3.2.2. Adrenergics I and II Flashcards
1
Q
Norepinephrine acts on which types of adrenergic receptors?
A
- alpha 1, alpha 2
- beta 1
2
Q
Epinephrine acts on which types of adrenergic receptors?
A
- alpha 1, alpha 2
- beta 1, beta 2, beta 3
3
Q
Dopamine (1st cousin of the adrenergic receptor) acts on which types of adrenergic receptors?
A
- beta 1
- D1 (and D5), D2 (and D3 & D4)
4
Q
Which adrenergic receptors are found in the heart?
A
beta 1
5
Q
What is the response to adrenergic agonists in the heart?
A
-increased contractility, increased automaticity, increased conduction velocity (remember these are beta 1 receptors)
6
Q
Which adrenergic receptors are found in blood vessels?
A
- alpha 1 (in most vascular beds)
- beta 2 (in skeletal muscle & liver)
- D1, dopamine, in kidney and mesentery
7
Q
On smooth muscle, what do alpha 1 receptors mediate?
How about beta 2 receptors?
A
Alpha 1 mediates constriction on smooth muscle, beta 2 mediates relaxation.
8
Q
What is the response to adrenergic agonists in blood vessels?
A
- arteriolar constriction (alpha 1 in most vascular beds)
- arteriolar dilation (beta 2 in skeletal muscles and liver, and D1 in kidney and mesentery)
- venoconstriction (alpha 1)
- venodilation (beta 2)
9
Q
Which adrenergic receptor is found in bronchioles?
A
beta 2
10
Q
What is the response to adrenergic agonists in the bronchioles?
A
Dilation (remember beta 2 mediates relaxation)
11
Q
Which adrenergic receptor is found in the iris?
A
alpha 1
12
Q
What is the response to adrenergic agonists in the iris?
A
radial muscle contraction (mydriasis–remember alpha 1 constricts)
13
Q
Which adrenergic receptors are present in the GI tract and urinary bladder?
A
- alpha 1
- beta 2
14
Q
What is the response to adrenergic agonists in the GI tract and urinary bladder?
A
- contraction of the sphincters (alpha 1)
- decreased motility (beta 2)
15
Q
Which adrenergic receptor is found in the uterus?
A
beta 2
16
Q
What is the response to adrenergic agonists in the uterus?
A
relaxation (beta 2)–> we give beta 2 agonist to slow labor
17
Q
Beta 1 is only found in these three places:
A
heart, fat and kidney
18
Q
Which adrenergic receptor is NEVER found at a synapse?
A
beta 2 (beta 2 is extra-junctional on end organs and beta 2 receptors are activated by circulating EPI)
19
Q
What are the metabolic effects of beta 2 and alpha 1?
A
stimulate glucose release from liver
20
Q
What are the metabolic effects of beta 1 and beta 3?
A
stimulate free fatty acid release from fat cells
21
Q
True or False: EPI increases all aspects of cardiac activity
A
True (cardiac effects of EPI (beta 1 actions) include: increased automaticity, increased heart rate, increased conduction velocity, increased contractile force, increased cardiac output and O2 consumption
22
Q
What is the effect of a low dose of EPI on HR, BP and peripheral resistance?
A
HR increases (beta 1), diastolic pressure decreases (beta 1) and increase in systolic pressure (alpha 1 & beta 2), peripheral resistance decreases (alpha 1 & beta 2)
23
Q
What is the effect of EPI on the bronchioles?
A
bronchioles dilate (beta 2)
24
Q
What are the metabolic effects of EPI?
A
EPI increases the availability of glucose and fatty acids for the skeletal muscle.
25
What is the effect of norepinephrine on HR, BP and peripheral resistance?
HR decreases (alpha 1 and beta 1), diastolic BP increases (alpha 1) and systolic blood pressure increases (beta 1), peripheral resistance goes way up (alpha 1)
26
What is the effect of isoproterenol on HR, BP and peripheral resistance?
BP slightly lowered, HR increased (beta 1), peripheral resistance decreased (beta 2) (*isoproterenol stimulates beta 1 and beta 2 but not alpha receptors)
27
What is the effect of dopamine on HR, BP and peripheral resistance?
BP slightly elevated, HR slightly increased, peripheral resistance slightly lowered
28
Which agents have an affinity for alpha 1 receptor (found in arterial smooth muscle)?
EPI>/=NE>>I
29
Which agents have an affinity for beta 1 receptor (found in the heart)?
I>EPI=NE
30
Which agents have an affinity for beta 2 (bronchial smooth muscle)?
I>/=EPI>>NE
31
What is Phenylephrine (neo-synephrine)?
An alpha 1 and alpha 2 (1>2) receptor agonist with little to no agonist activity at beta receptors
32
What kind of agonists are albuterol (Ventolin) and Ritodrine (Yutopar)?
Specific beta 2 agonists which cause less cardiac stimulation than nonselective beta 2 agonists.
33
What is Fenoldopam (Corlopam) and what does it do?
A peripheral D1 receptor agonist that lowers blood pressure and can increase renal blood flow. It is administered i.v. for short term management of severe hypertension in the hospital.
34
Describe the effects of amphetamines
Causes the release of NE from the nerve terminal. Peripheral actions are similar to sympathetic nerve stimulation or NE administration. It has power CNS stimulant actions in addition to peripheral a and bactions.
35
Describe the effects of ephedrine and pseudoephedrine (Sudafed):
They cause the release of NE from the nerve terminal and may also directly stimulate beta 2 receptors (to dilate bronchi). CNS actions are much less than those of amphetamine.
36
What is phenylpropanoloamine (PPA) and what are its effects:
A drug that is similar to ephedrine and pseudoephedrine that releases NE from nerve terminals, and may increase the risk of hemorrhagic stroke. (herbal supplement ephedra banned)
37
What are agents that displace stored catecholamines?
amphetamine, ephedrine and pseudoephedrine, phenylpropanolamine
38
What are agents that inhibit the uptake of released catecholamines?
cocaine, tricyclic antidepressants like imipramine (Tofranil), certain antiobesity drugs like sibutramine (Meridia)
39
What are monoamine oxidase inhibitors (MAOI) used for?
Nonspecific MAOI (phenelzine or tranylcypromine) are used occasionally to treat depression. (adverse effect=potentially lethal hypertensive crisis)
40
What are the therapeutic uses of agents that stimulate alpha 1 receptors (alpha agonists)?
1. Decongestion of mucous membranes
2. combined with local anesthetics to minimize distribution of anesthetic (dentists combine EPI and procaine)
3. Treatment of severe hypotension/orthostatic hypotension
4. Elicit reflex vagal discharge in response to inc. MBP to abolish attacks of paroxysmal supraventricular tachycardia
5. To produce mydriasis (pupillary dilation)
6. Treatment of glaucoma (brimonidine i.e. Alphagan)
7. Hypertension can be treated with clonidine (alpha 2 agonist that acts in CNS to decrease sympathetic activity)
41
What are the therapeutic uses of agents that stimulate beta 1 receptors?
1. Treatment of cardiac arrest and heart block
2. Acute treatment of heart failure
3. Cardiogenic shock
42
What are the therapeutic uses of agents that stimulate beta 2 receptors?
1. Treatment of bronchial asthma (albuterol)
| 2. Delay delivery of premature labor
43
What are the therapeutic uses of agents that stimulate D1 dopamine receptors?
1. Acute (IV) treatment of severe hypertension (fenoldopam, D1 selective agonist)
2. Acute (IV) renal vasodilation (dopamine and fenoldopam)
44
What are the vascular side effects of alpha 1 receptor stimulation?
hypertension, headache, cerebral hemorrhage
45
What are the urinary side effects of alpha 1 receptor stimulation?
urinary hesitancy or retention in patients with prostatic hyperplasia
46
What are the cardiac side effects of beta 1 receptor stimulation?
tachycardia (although reflex bradycardia may occur with an agonist), may precipitate angina attack or cardiac arrhythmias.
47
What is a side effects of sympathomimetic drugs that readily cross the BBB?
CNS stimulation, primarily in non-catecholamines
48
What are adrenergic antagonists?
Drugs that block adrenergic receptors or inhibit adrenergic neural function/
49
Define the role of adrenergic receptor blocking agents:
inhibit the ability of a neurotransmitter or a sympathomimetic amine to interact effectively with its receptor
50
Define the role of adrenergic neuron blocking agents:
interfere with the release of NE following nerve stimulation (by inhibition of the synthesis, storage, or release of NE)
51
List the different types of alpha adrenergic receptor blocking agents:
1. Noncompetitive (irreversible) alpha receptor antagonist (Phenoxybenzamine)
2. Non-selective reversible alpha receptor antagonist (Phentolamine)
3. Relatively-selective reversible alpha 1 receptor antagonists (most widely used class of antagonists--Prazosin)
52
Describe the mechanism of the noncompetitive (irreversible) alpha receptor Phenoxybenzamine:
Phenoxybenzamine binds covalently to alpha 1 and alpha 2 receptors to produce irreversible blockade. This agent has a slow onset but prolonged duration of action.
53
Describe the mechanism of the non-selective reversible alpha receptor Phentolamine:
Phentolamine blocks alpha1 and alpha 2 receptors (and has a direct effect on vascular smooth muscle. It decreases TPR and produces reflex sympathetic cardiac stimulation.
54
Describe the mechanism of the relatively-selective reversible alpha 1 receptor antagonists (most widely used class of antagonists) Prazosin:
Prazosin elicits little if any blockade of presynaptic alpha 2 receptors, and results in less reflex cardiac stimulation and greater antihypertensive efficacy than nonselective alpha 1 and alpha 2 receptor blockers
55
What are the therapeutic uses of alpha 2 receptor antagonists?
1. Hypertension
2. Pheochromocytoma (a catecholamine-secreting tumor)
3. Benign prostatic hyperplasia in males and bladder outlet obstruction in females
4. Peripheral vascular disease
5. Erectile dysfunction
56
What are the side effects of alpha 2 receptor antagonists?
1. Postural hypotension
2. nasal stuffiness
3. reflex cardiac stimulation (tachycardias, arrhythmias and anginas esp. with nonselective alpha receptor blockers)
4. impaired ejaculation
57
List the different types of beta adrenergic receptor blockers (beta blockers):
1. Cardiac Selective blockers (beta 1 selectivity)
| 2. Intrinsic sympathomimetic activity (partial agonist activity)
58
What is an advantage of using a beta 1 selective agents?
Beta 1 selective agent may be superior to a non-selective agents because it causes less bronchospasm in patients with asthma or COPD (but remember that large doses can block both beta 1 and beta 2 receptors and cause bronchospasm)
59
What is the mechanism of beta blocker agents with intrinsic sympathomimetic activity (partial agonist activity)?
Agents with this property (like Pindolol) slightly activate beta receptors (nonselective) in addition to preventing access of natural or synthetic sympathomimetic agent (NE or EPI) to the receptor). Partial agonist activity causes less slowing of HR at rest than those without agonist activity).
60
What is propranolol?
- A nonselective beta blocker with no intrinsic sympathomimetic activity
- blocks beta receptor-mediate effects of administered agonists as well as sympathetic nerve activity
61
What are the cardiac effects of propranolol?
dec. HR
dec. MCF
dec. CO
dec. conduction velocity (esp. in AV node)
dec. myocardial O2 demand
dec. spontaneous rate of depolarization (automaticity) of SA nodal and ectopic pacemakers
62
What are the vascular and BP effects of propranolol?
leads to a dec. TPR
| dec. plasma renin
63
What are the metabolic effects of Propranolol?
- normally does not alter plasma glucose BUT in diabetic patients, does slow the recovery of plasma glucose levels after insulin administration
- increase VLDL and decreases HDL, there is no change in LDL
64
What is the effect to the bronchioles after taking Propranolol?
Propranolol increases airway resistance (due to beta 2 blockade which leads to bronchoconstriction)
65
What is Metoprolol (Lopressor)?
- a relatively selective beta 1 blocker
| - cardiovascular effects similar to those seen in Propranolol
66
What is Pindolol (Visken)?
-a nonselective beta blocker that possesses some intrinsic sympathomimetic activity (it's a weak partial agonist at beta receptors)
67
What are the therapeutic uses of beta receptor antagonists?
1. hypertension
2. ischemic heart disease
3. cardiac arrhythmias
4. obstructive cardiomyopathy
5. congestive heart failure
6. open-angle glaucoma
7. prophylactic for migraine headaches
8. tremor (performance anxiety)
68
What are the side effects of beta blockers?
1. bronchoconstriction
2. bradycardia. AV block, cardiac arrest
3. cardiac failure
4. sudden withdrawal may cause angina, MI, and/or rebound elevation of BP
5. exacerbation of insulin-induced hypoglycermia (and masking of reflex tachycardia normally seen with developing hypoglycemia)
6. Decrease in exercise performance (fatigue)
7. Increase in plasma triglycerides (VLDL)
8. CNS effects may include sedation, sleep, disturbances and depression
69
What is Carvedilol and what does it do?
- mixed agonists (selective alpha 1 and nonselective beta blocking activities)
- used to treat hypertension, hypertensive emergencies, pheochromocytoma-induced hypertension, and angina
70
How do adrenergic neuron blocking agents, such as Guanethidine, work and what are they used for?
Mechanism: acts at post-ganglionic adrenergic nerve endings to interfere with NE release
Use: hypertension
71
What are the side effects of neuron blocking agents (like Guanethidine)?
1. postural hypotension
2. hypotension
3. fluid retention
4. impaired ability to ejaculate
5. increase in GI motility (diarrhea)
72
How do centrally acting sympatholytic agents, such as Clonidine, work and what are they used for?
Mechanism: directly stimulates CNS alpha 2 receptors to reduce activity in central sympathetic outflow--generalized decrease in sympathetic activity
Use: Antihypertensive agent
73
What are the side effects of centrally acting sympatholytic agents (like Clonidine)?
1. Sedation and or mental lassitude
2. dry mouth
3. rebound hypertension with abrupt withdrawal
