Pharmacology - Block 1 Flashcards Preview

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Flashcards in Pharmacology - Block 1 Deck (130):
1

Competitive antagonists - EC50 and Emax

Shift EC50 right, Emax no change

2

Irreversible or non-competitive antagonists - EC50 and Emax

EC50 no change, Emax lower

3

Acidic drugs ion trap on the ___

Basic side

4

pKa - pH =

pKa-pH = log(protonated/unprotonated)

5

Active transport enzyme pumps drugs back out

P-glycoprotein (MDR-1, ABC group)

6

Acidic drugs circulate with

Albumin (liver disease-> need lower dose)

7

Basic drugs circulate with

alpha1-glycoprotein (Crohn's disease-> need larger dose)

8

Brain efflux transporters

P-glycoprotein and OATP

9

Fetal plasma and breast milk are more acid/base

acidic

10

Dose, concentration, vol of dist, bioavailability eqn

Dose = Vd*Co/F

11

T1/2 =

T1/2 = .69/Kel
T1/2 = .69*Vd/CL

12

Slope of logC vs Time

slope = -Kel/2.3

13

CL =

CL = Vd*Kel

14

Maintence Dose / Interval =

Maintence Dose / Interval = Css*CL/F

15

Phase I enzymes located in

smooth ER

16

Phase II enzymes located in

cytosol

17

Cytochrome P450s in descending percentage of drugs metabolized

CYP3A (50%)
CYP2D6 (25%)
CYP2C9 (15%)
1A2, 2E1, 2C19

18

Most ubiquitous protein in liver

FMO3

19

Phase I enzymes need

NADPH

20

List Phase II enzymes

UGT (Glucuronidation)
SULT (Sulfation)
NAT (Acetylation)
Glutithione S-transferases

21

Ethanol induces

CYP2E1

22

Grapefruit juice inhibits

CYP3A

23

Can be inhibited near 0

CYP2D6

24

Not induced or inhibited

FMOs

25

When induced leads to APAP toxicity

2E1

26

NAT-2 (metabolizes, effect of dysfunction)

isoniazid (TB drug)
increased neuropathy

27

CYP2D6 (metabolizes, effect of dysfunction)

antidepressants
codeine->morphine
also, gene duplication-> ultra-fast

28

CYP2C19 (metabolizes, effect of dysfunction)

phenytoin (anti-convulsant)
omeprazole (PPI)
clopidogrel (activated by 2C19, anti-platelet)

29

CYP2C9 (metabolizes, effect of dysfunction)

Warfarin (anti-coagulant)
*3 has bigger impact than *2

30

Vit K Receptor (VKORC1) (drug, effect, clades)

Warfarin inhibits VKORC1,
A-clade=lower dose, B-clade=higher dose

31

Pseudocholinesterase (metabolizes, effect of dysfunction)

succinylcholine (muscle relaxant)

32

TPMT (metabolizes, effect of dysfunction)

6-mercaptopurine (6MP) (cancer drug)

33

P-glycoprotein (drug, effect)

digoxin (cardiac glycoside) (dysfunction increases net uptake)

34

Example of Intracellular steroid receptors

cortisol (travels with CBG) -> diffuses to cytosol, binds to glucocorticoid receptor (GR) -> conformational change releases inhibitory proteins -> binds to GRE on DNA promoter

35

GABA receptor agonist drugs

Benzodiazepines (valium)
Barbiturates (Phenobarbital)

36

Inositol-lipid pathway

GPCR->Gaq-GTP activates PLC -> PLC cleaves PIP2 to IP3 + DAG -> IP3 releases Ca from ER, DAG activates PKC

37

cAMP pathway

GPCR->Gas->adenylyl cyclase->cAMP->PKA->CREB->gene transcription

38

Monomeric G proteins are activated by / turned off by

ON: GEF
OFF: GAP
receptor linked tyrosine kinases

39

MAPKKK cascade

RAS-GTP->Raf->MKK1->ERK->phosphorylates transcription factors

40

Tyrosine kinase inhibitors (EGF receptor)

gefitinib
erlotinib

41

dopamine transported into storage vesicles by

VMAT2, vesicular monoamine transporter 2

42

Metabolic degradation of NE by

Monoamine Oxidase (MAO)
catechol-O-methyltransferase (COMT)

43

Acetylcholine release inhibited by

botulinum toxin

44

alpha1 receptor

Gq - activate PLC
eye (iris), vascular, smooth muscle, vas deferens
contraction and ejaculation

45

alpha2 receptor

Gi - inhibit AC (cAMP), activate PLC in vascular SM
pre-synaptic nerve terminals, CNS
decrease NE release, decrease sympathetic outflow

46

beta1 receptor

Gs - activate AC (cAMP)
cardiac muscle, kidney
increase force, rate, renin release

47

beta2 receptor

Gs - activate AC (cAMP)
arteries, skeletal muscle, liver, bronchi
dilation, glycogenolysis

48

beta3 receptor

Gs - activate AC (cAMP)
adipose tissue
lipolysis

49

Norepinephrine uptake (by NET) blocked by

cocaine

50

Dopamine1 receptor

Kidney - dilation of kidney vasculature

51

Norepinephrine

Adrenergic agonist - direct
Catecholamine
a1, a2, b1
mainly a1 -> cardio effects -> peripheral vasoconstriction, up BP, can cause reflex bradycardia

52

Epinephrine

Adrenergic agonist - direct
Catecholamine
a1, a2, b1, b2
mainly B2 -> cardio effects -> up HR, up CO, increase systolic, decrease diastolic BP, constrict most vasculature but dilate skeletal muscle vasculature, decrease peripheral resistance
Bronchodilation
Hyperglycemia and lipolysis
rapid hypersensitivity relief, co-admin w/ local anesthetic, ophthalmic uses, bradyarrhythmias

53

Isoproterenol

Adrenergic agonist - direct
Catecholamine
b1, b2
CV -> down peripheral resistance, up HR, up CO, down BP
bronchodilation
use in emergency to up HR

54

Dopamine

Adrenergic agonist - direct
Catecholamine
a1, b1, DA1
CV_> low dose, dilation of renal and mesenteric arteries
med dose = up HR, CO
high dose = vasoconstriction and up peripheral resistance
use in heart failure, shock

55

Dobutamine

Adrenergic agonist - direct
Catecholamine
b1
CV-> up HR, CO, no change in PR
use in cardiac decomp, and stress testing

56

Methyldopa

Adrenergic agonist - direct
Catecholamine
a2
orally bioavailable, prodrug
CNS-> decrease sympathetic outflow
down PR, HR, CO
use as anti-hypertensive in pregnant women, eclampsia
side effect = rebound hypertension, sedation, dry mouth, edema

57

Phenylephrine

Adrenergic agonist - direct
a1
up BP, down HR, down blood flow
use as nasal decongestant
also aphthalmic, w/ local anesthetics, and hypotension

58

Clonidine

Adrenergic agonist - direct
a2
orally active
CNS -> reduce sympathetic outflow -> down PR, HR, CO
use as anti-hypertensive
side effects = edema, sedation, dry mouth, rebound hypertension

59

Albuterol

Adrenergic agonist - direct
b2
short acting bronchodilator (asthma)
side effect = tremor, tachycardia, anxiety

60

Salmeterol

Adrenergic agonist - direct
b2
long acting bronchodilator
use in COPD, asthma

61

Tyramine

Adrenergic agonist - INdirect (release NE)
found in some foods
metabolized by MAO

62

Amphetamine

Adrenergic agonist - Mixed acting
CNS stimulant and weakly peripheral a and b
orally available
also weakly blocks NET
depresses appetite, narcolepsy, ADD

63

Ephedrine

Adrenergic agonist - Mixed acting
CNS releases NE and direct a and b agonist
orally effective
used to be in herbals, now FDA banned

64

Pseudoephedrine

Adrenergic agonist - Mixed acting
direct a1, with little b2 + release NE
orally available, but less CNS
use nasal decongestant (a1 effect)

65

Guanethidine
Guanadrel

Adrenergic neuron blockers
inhibit NE release
Guanethidine does not enter CNS
long acting anti-essential hypertensive
limited use b/c side effects -> orthostatic hypotension, sex function, edema, diarrhea

66

Reserpine

Adrenergic neuron blocker
Inhibits VMAT2
long-acting, orally active, use as anti-hypertensive, rarely used
has CNS side-effects, depression, suicide
also orthostatic hypotension, diarrhea

67

Phenoxybenzamine

Adrenergic receptor blocker
a1, a2
irreversible antagonist
orally active, long duration
vasodilation
use in pheochromocytoma

68

Phentolamine

Adrenergic receptor blocker
a1, a2
competitive antagonist
orally active, shorter duration
vasodilation
use in HTN, pheochromocytoma

69

Prazosin

Adrenergic receptor blocker
a1
orally active, competitive (prototypical)
minimal tachycardia
decrease vascular tone
produces favorable lipid profile
use in hypertension, heart failure, and BPH (prostate)

70

Tamsulosin

Adrenergic receptor blocker
a1, a1A > a1B
effective for BPH (prostate), less side effects

71

Propranolol

Adrenergic receptor blocker
B1, B2
competitive
use in hypertension, angina, myocardial infarction, pheochromocytoma, migraine
side effects= bradycardia, up airway resistance, mask hypoglycemia, sedation

72

Timolol

Adrenergic receptor blocker
B1, B2
competitive
similar to propranolol
also used for glaucoma to decrease intraocular pressure

73

Metoprolol

Adrenergic receptor blocker
B1 (prototypical)
competitive, more B1 selective at low doses
similar to propranolol, also used for heart failure
less bronchoconstriction than propranolol

74

Atenolol

Adrenergic receptor blocker
B1
similar to Metoprolol
once a day, orally
does not enter CNS

75

Labetalol

Adrenergic receptor blocker
a1, b1, b2
use in essential hypertension and hypertensive emergencies

76

Carvedilol

Adrenergic receptor blocker
a1, b1, b2
also has anti-oxidant and anti-inflammatory effects
use in chronic heart failure, hypertension, acute MI

77

Muscarinic receptor functions

Eye - contract ciliary muscle (lens), contract iris (miosis)
Heart - decrease rate
Lung - contrict bronchi, promote secretion
Bladder / GI - promote voiding/secretion/motility
Sweat glands - sweating
-Blood vessels - vasodilation (via NO)

78

Nicotinic receptor functions

Nm = skeletal muscle depolarization
Nn = autonomic ganglia, adrenals
CNS = control of NT release

79

Bethanechol

Muscarinic agonist - direct
choline ester
primarily on GI/GU tract, peripherally restricted
used orally for urinary retention

80

Pilocarpine

Muscarinic agonist - direct
CNS available
used orally to treat xerostomia (dry mouth)
miotic agent for glaucoma

81

Edrophonium

AChE inhibitor - reversible (non-subtrate)
rapid onset and short duration
IV (not oral)
use in diagnosis of myasthenia gravis
reversal of paralysis by neuromuscular blocking drugs

82

Physostigmine

AChE inhibitor - reversible (substrate)
slowly reversible (hours)
CNS available
used for glaucoma and to reverse toxicity of antimuscarinic drugs

83

Neostigmine

AChE inhibitor - reversible (substrate)
slowly reversible (hours)
NOT CNS available
used for treatment of myasthenia gravis (oral)
prevention of post-op gut atony
reversal of paralysis by NMJ blockers

84

Sarin

Nerve gas
irreversible AChE inhibitor
SLUDGE, hypotension, bradycardia, visual blurryness,
medullary respiratory center depression, muscle paralysis
Antidotes: atropine, pralidoxime

85

Malathion

Insecticide (rapidly detoxed in animals)
irreversible AChE inhibitor
SLUDGE, hypotension, bradycardia, visual blurryness,
medullary respiratory center depression, muscle paralysis
Antidotes: atropine, pralidoxime

86

Atropine

Muscarinic receptor antagonist
used to treat bradycardia
opthalmic use for mydriasis (dilation) and cylcoplegia (paralyze accomodation)
long duration
use in anesthesia to block vagal response
and treat anti-AChE toxicity

87

Scopolamine

Similar to Atropine (Muscarinic antagonist)
greater CNS penetration
used to treat motion sickness and vestibular disease
transdermal patch

88

Ipratropium

Muscarinic antagonist
used to treat COPD (inhalation)
NO CNS penetration
reduce bronchial constriction

89

Tropicamide

Muscarinic antagonist
used as opthalmic to mydriasis and cycloplegia
fast onset and short duration

90

Oxybutynin

Muscarinic antagonist
used to treat overactive bladder and incontinence
lots of anti-muscarinic side effects (xerostomia)

91

Darifenacin

Similar to Oxybutynin (Muscarinic antagonist)
M3 selective
less CNS effects

92

Glycopyrrolate

Muscarinic antagonist
used to block parasympatheticomimetic effects during reversal of NM blockade with anti-AChE agents
NO CNS effects

93

Muscarinic antagonist side-effects

Hot, dry, red, blurry, drowsy
high []-> ataxia, excitement, delerium
can use physotigmine for toxicity reversal

94

AChE inhibitor side effects

SLUDGE, hypotension, bradycardia, blurred vision
SLUDGE = salivation, lacrimation, urination, defecation, GI upset, emesis

95

Rocuronium

Neuromuscular blocker (non-depolarizing, competitive)
intermediate duration, rapid onset
used for intubation
metabolized by liver

96

Atracurium

Neuromuscular blocker (non-depolarizing, competitive)
intermediate duration
spontaneously degrades
minimal CV effect, slight histamine release

97

Vecuronium

Neuromuscular blocker (non-depolarizing, competitive)
intermediate duration
liver metabolism
no CV or histamine effects

98

Pancuronium

Neuromuscular blocker (non-depolarizing, competitive)
long duration
renal excretion
slight up BP, slight histamine release

99

Succinylcholine

Neuromuscular blocker (deploarizing)
NAChR agonist
NO CNS action
ultra short duration, rapid onset
used for intubation
can be problem if liver problem
side-effects = prolonged apnea, malignant hyperthermia (genetic), muscle pain, hyperkalemia

100

Non-depolarizing neuromuscular blocker side-effects

Prolonged apnea, cardiovascular collapse (from histamine)
toxicity can be reversed with neostigmine or edrophonium (co administer glycopyrrolate to reduce non-CNS muscarinic actions)

101

To dilate pupils

muscarinic antagonists
a1 agonists
epinephrine, phenylephrine, atropine, tropicamide

102

Treat glaucoma

muscarinic agonist
B antagonist
AChE inhibitors
timolol, pilocarpine, physostigmine

103

Restrict local drug washout

a1 agonist
epinephrine, phenylephrine

104

Treat nasal congestion

a1 agonist
phenylephrine, pseudoephedrine

105

Treat BPH (Prostate)

a1 antagonist
prazosin, tamsulosin

106

Treat bradycardia

muscarinic antagonist
B1 agonist
epinephrine, isproterenol, dobutamine, atropine

107

Treat tachycardia

muscarinic agonist
B1 antagonist

108

Treat shock, anaphylaxis

catecholamine agonist

109

Treat hypertension

B antagonists
isoproterenol, methyldopa, clonidine, phentolamine, prazosin, propranolol, timolol, metoprolol, atenolol, carvedilol

110

Cardiac stress test

B1 agonist
dobutamine

111

Treat Pheochromocytoma

a agonist
phenoxybenzamine, phentolamine, propranolol, timolol

112

Treat asthma

B2 agonist
muscarinic antagonist
epinephrine, albuterol, salmeterol, ipratropium

113

Treat GI hypermotility

muscarinic antagonist
oxybutynin, darifenacin

114

Treat urinary retention

muscarinic agonist
AChE inhibitor
bethanechol, neostigmine

115

a1 drugs

phenylephrine
blockers: prazosin, tamsulosin

116

a2 drugs

clonidine, methyldopa

117

a1,2 drugs

blockers: phenoxybenzamine, phentolamine

118

b1 drugs

dobutamine
blockers: metoprolol, atenolol

119

b2 drugs

albuterol, salmeterol

120

b1,2 drugs

isoproterenol
blockers: propranolol, timolol

121

a,b drugs

norepinephrine, epinephrine

122

a1,b1,b2 drugs

blockers: labetalol, carvedilol

123

DA1,a1,a2 drugs

dopamine

124

NE drugs

tyramine
blockers: guanethidine, guanadrel, reserpine

125

NE+a,b drugs

amphetamine, ephedrine, pseudoephedrine

126

M drugs

bethanechol, pilocarpine
blockers: atropine, scopolamine, ipratropium, tropicamide, oxybutynin, glycopyrrolate

127

M3 drugs

blockers: darifenacin

128

AChE drugs

blockers: edrophonium, physostigmine, neostigmine, sarin, malathion

129

nAChR drugs

blockers: rocuronium, atracurium, vecuronium, pancuronium, succylcholine

130

[LR]/RT =

[LR]/RT = [L] / (Kd + [L])