HTN-2 Flashcards
1
Q
Type 4: L-type calcium channels are sensitive to what
A
dihydropyridine (vascular)
phenylalkylamine (heart)
benzothiazepine (heart and vascular)
2
Q
Diphydropyrid”INE” medicines
A
Amlodipine
Nifedipine
Felodipine
3
Q
Phenylalkyl”AMI”ne
A
Verapamil
4
Q
Benzoth”IAZE”pine
A
Diltiazem
5
Q
An increase in cytosolic Ca2+ in vascular tissue causes what to smooth muscle
A
sustained contraction
6
Q
In cardiac cells Ca2+ bind to what to cause contraction
A
troponin C
7
Q
Voltage-gated calcium channels excite what
A
skeletal, smooth, and cardiac muscle
8
Q
What do voltage-gated calcium channels regulate
A
Aldosterone in the adrenal cortex
9
Q
What do voltage-gated calcium channels conduct
A
pacemaker signals
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
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
12
Q
What does hydralazine cause
A
tachycardia and tachyphylaxis
13
Q
Combination therapy with arteriolar vasodilators
A
beta receptor antagonist, diuretic, vasodiltor
14
Q
MOA of hydralazine
A
directly relaxes arteriolar smooth muscle
15
Q
Reflexes of hydralazine
A
NE (increase HR and contractility)
Increased plasma renin activity and fluid retention
16
Q
Pharmacological effects of hydralazine
A
decrease in vascular resistance in arterioles
17
Q
Arteriolar vasodilators have low bioavailability ___ in fast acetylators and ___ in slow acetylators
A
16%
35%
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
19
Q
In what hypertensive emergency do you use hydralazine
A
pregnant women (preeclampsia)
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
21
Q
Is minoxidil a pro-drug
A
yes
22
Q
MOA of minoxidil
A
K+ channel permitting K+ efflux
23
Q
Pharmacological effects of minoxidil
A
arteriolar vasodilation
myocardial contractility and in cardiac output
vasodilate renal artery
24
Q
Treatment uses for minoxidil
A
severe hypertension
renal insufficienct
children
25
Major adverse effects of minoxidil
retention of salt and water
cardiovascular effects
myocardial ischemia
beta-adrenergic blocker
hypertrichosis
26
What is a rare side effect of minoxidil
stevens-johnson syndrome
27
The influx of calcium can occur through what 4 sites
receptor-operated channels
Na/Ca exchange
Leak pathways
potential dependent channels
28
Arterial smooth muscle is more or less sensitive to ca2+ channels than venous smooth muscle
more
29
1,4-DHP are usually hydrophobic or hydrophilic
hydrophobic
30
What is essential for 1,4-DHP activity
pharmacophoric ring
31
What is at position 1 of 1,4-DHPs and has to be unsubstituted
nitrogen
32
What is at position 4 of 1,4-DHPs
aryl substituent (ortho or meta position)
33
What is the difference between nifedipine and felodipine compared to amlodipine
amlodipine is basic because it has an amine
34
At physiologic pH verapamil and diltiazem are primarily __________ whereas 1,4-DHPs are primarily ____________
ionized
unionzied
35
Rapid ester hydrolysis inactivates what drug
clevidipine (inactive metabolite is charge and not lipophilic anymore)
36
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
hydralazine
37
Minoxidil is not an active hypotensive drug until it is metabolized by hepatic thermolabile _________ _______________ (SULT1A1) to minoxidil N-O-sulfate
phenol sulfotransferase
38
Hyperglycemic agents work by preventing release of ______ from the pancreas
insulin
39
What are the medicine indications for African Americans
increased need for combo treatment
lower renin
thiazide and CCB first line option
40
Geriatric (>75) medicine indications
often isolated SBP
mat need to be more conservative with tx goals especially if orthostatic hypotension, high fall risk, or ADEs
41
Children medicine indications
lifestyle interventions is key
Goal to reduce BP below <95th percentile (<90 if comorbidities are present)
42
Indications of orthostatic/postural hypotension
laying or sitting to standing
BP drop in >10 mmHg with dizziness
Titrate slow and avoid volume depletion
43
Pregnancy chronic hypertension (early onset)
present before pregnancy or within 20 weeks of pregnancy
44
Gestational hypertension or pregnancy induced hypertension (PIH): early onset
hypertension onset (>140/90)
goes away after delivery
no previous hypertension
45
Pregnancy late onset HTN: preeclampsia
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
Pregnancy late onset HTN: eclampsia
Onset of convulsions in preeclampsia
medical emergency
delivery indicated
47
What are the typical treatments of pregnancy HTN
methyldopa, labetolol, metoprolol, carvedilol
48
Resistant HTN is difficult to treat. We should max the _________ and then add an aldosterone antagonist as first option
trifecta
49
Resistant hypertension indications
-failure to achieve BP goal despite adherence to full doses of 3 drug regimen
-volume overload
-use aldosterone antagonists as next option
50
What is the steps of managing resistant HTN
-Max trifecta
-Add mineralcoricoid receptor antagonist (MRA) spironolactone
-Add beta blocker
-Add hydralazine (vasodilator)
-Sub minoxidil for hydralazine
51
MOA of beta adrenergic receptor antagonists
reduction in myocardial contractility and heart rate to reduce renin secretion and RAS activity
52
What does the efficacy of beta-blockers depend on
-lipid solubility and membrane-stabilizing properties
-selectivity for the beta 1 adrenergic receptor subtype
-presence of partial agonist or intrinsic sympathomimetic activity (ISA)
53
What are the classification of these drugs: nadolol, propranolol, pindolol
1st generation non-selective
54
What are the classification of these drugs: acebutolol, esmolol, atenolol, metoprolol, bisoprolol
2nd generation beta 1 selective
55
What are the classification of these drugs: carvedilol and lavetalol
3rd generation non-selective
56
What are the classification of these drugs: nebivolol
3rd generation beta 1 selective
57
______ blockers are preferred drugs for patients with myocardial infarction, ischemic heart disease, congestive heart failure
beta
(less response in elderly and african americans)
58
Contraindications for beta-adrenergic receptor antagonists
contraindication for asthma, SA or AV nodal dysfunction, insulin-dependent diabetes
59
Sudden discontinuation of beta blockers produce what
rebound hypertension (needs to be slowly backed off)
60
What are the classification of these drugs: prazosin, doxazosin, terazosin
alpha 1 adrenergic receptor antagonists
61
What kind of therapy are alpha 1 adrenergic receptor antagonists not used for
monotherapy (need diuretic, beta blocker, etc with it)
62
alpha 1 adrenergic receptor antagonists are good for hypertensive patients with what but are not used for what
for: benign prostatic hyperplasia
not: pheochromocytoma
63
major adverse effects of alpha 1 adrenergic receptor antagonists
orthostatic hypotenstion
doxazosin increase risk of CHF if monotherapy (retention of salt and water)
64
Labetalol has how many isomers
4
65
Labetalol is _____ antagonist and nonselective _______ antagonist with partial agonist activity
alpha 1
beta
66
Disadvantage of labetalol
fixed-dose combination products: alpha receptor antagonism is unpredictable and varies
67
What is labetalol FDA approved for
Eclampsia, preeclampsia, hypertension, hypertensive emergencies (pregnancy)
68
Carvedilol is a ____ blocker but has ________ receptor antagonist activity
beta
alpha 1
(a1 to B is 1:10)
69
What is carvedilol used for
hypertension and symptomatic heart failure
70
MOA of alpha 2 adrenergic receptor agonists (-clonidine catapres)
stimulate a2A receptors in the brainstem and decrease plasma concentrations of NE
71
What can alpha 2 adrenergic receptor agonists cause
lower arterial pressure
postural hypotension
reduction in HR and SV (cause congestive heart failure)
72
What are the major adverse effects of alpha 2 adrenergic receptor agonists
symptomatic bradycardia and sinus arrest
sedation and xerostomia
postural hypotension and erectile dysfunction
73
What kind of sympatholytic agent is methyldopa
centrally acting activator
74
Methyldopa is a ________ that exerts its antihypertensive action via active metabolite
prodrug
75
Methyldopa is an __________ at presynaptic alpha2 adrenergic receptors
agonist
76
Can methyldopa be used in hypertension for pregnacy
yes
77
Main CNS adverse effect of methyldopa
diminution in psychic energy
78
NE and EPI are endogenous substrates known as what active substances
catecholamines
79
What three drugs are antihypertensive quinazoline selective alpha 1 blockers
prazosin
terazosin
doxasosin
80
Alpha 1 blockers possess a ___________ effect which means that orthtostatic hypotension frequently occurs within the first couple doses of the drug
first-dose
(decreased by increasing dose slowly)
81
What parts of alpha 1 selective adrenergic blockers are part of the drug class pharmacophore
quinazoline ring (2 rings, one has two nitrogens)
Piperazing ring (ring with 2 nitrogens)
Acyl Moiety
82
What part of alpha 1 selective adrenergic blockers changes with each drug
acyl moiety (attached to second nitrogen on piperazine)
83
alpha 1 selective adrenergic blockers block the effect of sympathetic nerves on blood vessels by selectively binding to alpha 1 adrenoceptors located where
vascular smooth muscle
84
Do alpha blockers dilate both arteries and veins
yes because they are both innervated by the sympathetic adrenergic nerves (used for stress)
85
Vasodilation via alpha 1 blockers lower peripheral vascular resistance to maintain cardiac output preventing __________ more effectively when compared to BB
bradycardia
86
How many chiral centers and stereoisomers does carvedilol have
one chiral
2 stereoisomer
87
How many chiral centers and stereoisomers does labetalol have
2 chiral
4 stereoisomers
88
Carvedilol has a 10 to 100 fold alpha 1 blocking activity due to the presence of the _________________ amine pharmacophore
aryloxypropanol
89
What group in labetalol is responsible for its alpha-adrenergic blocking effect
methyl attached to N-arylalkyl
90
Dilevalol is a ________ isomer which is a mixed non-selective beta-adrenergic receptor blocker and selective alpha 1 blocker
RR
91
Hypertension is sometimes caused by emotional stress which causes ______ blockers to be effective
beta
92
When using BB in treating hypertension caused by pheochromocytoma this results in elevated circulating _______________
catecholamines
93
The first-generation nonselective beta adrenergic blockers all have what two things and have no _______ substituents
aryloxypropanolamine pharmacophore and 2 rings
ortho
94
The first-generation beta 1 selective adrenergic blockers all have what and what kind of substituents
one ring
para
95
beta 1 selective adrenergic blockers are characterized by the presence of a substituent at _______ position of the aryloxy ring
para
96
aryloxypropanolamine BBs are active in the ___ absolute configuration
S
97
What is the stereochemical nomenclature difference between arylethanolamines and aryloxypropanolamines
aryloxypropanolamines have an extra oxygen atom which changes the absolute configuration to the S stereoisomer
98
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
aryloxypropanolamines
99
Nebivolol is highly cardioselective at low doses, but at higher doses, it loses its cardioselectivity and block both ______ and ______ receptors
beta 1
beta 2
100
Nebivolol also acts on the vascular endothelium by stimulating ______________ synthase which induces ____-mediated vasodilation
nitric oxide
NO
101
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
NO
102
What short-acting cardioselective beta 1 blocker is administered by infusion because it rapidly excretes as a zwitterionic metabolite
esmolol
103
What makes esmolol susceptible to hydrolysis by serum esterases to inactive metabolite and readily excreted as a zwitterion
methyl ester of a carboxylic acid
104
The more lipophilic drugs are primarily cleared by the _______ whereas hydrophilic agents are cleared by the _______
liver
kidney
105
____________ is not cardioselective when taken by patients who are poor CYP2D6 metabolizers
Nebivolol
106
What amino acid does methyldopa most closely mimic causing the methyldopa to use its carrier to transport it across the BBB
tyrosine
107
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
methyldopa
clonidine
108
____________ is structurally and chemically related to L-DOPA and the catecholamines. Also at physiological pH, it is found under zwitterion form
methyldopa
109
Methyldopa is unstable in the presence of ___________ agents, and since they are closely related to catecholamines, patients with asthma can experience _________ hypersensitivity reactions
oxidative (pH and light)
sulfite
110
Steric crowding by the bulky ortho-chlorine groups in clonidine does not permit a __________ conformation of the two rings
coplanar
111
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
prodrug
needs to mimic tyrosine before crossing barrier, also needs to be more lipophilic
