Autonomic Pharm Flashcards
(211 cards)
1
Q
2 common first line therapies for pregnancy
A
Methyldopa, Labetalol
2
Q
4 Primary effects of ACh on CV system
A
Vasodilation, Dec HR, Dec AV Node conduction velocity, Dec force of contraction
3
Q
a2 agonists are a useful adjuntive Rx, especially to block __
A
reflex tachycardia
4
Q
A2 agonists are particularly useful in what type of patients
A
Diabetics and Asthmatics
5
Q
a2 agonists have dose-dependent __
A
salt and water retention
6
Q
A2 agonists that do not penetrate BBB, do not ___
A
decrease blood pressure
7
Q
ACh acts on what receptors in vascular endothelial cells
A
M3 receptors
8
Q
Action of a2 adrenergic autoreceptors
A
Limit release of NE from sympathetic nerves and Epi from adrenal chromaffin cells
9
Q
Action of Clonidine
A
Binds auto-receptors (a2 agonist)
10
Q
Action of Ephedrine
A
Mixed-actining sympathomimetic: direct agonist of a and b receptors
11
Q
Action of Isopreterenol
A
Acts on beta in SM –> Vasodilation –> Reduction in Diastolic BP; Also increase HR
12
Q
Action of Labetolol
A
A and B blocker
13
Q
Action of Metyrosine
A
In tx of Pheochromocytoma, decreases excessive production of catecholamines by blocking tyrosine hydroxylase
14
Q
Action of Phentolamine
A
Competitive antagonist at alpha1 and 2 receptors
15
Q
Activation of alpha2 receptor:
A
Decreases production of cAMP –> Inhibition of further release of NE from Neuron (pre-synaptic)
16
Q
Activation of beta 2 in skeletal muscle
A
Vasodilation
17
Q
Activation of M2 Muscarinic Receptors –>
A
Gi/Go inhibit AC, decrease cAMP, activate inward rectifying K channels, inhibit v-gated Ca channels = Hyperpolarization/ inhibition
18
Q
Activation of M3 Muscarinic Receptors –>
A
Gq/11, Activation of PLC, Increased IP3 and DAG, Increased Ca and PKC –> Depolarization and Excitation
19
Q
Activation of vascular a2 adrenoreceptors leads to
A
vasoconstriction (when given locally, by rapid IV, or in very high oral doses)
20
Q
Additional actions of Carvedilol, Acebutolol, Propranolol
A
Block fast Na+ channels (and thus rapid depolarization, phase 0) in non-nodal cardiomyocytes –> Decrease slope of phase 0, decrease amplitude of AP
21
Q
Advantage of drugs with ISMA
A
Can stimulate resting heart to provide relief from bradycardia, but also inhibit stimulation by sympathetics
22
Q
Adverse effects of Epi
A
Cerebral hemm; Vent Arrhythmias; Angina
23
Q
Adverse effects of Ganglionic Blockers
A
Postural Hypotension, Tachycardia, Arrhythmias, etc.
24
Q
AE’s of Ephedrine
A
Angina, Vent dysfunction/arrhythmias, Fatal arrythmias
25
AE's of NE
Similar to Epi, but BP increase more prominent
26
AE's of Phenoxybenzamine
Sinus tach, Nasal Congestion
27
AE's of Phentolamine
Postural Hypotension, Reflex Tach that precipitates cardiac arrhythmias
28
After pretreat with alpha-blocker, what is effect of Epi
decrease in BP (vasodilation still intact (beta2), vasoconstriction blocked (alpha))
29
After pretreat with alpha-blocker, what is effect of NE
Very minimal rise in BP
30
After pretreat with beta-blocker, what is effect of Epi
Rise in BP (vasodilation blocked (beta2), vasocontriction intact (alpha))
31
After pretreat with beta-blocker, what is effect of isoproterenol
Elimination of drop in BP (beta only, mostly 2)
32
After pretreat with beta-blocker, what is effect of NE
Reletively normal rise in BP
33
Alfuzosin is used for
BPH (alpha-1a blocker)
34
Alpha blockers prevent ___ effect of NE
Vasoconstrictive (increase BP)
35
Alpha vs Beta blockers: prevent vasoconstrictive effect of NE
Just alpha
36
Alpha-1a receptors represent 70% of alpha receptors in
prostate
37
Alpha-1b and Alpha-1d receptors are in
vasculature
38
Alpha-blockers DTP have much higher affinity for which subtype
Alpha 1
39
Alpha: Post-synaptic, down-stream signaling
Alpha 1
40
Alpha: Pre-synaptic, auto-receptors
Alpha 2
41
Alpha1 receptor antagonism would prevent
reflex vasoconstrictive effect produced by beta blockers
42
Alpha2 agonist prodrug
methyldopa
43
Alpha2 agonists
Clonidine, Guanabenz, Guanfacine
44
At low conc., DA acts predominantly
on DA receptors in renal vasculature
45
Atropine with higher dose
Progressive tachycardia: Blockade of M2 receptors on SA nodal pacemaker cells (vagal tone antagonized)
46
Atropine with low dose
Blockade of presynaptic M1 receptors --> Increased ACh release
47
Autonomic control of resting heart is primarily
Parasympathetic
48
BB's with __ tend to have less effect on TG's and HDLs
ISMA OR Cardio-selectivity
49
BB's with ___ tend to reduce total cholesterols and LDLs
BOTH ISMA AND Cardio-selectivity
50
BB's with Membrane Stabilizing Activity
Carvedilol, Acebutolol, Propranolol
51
beta 2 receptor role in glucose regulation
Normally stimulate hepatic glycogen breakdown and pancreatic glucagon release (increase plasma glucose)
52
Block fast Na+ channels (and thus rapid depolarization, phase 0) in non-nodal cardiomyocytes --> Decrease slope of phase 0, decrease amplitude of AP
Additional actions of Carvedilol, Acebutolol, Propranolol
53
Blockade of alpha-1a in bladder neck and prostate can
improve urine flow and reduce symptomes of BPH
54
Cat. B a2 agonists
Methyldopa and Guanafacine
55
Cholinergic innervation in skeletal muscle
none
56
Clinical use of Dobutamine
Short-term tx of cardiac decompensation; After cardiac surgery, CHF, or Acute MI
57
Clinical use of Ephedrine
Hypotension
58
Clinical use of Phenylephrine
Control of Hypotension
59
CNS depression can occur with what type of BB drugs
Lipophilic
60
CNS effects of BB's
Mental disorders, fatigue, vivid dreams
61
Concentration-dependent receptor effects of DA:
D1 --> B1 --> A
62
Correlation b/t serum levels of a2 agonists and duration of central effect
Poor
63
Difference b/t NE and Epi action
Epi also activates beta2 in skeletal muscle vessels --> Vasodilation and decline in BP
64
Direct cardiac effects of ACh are mediated primarily by
M2 receptors
65
Direct cardiac effects of ACh mediated primarily by M2 receptors
Activation of K-ACh channels; Inhibition of L-type Ca channels
66
Drugs that prevent Ca entry can cause
vasodilation of smooth muscle
67
Duration of Phenoxybenzamine vs Phentolamine
Phenoxy is longer duration
68
Effect of BB's on Plasma Glucose
Hypoglycemia
69
Effect of beta-blockers on renin-angiotensin pathway
Blocks renin release from JGA of kidney
70
Effect of DA on CV system
Increased CO (contractility >> HR), D1 vasodilation; At high doses: Inc PVR and Renal vasoconstriction (alpha-agonism predominates)
71
Effect of Epi on Coronary BF
Increased (decreased systole duration)
72
Effect of Epi on Lungs
Inc Pulmonary pressures
73
Effect of Epi on Pulse Pressure
Inc in Systolic > Diastolic --> Increase in PP
74
Effect of Epi on Pulse Rate
Increase
75
Effect of Epi on TPR
Decrease
76
Effect of ganglionic blockade in Arterioles
Vasodilation; Increased Peripheral Blood Flow; Hypotension
77
Effect of ganglionic blockade in Veins
Dilation; Peripheral pooling of blood, Decreased venous return, Decreased cardiac output
78
Effect of ganglionic blockade on Heart
Tachycardia
79
Effect of Isoproterenol on Pulse
Increase
80
Effect of Isoproterenol on TPR
Decrease
81
Effect of M2 receptors on Peripheral Nerves
Inhibition via auto- and heter-receptors = Decreased ganglionic transmission
82
Effect of M2 receptors on SA node
Slowed, spontaneous depolarization; Hyperpolarization, decreased HR
83
Effect of M2 receptors on SM
Contraction
84
Effect of NE infusion
Predominantly activates a-adrenergic --> Raises BP --> Increased MAP and TPR --> Reflexive decrease in HR
85
Effect of NE on CO, TPR, SV
Down, Up, Up
86
Effect of NE on Coronary BF
Up
87
Effect of NE on Pulse Rate
Decrease (reflexive)
88
Effect of NE on TPR
Increase
89
Effect of SC Epi on BP
Inc in SBP secondary to inotropic effect (inc CO); Dec DBP (b2-mediated dec. TPR)
90
Effects of BB's on Total cholesterol, LDL, HDL, TG
Little effect on Total, LDL; Increased TG's and decreased HDL
91
Effects of Dobutamine on CV system
Inc CO, SV w/o effect on HR
92
Effects of Ephedrine on CV system
Inc HR and CO; Inc TPR (BP)
93
Effects of Epi on Kidneys
Inc Renal Vascular Resistance; Dec Renal BF; GFR unchanged; Increase Renin secretion (b-1); Dec excretion of Na, K, Cl
94
Effects of Isoproteronol on CO, BP, TPR
Inc CO, Dec Diastolic BP, Dec TPR
95
Effects of NE on CV emanate predominantly from
Alpha-1-mediated action = Vasoconstriction
96
Effects of Phenylephrine on CV system
Alpha: systemic arterial vasoconstriction --> Inc BP (reflex HR and CO)
97
Effects of Reserpine on response to Mixed-Acting CV stims
blunted, but not abolished
98
Epi acts on what receptors
Alpha1, 2, Beta1, 2
99
Epinephrine is agonist except at
Sweat glands and facial arteries
100
For whom is Reserpine contraindicated
Depression, PUD, Ulcerative Colitis, Pregnancy/Breastfeeding
101
General clinical utility of Atropine
Inhibit temporary overactivity of vagal tone on heart; Abolish effects of para-sympathomimetic drugs in circulation
102
Half life of Dobutamine
Very short
103
In atria, ACh causes
hyperpolarization and a dec. AP duration by increasing Ik-ACh (also dec. cAMP formation -> dec. NE release)
104
In AV node, ACh ___
decreases conduction and inc. refractory period by inhibiting Ica-L (responsible for drug-induced complete heart block)
105
In high doses, what is effect of Atropine on blood vessels
Dilate cutaneous vessels (Atropine Flush)
106
In larger doses of Phentolamine, what effect predominates
Peripheral vascular vasodilation --> Decrease BP
107
In smaller doses of Phentolamine, what effect predominates
Positive inotropic effect --> Increase BP
108
In the SA node, ACh dec HR primarily by
Decreasing the rate of spontaneous depolarization
109
In which alpha blocker is Orthostatic Hypotension most prominent
Prazosin
110
Indirect cardiac effects of ACh
Opposition of B-1-mediated increase in cAMP; Inhibition of NE from sympathetic nerve terminals
111
Indirect-acting CV stimulants ultimately increase
availability of NE or Epi
112
Inhibits vesicular catecholamine transporter: VMAT2
MOA of Reserpine
113
Intracellular actions of Epi are mediated by
cAMP
114
Isoproterenol acts on which receptors
Beta1 and 2
115
IV formulation available to treat hypertensive emergencies in pregnancy
Hydralazine, Labetolol
116
Locations of nAChR's
Paravertebral chain, Parasympathetics
117
Long-term administration of BB's leads to fall in
peripheral vascular resistance
118
M3 Muscarinic receptor activation leads to synthesis of
NO
119
Main effect of alpha 1
Smooth muscle contraction
120
Main effect of Atropine is to
alter HR
121
Mecamylamine is used for
Tourette's (orphan)
122
Mechanism of signaling for Alpha 1
Formation of IP3 and DAG --> Inc. Ca
123
Mechanism of signaling for Alpha 2
Inhibition of AC --> Decrease cAMP
124
Mechanism of signaling for Beta 1
Stimulation of AC --> Increase cAMP
125
Mechanism of signaling for Beta 2
Stimulation of AC --> Increase cAMP; Activates cardiac Gi under some conditions
126
Mechanism of signaling for D1, D5
Stimulation of AC --> Increase cAMP
127
Mechanism of signaling for D2
Inhibition of AC; Increase K+ conductance
128
Membrane Stabilizing Activity
Block fast Na+ channels (and thus rapid depolarization, phase 0) in non-nodal cardiomyocytes --> Decrease slope of phase 0, decrease amplitude of AP
129
Methyldopa interferes with
catecholamine quantitation
130
Methyldopa is relatively contraindicated in
Pheochromocytoma
131
MOA of Ganglionic Blockers
Compete with ACh for nicotinic receptor sites, or block the channel --> Initial EPSP is blocked --> Ganglionic transmission inhbited
132
MOA of Hydralazine
Peripheral Vasodilator
133
MOA of Phenoxybenzamine
Non-competitive (covalent) alpha1 and 2 antagonist
134
MOA of Reserpine
Inhibits vesicular catecholamine transporter: VMAT2
135
More important receptor subtypes activated by A2 agonists
Hetero-receptors --> Vagal activation
136
Most beta blockers are specific for which subtype
beta1
137
Most common anti-hypertensive classes
ACEi, ARBs > B-Blockers > Diuretics
138
Most common reason for prescription in US
HTN
139
Most prominent AE of alpha blockers
First Dose Orthostatic Hypotension
140
Most significant CNS Toxicities of Reserpine
Sedation, Inability to concentrate, Psychosis
141
NE acts on what receptors
Alpha1, 2, Beta1
142
NE storage depletion drug
Reserpine
143
Notable AE for Prazosin
First Dose Orthostatic Hypotension
144
NT's affected by Reserpine
NE and DA
145
Off Target Lipid Profile effects of BB's
Alpha1, beta1,2,3 mediate lipolysis
146
Off Target Pulmonary Effects of BB's
Blockade of bronchial SM beta2 receptors --> bronchodilation
147
Onset and duration of Phenoxybenzamine
Slow onset and long duration (3-4 days)
148
Other AE's for alpha blockers
Sinus-tach, syncope, vertigo
149
Plasmin renin activity when taking a2 agonists
Decreased
150
Predominant tone in Arterioles
Sympathetic
151
Predominant tone in Heart
Parasympathetic
152
Predominant tone in Veins
Sympathetic
153
Primary CV conditions for BB tx
HTN, Acute MI
154
Primary sympathetic receptor in skin and splanchnic vessels
Alpha
155
Principal alpha blockers for essential HTN
Doxazosin, Terazosin, Prazosin
156
Propanolol is most effective in patients with
Elevated plasma renin
157
Receptor affinity of Phenoxyenzamine
A1 > A2
158
Receptor affinity of Phentolamine
A1 = A2
159
Receptor specificity of Dobutamine
Increase BP via alpha; Increase HR, CO via beta
160
Receptor specificity of Ephedrine
Increase BP via alpha; Increase HR, CO via beta
161
Receptor specificity of epi
Vasoconstrictor locally via alpha; Increase HR and CO via beta
162
Receptor specificity of Isoproterenol
No alpha; Increase HR, CO via beta receptors
163
Receptor specificity of NE
Increase BP via alpha receptors
164
Receptor specificity of Phenylephrine
Increase BP via alpha; No beta
165
Responses to ACh may be obscured by
CV reflexive effects
166
Rise in BP not as pronounced with ___ (epi vs ne)
Epi, due to vasodilation in skeletal muscle
167
Route of Isoproterenol
Parenteral or by Aerosol
168
Special AE's of Phenylephrine
CNS: Hallucinations, Psychosis
169
Stimluation of postsynaptic alpha 2 by epi leads to
Arteriolar Vasoconstriction
170
Stimulation of alpha 1 by Epi leads to
Arteriolar Vasoconstriction
171
Stimulation of beta1 by epi induces
positive chronotropic and inotropic response
172
Stimulation of beta2 by epi leads to
Arteriolar Vasoconstriction, Bronchial SM relaxation, Increased Glycogenolysis
173
Stimulation of M3, 5 receptors in endothelium does what
Synthesis and release of EDRF --> Vasodilation
174
Stimulation of presynaptic alpha 2 by epi leads to
inhibition of NE release
175
T/F: BB's will reduce BP in all patients
False, just patients with hypertension
176
The production of cAMP is augmented by __, and attenuated by ____
Beta stim; Alpha stimulation
177
Top Adverse Event in alpha 2 agonists
Drowsiness
178
Tx Utility of Epi
Restoring cardiac rhythm in patients with cardiac arrest
179
Use of ACE inhibitors or ARBs in pregnancy
Contraindicated
180
Uses for Phentolamine
Pheochromocytoma and Hypertensive emergency
181
Vascular effects of a2 receptors are normally obscured by
Central inhibition of sympathetic tone and decreased BP
182
Very low doses of Epi will
decrease BP, activation Beta-2 in absence of action on alpha-1
183
What dose of Phentolamine would you want to give to decrease BP
Larger --> Peripheral vascular vasodilation predominates
184
What is advantage of Esmolol
BB with extremely short half life, given IV, precise and regulated drug levels
185
What patients decline after admin of BB
Relying on sympathetic stimulation to compensate for CHF
186
When given alone, how does Atropine affect vessels
Inconsistently, not significant
187
When is ISMA indicated
Low resting heart rate
188
When is Isoproterenol used
Emergencies to stimulate HR in pts w/ bradycardia or heart block; particularly in anticipation of inserting an artificial cardiac pacemaker, or torsades de pointes
189
When is Phenoxybenzamine Rx'd
Sympathetic excess secondary to pheochromocytoma, Raynaud's, frostbite, and acrocyanosis
190
Where is beta 2 mostly located
Skeletal Muscle, Lungs
191
Where is DA synthesized and released
Proximal tubule
192
Which BB has alpha-1 receptor antagonism
Carvedilol, Labetalol
193
Which BB has beta-2 receptor agonism
Carteolol
194
Which BB has NO production activity
Carteolol, Nebivolol
195
Which beta blockers are beta-1-specific
A-N, after that, non-specific
196
Which CV stimulant acts only of Beta
Isoproterenol
197
Which CV stimulant acts only on Alpha
NE, Phenylephrine
198
Which drugs have ISMA
Pindolol, Acebutolol
199
Which effect of Epi is greater: Systolic vs Diastolic BP
Systolic --> Increase in MAP and widening of pulse pressure
200
Which muscarinic receptor couples by Gi/Go
M2
201
Which muscarinic receptor couples by Gq/11
M3
202
Which receptors are more sensitive to the effects of Epi
Beta 2 > Alpha
203
Which responses are reduced by prior treatment with Reserpine: Direct or Indirect
Indirectly-Acting
204
Which SNS receptors decrease cAMP
Alpha2, D2
205
Which SNS receptors increase cAMP
Beta1, Beta2, Beta3, D1, D5
206
Who shouldn't receive non-specific beta blockers because of pulmonary effects
COPD, Asthma (need sympathetic bronchodilation)
207
Why are BB's dangerous in Diabetics
Beta-1 blockers mask tachycardia which serves as a warning sign for insulin-induced hypoglycemia
208
Why give precursor instead of Dopamine
DA does not cross BBB
209
Why is action of Phenoxybenzamine longer than Phentolamine
Covalent binding (noncompetitive)
210
Why is rise in BP not as pronounced with Epi compared to NE
Vasodilation in skeletal muscle with epi
211
With increasing concentrations, DA acts
on Beta-1-adrenergic receptors, then alpha at higher
