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adrenergic receptors Flashcards

1
Q

Alpha receptors generally mediate

A

Excitation

except in GI

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2
Q

Beta receptors generally mediate

A

Inhibition

except in heart

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3
Q

Alpha 1

A

Radial muscle - contracts
vascular smooth muscle, skin, splanchnic vessels - contracts
skeletal muscle vessels - contracts
GI - contracts sphincters

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4
Q

Alpha 2

A

GI - walls relax

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5
Q

Beta 1

A

SA node - accelerates
Ectopic pacemakers - accelerates
contractility - increases
renin release

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6
Q

Beta 2

A 
ciliary muscle - relaxes (lens thins) 
skeletal muscle - relaxes 
bronchiolar smooth muscle - relaxes 
GI smooth muscle - relaxes walls 
GU smooth muscle - bladder wall relaxes 
uterus - relaxes
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7
Q

What tissues have alpha receptors?

A 
vascular smooth muscle, skin, splanchnic vessels - contracts 
skeletal muscle vessels - contracts 
enteric NS - inhibits 
uterus - contracts 
Ejaculation 
pilomotor smooth muscle - contracts 
apocrine (stress) - increases 
liver gluconeogenesis and glycogenolysis
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8
Q

In general, Alpha 1 receptors are found on

A

postsynaptic sympathetic effector sites

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9
Q

In general, Alpha 2 receptors are found on

A

presynaptic neurons (some postjunctional sites)

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10
Q

In general, Beta 1 receptors are found on

A

adipocytes and the heart

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11
Q

In general, Beta 2 receptors are found on

A

smooth muscle (some presynaptic neurons)

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12
Q

In general, Beta 3 receptors are found on

A

adipocytes but has a low affinity for endogenous catecholamines

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13
Q

what type of receptors are alpha and beta adrenergic receptors?

A

G protein coupled

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14
Q

What effector systems does alpha 1 activate?

A

stimulates PLC-IP3-DAG-PKC pathway via the Gq protein
=similar to M1, M3,M5
pathway stimulates intracellular calcium signaling mechanisms (contraction of smooth muscle)

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15
Q

What effector systems does alpha 2 activate?

A

inhibit adenylylcyclase activity via Gi protein

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16
Q

what effector systems do Beta receptors activate?

A

all subtypes stimulate activity of adenylyl cyclase via Gs protein
though B1 also does increase L type Ca+2 channel activation

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17
Q

Alpha 1 agonists

A

phenylephrine

methoxamine

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18
Q

phenylephrine

A

potent vasoconstrictor
increases both systolic and diastolic pressure with little cardiac effect
induce reflex bradycardia
nasal decongestant (long term can damage mucosa)
mydriatic agent
not a substrate for COMT

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19
Q

Methoxamine

A

potent vasoconstrictor
used to treat hypotensive states (shock, spinal anesthesia)
induces reflex bradycardia

longer duration of action then Phenylephrine
not substrate for COMT or MAO

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20
Q

Alpha 2 agonists

A

clonidine

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21
Q

Clonidine

A

IV infusion causes acute increase in BP due to a2 stimulation in vascular beds. Hypertensive response is transient

followed by prolonged hypotension - due to stimulation of a2 in the CNS which depresses sympathetic outflow to periphery

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22
Q

Beta 1 agonists

A

dobutamine

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23
Q

Dobutamine

A

similar to dopamine in structure but has higher affinity for beta 1 receptors
Inotropic agent to tx CHF
greater affect on contractility than HR
dilates renal vasculature to preserve kidney function

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24
Q

beta 2 agonists

A

terbutaline

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25
Terbutaline
bronchodilator with minimal cardiac effects at normal doses inhaled to relieve bronchospasm given orally, delay of 1 to 2 hours in effect, can be long term for Asthma, emphysema, bronchitis inhibit premature labor not metabolized by COMT or MAO and not taken up into adrenergic terminals
26
What drug is Albuterol similar to?
Terbutaline
27
Indirect adrenergic agonists
Amphetamine Dextroamphetamine methamphetamine promote the release of NE from adrenergic nerve terminals
28
* Heart failure (inotropic > chronotropic), cardiac stress testing
Dobutamine | b1>b2,a
29
* hypotension (vasoconstrictor), ocular procedures (mydriatic), rhinitis (decongestant)
phenylephrine | a1>a2
30
Acute asthma*
Albuterol | b2>b1
31
salmeterol*
long term asthma or COPD control | b2>b1
32
*Reduce premature uterine contractions
Terbutaline | b2>b1
33
*indirect general agonist, releases stored catecholamines | nasal decongestant, urinary incontinence, hypotension
Ephedrine
34
Ephedrine
releases NE from nerve terminals effects resemble NE - both alpha and beta also has some direct agonistic effects on alpha and beta Alpha - tx urinary incontinence Beta - bronchodilation CROSSES BBB - potent CNS stimulant = high dose Insomnia and hypertension
35
Primary use of Ephedrine
beta - relieve bronchoconstriction and mucosal congestion associate with asthma, bronchitis and bronchial spasms. Effective oral and long lasting. not metabolized by MAO or COMT Alpha - pressor agent and nasal decongestant and tx stress incontinence in women
36
What is gradually replacing Ephedrine as a bronchodilator?
Terbutaline and Albuterol | they are more selective for bronchiolar receptors
37
Amphetamine
induces NE release, indirectly stim a and b receptors systolic and diastolic pressure are increased powerful CNS stimulants highly potent sympathomimetic - increases alertness and decreases fatigue, relieves narcolepsy, elevates mood, and improve concentration suppresses appetite, tolerance rapidly develops
38
* Narcolepsy, obesity, ADD | indirect general agonist, reuptake inhibitor, release stored catecholamines
Amphetamines
39
mixed acting adrenergic agonists
Ephedrine | metaraminol
40
Metaraminol
similar to phenylephrine a1 agonist, weak b effects false neurotransmitter (may be uptaken into vesicles with NE) Pressor agent - both direct and indirect a1 in VSM Tx hypotensive states (shock)
41
Tx bouts of paroxysmal atrial tachycardia
Metaraminol (a1 agonist) txs hypotensive states get reflex suppression of cardiac activity in response to increased pressure
42
Alpha adrenoreceptor antagonists
Phenoxybenzamine phentolamine prazosin
43
Phenoxybenzamine
alpha1 and 2, irreversible block mostly a1 Prevent hypertensive crisis associated with pheochromocytoma pre-op for to prevent dangerous elevation in BP BPH - blocks alpha in the SM of the prostate and bladder to alleviate obstructive symptoms control autonomic hyperreflexia with spinal cord injuries
44
Adverse effects of phenoxybenzamine
orthostatic hypotension and reflex tachycardia | Ejaculatory dysfunction - impaired smooth muscle contraction
45
* Pre-op for Pheochromocytoma removal to prevent catecholamine crisis Tox - orthostatic hypotension, reflex tachycardia
Phenoxybenzamine
46
Phentolamine
reversible blockade of a1 and a2 a1 = a2 blocks hypertensive response to alpha agonists tx hypertension associated with pheochromocytoma tx erectile dysfunction
47
Side effects of Phentolamine
orthostatic hypotension reflex cardiac stimulation may augment NE release "dirty" drug does more than just block alpha receptors, also hits serotonin, K+ channels, causes histamine release
48
*give to pts on MAO inhibitors who eat tyramine-containing foods
Phentolamine
49
Prazosin
1000x affinity for a1 over a2 effective inhibitor of cyclic nucleotide phosphodiesterase - block contributes to direct vasodilatory effect can act in CNS to depress sympathetic outflow tx - hypertension, lowers BP by promoting dilation of arterial and venous smooth muscle Both peripheral resistance and venous return are diminished
50
Side effects of Prazosin
tends less to produce orthostatic hypotension | dizziness
51
Terazosin
analogue to Prazosin | tx hypertension but can also tx of BPH b/c reduces obstructive symptoms and urinary urgency
52
Major potential adverse effect of prazosin and terazosin
first dose phenomenon or marked postural hypotension and syncope. Tell pts to take first does at bedtime
53
*For BPH, PTSD, HTN | has first dose effect (hypotension, dizzy,HA)
alpha 1 selective blockers Prazosin - PTSD Terazosin Doxazosin Tamsulosin
54
Beta blockers
end with olol may cause slight, transient increase in BP acutely, but long term effect will be lowering of blood pressure decrease HR, contractility, CO and conduction velocity (increased PR interval) with high sympathetic activity decreased renin release, effective hypotensive agents when renin is low CNS effects
55
Propranolol
blocks b1 and b2 competitively, b1 = b2 tx - HTN, angina, MI, glaucoma (due to depression of aq. humor secretion), reduce peripheral manifestations of hyperthyroidism (cardiac stimulation, tremor), anxiety, migraine,
56
Propranolol contraindications
can produce life threatening bronchoonstriction in pts with asthma or COPD potentiate hypoglycemia by antagonizing catecholamine induced mobilization of glycogen - used with great caution in diabetics CNS - fatigue, sleep disturbances, nightmares, and depression membrane stabilizing effect - leads to depression of membrane excitability undergoes extensive first pass metabolism
57
Metoprolol
cardioselective beta blocker, high affinity for b1 | used to induce beta blockade in patients prone to bronchoconstriction
58
Agents that inhibit NE release/storage
Gaunethidine | Reserpine
59
Guanethidine
produce sympathoplegia by depleting neuronal storage of NE | transported into adrenergic neurons by uptake 1 and enters storage vesicles, release of NE causes NE to be depleted
60
Primary use of Guanethidine
powerful hypertensive agent, to tx severe hypertension that is resistant to other agents lowers both arterial and venous tone among most potent orally effective hypotensive agents
61
Side effects of Guanethidine
imbalance btw sympathetic and parasympathetic tone (orthostatic hypotension, diarrhea) sexual dysfunction - delayed or retrograde ejaculation into the bladder no direct effect on catecholamines in adrenal medulla does NOT cross BBB
62
Reserpine
inhibits uptake of catecholamines (both dopamine and NE) into neuronal storage vesicles depletes NE reduces catecholamine concentration in adrenal medulla
63
Reserpine treats
mild to moderate HTN
64
Side effects of Reserpine
orthostatic hypotension is less than guanethidine can have more prominent CNS effects sedation, nightmares, severe mental depression and thoughts of suicide
65
Methyl Tyrosine
inhibits tyrosine hydroxylase, rate limiting enzyme | for management of Pheochromocytoma
66
Methyldopa
false transmitter analog of L-DOPA stored in granules of adrenergic nerve terminals used as antihypertensive agent, probably due to its action on the CNS valueable in tx HTN complicated by renal disease
67
side effects of methyldopa
CNS - sedation, drowsiness | sympathetic depression - orthostatic hypotensin, nasal congestion
68
Cocaine
local anesthetic inhibitor of uptake 1, which is primary mens of removing NE from synaptic cleft after release = leads to local accumulation of NE t receptors and overstimulation of postsynaptic effector site.

CPR Exam 1 (2 decks)

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