chpt 1

Question 1

rx: removal of toxins during hepatic encephalopathy

Answer 1

lactulose

will turn into lactic acid and convert ammonia into ammonium for excretion

Question 2

describe filtration of unionized and ionized drugs

Answer 2

both ionized and unionized are filtered. only unionized can be reabsorbed / secreted

Question 3

why does sulfonamides in neonate give kernicterus? similarly, why does warfarin toxicity increase w/ sulfonamides?

Answer 3

sulfonamides compete with protein-binding sites (i.e. on albumin) w/ bilirubin. will displace bilirubin and make it free.

98% of warfarin = plasma protein bound. when give sulfonamides, will increase free conc of warfarin

Question 4

why does Li+ and ethanol get through BBB despite being charged / polar?

Answer 4

bc they are small (low molecular weight!)

Question 5

how to make a drug safer for pregnancy? [3]

Answer 5

1. water soluble
2. large
3. protein-bound

Question 6

formula for volume of distribution

Answer 6

volume of distribution = dose / plasma concentration at time 0

Vd = dose/[plasma]

Question 7

approximate volume of distribution values (70kg man) for plasma, blood, ECF, TBW

Answer 7

plasma 3L
blood 5L
ECF 12-14L
TBW 40-42L

Question 8

describe thiopental’s half-life

Answer 8

very long 9hrs, even though only has a duration of effect in the brain of <1min. bc quickly redistributes into fat

Question 9

example of drug whose metabolites are active

Answer 9

benzodiazepines

Question 10

P450 – absolute requirement for … [2]

Answer 10

O2 and NADPH

Question 11

oxidations include [2 things]

Answer 11

hydroxylation and dealkylations

Question 12

smoking has what effect on p450 system?

Answer 12

induces. need to up dose. or lower if quit

Question 13

what time to reach steady state depend on?

Answer 13

only depends on elimination half-life (independent of dose size and freq of administration)

Question 14

50% of the way to steady state after…

Answer 14

1 x half-life

Question 15

90% of the way to steady state after…

Answer 15

3.3 x half-life

Question 16

95% of the way to steady state after…

Answer 16

4-5 x half-life; considered clinical steady state

Question 17

“100%” at steady state at..

Answer 17

> 7 x half-life

Question 18

process of getting to steady state..

Answer 18

dose w/ fixed amount after 1 half-life. steady state oscillates between minimum toxic dose & minimum effective dose

Question 19

what is steady state?

Answer 19

rate in = rate out

Question 20

what dose the rate of infusion/maintenance dose determine?

Answer 20

the plasma level at steady state (amt of time needed to reach steady state is not affected by infusion rate)

Question 21

if cannot wait 4-5 half-lives to achieve effective blood concentrations, what can you do?

Answer 21

give 1 loading dose + maintenance doses after 1 half-life

Question 22

loading doses are.. formula?

Answer 22

one time only, estimated to put amt of drug in body that would be there at steady state. usu 2x maintenace dose. LD = Conc in plasma x volume od distribution

Question 23

volume of distribution equation

Answer 23

Vd = Dose/C0. will be given C0 and Vd, will be asked to calculate dose.

Question 24

half-life equation

Answer 24

t1/2 = 0.7 x Vd/Cl.
note: 1. increases Vd will increase half-life (directly proportional) 2. half-life and clearance are inversely proportional.

Question 25

infusion rate equation:

Answer 25

infusion rate = Cl x Conc at steady state

Question 26

loading dose equation

Answer 26

LD = (Vd x conc in plasma) / f, or bioavailability

note: renal fxn is not considered

Question 27

maintenance dose equation

Answer 27

MD = (Cl x Conc at steady state x dosing interval, or tau)/ f, or bioavailability. note: renal fxn (clearance) is considered

Question 28

definition of an antagonist

Answer 28

binds to receptor and prevents agonist from binding / functioning

Question 29

affinity

Answer 29

like Km. inversely related to Kd (amount needed for half maximal binding). can only be compared on dose response curve if parallel (meaning they work on same receptor)

Question 30

efficacy

Answer 30

like Vmax

Question 31

potency

Answer 31

can only be compared on dose v. response curve if lines do not cross. if they cross, can specific specific doses where one is more potent than the other.

Question 32

competitive antagonist on drug

Answer 32

decrease in potency, will shift dose v. response curve to right.

Question 33

it is safe to assume that most drugs = competitive antagonists. name some noncompetitive antagonists (5)

Answer 33

phenoxybenzamine, digoxin, allopurinol, PPI, aspirin. decreased efficacy

Question 34

competitive antagonist on pharmacodynamics? noncompetitive antagonist?

Answer 34

competitive antagonist, alters drug potency. noncompetitive antagonist, alters drug efficacy.

Question 35

drugs w/ low therapeutic index (TD50/ED50) (4)

Answer 35

theophylline, digoxin, warfarin, lithium

Question 36

intracellular receptors (4)

Answer 36

glucocorticoids, thyroid hormones, gonadal hormones, vitamin D

Question 37

cGMP and NO. 4 drugs that use this pathway

Answer 37

facilitates dephosphorylation of myosin light chain in vasculature, preventing their intxn w/ actin. nitrates, muscarinic agonists, bradykinin, histamine (via protein kinase G)

Question 38

JAK STAT signals (4 stimuli) and intracellular signal transduction

Answer 38

1. cytokines like EPO, somatotropin, and interferons. membrane spanning receptors that activate cytoplasmic tyrosine kinases (JAK). JAK go on to phosphorylate signal transducers and activators of transcription (STATs). STATs dimerize then dissociate, cross nuclear membrane, and modulate gene transcription. like an insulin receptor + steroid receptor combined.

Question 39

clinical trials: preclinical

Answer 39

safety & biological activity (animal)

Question 40

phase 1 clinical trial

Answer 40

50 healthy volunteers, safety & dosage

Question 41

phase 2 clinical trial

Answer 41

200 patients, effectiveness

Question 42

phase 3 clinical trial

Answer 42

2000 patients. confirm effectiveness & common side-effects

Question 43

phase 4 clinical trial

Answer 43

post-marketing surveillance, after FDA approval. common and rare side effects.

Question 44

FDA classification of teratogenicity

Answer 44

A (no risks – folic acid)
B (some evidence for risk in animals, none in humans, so considered safe)
C (risk in animals, unknown risk in humans. don’t know if safe or not)
D (teratogenic, but benefits outweigh risk; anticonvulsant)
X (teratogenic in humans & animals, absolutely contraindicated)