Test 1 Part V

Question 1

what is the fx of the transferase enzyme during a phase II biotransformation reaction

Answer 1

catalyze the coupling of an activated endogenous substance and a drug

Question 2

which biotransformation reaction occurs faster, the P450 reaction of phase I or the conjugation reaction of phase II

Answer 2

conjugation (phase II)

Question 3

which reaction/enzyme of phase II biotransformation is microsomal

Answer 3

glucuronide conjugation

Question 4

which enzymes/reactions of a phase II biotransformation is non-microsomal

Answer 4

acetic acid
sulfate
glutathione
methyl

Question 5

why does a toxic dose of tylenol cause liver failure?

Answer 5

CYP (phase I) works great, but the glutathione required for conjugation of phase II is depleted faster than it can be regenerated –> toxic metabolite build up in liver –> liver failure

Question 6

__________________ is based on genetic inheritance of P450s

Answer 6

allergic reactions

Question 7

what is a genetic polymorphism

Answer 7

the occurrence of a variant allelle of a gene at a population frequency of >/= 1% resulting in altered expression or functional activity of the gene product or both

Question 8

___________________ results in altered efficacy of drug therapy or adverse drug reactions

Answer 8

genetic polymorphism

Question 9

what is the phase II biotransformation genetic difference that is found in 50% of blacks and whites in the US causing longer time to metabolize certain drugs

Answer 9

slow acetylator

Question 10

genetic differences causing changes in biotransformation and drug metabolism is predominately a ___________________ trait

Answer 10

autosomal recessive

Question 11

slow acetylators are seen in _____________ of blacks and whites in the US, and there is an increased incidence in ____________________ living in high northern latitudes

Answer 11

50%; europeans

Question 12

slow acetylation is less common in which people

Answer 12

asians and eskimos

Question 13

in what age groups of people are there an increased pharmacologic and toxic activity

Answer 13

very young; very old

Question 14

who metabolize certain drugs (ethanolol, propranolol, benzos, estrogens, and salicylates) faster men or women

Answer 14

men

Question 15

your patient states in a genetic test they had done they are a slow acetylator, this means you would do what to their benzodiazepine dose prior to entering the OR

Answer 15

lower it

Question 16

what diseases can affect drug metabolism

Answer 16

1. acute or chronic disease of the liver
2. cardiac disease
3. thyroid dysfunction
4. pulmonary disease
5. infections (bacterial or viral)
6. cancer
7. inflammation

Question 17

how does cardiac disease cause impairment of drug metabolism?

Answer 17

limits the blood flow to the liver, thus impairing the metabolism of the drugs that are flow limited or flow dependent

Question 18

how does bacterial infections, viral infections, cancers, and inflammatory processes impair the metabolism of drugs?

Answer 18

causes release of inflammatory mediators impairing the function of P450

Question 19

what is the first step in drug development

Answer 19

discovery/synthesis of a new drug compound or a new target (receptor)

Question 20

in the U.S. ______________ and ____________ of drug must be defined before marketing can legally begin

Answer 20

safety; efficacy

Question 21

in the US _______ - _______ % of healthcare money is spent on prescription drugs

Answer 21

10; 12

Question 22

less than ____________ of drugs tested in clinical trials make it to market

Answer 22

1/3

Question 23

what is teh approximate cost of developing a new drug

Answer 23

150 million to several billion

Question 24

where do most drugs orginate?

Answer 24

private sector (universities, research institutes)

Question 25

of the new drugs that achieve marketing approval, ____________% are drugs with significant advances in safety and efficacy; the rest are molecular varient compounds that are already in circulation

Answer 25

10-15

Question 26

only _______ out of 10 drugs produce a return on investment

Answer 26

2

Question 27

what is the purpose of "drug screening"

Answer 27

to define the pharmacologic profile of the drug at the molecular, cellular, organ, organ system, and organism level

Question 28

they type and number of initial drug screening tests depends on what factors?

Answer 28

the pharmacologic and therapeutic goal of a new potential drug

Question 29

drug screening results must be ______________ and ____________ to develop a pharmacologic profile

Answer 29

reliable; reproduceable

Question 30

drug screen at the molecular level

Answer 30

screen for activity on the target receptor effects evaluated on P450 enzymes

Question 31

which level of the drug screen determines whether the drug is an antagonist, agonist, partial agonist, or inverse agonist at the target receptor

Answer 31

cellular level drug screen

Question 32

what part of the drug screen is the new drug characterized by its pharmacologic activity and selectivity

Answer 32

organ drug screen

Question 33

what part of the drug screen is the drug tested in animal studies?

Answer 33

organ system

Question 34

what information is derived from the organ system drug screen?

Answer 34

duration of action and efficacy after oral and IV administration

Question 35

drug screen at the level of the organism examines what?

Answer 35

signs and sx of adverse effects on all major organ systems

Question 36

what drug screen level is there an estimation of tolerance and/or abuse potential, physical or psychological dependence, and drug-drug interaction information obtained

Answer 36

organism level

Question 37

successful drug screening leads to the development of a ________________

Answer 37

lead compound

Question 38

what is a lead compound

Answer 38

A compound demonstrating a property that is likely to be therapeutically useful (through drug screening)

Question 39

when can someone apply for a patent on a new drug they are developing

Answer 39

after drug screening

Question 40

__________________________ is an essential step in the drug development process where limiting toxicities, therapeutic index, and risk and benefits are identified

Answer 40

preclinical safety and toxicity testing

Question 41

what is the goal of preclinical safety and toxicity testing

Answer 41

1. ID potential human toxicities 2. design tests to further define the toxic mechanisms 3. predict the most relevant toxicities to be monitored during clinical trials 4. quantitative dose estimates (used to calculate initial dose for human trials)

Question 42

in preclinical safety and toxicity testing what is the no-effect dose?

Answer 42

the max dose at which a specific toxic effect is not seen in animals

Question 43

what quantitative estimate dose from preclinical safety and toxicity testing is used as the start dose for human trials

Answer 43

1/10th - 1/100th of no-effect dose

Question 44

what is the minimal lethal dose that is obtained from preclinical safety and toxicity testing

Answer 44

smallest dose that is observed to kill any experimental animal

Question 45

what is the medial lethal dose obtained from preclinical safety and toxicity testing?

Answer 45

the dose that kills approx 50% of animals, estimated from the smallest number of animals possible

Question 46

what are the limits to preclinical safety and toxicity testing?

Answer 46

1. time consuming and expensive 2. large numbers of animals needed 3. data from animal studies may not translate all potential toxicities in humans 4. rare adverse effects are unlikely to be detected

Question 47

how long does preclinical safety and toxicity testing potentially take before a drug is ready for human testing?

Answer 47

2-6 years

Question 48

what are the 3 major confounding factors in human evaluation of a new drug

Answer 48

1. variable natural hx of diseases 2. presence of other diseases and risk factors 3. subject and observer bias

Question 49

if the FDA approves a drug or food as "safe and effective" is does NOT mean ___________________________

Answer 49

free of side effects

Question 50

the pure food and drug act of 1906 is a response to what?

Answer 50

unsanitary and unethical practices in the meat packing industry