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october exam > pharm 1 > Flashcards

pharm 1 Flashcards

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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
when pka and ph are the same
50% of the drug is ionized and 50% is non ionized
26
solubility of ionized drug
hydrophilic and lipophobic
27
non ionized solubility
lipophillic and hydrophobic
28
is ionized or non ionized pharmacologically effective
non ionized
29
is ionized or non ionized more likely to go through hepatic biotransformation
non ionized
30
is ionized or non ionized more likely to go through renal elimination
ionized
31
does ionized or non ionized diffuse across lipid bilayer
non ionized can go through: blood brain barrier, Gi tract, placenta
32
what happens with weak bases in an acidic solution or in a basic solution
in acidic solution: weak bases are more ionized and water soluble in basic solution: weak bases are more non ionized and lipid soluble
33
what happens to weak acids in acidic and basic solutions
in acidic solution: weak acids are more non ionized and lipid soluble in basic solution: weak acids are more non ionized and water soluble
34
how to tell by the name if a drug is weak acid or weak base
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
what are the 3 key plasma proteins
albumin, a1 acid glycoprotein, beta globulin
36
what plasma protein primarily binds to acidic drugs but can also bind to some neutral and basic drugs
albumin
37
what plasma protein binds to basic drugs
a1 acid glycoprotein and beta globulin
38
what conditions will reduce serum albumin concentration
liver dz, renal dz, old age, malnutrition, pregnancy
39
what will increase or decrease a1 acid glycoprotein concentration
increase: surgical stress, MI, chronic pain, RA, old age decrease: neonates, pregancy
40
decreased plasma protein binding-> __ cp (plasma drug concentration)
increased
41
what is first order kinetics
constant fraction of drug is eliminated per unit of time
42
what is zero order kinetics
-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
phase 1 reactions result in
small molecular changes that increase the polarity (water solubility) of a molecule to prepare it for phase 2
44
most phase 1 biotransformations are carried out by what system
p450
45
what are the 3 main phase 1 reactions
oxidation, reduction and hydrolysis
46
this removes electrons from a compound
oxidation
47
this adds electrons to a compound
reduction
48
this adds water to a compound to split it apart (usually an ester)
hydrolysis
49
function of phase 2 rxn
conjugates (adds on) an endogenous, highly polar, water soluble substrate to the molecule results in water soluble, biologically inactive molecule ready for excretion
50
typical substrates for conjugation reactions include
glucuronic acid, glycine, acetic acid, sulfuronic acid, methyl group
51
do all drugs need to do phase 1 rxn before phase 2
no can go right to p2
52
enterohepatic circulation
some conjugated compounds are excreted in the bile, reactivated in the intestine and then reabsorbed into systemic circulation
53
what are some examples of durgs that undergo enterohepatic circulation
diazepam and warfarin
54
extraction ratio
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
increased liver blood flow -> __ clearance
increased called perfusion dependent elimination
56
a drug with a high hepatic extraction ratio means what
> 0.7 clearance is dependent on liver blood flow! not hepatic enzyme activity
57
what is low hepatic extration ratio
<0.3
58
what is clearance dependent on if drug has low hepatic extraction ratio
dependent on the ability of the liver to extract the drug from the blood
59
enzyme induction ->
increases clearancee
60
enzyme inhibition->
decreases clearance
61
what is the most important mechanism of drug biotransformation in the body
p450 system
62
where do the enzymes for p450 reside
in the liver in smooth endoplasmic reticulum
63
2 drug classes and 7 drugs that are metabolized by pseudocholinesterase
nmb: succinylcholine, mivacurium ester type local anesthetics: chloroproacine, tetracaine, procaine, benzocaine, cocaine
64
6 drugs metabolized by plasma esterases
esmolol remifentanil remimidazolam clevidipine atracurium etomidate
65
drug biotransormed by alkaline phosphatase hydrolysis
fospropofol
66
pharmacokinetics
what the body does to the drug. absorption, distribution, metabolism, elimination
67
phamacobiophysics
drugs concentration in the plasma and the effect side (biophase)
68
pharmacodynamics
what the drug does to the body. relationship between effect site concentration and clinical effect
69
how is potency measured
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
what is an inverse agonist vs antagonist
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
competitive antagonism
is REVERSIBLE. increasing concentration of agonist can overcome competitive antagonism ex: atropine, vecuronium, rocuronium
72
noncompetitive antagonism
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
examples of noncompetitive antagonism
aspirin and phenoxybenzamine
74
ed50
effective dose 50 dose that produces expected clinical response in 50% of population measure of potency
75
td50
toxic dose 50- dose that produces toxicity in 50% of the population
76
therapeutic index
helps us determine safety margin for desired clinical effect
77
wide vs narrow therapeutic index
narrow TI- narrow margin of safety wide TI- wide margin of safety
78
chirality
division of sterochemistry. deals with molecules that have a center of 3- dimensional asymetry
79
where does the asymmetry in chirality usually stem from
tetrahedral bonding of carbon- carbon binds to 4 different atoms
80
a molecule with 1 chiral carbon will exist as
2 enantiomers- the more chiral carbons in a molecule, the more entantiomers created
81
enantiomers
chiral molecules that are non superimposable mirror images of one another. different entantiomers can produce other clinical effects
82
racemic mixture
contains 2 enantiomers in = amounts about 1/3 of the drugs we give are entantiomers- most are racemic mixtures
83
ex of racemic mixtures
bupivicaine, ketamine, iso, des (not sevo)
84

october exam (12 decks)

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