Question 81

give example of drugs that get activated in the body?

Answer 81

levodopa.

Question 82

give example of drugs with irreversible action?

Answer 82

organophosphates.