2.2 Anti-Angina Drugs Flashcards
1
Q
prototype, used for dynamite manufacture
A
Nitroglycerin
2
Q
Release nitric oxide in vascular smooth muscle target tissues
A
NITRATES & NITRITES
3
Q
removal of nitrates in a stepwise fashion
A
organic nitrate reductase
4
Q
Oral bioavailability: nitroglycerin and isosorbide dinitrate is
A
low (10-20%)
5
Q
Nitroglycerin concentrations are not affected by the route of administration (T/F)
A
False
6
Q
NITRATES & NITRITES
Preferred route
A
sublingual route - Avoids first pass effect
7
Q
NITRATES & NITRITES
Preparations
A
Sublingual, Tablet forms, Topical
8
Q
NITRATES & NITRITES
Duration of effect
A
BRIEF (15-30 minutes)
9
Q
NITRATES & NITRITES
Total dose to be given must be limited
A
True
to avoid excessive effect
10
Q
Organic nitrate; ORAL long acting (>6 hrs)
A
Pentaerythritol (PETN)
11
Q
highly volatile liquids
Available in fragile glass ampules
Obsolete now for angina
A
Amyl nitrite and other nitrates
12
Q
2 metabolites of nitrates
A
2-dinitroglycerin derivative
5-mononitrate
13
Q
Metabolite of nitrate that has significant vasodilator efficacy & probably provides most of the therapeutic effect (oral nitroglycerin)
A
2-dinitroglycerin derivative
14
Q
Metabolite of nitrate that an active metabolite of nitroglycerin. Available as isosorbide mononitrate (oral).
A
5-mononitrate
15
Q
Nitroglycerin activation requires
A
enzymatic action.
16
Q
NITRATES & NITRITES
Can be denitrated by
A
glutathione S-transferase in Smooth muscle & other cells
17
Q
2 Dehydrogenase isoforms that are key in (+) and release of Nitric Oxide from nitroglycerin & pentaerythritol tetranitrate
A
Dehydrogenase isoform 2 (ALDH2) & Isoform 3 (ALDH3)
18
Q
response evoked when hypotensive doses are given.
A
Autonomic reflex
19
Q
Nitroglycerin relaxes all types of smooth muscle regardless of cause of preexisting muscle tone.
A
True
20
Q
(T/F)
Arteries: respond in lowest concentration
Veins: slightly higher
A
False
Veins: respond in lowest concentration
Arteries: slightly higher
21
Q
result with effective dose:
- Marked relaxation of veins
- Increase venous capacitance
- Decrease ventricular preload
- Decrease pulmonary vascular pressure and heart size.
A
Nitrates
22
Q
Common SE of nitroglycerin & amyl nitrate (2)
A
Temporal artery pulsations & throbbing headache + meningeal artery pulsations
23
Q
compensatory responses (+) by Baroreceptors & hormonal mechanism responding to decrease arterial pressure are indirect effects of
A
Nitrates
24
Q
diverts blood from normal to ischemic areas of the myocardium through dilation of collateral vessels.
A
Nitroglycerin
25
Nitroglycerin also exerts a strong negative inotropic effect on the heart via nitric oxide. *T/F)
False
| weak negative inotropc effect
26
Nitrates readily release nitric oxide in erectile tissue as well as vascular smooth muscle and activate guanylyl cyclase > inc cGMP > dephosphorylation (myosin light chains & relaxation > enhance erection (T/F)
True
27
NO release from nitroglycerin > (+) guanylyl cyclase (platelets e.g. smooth m.) > inc cGMP > dec in platelet aggregation (T/F)
True
28
No survival benefit when nitroglycerin is used in acute myocardial Infarction
True
29
IV nitroglycerin may be able in unstable angina.
True
30
Methemoglobin: has very high affinity to oxygen
False
| Very low affinity
31
In adults: the plasma level of nitrate resulting from large doses (organic & inorganic nitrates) is too high and causes significant methemoglobinemia (T/F).
False
| too low to cause significant methemoglobinemia
32
Methemoglobinemia: if excessive > treated with (1) which is now being replaced by (2)
IV methylene blue
| hydroxocobalamin (form of vit.B12
33
Nitrates
| Contraindication
elevated intracranial pressure
34
Continuous exposure to nitrates > isolated smooth muscle may develop complete tolerance (tachyphylaxis) (T/F)
True
35
Nitrates
| Tolerance may be due to (3)
(a) systemic compensation
(b) significant sympathetic discharge occurs
(c) Diminished bioactivation of organic nitrates and to a lesser degree loss of soluble guanylate cyclase responsiveness
36
Nitrates
| What supplementation may partially reverse tolerance, reduce availability of sulfhydryl donors
Cysteine
37
Other organic nitrates: less susceptible than nitroglycerin to tolerance (T/F)
True
38
Nitrate
| Tolerance Prevented by: treatment with antioxidants that protect ALDH3 (T/F)
False
| ALDH2
39
Nitrates
| Carcinogenic derivative:
Nitrosamines
40
Nitrate Effects in Angina of Effect: (True except)
A. Decreased venous return to the heart & resulting reduction of intracardiac volume are important beneficial hemodynamic effects.
B. Decrease arterial pressure
C. Decreased intraventricular pressure, dec left ventricular pressure assoc with dec wall tension (Laplace relation)
D. Inc myocardial oxygen requirement
E. Increase caliber of large epicardial coronary arteries
Dec myocardial oxygen requirement
41
Major mechanism of relief of effort angina:
reduction of oxygen demand
42
Nitrate Effects in Variant Angina
| By relaxing the epicardial cardiac veins’ smooth muscle > relieving cardiac vein spasm.
False
| By relaxing the epicardial coronary arteries’ smooth muscle > relieving coronary artery spasm
43
```
Nitrate Effects in Unstable angina (True except)
A. Dilate epicardial coronary erteries
B. Reduce myocardial oxygen demand
C. Decrease platelet aggregation
D. All
E. None
```
None
44
Clinical Use of Nitrates:
| most frequently used
NTG, SL
45
```
Clinical Use of Nitrates:
rapid onset (1-3 min), for immediate treatment
```
NTG, SL
46
Clinical Use of Nitrates:
| not suitable for maintenance therapy
NTG, SL
47
Clinical Use of Nitrates:
(restricted to) Severe, recurrent rest angina
Hemodynamic effects quickly reversed by discontinuation
NTG, IV
48
Clinical Use of Nitrates:
| Prolonged blood conc. > develop tolerance
NTG- Buccal, oral, transdermal
49
Nitro-Vasodilator with vasodilating effect in normal coronary arteries and with angina that reduces relative risk of fatal and nonfatal coronary events in patients receiving the drug
Nicorandil
50
A nicotinamide nitrate ester that reduces both preload & afterload
Nicorandil
51
prodrug that is converted to a nitric oxide-releasing metabolite and is efficient comparable to that of organic nitrates and is not subject to tolerance
Molsidomine
52
necessary for the contraction of smooth and cardiac muscle
transmembrane calcium influx
53
first clinically useful member of Calcium channel - blockung drugs
Verapamil
54
a vasodilator alkaloid found in the opium poppy
papaverine
55
prototype of the dihydropyridine family of calcium channel blockers
Nifedipine
56
The voltage-gated T-type calcium channel is the dominant type in cardiac and smooth muscle (T/F)
False
| L-type calcium channel is dominant
57
Calcium channel - blocking drugs consists of α1 (the larger, pore-forming subunit), α2, β, γ, and δ subunits (T/F)
True
58
Which Calcium channel - blocking drugs have been demonstrated to bind to one site on the α1 subunit (2)?
Nifedipine and other dihydropyridines
59
verapamil and diltiazem appear to bind to identical receptors (T/F)
False
| bind to closely related but not identical receptors in another region of the same subunit
60
Binding of a drug to the verapamil or diltiazem receptors allosterically affects dihydropyridine binding (T/F)
True
61
receptor regions of verapamil and diltiazem are stereospecific (T/F)
False
receptor regions are stereoselective, since marked differences in both stereoisomer-binding affinity and pharmacologic potency are observed for enantiomers of verapamil, diltiazem, and optically active nifedipine congeners.
62
Blockade of calcium channels by verapamil and diltiazem resembles that of sodium channel blockade by local anesthetics (T/F)
True
63
verapamil and diltiazem act from the inner side of the membrane (T/F)
True
64
verapamil and diltiazem bind more effectively to open channels and activated channels (T/F)
False
| OPEN channels and INACTIVATED channels
65
In verapamil and diltiazem: binding of the drug reduces the frequency of opening in response to depolarization > decrease in transmembrane calcium current > smooth muscle results in long-lasting relaxation (T/F)
True
66
In verapamil and diltiazem: decrease in transmembrane calcium current > smooth muscle results in long-lasting relaxation > reduction in contractility throughout the heart (T/F)
True
67
In verapamil and diltiazem: decrease in transmembrane calcium current > smooth muscle results in long-lasting relaxation > decreases in AV node pacemaker rate and SA node conduction velocity (T/F)
False
| decreases in sinus node pacemaker rate and atrioventricular node conduction velocity
68
Smooth muscle responses to calcium influx through
ligand-gated calcium channels
69
elevating the concentration of calcium will completely reverse blocks
False
| Partially reverse
70
Block can also be partially reversed by the use of drugs that decrease the transmembrane flux of calcium
False
Block can also be partially reversed by the use of drugs that increase the transmembrane flux of calcium, such as sympathomimetics
71
Potassium channels in vascular smooth muscle are inhibited by verapamil, thus limiting the vasodilation produced by this drug
True
72
a selective T-type calcium channel blocker that was introduced for antiarrhythmic use but has been withdrawn
Mibefradil
73
This drug block Sodium channels as well as calcium channels byt is an obsolete antiarrhythmic drug
Bepridil
74
In Calcium channel - blocking drugs, arterioles appear to be more sensitive than veins (T/F)
True
75
In Calcium channel - blocking drugs, Vascular smooth muscle appears to be the most sensitive, (T/F)
True
76
In Calcium channel - blocking drugs, orthostatic hypotension is a common adverse effect (T/F)
False
| not common
77
Men may be more sensitive than women to the hypotensive action of diltiazem (T/F)
False
| Women may be more sensitive than men
78
In Calcium channel - blocking drugs, reduction of coronary artery spasm has been demonstrated in patients with what type of angina
variant angina
79
have a greater ratio of vascular smooth muscle effects relative to cardiac effects than do diltiazem and verapamil
Dihydropyridines
80
Which dihydropyridine is claimed to be particularly selective for cerebral blood vessels
nimodipine
81
Impulse generation in the sinoatrial node and conduction in the atrioventricular node—so-called
slow-response, or Calcium-dependent, action potential
82
Sodium channel block is more with verapamil, and still less marked with diltiazem (T/F)
False
| Sodium channel block is modest with verapamil, and still less marked with diltiazem
83
dihydropyridines appear to block smooth muscle calcium channels at concentrations above those required for significant cardiac effects;(T/F)
False
| at concentrations below those required
84
verapamil or diltiazem is less depressant on the heart than dihydropyridines (T/F)
False
| dihydropyridines is less depressant on the heart than verapamil or diltiazem
85
Skeletal muscle is not depressed by the calcium channel blockers because it uses
A. Intracellular pools of calcium
B. Extracellular pools of calcium
Intracellular pools of calcium
86
approved for use in patients who have had a hemorrhagic stroke, but it has recently been withdrawn
Nimodipine
87
used by intravenous and intracerebral arterial infusion to prevent cerebral vasospasm associated with stroke
Nicardipine
88
used by the intra-arterial route in stroke
Verapamil
89
Calcium channel blockers minimally interfere with stimulus-secretion coupling in glands and nerve endings (T/F)
True
90
has been shown to inhibit insulin release in humans, but the dosages required are greater than those used in management of angina and other cardiovascular conditions
Verapamil
