PHARM Flashcards
1
Q
what are the 5 key features of NT function that provide targets for drug therapy
A
synthesis storage release termination of action receptor effects
2
Q
sympathomimetic
A
mimicking the effects of impulses conveyed by adrenergic postganglionic fibers of the sympathetic nervous system (an agent that produces such an effect)
3
Q
sympatholytic
A
antiadrenergic; opposing the effects of impulses conveyed by adrenergic postganglionic fibers of sympathetic nervous system
4
Q
what are the 2 choline esters that have no susceptibility to cholinesterase
A
carbachol chloride
bethanechol chloride
5
Q
what is a pheochromocytoma
A
chromaffin tumor that typically arises in the adrenal glands secreting excessive catecholamines
6
Q
Tachyphylaxis
A
when you have chronic administration of drug and this causes a down-regulation or desensitization of receptors that can require dose adjustments to maintain adequate therapy
7
Q
what 2 receptors when stimulated cause glycogenolysis and gluconeogenesis in response to hypoglycemia
A
alpha-1, beta-2
8
Q
why are non-selective beta blockers dangerous for type 1 diabetics?
A
the beta blockers can interfere with counter-regulatory effects by blunting the perception of symptoms such as tremor, tachycardia, and nervousness
9
Q
a ______-selective antagonist is preferred because it is less likely to delay recovery from hypoglycemia
A
beta1
10
Q
alpha2 activation significantly _________ insulin secretion
A
decreases
11
Q
beta receptors mediate activation of ___________ in fat cells
A
HSL (important source of energy for exercising muscle)
12
Q
nonselective ____________ consistently decrease HDL cholesterol and increase triglycerides, with little effect on total cholesterol and LDL
A
beta blockers
13
Q
an alpha1 receptor blockade can cause what adverse effect?
A
orhtostatic hypertension (alpha1 receptors are involved in vascular tone)
14
Q
what kind of blockade can provide relief for BPH symptoms
A
alpha 1 blockade (involved in urethral tone)
15
Q
blockade of which kind of receptors can produce sexual dysfunction?
A
alpha 1 (involved in ejaculation process)
16
Q
blockade of which receptors can produce persistent priapism?
A
alpha1 receptors (typical treatment involves phenylephrine (alpha agonsit))
17
Q
which drug has potent alpha-adrenoceptor blocking activity in addition to its sedative, antianxiety effect?
A
promethazine (antihistaminic phenothiazine that may cause orthostatic hypotension via alpha-adrenergic blockade, which is infrequent when used in prescribed doses)
18
Q
what 2 pathways are intimately connected in the hippocampus and basal forebrain complex and may combine nto exert their effects on cognition, attention, and arousal
A
cholinergic and GABAergic
19
Q
what are the 5 categories of SNS drugs
A
alpha-blockers beta-blockers centrally-acting drugs transmitter depleting drugs ganglionic blocking drugs
20
Q
Norepinephrine acts on which receptors
A
alpha-1
alpha-2
beta-1
21
Q
epinephrine acts on which receptors
A
alpha-1
alpha-2
beta-1
beta-2
22
Q
isoproterenol acts on which receptors
A
beta-1
beta-2
23
Q
what happens when alpha receptors in skin and splanchnic vessels are agonized
A
contraction of blood vessel
24
Q
what happens when beta-2 receptors in skeletal muscles are agonized
A
vasodilation of blood vessel
25
what happens when alpha receptors in many different blood vessels are agonized
vasoconstriction
26
what are the 3 drugs that have a very high affinity for alpha-1 receptors
terazosin
doxazosin
prazosin
27
what are the 2 drugs which have affinity for both alpha-1 and alpha-2 receptors
phenoxybenzamine and phentolamine
28
orthostatic hypotension is most prominent with which alpha blocker
prazosin
29
what are the adverse effects of the alpha blockers
```
orthostatic hypotension (prazosin prom.)
sinus-tachycardia (angina, palpitations) syncope, vertigo
```
30
Tachycardia is more common with blockade of cardiac __________________ receptors (augments the release of NE)
alpha-2 presynaptic
31
which drug is a non-competitive covalent alpha-1 and alpha-2 antagonist
phenoxybenzamine
32
what are the clinical uses of phenoxybenzamine (alpha-1>alpha-2)
treating sympathetic excess secondary to pheochromocytoma
Raynaud's phenomenon
frostbite
acrocyanosis
33
phenoxybenzamine has what kind of onset and duration?
slow onset (several hours) and long duration (3-4 days)
34
what are the adverse effects of phenoxybenzamine?
orthostatic HTN
sinus-tachycardia
nasal congestion
```
drowsiness
fatigue
weakness
malaise
confusion
headache
xerostomia
ejaculation dysfunction
```
35
which drug is a short-acting competitive anatagonist at alpha-1 and alpha-2 receptors?
phentolamine
36
what are the clinical uses of phentolamine
pheochromocytoma
| hypertensive emergency
37
what is the effect on heart of phentolamine in small doses?
positive inotropic effect predominates (increase BP, greater effect on alpha-2 (auto) receptors-->increase NE release)
38
what is the effect of phentolamine in large doses?
peripheral vasodilation predominates (decrease BP, effect on postsynaptic alpha-1 receptor predom.)
39
postural hypotension is a prominent feature of which alpha blocker?
phentolamine
40
what are the adverse effects of phentolamine
orthostatic hypotension
| reflex tachycardia that precipitates cardiac arrhythmias
41
MOA of trimethaphan
compete w/ ACh for receptor binding on ganglionic nicotinic receptor Nn sites or block the ion channel
42
Why don't we use trimethaphan anymore
it has a nonspecific action on both sympathetic and parasympathetic -->many side effects
43
what are the cardiovascular side effects of trimethaphan
due mostly to loss of sympathetic tone to the vasculature
postural hypotension
tachycardia
arrhythmias
44
what is the effect of ganglionic blockade on arterioles
the predominant tone is sympathetic, so blocking this will cause vasodialtion; increased peripheral blood flow; hypotension
45
what is the effect on ganglionic blockade on the veins?
predominant tone is symp., so blocking this will cause dilation;: peripheral pooling of blood; decreased venous return; decreased CO
46
what is the effect of ganglionic blockade of the heart
the predom. tone is parasympathetic (cholinergic) so this will cause tachycardia
47
clonidine (IV) MOA
alpha-2 agonist, removes SNS activity to lower TPR and BP
48
Guanabenz (oral) MOA
alpha-2 agonist, removes SNS activity to lower TPR and BP
49
Guanfacine (oral) MOA
alpha-2 agonist, removes SNS activity to lower TPR and BP
50
what happens when alpha-2 agonists are given by rapid IV injection or very high oral doses?
activation of vascular (auto) alpha-2 adrenoreceptors leads to vasoconstriction
(vascular effects are normally obscured by central inhibition of symp. tone and decrease BP)
51
which alpha agonist is a prodrug that can be used during pregnancy
methyldopa (short half-life)
52
Reserpine MOA
binds to VMAT2 on presynaptic vesicles and prevents entrance of dopamine into vesicle (long lasting, binds tightly to VMAT2, recovery from drugs takes weeks, b/c need to make new vesicles), depletes NE and 5-HT from neurons and epinephrine from adrenal gland
53
which 2 alpha-2 agonists are safe to use during pregnancy
methyldopa (first line), (guanfacine)
54
how do alpha-2 agonists work on presynaptic autoreceptors?
limit release of NE from sympa. nerves and epinephrine from adrenal chromaffin cells at rest, (decrease SNS signals, cause minor bradycardia and hypotension)
55
how do alpha-2 agonists work on alpha-2 heteroreceptors on non-adrenergic neurons
MAJOR EFFECT, they cause vagal activation (cholinergic action) which causes bradycardia and hypotension, analgesia, sedation, hypothermia, anesthetic-sparing effect
56
what are the clinical effects of the alpha-2 agonists
balanced fall in PVR and BP (long lasting effect)
no reflex tachycardia
CO and renal blood flow unaffected
decrease plasma renin activity
regression of left ventricular hypertrophy
dose-dependent salt and water retention (prescribe diuretic)
57
methyldopa is metabolized to what
alpha-methylnorepinephrine
58
what might be a good clinical use of alpha-2 agonists
adjunctive med to block reflex tachycardia
| has no effect on blood glucose or lung function
59
what are the adverse effects of the alpha-2 agonists
```
somnolence (take at night, avoid CNS depressants)
dry mouth (alpha-2 mediated decrease saliva, increase caries, periodontal disease, oral candidiasis)
```
less likely:abd pain, constipation, hypotension, sinus bradycardia, decrease libido, impotence
60
which drug interferes w/ catecholamine quantitiation if you were trying to measure the catecholamine count in a pheochromocytoma?
methyldopa
61
what duration of action does reserpine have
recovery requires synthesis of new storage vesicles (so days to weeks)
62
what happens to the catecholamines that are blocked by reserpine?
they leak into the cytoplasm and are metabolized
63
what are the major adverse effects for reserpine?
CNS toxicities: sedation, can't concentrate
sometimes psychotic depression-->suicide
contraindicated in PUD or ulcerative colitis
can't use if pregnant (teratogenic avoid breastfeeding)
64
why are the alpha-2 agonists and reserpine pretty good drugs to start rethinking about using?
they are cheap and have much mild side-effects
65
alpha 1 receptor has which G protein
Gq (increase Ip3, DAG), increase intracellular Ca2+, contraction
66
alpha 2 receptor has which G protein
Gi (decrease cAMP, by inhibition of adenylyl cyclase), decrease transmitter release (nerves), causes contraction of muscle
67
Beta 1 receptor has which G protein
Gs (increases cAMP, by stimulation of adenylyl cyclase), increases HR, increase contractility, increased renin release
68
Beta 2 receptor has which G protein
Gs (increases cAMP), RELEAX SMOOTH MUSCLE, INCREASE GLYCOGENOLYSIS, INCREASE HEART RATE, increase contractility
activates cardiac Gi under some conditions
69
which drugs are the azosins
the alpha 1-adrenergic receptor blockers
70
what is the MOA of alpha1 adrenergic receptor blockers
block peripheral alpha 1 adrenergic receptors in arterioles and venules, this leads to decreased TPR and BP
71
what are the pharmacological effects of the azosins
decrease TPR, decrease BP, relieve symptoms of BPH, increase HDL-cholesterol and lower LDL-cholesterol and have beneficial effect on insulin resistance
72
which 4 beta blockers have intrinsic sympathomimetic activity?
acebutolol (2nd gen.)
Cartelol (3rd gen.),
Labetalol (3rd gen.)
Pindolol (1st gen.)
(ISA-Always CARies LAkers Pins)
73
which 3 beta blockers are considered membrane stabilizing?
acebutolol (2nd gen.)
Carvedilol (3rd gen.)
propanolol (1st gen.)
(Stable ACE CARVEs Props)
74
which 2 beta blockers have high lipid solubility?
pindolol (1st gen.)
propanolol (1st gen.)
(HeLikesSeeing Pink Panthers)
75
which beta blocker has a very short half life and has to be given IV infusion?
esmolol
76
what is the MOA of beta-blockers with no ISA
block the myocardial Beta-1 adrenergic receptors
decrease: HR, contractility-->decrease CO
block renin release
overall: decrease CO and TPR, -->BP
77
what kind of people have high renin htn
young and whites
78
what kind of people have low renin htn
elderly and blacks
79
which beta blockers have a lot of beta-1 receptor specificity
```
Metoprolol (2nd gen.)
acebutolol (2nd gen.)
atenolol (2nd gen.)
esmolol (2nd gen.)
betaxolol (3rd gen.)
Bisoprolol (2nd. Gen.)
Nebivolol (3rd gen.)
```
(MET ACE AT Ed's BETer Busy Neighborhood)
80
what are the 2 compelling indications you have to know for the use of beta blockers?
1. hypertensive pts w/ conditions like: MI, IHD, or CHF
| 2. preferred in hypertensive pts who have hyperthyroidism w/ migraines
81
what is the only class of drugs that can decrease the incidence of a second MI in pts w/ IHD, perhaps by causing bradycardia
beta-blockers
82
a most important use of 3rd gen. beta blockers (carvedilol, metoprolol, and bisoprol) is to decrease mortaility in ___________________
pts w/ HF, particularly useful for HTN in that pt population
83
which 2 drugs have 50-100 fold more selective in blocking Beta-1 adrenergic receptors (cardio-selective)
metoprolol and atenolol
| Select Me ATEN
84
propanolol is a non-selective BB that produces resting bradycardia and membrane stabilizing activity, also produces bronchospasm which is contraindicated in _____________
asthmatics
85
which 2 beta blockers are non-selective drugs w/ partial agonist activity, meaning they decrease the CO and HR less than other drugs
pindolol and acebutol
86
what are 4 major categories of adverse effects of beta blockers
cold extremities (unopposed alpha drenergic action constricts BV)
bradycardia (decrease AV nodal conduction)
bronchospasm (avoid w/ asthmatics)
CNS side effects (bad dreams)
87
what happens to blood glucose when beta-2 adrenoreceptors are activated?
increases, beta-2 activation stimulates glycogenolysis and pancreatic glucagon release
88
beta receptor activation increases insulin receptor sensitivity, so what happens to insulin sensitivity when you give beta blockers?
you decrease the insulin sensitivity
89
beta 2 receptors in pancreatic beta cells cause __________insulin secretion when activated
increased
90
what happens when you take beta blockers for a long time and then suddenly stop taking them?
tachycardia (prolonged use upregulates beta-receptors in the heart)
need to withdraw slowly
91
which beta blocker is given IV for hypertensive emergencies
labetalol
92
what is unique about carvedilol?
non-selective Beta and alpha-1 receptor antagonist so it can maintain the CO and still decrease the TPR
93
Which beta blocker is an antioxidant that binds and scavenges ROS, and has the effect of protecting membranes from lipid peroxidations (prevents LDL oxidation and decreases LDL uptake into coronary blood vessels)
carvedilol
94
which beta blocker is primarily used for CHF and HTN; also decreases mortality and morbidity in pts w/ mild/mod. CHF
carvedilol
95
what is the drug of choice for HTN w/ metabolic syndrome
nebivolol
96
this drug is considered the #1 beta blocker, IS highly beta-1 selective, and promotes endothelial NO-mediated vasodilation (decrease BP by decreasing HR and TPR)
nebivolol
97
which drugs cause increase in bradykinin because ACE is no longer inhibiting the destruction of bradykinin?
ACE inhibitors
98
when you are giving ACE inhibitors what happens to the production of renin and aldosterone?
both increase
99
which drug increases synthesis of vasodilatory prostaglandins in vascular and renal endothelium. Delays or prevents prog. of renal disease in type 1 diabetics
captopril
100
which ace inhibitor is a prodrug available for hypertensive emergencies?
enalapril (prodrug that is converted to enalaprilat)
101
what are 5 main adverse effects of ACE inhibitors?
1. hypotension in hypovolemic/Na+ depleted pts
2. hyperkalemia (contraindicated in pts taking K+)
3. dry crough (angioneurotic edema or angiodema, related to bradykinin)
4. angioedema: infreq. but potentially fatal
5. fetotoxicity
102
what is the substitute drug when pts have cough with ACE inhibitors
ARBs
103
which ARB is a competitive antagonist of thromboxane A2 receptor?
Losartan
104
which ARB is unique in that it increases uric acid urinary excretion?
losartan
105
which 2 ARBs are prodrugs
Losartan and Valsartan
106
which ARB has shortest half life
valsartan
107
which ARB has longest half life and is good for once daily dosing
telmisartan
108
which ARB do you prescribe to your pt if they have HTN and renal disease
telmisartan, b/c very little is cleared by kidneys
109
which ARB is a CYP3A4 inhibitor
losartan
110
MOA aliskiren
nonpeptide inhibitor of renin
111
what are the 4 L-type Ca2+ channel blocker drugs that have effects only in the blood vessels
Dihydropyridines: amlodipine, nifedipine, nicardipine, nimodipine
112
what are the 2 cardio-specific L-type Ca2+ channel blockers
verapamil, diltiazem
113
what is the MOA of the dihydropyridines
selectively blocks L-type Ca2+ channels in blood vessels
prevents contraction of vascular smooth muscles by inhibiting the voltage sensitive Ca2+ channels, and decreases the total amount of Ca2+ that reaches intracellular sites
114
which calcium channel blocker shouldn't be used for HTN b/c it increases HR by reflexively activating the SNS
Nifedipine (b/c its short acting)
115
which class of drugs are more effective in lowering BP than other drugs in pts w/ low renin HTN like elderly and blacks
dihydropyridines (act on blood vessels)
116
what are general adverse effects dihydropyridines?
peripheral ankle edema
reflex sympathetic response
hypotension
constipation
117
which drug is a selective arteriolar smooth muscle relaxer that has reflex SNS stim.-->increase catecholamine/renin secretion
hydralazine
118
which drug is used IV in for hypertensive emergency for eclampsia
hydralazine
119
what are the adverse effects of hydralazine
palpitations, tachycardia
| autoimmune reactions: hemolytic anemia, GN, LUPUS-LIKE SYNDROME
120
which drug relaxes arteriolar smooth muscle by opening K+ channels in smooth muscles and dilates arterioles but not veins?
minoxidil (also has reflex tachycardia and powerful activator of renin secretion)
121
which smooth muscle relaxing drug can cause hirsutism and is used to treat baldies?
minoxidil
122
Nitroprusside MOA
works as a prodrug to form NO, which stimulates relaxation of smooth muscle
123
which drug decreases CO in normal pts, but increases CO in pts with LVF?
nitroprusside, b/c TPR is reduced (lowering the afterload)
124
what is a clinical use of nitroprusside?
short half life and is given IV for hypertensive emergencies in pts with LVF
125
what are the adverse effects of nitroprusside
hypotension
tachycardia, palpitations
metabolized to CYANIDE
126
how do the alpha-2 adrenoreceptor agonists work to lower the TPR and HR?
they agonize postsynaptic alpha-2a adrenoreceptors in rostral ventrolateral medulla
this decreases symp. impulse to heart and blood vessels
127
which alpha-2 adrenoreceptor agonist releases endogenous opiates and is used as an analgesic for neuropathic pain?
clonidine
128
what happens if you stop taking clonidine suddenly?
clonidine withdrawal which causes htn
129
which drug is used in the treatment of HTN in preeclampsia?
methyldopa
130
what are some of the side-effects of alphamethyldopa
sedation, ED
Na+/water retention
lactation due to prolactin secretion
+coombs test
131
Bosentan MOA
endothelin-1 and endothelin-2 receptor antagonist (endothelin is a powerful vasoconstrictor)
sales only in special pharmacies b/c hepatotoxicity and fetotoxicity
132
which 2 classes of drugs are considered the best monotherapy for HTN
diuretics and ACE inhibitors
133
which beta blocker is considered as standard treatment option used with ACEIs and diuretics
beta-1 blocker bisoprolol
134
beta-3 adrenoreceptor activation causes what mechanism of downstream signaling?
stimulation of adenylol cyclase (increase in cAMP)
135
D1, D5 receptor activation has what mechanism of downstream signaling?
stimulation of adenylyl cyclase and increased cAMP
136
D2 receptor activation has what mechanism of downstream signaling?
inhibition of adenylyl cyclase, increase in K+ conductance
137
what do the direct acting drugs do
they stimulate postsynaptic receptors
138
what do the indirect acting drugs do
they increase the availability of epinephrine or norepinephrine
139
which receptors are more sensitive to the effects of epinephrine if given IV, alpha-1 or beta-2 receptors?
beta-2, explains why there is vasodilation when epinephrine is given IV
140
what are some adverse effects of epinephrine
cerebral hemorrhage (esp. w/ nonspecific beta blockers)
ventricular arrhythmias
angina
141
what are the clinical uses of epinephrine
emergency relief from hypersensitivity reactions (including anaphylaxis)
vasoconstrictor w/local anesthetics;
restoring cardiac rhythm in pts w/ cardiac arrest
142
why does giving epinephrine subq cause vasoconstriction in the skin?
the predominant receptors are alpha receptors, no beta-2 receptors there
143
at low doses of dopamine, which receptor action predominates?
D1 (vasodilation)
144
at moderate doses of dopamine, which receptor action predominates?
D1 and Beta-1, increased CO and D1-induced vasodilation
145
at high doses of dopamine which receptor action predominates?
alpha, increases peripheral vascular resistance and renal vasoconstriction
146
at low doses of dopamine, which receptor action predominates?
D1 (vasodilation)
147
at moderate doses of dopamine, which receptor action predominates?
D1 and Beta-1, increased CO and D1-induced vasodilation
148
at high doses of dopamine which receptor action predominates?
alpha, increases peripheral vascular resistance and renal vasoconstriction
149
activation of dopamine receptors has what effect on renal and other splanchnic blood vessels?
dilates
150
what is the MOA of dobutamine
racemic mixture: beta agonist, (+) -->alpha-1-antagonist, (-)-->alpha-1-agonist
151
what is the clinical use of dobutamine
to increase CO and SV w/o affecting the HR (increases myocardial contractility w/ decreased LV filling pressures)
for short-term treatment of cardiac decompensation (like after cardiac sugery, CHF, or MI)
152
what is the MOA of isoproterenol?
beta-1, beta-2 agonist
increase CO (inotropic and chronotropic effects)
decrease in diastolic BP
153
what is the clinical use of isoproterenol?
used in emergencies to stim. HR in pts w/ bradycardia or heart block, part. in anticipation of inserting cardiac pacemaker or pts w/ ventricular arrhythmia torsades de pointes)
154
what is the MOA of phenylephrine?
alpha1, alpha2 agonist
systemic arterial vasoconstriction
(causes reflex decrease in HR and CO)
155
what is the clinical use of phenylephrine?
control hypotension, including hypotension associated w/ regional or spinal anesthesia
156
what are the adverse effects of phenylephrine?
```
angina
anxiety
hallucinations
HTN
excitability
dizziness
insomnia
pallor
restlessness
```
157
what is the MOA of ephedrine?
mixed acting sympathomimetic
direct agonist at both alpha, and beta receptors
enhances release of NE from symp. neurons
158
what is the clinical use of ephedrine?
used for hypotension and hypotension of analgesia
159
what are the 4 primary effects of ACh on the CV system?
1. vasodilation
2. decrease HR
3. decrease AV node conduction velocity
4. decrease force of atrial cardiac contraction
160
what happens if M2 receptors at the Sinoatrial node are activated?
slows down the pace of SA node
161
what happens to contractility if M2 receptors in the heart are activated?
decreases contractility of the atria
162
what happens if M3 and M5 receptors in the endothelium of vessels in heart brain and viscera are activated?
synthesizes and releases NO (remember there is no parasympathetic innervation to skeletal muscles, but there are the M3 receptors that, when activated, stimulate a pathway to make NO)
163
low doses of atropine have what effect on the heart?
transient decrease in HR (blockade of presynaptic M1 autoreceptors, causes increased ACh release)
164
high doses of atropine have what effect on the heart?
progressive tachycardia (blockade of M2 receptors on the SA nodal pacemaker cells, vagal tone antagonized)
165
which drug can dilate cutaneous blood vessels and cause flushing?
atropine (compensatory reaction permitting the radiation of heat to offset the atropine-induced rise in temp, that can come w/ inhibiting sweating)
166
what are the 3 main clinical uses of atropine?
1. abolishes reflex vagal cardiac slowing or asystole
2. prevents or abolishes bradycardia or asystole from parasympathomimetic drugs, or electrical stim. of vagus
3. Facilitates AV conduction (shortens refractory period in AV node)
improves pts w/ inferior or posterior MI by relieving severe sinus or nodal bradycardia or AV block
167
Nitrates MOA
converted to NO-->↑guanylyl cyclase activity-->↑cGMP-->increasesmooth muscle relaxation
168
dihydropyridines MOA
Ca2+ channel blockers, cause arterial vasodilation, decreased afterload
169
nondihydropyridines MOA
Ca2+ channel blockers, negative inotropic and chronotropic effects
170
whats the term for chest pain that is prolonged and frequent w/ basically no exertion
unstable angina
171
term for chest pain as a direct result of reduction in coronary flow due to vasospasm
Prinzmetal's angina
172
term for exercise induced chest pain
Chronic Stable angina (aka exertional angina)
173
what is the most effective approach for treating angina?
reducing the myocardial oxygen demand
174
what are the adverse effects of nitrates
at higher doses: hypotension, headache (dilation of meningeal arteries), rash
175
what is an important contraindication with nitrates?
VIAGRA (sildinafil) both increase cGMP, cause massive vasodilation=severe hypotension
176
continuous nitrate exposure leads to what?
tolerance: causes decrease in biological effects (recommended 8-12 hr nitrate free interval each day, usually at night)
177
name the 2 nondihydropyridines
diltiazem
| verapamil
178
name the 3 dihydropyridine CCBs
nifedipine
felodipine
amlodipine
179
what is the main difference in MOA of the dihydropyridines vs. nondihydropines?
the nondihydropyridines target cardiac cells by the nature of the channel which is open much more in cardiac tissue
the dihydropyridines are voltage-dependent and they target smooth muscle cells
180
How do the NDP CCBs work on the heart?
they decrease HR, decrease, myocardial contractility, and slow AV conduction
reduces demand (MvO2) and prevents/reverses vasospasm
181
How do the DHP CCBs work on the vasculature?
Primary Mech. of antianginal effect: reduce afterload and cause coronary vasodilation
they are potent vasodilators=reflex cardiac stimulation
reduces MvO2 by reducing afterload
182
why don't you want to use a dihydropyridine CCB like nifedipine alone?
can cause reflex cardiac stimulation, instead use this w/ a beta-blocker (which prevent reflex tachycardia and positive inotropism)
183
what are some of the adverse effects of dihydropyridine CCB?
excessive vasodilation: dizziness, hypotension, headache
- cerebral ischemic reflex may worsen angina
- preg. category C
184
what are some adverse effects of nondihydropyridine CCBs?
bradycardia, asystole, AV block, constipation (verapamil), contraindicated in CHF, preg. category C (crosses placenta and found in breast milk)
185
which class of drugs is considered the class of choice for angina?
beta-blockers
| CCBs reserved for pts who can't tolerate beta-blockers, or add on therapy
186
how do beta blockers have an anti-anginal effect?
```
blunts HR and inotropic response to exercise
reduces afterload (CNS effect from lipophilic beta-blockers)
```
187
what are important side effects of beta-blockers w/ anti-anginal therapy?
1. can cause CHF in pts with decreased contractility
2. cold extremities
3. avoid abrupt withdrawl (arrhythmias)
contraindicated with Nondihydropyridine CCBs (AV block, asystole)
188
ranolazine MOA
unknown
189
what are overall effects of ranolazine?
1. they increase glucose and efficiency O2 utilization by heart
2. late Na+ current inhibitor
3. used for chronic stable angina in combo w/ DHP, BB, or nitrates
190
what are the adverse effects of ranolazine?
preg. category C
| Dizziness, kidney damage, syncope
191
what are the contraindications for ranolazine?
CYP3A4 inhibitors
class Ia and III antiarrhythmics
tricyclic antidepressants
192
describe PK profile of mucosal sublingual nitrates
```
small dose
fast onset (1-3 mins)
short duration (30 mins)
```
193
describe PK profile of oral nitrates
larger doses
onset after 15-45 mins
duration of 4-12 hours
metabolized by liver
194
describe the PK profile of transdermal nitrates
small dose
onset of 40-60 mins
duration about 24 hr
195
describe the PK profile of IV nitrates
5 micrograms/min-100micrograms/min
| immediate onset
196
4. Recognize the impact of antianginal drugs on survival and prevention of recurrent cardiac events in patients w/ coronary heart disease
if a pt is having angina they have at least a 75% occlusion of a coronary vessel from an atherosclerotic plaque. Myocardial ischemia will eventually damage cardiac myocytes. Vasodilate or reduce vasospasm to prevent an MI... and for God’s sake put them on aspirin.
197
what are 3 questions you want to ask yourself when evaluating an arrhythmia?
1. is the rhythm regular or irregular?
2. is there evidence of atrial depolarization?
3. is the QRS complex narrow or widened?
198
name the prototypical Class IA Na+ channel blocker
procainamide (Ia, III), >1 second, blocks Na+ on intermediate rates
199
what does procainamide work well to fix? (2)
atrial and ventricular arrhythmias
200
which antiarrhymetic drug is known to cause drug induced lupus, w/ arthralgia, skin rash, pleural and pericardial effusions, and torsades de pointes
procainamide
201
what is the prototypical Class Ib drug
lidocaine (Ib) <1 second, blocks Na+ on fast rates
202
what is the prototypical Class Ic drug
flecanide (Ic) >10 seconds, blocks Na+ on very slow rates
203
explain how the Class I antiarrhythmic drugs work?
when drug is bound to channel that channel can't respond to stimulus and depolarize
-makes it harder for that cell to have its own automaticity, and harder to conduct an ectopic pot'l
204
Name the 3 class II antiarrhythmic drugs?
propanolol (II)
metoprolol (II)
acebutolol (II)
205
name the 4 class III antiarrhythmics
amiodarone (III, I, II, IV)
sotolol (III, II)
ibutilide (III)
dofetilide (III)
206
name the 2 class IV antiarrhythmic drugs
verapamil
| diltiazem
207
how does ephedrine work?
mixed-acting sympathomimetic
-direct agonist at both alpha and beta receptors
enhances release of NE from symp. neurons
208
what is the clinical use of lidocaine?
short term suppression of VPB and ventricular tachycardia in CCU
209
which antiarrhythmic drug is contraindicated in pts w/ structural heart disease?
flecainide
210
which drugs would be effective to stop re-entry that is causing ventricular tachycardia?
Procainamide, Lidocaine
| also, sotolol, amiodarone
211
explain how Class III antiarrhythmics drugs work to stop reentry?
blocks K+ channels, prolongs phase 3 of action pot'l, prolongs the Effective refractory period, prevents reentry
212
what is the drug of choice in cardiac resuscitation?
amiodarone
213
what are 2 important PK facts about amiodarone?
```
highly lipophilic (so eliminated very slowly)
metabolized by CYP3A4
```
214
what is the side effect you have to know about amiodarone?
causes pulmonary fibrosis
215
Which class III antiarrhythmic drug do you want to avoid giving to someone who has asthma or COPD?
amiodarone (causes pulmonary fibrosis)
216
which class of antiarrhythmic drugs is guilty of causing torsades de pointes?
Class III antiarrhythmics
(it prolongs the QT so much that you have a risk of early afterdepolarization, cell becomes unstable, begins oscillating, causes early after depolarization)
217
Name the 2 pure antiarrhythmic K+ channel blockers?
Defetilide & Ibutilide, both are primarily used to treat atrial arrhythmias
218
what are the 3 go to antiarrhythmic drugs for treating v. tach?
1. amiodarone
2. Lidocaine
3. Procaineamide
219
which class of drugs would slow conduction of impulses through the AV node?
Class IV antiarrhythmics (verapamil, diltiazem)
220
what are the clinical uses of verapamil and diltiazem?
reduce SA node automaticity, and slow conduction through AV node
221
what are the characteristic adverse effects of Class IV antiarrhythmics?
SA and AV block
| also, decreased contractility, hypotension
222
why don't you want to use Class IV antiarrhythmics on pts with CHF or left ventricular dysfunction?
because an adverse effect is decreasing myocardial contractility
223
explain how digoxin can have antiarrhythmic effects?
these effects are mediated through its ability to increase vagal nerve activity
224
explain how digoxin can have arrythmogenic effects?
it inhibits Na+/K+ ATPase pump indirectly leading to calcium overload and Delayed after depolarizations
(the extra calcium explains why digoxin improves contractility)
225
what is paroxysmal supraventricular tachycardia?
re-entry w/in the AV node, rapid simultaneous activation of ventricle and atria (retrograde)
narrow QRS, regulatr activation, no identifiable p wav b/c it's embedded in the QRS
226
what is wolff-parkinson white syndrome?
when pts have alternate tract that allows impuse to go around atrium straight to the ventricle (asymetric ativation of ventricle is reflected on ECG by short PR interval and delta wave)
227
the use of what drug alone in pts w/ WPW syndrome is contraindicated?
digoxin (b/c digoxin increases vagal stimulation, and increased vagal stim. to heart causes increase transmission of atrial impulses across accessory pathway to ventricle and can induce v. fib.)
228
what is the definitive treatment to kill the re-entrant pathways in WPW pts?
radiofrequency catheter ablation of bypass tract
229
STATINS MOA
inhibits HMG-CoA-Reductase, the rate-limiting step of cholesterol synthesis
- upregulates LDL receptor in liver (SREBP mediated)
- reduces lipoprotein secretion by liver
- reduces LDL cholesterol 60%
- reduce TG 37%
- increase HDL 15%
230
which statin is safest to use in pts with CKD?
atorvastatin (98% fecal excretion)
231
which 2 statins are metabolized mostly by CYP3A4?
lovastatin, simvastatin (atorvastatin CYP3A4 and other metabolism paths)
232
which drug inhibits gluconyltransferase and is contraindicated with prescribing statins?
gemfibrozil
233
adverse effects of STATINS
```
GI
increased liver enzymes
CNS effects (sleep disturbance)
myalgia
myositis
rhabdomyolysis
TERATOGENIC (category X)
```
234
what are the 3 bile acid sequestrant drugs?
colestipol
cholestyramine
colesevalam
235
MOA of bile acid sequestrants
interrupt enterohepatic recycling of cholesterol by binding negatively charged bile acids in the gut (lowers LDL cholesterol by 25%)
236
adverse effects of bile acid sequestrants
GI: bloating and constipation
gritty texture
fecal impaction (take w/ water)
hypertriglyceridemia
237
which class of drugs has hypertriglyceridemia as an adverse effect?
bile acid sequestrants
238
what are the important drug interactions w/ bile acid sequestrants?
prevents absorption of other drugs
239
what are 3 important contraindications for bile acid sequestrants?
hypertriglyceridemia
complex drug regimens and critical meds
hx of constipation (elderly)
240
ezetimibe MOA
prevents intestinal uptake of cholesterol by small intestine (50%)
- reduces cholesterol delivery to liver
- upregulates LDL receptors, increased clearance of LDL from plasma
- distinct and complementary w/ STATINs
241
which antilipemic drug do you want to avoid giving w/ ezetimibe?
bile acid sequestrants (decreases absorption of ezetimibe)
242
what class of drugs do you want to avoid giving w/ ezetimibe which has the risk of increasing bilary cholesterol ecretion and increases the risk of gallstones?
fibrates (gemfibrozil, fenofibrate)
243
what are the adverse effects of ezetimibe?
liver enzyme elevations
| minor (fatigue, abd. pain, diarrhea)
244
which 3 classes of drugs lower triglyceride and raise HDL-cholesterol?
1. Fibrates
2. Niacin
3. omega-3 olyunsaturated fatty acids (fish oil)
245
what is the MOA of fibrates
ligand for the ligand-activated PPARalpha nuclear receptor
- TG decreased by 50%
- HDL increase by 15%
246
what are the important adverse effects of fibrates?
1. GERD, diarrhea, increased liver enzymes
2. lithogenic bile: gallstones
3. teratogen
4. fenofibrate (rev. increase in creatinine)
247
PPAR-alpha mediates what 5 lipid effects of fibrates?
1. suppress transcription of ApoCIII (increased LPL activity, promotes clearance of TG-rich lipoproteins)
2. increase ApoA1 synth. (increased HDL #)
3. increase phospholipid transfer protein activity
4. increased fatty acid oxidation
5. icnreased bilary cholesterol excretion
248
which fibrate drug is contraindicated w/ STATINS
gemfibrozil
249
which fibrate drug do you avoid in pts w/ kidney failure
fenofibrate
250
niacin MOA
- inhibits mobilization of FFA from adipocytes
- reduces hepatic TG synth.
- reduces hepatic apoB synth. and secretion (VLDL)
- enhances transfer of cholesterol from macrophage to HDL
- promotes conversion of VLDL to LDL via enhanced lipoprotein lipase
251
adverse effects of niacin
- cutaneous flushing (due to release of PG and histamines)
- elevated transaminases, hepatitis
- GI irritation
- conjuctivitis
- dry skin
- insulin resistance
252
MOA of omega-3 fatty acids
```
hypotriglyceridemic effect (reduce by 35%)
-also antiplatelet, antiarrhythmic, BP lowering effect
```
253
which alpha 2 agonist is also used to treat opiate withdrawal
clonidine
254
what is the drug of choice for malignant htn
nitroprusside
255
which 2 drugs famously cause gingival hyperplasia
phenytoin
| nifedipine
256
which drug causes a classic premature ventricular beat in a 1:1 fashion?
digoxin (PVB's are caused by DADs)
257
fun facts about captopril (1)
drug of choice in DM and HTN
258
fun facts about nebivolol (3)
1. drug of choice in metabolic syndrome
2. has vasodilatory effects (NO)
3. has anti-oxidant effects
259
fun facts about losartan (3)
1. used in pts w/ HTN and Gout
2. TxA2 receptor antagonist
3. CYP3A4 metabolized
260
fun facts about carvedilol (4)
1. drug of choice in HF
2. alpha-1 and beta antagonist
3. anti-oxidant effects
4. Ca2+ blockade activity
261
how do you treat class I HF (no symptoms)
ACEi or ARB
| BB
262
how do you treat class II HF (dyspnea w/ mod. exertion)
ACEi or ARB
BB
Diuretic
263
how do you treat class III HF (dyspnea w/ min. exertion)
```
ACEi or ARB
BB
diuretic
dogoxin
spironolactone
```
264
how do you treat class IV HF (refractory edema, dyspnea at rest)
above plus combo diuretics, IV vasodilators, transplant/assist devices
265
which is better to use in CHF ACEi or ARBs ?
ACEis unless the pt cant tolerate the side effects
266
which 2 classes of drugs stops the mitogenic effects of ATII?
ACEi
| ARB
267
Understand why BB are effective in treating CHF
short term: decrease CO and BP
| long term: increase CO, decrease preload
268
once a pt moves into decompensated CHF you should switch them from a BB to what
an inotrope like dobutamine
269
why are spironolactone and eplerenone have such beneficial effects on HF pts?
they inhibit aldosterone effects (Na+ and water retention)
they also inhibit aldosterone's direct mitogenic and fibrogenic effects on myocardium (combines w/ ATII to stimulate fibrosis)
270
how does nesirtide work and who do we use it on?
binds to BNP receptor in vascular smooth muscle, veno and vasodilation (via cGMP)
- reduced preload/afterload
- increase GFR, increase FF, natriuresis
- suppresses RAAS and SNS
used in class IV HF (used for those who don't respond to nitroglycerin)
271
which HF drugs are anti-mitogenic
```
ACEi
ARB
Spironolactone
nesirtide
beta-blocker
```
272
which drugs HF drugs show survival benefit?
```
digoxin
hydralazine
ACEi
ARBs
Spironolactone
beta-blocker
```
