adrenergic receptors Flashcards
Alpha receptors generally mediate
Excitation
except in GI
Beta receptors generally mediate
Inhibition
except in heart
Alpha 1
Radial muscle - contracts
vascular smooth muscle, skin, splanchnic vessels - contracts
skeletal muscle vessels - contracts
GI - contracts sphincters
Alpha 2
GI - walls relax
Beta 1
SA node - accelerates
Ectopic pacemakers - accelerates
contractility - increases
renin release
Beta 2
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
What tissues have alpha receptors?
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
In general, Alpha 1 receptors are found on
postsynaptic sympathetic effector sites
In general, Alpha 2 receptors are found on
presynaptic neurons (some postjunctional sites)
In general, Beta 1 receptors are found on
adipocytes and the heart
In general, Beta 2 receptors are found on
smooth muscle (some presynaptic neurons)
In general, Beta 3 receptors are found on
adipocytes but has a low affinity for endogenous catecholamines
what type of receptors are alpha and beta adrenergic receptors?
G protein coupled
What effector systems does alpha 1 activate?
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)
What effector systems does alpha 2 activate?
inhibit adenylylcyclase activity via Gi protein
what effector systems do Beta receptors activate?
all subtypes stimulate activity of adenylyl cyclase via Gs protein
though B1 also does increase L type Ca+2 channel activation
Alpha 1 agonists
phenylephrine
methoxamine
phenylephrine
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
Methoxamine
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
Alpha 2 agonists
clonidine
Clonidine
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
Beta 1 agonists
dobutamine
Dobutamine
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
beta 2 agonists
terbutaline
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
What drug is Albuterol similar to?
Terbutaline
Indirect adrenergic agonists
Amphetamine
Dextroamphetamine
methamphetamine
promote the release of NE from adrenergic nerve terminals
- Heart failure (inotropic > chronotropic), cardiac stress testing
Dobutamine
b1>b2,a
- hypotension (vasoconstrictor), ocular procedures (mydriatic), rhinitis (decongestant)
phenylephrine
a1>a2
Acute asthma*
Albuterol
b2>b1
salmeterol*
long term asthma or COPD control
b2>b1
*Reduce premature uterine contractions
Terbutaline
b2>b1
*indirect general agonist, releases stored catecholamines
nasal decongestant, urinary incontinence, hypotension
Ephedrine
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
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
What is gradually replacing Ephedrine as a bronchodilator?
Terbutaline and Albuterol
they are more selective for bronchiolar receptors
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
- Narcolepsy, obesity, ADD
indirect general agonist, reuptake inhibitor, release stored catecholamines
Amphetamines
mixed acting adrenergic agonists
Ephedrine
metaraminol
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)
Tx bouts of paroxysmal atrial tachycardia
Metaraminol (a1 agonist)
txs hypotensive states
get reflex suppression of cardiac activity in response to increased pressure
Alpha adrenoreceptor antagonists
Phenoxybenzamine
phentolamine
prazosin
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
Adverse effects of phenoxybenzamine
orthostatic hypotension and reflex tachycardia
Ejaculatory dysfunction - impaired smooth muscle contraction
- Pre-op for Pheochromocytoma removal to prevent catecholamine crisis
Tox - orthostatic hypotension, reflex tachycardia
Phenoxybenzamine
Phentolamine
reversible blockade of a1 and a2
a1 = a2
blocks hypertensive response to alpha agonists
tx hypertension associated with pheochromocytoma
tx erectile dysfunction
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
*give to pts on MAO inhibitors who eat tyramine-containing foods
Phentolamine
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
Side effects of Prazosin
tends less to produce orthostatic hypotension
dizziness
Terazosin
analogue to Prazosin
tx hypertension but can also tx of BPH b/c reduces obstructive symptoms and urinary urgency
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
*For BPH, PTSD, HTN
has first dose effect (hypotension, dizzy,HA)
alpha 1 selective blockers
Prazosin - PTSD
Terazosin
Doxazosin
Tamsulosin
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
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,
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
Metoprolol
cardioselective beta blocker, high affinity for b1
used to induce beta blockade in patients prone to bronchoconstriction
Agents that inhibit NE release/storage
Gaunethidine
Reserpine
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
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
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
Reserpine
inhibits uptake of catecholamines (both dopamine and NE) into neuronal storage vesicles
depletes NE
reduces catecholamine concentration in adrenal medulla
Reserpine treats
mild to moderate HTN
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
Methyl Tyrosine
inhibits tyrosine hydroxylase, rate limiting enzyme
for management of Pheochromocytoma
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
side effects of methyldopa
CNS - sedation, drowsiness
sympathetic depression - orthostatic hypotensin, nasal congestion
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.
