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october exam > pharm 1 > Flashcards

pharm 1 Flashcards

1
Q

volume of distribution describes relationship between

A

drugs plasma concentration following a specific dose. it is a theoretical measure of how a drug distributes throughout the body.

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2
Q

what 2 things does vD assume

A

-drug distributes instantaneously
-drug is not subjected to biotransformation or elimination before it fully distributes

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3
Q

what are the implications when a drugs vd exceeds TBW?

A

vd > TBW it is assumed to be lipophilic

distributes into TBW and fat

need a HIGHER dose to achieve a given plasma concentration

ex: propofol and fentanyl

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4
Q

if vd < tbw the drug is assumed to be

A

hydrophiilic

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5
Q

hydrophilic distributes into where

A

some or all of the body water. but it does not distribute into fat.

requires a lower dose to achieve a given plasma concentration

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6
Q

examples of hydrophilic drugs

A

NMB, albumin

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7
Q

for an IV drug what is the bioavaliability

A

always 1- b/c the drug enters the blood stream

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8
Q

what is the bioavaliability of drugs via routes other than IV

A

drug administered by any other route may not be absorbed completely- may be subject to first pass metabolism in the liver- reduces bioavaliability and explains why the dose achieves a given plasma concentrration- dependent on route of administration

bioavaliability less than 1

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9
Q

what is clearance

A

volume of plasma that is cleared of a drug per unit of time

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10
Q

clearance is directly proportional to

A

blood flow to cleansing organ, extraction ratio, drug dose

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11
Q

clearance is indirectly proportional to

A

half life, drug concentration in central compartment

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12
Q
A
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13
Q

how many half times until steady state is achieved

A

5

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14
Q

what is steady state

A

occurs when the amount of drug entering the body is equivalent to the amount of drug eliminated from the body

  • a stable plasma concentration
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15
Q

is the drug in each compartment = during steady state

A

no- each compartments equilibrated although total amount of drug may be different in each

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16
Q

what are the phases of distribution

A

alpha and beat

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17
Q

alpha distribution phase

A

drug distribution from plasma to tissues

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18
Q

beta distribution phase

A

begins as plasma concentration falls below tissue concentration. concentration gradient reverses, causes drug to re-enter the plasma. beta phase describes drug elimination from central compartment

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19
Q

how do you figure out how much of a drug is left after a certain amount of half times

A

50% for each half time - picture on phone

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20
Q

what is context sensitive half time

A

half times DO NOT consider time

context sensitive half time does! - time required for plasma concentration to decline by 50% after d/c the drug

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21
Q

what is the difference bwteen a strong and weak acid or base

A

if you put a strong acid or strong base in water- it will ionize completely

if you put a weak acid or weak base in water- a fraction of it will be ionized, the remaining fraction will be unionized

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22
Q

acid vs base

A

acid donates a proton
HA - H+ + A

base accepts proton

B + H+ - BH

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23
Q

what is ionization

A

the process where a molecule gains a pos or neg charge

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24
Q

what is ionization dependent on

A

ph of the solution and ph of the drug

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25
Q

when pka and ph are the same

A

50% of the drug is ionized and 50% is non ionized

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26
Q

solubility of ionized drug

A

hydrophilic and lipophobic

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27
Q

non ionized solubility

A

lipophillic and hydrophobic

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28
Q

is ionized or non ionized pharmacologically effective

A

non ionized

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29
Q

is ionized or non ionized more likely to go through hepatic biotransformation

A

non ionized

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30
Q

is ionized or non ionized more likely to go through renal elimination

A

ionized

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31
Q

does ionized or non ionized diffuse across lipid bilayer

A

non ionized

can go through: blood brain barrier, Gi tract, placenta

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32
Q

what happens with weak bases in an acidic solution or in a basic solution

A

in acidic solution: weak bases are more ionized and water soluble

in basic solution: weak bases are more non ionized and lipid soluble

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33
Q

what happens to weak acids in acidic and basic solutions

A

in acidic solution: weak acids are more non ionized and lipid soluble

in basic solution: weak acids are more non ionized and water soluble

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34
Q

how to tell by the name if a drug is weak acid or weak base

A

weak acid is paired with pos ion (sodium, calcium or mag)
ex: sodium thiopental

weak base is prepared with neg ion: chloride or sulfate
(lidocaine hydrochloride, morphine sulfate)

35
Q

what are the 3 key plasma proteins

A

albumin, a1 acid glycoprotein, beta globulin

36
Q

what plasma protein primarily binds to acidic drugs but can also bind to some neutral and basic drugs

A

albumin

37
Q

what plasma protein binds to basic drugs

A

a1 acid glycoprotein and beta globulin

38
Q

what conditions will reduce serum albumin concentration

A

liver dz, renal dz, old age, malnutrition, pregnancy

39
Q

what will increase or decrease a1 acid glycoprotein concentration

A

increase: surgical stress, MI, chronic pain, RA, old age

decrease: neonates, pregancy

40
Q

decreased plasma protein binding-> __ cp (plasma drug concentration)

A

increased

41
Q

what is first order kinetics

A

constant fraction of drug is eliminated per unit of time

42
Q

what is zero order kinetics

A

-more drug than enzyme
-constant amount of drug is eliminated per unit of time
-rate of elimination is independent of plasma drug concentration

-ex: aspirin, phenytoin, warfarin, heparin, theophylline

43
Q

phase 1 reactions result in

A

small molecular changes that increase the polarity (water solubility) of a molecule to prepare it for phase 2

44
Q

most phase 1 biotransformations are carried out by what system

A

p450

45
Q

what are the 3 main phase 1 reactions

A

oxidation, reduction and hydrolysis

46
Q

this removes electrons from a compound

A

oxidation

47
Q

this adds electrons to a compound

A

reduction

48
Q

this adds water to a compound to split it apart (usually an ester)

A

hydrolysis

49
Q

function of phase 2 rxn

A

conjugates (adds on) an endogenous, highly polar, water soluble substrate to the molecule

results in water soluble, biologically inactive molecule ready for excretion

50
Q

typical substrates for conjugation reactions include

A

glucuronic acid, glycine, acetic acid, sulfuronic acid, methyl group

51
Q

do all drugs need to do phase 1 rxn before phase 2

A

no can go right to p2

52
Q

enterohepatic circulation

A

some conjugated compounds are excreted in the bile, reactivated in the intestine and then reabsorbed into systemic circulation

53
Q

what are some examples of durgs that undergo enterohepatic circulation

A

diazepam and warfarin

54
Q

extraction ratio

A

a measure of how much of a drug is delivered to clearing organ vs how much of a drug is removed by that organ

ER of 1 means that clearing organ removes 100% of the delivered drug

ER of 0.5 means that the clearning organ removes 50% of the delivered drug

55
Q

increased liver blood flow -> __ clearance

A

increased

called perfusion dependent elimination

56
Q

a drug with a high hepatic extraction ratio means what

A

> 0.7

clearance is dependent on liver blood flow! not hepatic enzyme activity

57
Q

what is low hepatic extration ratio

A

<0.3

58
Q

what is clearance dependent on if drug has low hepatic extraction ratio

A

dependent on the ability of the liver to extract the drug from the blood

59
Q

enzyme induction ->

A

increases clearancee

60
Q

enzyme inhibition->

A

decreases clearance

61
Q

what is the most important mechanism of drug biotransformation in the body

A

p450 system

62
Q

where do the enzymes for p450 reside

A

in the liver in smooth endoplasmic reticulum

63
Q

2 drug classes and 7 drugs that are metabolized by pseudocholinesterase

A

nmb: succinylcholine, mivacurium

ester type local anesthetics: chloroproacine, tetracaine, procaine, benzocaine, cocaine

64
Q

6 drugs metabolized by plasma esterases

A

esmolol
remifentanil
remimidazolam
clevidipine
atracurium
etomidate

65
Q

drug biotransormed by alkaline phosphatase hydrolysis

A

fospropofol

66
Q

pharmacokinetics

A

what the body does to the drug. absorption, distribution, metabolism, elimination

67
Q

phamacobiophysics

A

drugs concentration in the plasma and the effect side (biophase)

68
Q

pharmacodynamics

A

what the drug does to the body. relationship between effect site concentration and clinical effect

69
Q

how is potency measured

A

potency- dose required to achieve a given clinical effect

ed50 and ed90 are measures of potency. represent dose required to achieve a given effect in 50% and 90% of the population respectively

70
Q

what is an inverse agonist vs antagonist

A

inverse: binds to receptor and causes opposite effect of full agonist. negaive efficacy

antagonist: occupies receptor and prevents agonist from binding to it. does not tell the cell to do anything. does not have efficacy

71
Q

competitive antagonism

A

is REVERSIBLE. increasing concentration of agonist can overcome competitive antagonism

ex: atropine, vecuronium, rocuronium

72
Q

noncompetitive antagonism

A

NOT REVERSIBLE. drug binds to receptor- through covalent bonds.

effect cannot be overcome by increasing concentration of an agonist.

only by creating new receptors can the effect of a noncompetitive agonist be reversed. explains why these drugs have a long duration of action

73
Q

examples of noncompetitive antagonism

A

aspirin and phenoxybenzamine

74
Q

ed50

A

effective dose 50
dose that produces expected clinical response in 50% of population

measure of potency

75
Q

td50

A

toxic dose 50- dose that produces toxicity in 50% of the population

76
Q

therapeutic index

A

helps us determine safety margin for desired clinical effect

77
Q

wide vs narrow therapeutic index

A

narrow TI- narrow margin of safety

wide TI- wide margin of safety

78
Q

chirality

A

division of sterochemistry. deals with molecules that have a center of 3- dimensional asymetry

79
Q

where does the asymmetry in chirality usually stem from

A

tetrahedral bonding of carbon- carbon binds to 4 different atoms

80
Q

a molecule with 1 chiral carbon will exist as

A

2 enantiomers- the more chiral carbons in a molecule, the more entantiomers created

81
Q

enantiomers

A

chiral molecules that are non superimposable mirror images of one another.

different entantiomers can produce other clinical effects

82
Q

racemic mixture

A

contains 2 enantiomers in = amounts

about 1/3 of the drugs we give are entantiomers- most are racemic mixtures

83
Q

ex of racemic mixtures

A

bupivicaine, ketamine, iso, des (not sevo)

84
Q
A

october exam (12 decks)

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