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z S1: Module > HTN-2 > Flashcards

HTN-2 Flashcards

1
Q

Type 4: L-type calcium channels are sensitive to what

A

dihydropyridine (vascular)
phenylalkylamine (heart)
benzothiazepine (heart and vascular)

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2
Q

Diphydropyrid”INE” medicines

A

Amlodipine
Nifedipine
Felodipine

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3
Q

Phenylalkyl”AMI”ne

A

Verapamil

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4
Q

Benzoth”IAZE”pine

A

Diltiazem

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5
Q

An increase in cytosolic Ca2+ in vascular tissue causes what to smooth muscle

A

sustained contraction

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6
Q

In cardiac cells Ca2+ bind to what to cause contraction

A

troponin C

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7
Q

Voltage-gated calcium channels excite what

A

skeletal, smooth, and cardiac muscle

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8
Q

What do voltage-gated calcium channels regulate

A

Aldosterone in the adrenal cortex

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9
Q

What do voltage-gated calcium channels conduct

A

pacemaker signals

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10
Q

dihydropyridine, phenylalkylamine, benzothiazepine have a greater frequency of achieving blood pressure control with Ca2+ channel blockers as monotherapy in what patients

A

african americans
elderly

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11
Q

What are the adverse effects of dihydropyridine, phenylalkylamine, and benzothiazepine

A

-invoke baroreceptor reflex-mediated sympathetic discharge, dihydropyridines causing tachycardia
-bradycardia and sinoatrial arrest
-peripheral edema

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12
Q

What does hydralazine cause

A

tachycardia and tachyphylaxis

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13
Q

Combination therapy with arteriolar vasodilators

A

beta receptor antagonist, diuretic, vasodiltor

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14
Q

MOA of hydralazine

A

directly relaxes arteriolar smooth muscle

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15
Q

Reflexes of hydralazine

A

NE (increase HR and contractility)
Increased plasma renin activity and fluid retention

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16
Q

Pharmacological effects of hydralazine

A

decrease in vascular resistance in arterioles

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17
Q

Arteriolar vasodilators have low bioavailability ___ in fast acetylators and ___ in slow acetylators

A

16%
35%

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18
Q

The acetylated compound of arteriolar vasodilators is inactive meaning the dose necessary to produce a systemic effect is ______ in fast acetylators

A

larger

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19
Q

In what hypertensive emergency do you use hydralazine

A

pregnant women (preeclampsia)

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20
Q

What are two main adverse effects of hydralazine

A

Extensions of the pharmacological effects of the drug (palpitations, tachycardia, angina pectoris, myocardial ischemia)

Immunological Reactions: drug-induced lupus syndrome

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21
Q

Is minoxidil a pro-drug

A

yes

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22
Q

MOA of minoxidil

A

K+ channel permitting K+ efflux

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23
Q

Pharmacological effects of minoxidil

A

arteriolar vasodilation
myocardial contractility and in cardiac output
vasodilate renal artery

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24
Q

Treatment uses for minoxidil

A

severe hypertension
renal insufficienct
children

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25
Q

Major adverse effects of minoxidil

A

retention of salt and water
cardiovascular effects
myocardial ischemia
beta-adrenergic blocker
hypertrichosis

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26
Q

What is a rare side effect of minoxidil

A

stevens-johnson syndrome

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27
Q

The influx of calcium can occur through what 4 sites

A

receptor-operated channels
Na/Ca exchange
Leak pathways
potential dependent channels

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28
Q

Arterial smooth muscle is more or less sensitive to ca2+ channels than venous smooth muscle

A

more

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29
Q

1,4-DHP are usually hydrophobic or hydrophilic

A

hydrophobic

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30
Q

What is essential for 1,4-DHP activity

A

pharmacophoric ring

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31
Q

What is at position 1 of 1,4-DHPs and has to be unsubstituted

A

nitrogen

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32
Q

What is at position 4 of 1,4-DHPs

A

aryl substituent (ortho or meta position)

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33
Q

What is the difference between nifedipine and felodipine compared to amlodipine

A

amlodipine is basic because it has an amine

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34
Q

At physiologic pH verapamil and diltiazem are primarily __________ whereas 1,4-DHPs are primarily ____________

A

ionized
unionzied

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35
Q

Rapid ester hydrolysis inactivates what drug

A

clevidipine (inactive metabolite is charge and not lipophilic anymore)

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36
Q

What drug is the only one in its class and is well absorbed from the GI tract and is metabolized in the GI mucosa and in the liver

A

hydralazine

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37
Q

Minoxidil is not an active hypotensive drug until it is metabolized by hepatic thermolabile _________ _______________ (SULT1A1) to minoxidil N-O-sulfate

A

phenol sulfotransferase

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38
Q

Hyperglycemic agents work by preventing release of ______ from the pancreas

A

insulin

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39
Q

What are the medicine indications for African Americans

A

increased need for combo treatment
lower renin
thiazide and CCB first line option

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40
Q

Geriatric (>75) medicine indications

A

often isolated SBP
mat need to be more conservative with tx goals especially if orthostatic hypotension, high fall risk, or ADEs

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41
Q

Children medicine indications

A

lifestyle interventions is key
Goal to reduce BP below <95th percentile (<90 if comorbidities are present)

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42
Q

Indications of orthostatic/postural hypotension

A

laying or sitting to standing
BP drop in >10 mmHg with dizziness
Titrate slow and avoid volume depletion

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43
Q

Pregnancy chronic hypertension (early onset)

A

present before pregnancy or within 20 weeks of pregnancy

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44
Q

Gestational hypertension or pregnancy induced hypertension (PIH): early onset

A

hypertension onset (>140/90)
goes away after delivery
no previous hypertension

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45
Q

Pregnancy late onset HTN: preeclampsia

A

BP >140/80 with proteinuria after 20 wks gestation
(bed rest , use hydralazine or labetalol in BP >105)
Could use ASA in high risk patients

46
Q

Pregnancy late onset HTN: eclampsia

A

Onset of convulsions in preeclampsia
medical emergency
delivery indicated

47
Q

What are the typical treatments of pregnancy HTN

A

methyldopa, labetolol, metoprolol, carvedilol

48
Q

Resistant HTN is difficult to treat. We should max the _________ and then add an aldosterone antagonist as first option

A

trifecta

49
Q

Resistant hypertension indications

A

-failure to achieve BP goal despite adherence to full doses of 3 drug regimen
-volume overload
-use aldosterone antagonists as next option

50
Q

What is the steps of managing resistant HTN

A

-Max trifecta
-Add mineralcoricoid receptor antagonist (MRA) spironolactone
-Add beta blocker
-Add hydralazine (vasodilator)
-Sub minoxidil for hydralazine

51
Q

MOA of beta adrenergic receptor antagonists

A

reduction in myocardial contractility and heart rate to reduce renin secretion and RAS activity

52
Q

What does the efficacy of beta-blockers depend on

A

-lipid solubility and membrane-stabilizing properties
-selectivity for the beta 1 adrenergic receptor subtype
-presence of partial agonist or intrinsic sympathomimetic activity (ISA)

53
Q

What are the classification of these drugs: nadolol, propranolol, pindolol

A

1st generation non-selective

54
Q

What are the classification of these drugs: acebutolol, esmolol, atenolol, metoprolol, bisoprolol

A

2nd generation beta 1 selective

55
Q

What are the classification of these drugs: carvedilol and lavetalol

A

3rd generation non-selective

56
Q

What are the classification of these drugs: nebivolol

A

3rd generation beta 1 selective

57
Q

______ blockers are preferred drugs for patients with myocardial infarction, ischemic heart disease, congestive heart failure

A

beta
(less response in elderly and african americans)

58
Q

Contraindications for beta-adrenergic receptor antagonists

A

contraindication for asthma, SA or AV nodal dysfunction, insulin-dependent diabetes

59
Q

Sudden discontinuation of beta blockers produce what

A

rebound hypertension (needs to be slowly backed off)

60
Q

What are the classification of these drugs: prazosin, doxazosin, terazosin

A

alpha 1 adrenergic receptor antagonists

61
Q

What kind of therapy are alpha 1 adrenergic receptor antagonists not used for

A

monotherapy (need diuretic, beta blocker, etc with it)

62
Q

alpha 1 adrenergic receptor antagonists are good for hypertensive patients with what but are not used for what

A

for: benign prostatic hyperplasia
not: pheochromocytoma

63
Q

major adverse effects of alpha 1 adrenergic receptor antagonists

A

orthostatic hypotenstion
doxazosin increase risk of CHF if monotherapy (retention of salt and water)

64
Q

Labetalol has how many isomers

A

4

65
Q

Labetalol is _____ antagonist and nonselective _______ antagonist with partial agonist activity

A

alpha 1
beta

66
Q

Disadvantage of labetalol

A

fixed-dose combination products: alpha receptor antagonism is unpredictable and varies

67
Q

What is labetalol FDA approved for

A

Eclampsia, preeclampsia, hypertension, hypertensive emergencies (pregnancy)

68
Q

Carvedilol is a ____ blocker but has ________ receptor antagonist activity

A

beta
alpha 1
(a1 to B is 1:10)

69
Q

What is carvedilol used for

A

hypertension and symptomatic heart failure

70
Q

MOA of alpha 2 adrenergic receptor agonists (-clonidine catapres)

A

stimulate a2A receptors in the brainstem and decrease plasma concentrations of NE

71
Q

What can alpha 2 adrenergic receptor agonists cause

A

lower arterial pressure
postural hypotension
reduction in HR and SV (cause congestive heart failure)

72
Q

What are the major adverse effects of alpha 2 adrenergic receptor agonists

A

symptomatic bradycardia and sinus arrest
sedation and xerostomia
postural hypotension and erectile dysfunction

73
Q

What kind of sympatholytic agent is methyldopa

A

centrally acting activator

74
Q

Methyldopa is a ________ that exerts its antihypertensive action via active metabolite

A

prodrug

75
Q

Methyldopa is an __________ at presynaptic alpha2 adrenergic receptors

A

agonist

76
Q

Can methyldopa be used in hypertension for pregnacy

A

yes

77
Q

Main CNS adverse effect of methyldopa

A

diminution in psychic energy

78
Q

NE and EPI are endogenous substrates known as what active substances

A

catecholamines

79
Q

What three drugs are antihypertensive quinazoline selective alpha 1 blockers

A

prazosin
terazosin
doxasosin

80
Q

Alpha 1 blockers possess a ___________ effect which means that orthtostatic hypotension frequently occurs within the first couple doses of the drug

A

first-dose
(decreased by increasing dose slowly)

81
Q

What parts of alpha 1 selective adrenergic blockers are part of the drug class pharmacophore

A

quinazoline ring (2 rings, one has two nitrogens)
Piperazing ring (ring with 2 nitrogens)
Acyl Moiety

82
Q

What part of alpha 1 selective adrenergic blockers changes with each drug

A

acyl moiety (attached to second nitrogen on piperazine)

83
Q

alpha 1 selective adrenergic blockers block the effect of sympathetic nerves on blood vessels by selectively binding to alpha 1 adrenoceptors located where

A

vascular smooth muscle

84
Q

Do alpha blockers dilate both arteries and veins

A

yes because they are both innervated by the sympathetic adrenergic nerves (used for stress)

85
Q

Vasodilation via alpha 1 blockers lower peripheral vascular resistance to maintain cardiac output preventing __________ more effectively when compared to BB

A

bradycardia

86
Q

How many chiral centers and stereoisomers does carvedilol have

A

one chiral
2 stereoisomer

87
Q

How many chiral centers and stereoisomers does labetalol have

A

2 chiral
4 stereoisomers

88
Q

Carvedilol has a 10 to 100 fold alpha 1 blocking activity due to the presence of the _________________ amine pharmacophore

A

aryloxypropanol

89
Q

What group in labetalol is responsible for its alpha-adrenergic blocking effect

A

methyl attached to N-arylalkyl

90
Q

Dilevalol is a ________ isomer which is a mixed non-selective beta-adrenergic receptor blocker and selective alpha 1 blocker

A

RR

91
Q

Hypertension is sometimes caused by emotional stress which causes ______ blockers to be effective

A

beta

92
Q

When using BB in treating hypertension caused by pheochromocytoma this results in elevated circulating _______________

A

catecholamines

93
Q

The first-generation nonselective beta adrenergic blockers all have what two things and have no _______ substituents

A

aryloxypropanolamine pharmacophore and 2 rings
ortho

94
Q

The first-generation beta 1 selective adrenergic blockers all have what and what kind of substituents

A

one ring
para

95
Q

beta 1 selective adrenergic blockers are characterized by the presence of a substituent at _______ position of the aryloxy ring

A

para

96
Q

aryloxypropanolamine BBs are active in the ___ absolute configuration

A

S

97
Q

What is the stereochemical nomenclature difference between arylethanolamines and aryloxypropanolamines

A

aryloxypropanolamines have an extra oxygen atom which changes the absolute configuration to the S stereoisomer

98
Q

Nebivolol is a cardioselective beta 1 receptor blocker that differs chemically and pharmacologically from other BBs because it has a bis-p-substituted ________________ where the oxymethylene bridge is part of the ring

A

aryloxypropanolamines

99
Q

Nebivolol is highly cardioselective at low doses, but at higher doses, it loses its cardioselectivity and block both ______ and ______ receptors

A

beta 1
beta 2

100
Q

Nebivolol also acts on the vascular endothelium by stimulating ______________ synthase which induces ____-mediated vasodilation

A

nitric oxide
NO

101
Q

Patients with DM, erectile dysfunction, and vascular disease may have abnormal endothelial function, and nebivolol is more effective in these population due to its ____-induced vasodilatory effect

A

NO

102
Q

What short-acting cardioselective beta 1 blocker is administered by infusion because it rapidly excretes as a zwitterionic metabolite

A

esmolol

103
Q

What makes esmolol susceptible to hydrolysis by serum esterases to inactive metabolite and readily excreted as a zwitterion

A

methyl ester of a carboxylic acid

104
Q

The more lipophilic drugs are primarily cleared by the _______ whereas hydrophilic agents are cleared by the _______

A

liver
kidney

105
Q

____________ is not cardioselective when taken by patients who are poor CYP2D6 metabolizers

A

Nebivolol

106
Q

What amino acid does methyldopa most closely mimic causing the methyldopa to use its carrier to transport it across the BBB

A

tyrosine

107
Q

Which two drugs are used alone or in combination with other antihypertensive drugs to manage severe hypertension in patients that fail to respond to therapy with a stage 1 drug

A

methyldopa
clonidine

108
Q

____________ is structurally and chemically related to L-DOPA and the catecholamines. Also at physiological pH, it is found under zwitterion form

A

methyldopa

109
Q

Methyldopa is unstable in the presence of ___________ agents, and since they are closely related to catecholamines, patients with asthma can experience _________ hypersensitivity reactions

A

oxidative (pH and light)
sulfite

110
Q

Steric crowding by the bulky ortho-chlorine groups in clonidine does not permit a __________ conformation of the two rings

A

coplanar

111
Q

Methyldopa is transported across the BBB and then is changed in order to produce its effect, what kind of drug is this and why does it do this

A

prodrug
needs to mimic tyrosine before crossing barrier, also needs to be more lipophilic

z S1: Module (8 decks)

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