Term
| What adrenergic receptors mediate the broncial smooth muscle? |
|
Definition
|
|
Term
| Effect
β2 agonist on bronchial smooth muscle |
|
Definition
| bonchodilation (thus β2 agonists are used in asthma) |
|
|
Term
| What adrenergic receptors mediate the iris radial muscle? |
|
Definition
|
|
Term
| Effect
α1 agonist on iris radial muscle |
|
Definition
| contraction => mydriasis (thus α1 agonists are used in opthalmology) |
|
|
Term
| What adrenergic receptors are in GI smooth muscle? |
|
Definition
|
|
Term
| Effect
α1 & β2 agonists in GI smooth muscle together |
|
Definition
| relaxation (tho sphincter muscles may contract) |
|
|
Term
| Why do α1 agonists cause relaxation in GI smooth muscle? |
|
Definition
| hyperpolarization => prevention of pacemaker potentials reaching threshold for AP => relaxation |
|
|
Term
| What adrenergic receptors are in bladder smooth muscle? |
|
Definition
|
|
Term
| What adrenergic receptors are dominant in the bladder detrussor muscle? |
|
Definition
|
|
Term
| Effect
β2 on bladder detrussor muscle |
|
Definition
|
|
Term
| Where are α1 receptors concentrated in the bladder? |
|
Definition
|
|
Term
| Effect
α1 agonists in the trigone region of the bladder |
|
Definition
|
|
Term
| What adrenergic receptors are in uterus smooth muscle? |
|
Definition
|
|
Term
Effect
NE on uterus smooth muscle |
|
Definition
|
|
Term
Effect
Epi on uterus smooth muscle |
|
Definition
|
|
Term
| Effect
β2 agonist on uterus smooth muscle |
|
Definition
| relaxation (thus β2 agonists are used to delay premature labor) |
|
|
Term
| What adrenergic receptors are dominant in spleen smooth muscle? |
|
Definition
|
|
Term
| Effect
α1 agonist in spleen |
|
Definition
| contraction => blood expulsion |
|
|
Term
| What adrenergic receptors are dominant in the vas deferens & seminal vesicles? |
|
Definition
|
|
Term
| Effect
α1 agonist in vas deferens & seminal vesicle smooth muscle |
|
Definition
|
|
Term
| How does an α1 agonist lead to contraction in vas deferens & seminal vesicles? |
|
Definition
| => membrane depolarization => AP generation => contraction |
|
|
Term
| What intracellular response is seen in β receptor activation? |
|
Definition
| increased cAMP => hyperglycemia, hyperlactemia, increase in FFA & overall increase in caloigenic effect |
|
|
Term
| Do Epi & NE readily cross the BBB? |
|
Definition
|
|
Term
| What CNS manifestation can EPI (& NE to a lesser extent) produce if given systemically? |
|
Definition
| resp. stimulation, restlessness & anxiety |
|
|
Term
| How do Epi & NE cause CNS manifestations? |
|
Definition
unclear
either direct action on CNS or indirect result of systemic effects |
|
|
Term
| Where is the CNS do neurons contain NE? |
|
Definition
|
|
Term
| Are there adrenergic receptors & NET in the CNS? |
|
Definition
|
|
Term
| What type of drugs are indirect-acting adrenergics? |
|
Definition
|
|
Term
| What are the 3 phenylethylamines? |
|
Definition
1) tyramine
2) amphetamine
3) ephedrine |
|
|
Term
| How do indirectly-acting adrenergic drugs (sympathomimetic) agents work? |
|
Definition
| releasing NE from sympathetic neurons (do NOT directly stimulate adrenergic receptors) => NE action on α & β receptors |
|
|
Term
| How do indirectly-acting adrenergic drugs cause release of NE? |
|
Definition
|
|
Term
| How do we know that NE is released by a non-exocytotic process via indirectly-acting adrenergic drugs? |
|
Definition
| Ca2+ not required and DBH & other NE vesicle contents are not released |
|
|
Term
|
Definition
| dose-dependent increase in BP, HR, & other NE effects for several minutes |
|
|
Term
| How does tyramine produce it's effect? |
|
Definition
accumulated by adrenergic neurons by NET => NE release from synaptic vesicles => NE diffusion out of nerve terminal
it also delays oxidation of NE in nerve terminal b/c it's a substrate of MAO |
|
|
Term
| How is tyrosine formed naturally? |
|
Definition
| product of decarboxylation of tyrosine (occurs in aged cheeses & some wines) |
|
|
Term
| Why can't tyramine be a drug? |
|
Definition
| When ingested in foods, it's oxidized by MAO to inactive product in gut mucosa & liver |
|
|
Term
| When can tyramine effects by profoundly potentiated, even life threatening? |
|
Definition
| when foods are administered with tyramine while on MAO inhibitors |
|
|
Term
| How do amphetamine & ephedrine differ from tyramine? |
|
Definition
| Same mechanism, same high affinity for MAO, just are not metabolized by MAO (therefore can be used as stong sympathomimetic drugs) |
|
|
Term
| What prevents MAO metabolism of amphetamine & ephedrine? |
|
Definition
|
|
Term
| What phenylethylamines can penetrate the BBB? |
|
Definition
|
|
Term
| What CNS effects are seen when amphetamine & ephedrine penetrate the BBB? |
|
Definition
| arousal - restlessness, remor, reduction of fatigue, loss of appetite (by release of NE and/or DA) |
|
|
Term
| What is the duration of action of amphetamine & ephedrine? |
|
Definition
|
|
Term
Effect
acute overdose of amphetamine & ephedrine |
|
Definition
confusion & anxiety
elevated BP
angina
cardiac arrhythmia
psychotic behavior (therefore supervise carefully) |
|
|
Term
| What develops in chronic amphetamine use? |
|
Definition
|
|
Term
|
Definition
phenomenon of rapid tolerance via lg doses of amphetamine
(BP response decreases over time with each subsequent dose) |
|
|
Term
| Why does tachyphylaxis occur? |
|
Definition
| gradual depletion of NE storage => decrease of NE release |
|
|
Term
Do NE & Epi injections demonstrate tachyplaxis?
Why? |
|
Definition
| no since they act directly on receptors and don't affect NE storage |
|
|
Term
| How does ephedrine differ from amphetamine? |
|
Definition
| ephedrine has some minor direct effects on adrenergic receptors |
|
|
Term
| Is ephedrine used as a drug? |
|
Definition
| not in the U.S., but psudoephedrine is used as an OTC decongestant |
|
|
Term
| What is the most important use of adrenergic drugs? |
|
Definition
|
|
Term
| How do anti-hypertensives decrease BP? |
|
Definition
| interefere with sympathetic neurotransmission at different steps to reduce release/action of NE => decreased sympathetic tone in vascular smooth muscle & in heart => decreased BP |
|
|
Term
| What are the 5 anti-ATN drugs? |
|
Definition
1) α-methyl tyrosine
2) Reserpine
3) Guanethidine
4) Clonidine
5) Methyldopa |
|
|
Term
| How does α-methyl tyrosine exhert it's antihypertensive effects? |
|
Definition
| TH inhibition (competes with tyrosine => inhibition of of L DOPA formation) |
|
|
Term
| What was the clinical use of α-methyl tyrosine? |
|
Definition
| pheochromocytoma to reduce catecholamines prior to surgical removal |
|
|
Term
| Why is α-methyl tyrosine no longer used? |
|
Definition
| produces renal damage via crystallization |
|
|
Term
| How does reserpine exert impairment to both autonomic nervous system & CNS? |
|
Definition
reduces NE storage by blacking NE carrier of synaptic vesicles => blacking of NE transport & permitting NE to accumulate in cytosol for metabloism by MAO => decreased adrenergic function in ANS
may also impair DA transport by synaptic vesicles => decreased adrenergic effect in CNS |
|
|
Term
| What 2 other non-adrenergic transmitters can be depleated by reserpine? |
|
Definition
| depletion of 5-HT from serotonergic neurons & histamine from platelets |
|
|
Term
| How long do the effects of reserpine last? |
|
Definition
| up to a week or more after the last dose |
|
|
Term
parasympathetic SE
reserpine |
|
Definition
miosis
excessive salivation
gastric hypersecretion
peptic ulceration
hyperperistalsis
diarrhea
bradycardia
hypotension |
|
|
Term
| Why is the SE profile for reserpine so extensive? |
|
Definition
| doesn't impair parasympathetic function |
|
|
Term
|
Definition
depression (=> suicide)
tremors |
|
|
Term
|
Definition
| alkaloid from snakeroot plant |
|
|
Term
|
Definition
|
|
Term
| What was one of the first synthetic anti-HTN medication? |
|
Definition
|
|
Term
|
Definition
| lower bp, HR, 7 renin secretion |
|
|
Term
|
Definition
1) uptaken to the sympathetic neuron by NET => blockage of NET (acute)
2) blocks exocytosis of NE & therefore transmission (acute)
3) with continued exposure, decreases NE stores (chronic) |
|
|
Term
| How is guanethidine used clinically? |
|
Definition
|
|
Term
| What is clonidine highly specific for? |
|
Definition
|
|
Term
| What is the rank of potency of α2 vs. α1 receptors for clonidine, α-methyl NE, NE, & phenylephrine? |
|
Definition
clonidine > α methyl NE > NE >>>> phenylephrine
α2 receptors α1 receptors |
|
|
Term
|
Definition
|
|
Term
| What adrenergic receptors does clonidine act on? |
|
Definition
| α2 receptors of CNS & imidazoline receptors |
|
|
Term
| Effect
clonidine on α2 receptors |
|
Definition
| reduce sympathetic outflow |
|
|
Term
Effect
clonidine on imidazoline receptors |
|
Definition
| decrease sympathetic outflow |
|
|
Term
|
Definition
| dizziness, nausea, impotense, dry mouth |
|
|
Term
| What SE are seen in sudden withdrawl of clonidine after long-term use? |
|
Definition
hypertensive crisis (due to over activity of sympathetic nerves)
Sx include:
nervousness, headache, tachycardia, hypotension, sweating, etc. |
|
|
Term
| What special Tx can clonidine or it's related agents be used for clinically? |
|
Definition
reduce intraoccular pressure
analgestic effects to help with withdrawl |
|
|
Term
| What other antihypertensive does methyldopa's MOA resemble? |
|
Definition
|
|
Term
| What is methyldopa metabolized to? |
|
Definition
|
|
Term
| Where is α-methyl NE stored? |
|
Definition
| in synaptic vesicles of adrenergic neurons => releasesame way NE is released |
|
|
Term
| How does α-methyl NE differ from NE? |
|
Definition
| much lower affinity for β receptors than NE |
|
|
Term
| Which α receptor does α-methyl NE have a much higher affinity for? |
|
Definition
|
|
Term
|
Definition
| reduce sympathetic nerve impulse activity in medulla via activation of α2 receptors
reduce renal vascular resistance |
|
|
Term
| What anti-depressants affect the adrenergic system? |
|
Definition
|
|
Term
| What are 3 examples of TCAs? |
|
Definition
1) imipramine
2) desipramine
3) amitryptyline |
|
|
Term
|
Definition
| block NET => enhanced NE action |
|
|
Term
| Which TCA is the most potent NET inhibitor & a weak 5-HT transport inhibitor? |
|
Definition
|
|
Term
| Which TCA inhibits 5-HT & NE equally well, but 20x less potent than desipramine? |
|
Definition
|
|
Term
| What other receptors can be blocked by TCAs at higher concentrations? |
|
Definition
|
|
Term
|
Definition
tremor
insomnia
blurred vision
orthostatic hypotension |
|
|
Term
| What 2 abusive drugs use adrenergic receptors? |
|
Definition
|
|
Term
|
Definition
| reversibly binds to NET, completely blocking the uptake of NE & Epi => marked enhancement of NE & Epi response |
|
|
Term
|
Definition
CNS stimulation (followed by depression-like action)
local anesthetic action (via nerve conduction block), but NOT at the same concentrations for NE & Epi potentiation |
|
|
Term
| How are amphetamines used clinically? |
|
Definition
|
|
Term
|
Definition
CNS arousal
suppress appetite & sleep |
|
|
Term
SE
chronic amphetamine overdose |
|
Definition
|
|
Term
|
Definition
restlessness
tremor
reduction of fatigue
loss of appetite |
|
|
Term
Sx
acute overdose
amphetamines |
|
Definition
severe confusion & anxiety
increased BP
angina
arrythmia
other adrenergic effects |
|
|
Term
| What are 3 amphetamines used to treat ADHD? |
|
Definition
1) methamphetamine
2) dextroamphetamine
3) adderall |
|
|
Term
| What ADHD amphetamine is the most abused? |
|
Definition
| methamphetamine (ritalin) aka crystal meth |
|
|
Term
| What are 2 potent β2 agonists that cause relaxation of cronchial smooth muscle? |
|
Definition
|
|
Term
| What 2 drugs are used to treat asthma, chronic bronchitis, nasal decongestant & mydriasis? |
|
Definition
|
|
Term
| Why isn't Iso used to Tx asthma? |
|
Definition
| risk of cardiac stimulation => need more selective β2 agonists |
|
|
Term
| What are the 2 cardiovascular emergencies? |
|
Definition
| Anaphylactic shock & Circulatory shock |
|
|
Term
| What 3 adrenergics are used to treat anaphylactic shock? |
|
Definition
1) Epi
2) NE
3) PE (parenteral) |
|
|
Term
| What 2 adrenergics are used to treat circulatory shock? |
|
Definition
1) NE
2) metaraminol (limited usefulness; may worsen condition) |
|
|
Term
| Why is local anesthetic often mixed with Epi or PE? |
|
Definition
| to decrease removal rate from injection site & increase duration of action |
|
|
Term
| What adrenergic agents are used to maintain blood pressure in spinal anesthesia? |
|
Definition
| Epi, PE, methoxamine, NE, etc. |
|
|
Term
| What adrenergic is used to treat urticaria (hives)? |
|
Definition
|
|
Term
| What 2 adrenergics are used as a nasal degongestant? |
|
Definition
|
|
Term
| What 2 adrenergics are used to cause mydriasis? |
|
Definition
1) PE
2) Ephedrine (topical) |
|
|
Term
| What 2 adrenergics are used to stimulate the CNS? |
|
Definition
1) amphetamine
2) methamphetamine |
|
|
Term
| What are the 2 isomer types of the adrenergic agonist dobutamine? |
|
Definition
|
|
Term
Function
L isomer Dobutamine |
|
Definition
| α agonist & weak β1 agonist |
|
|
Term
Function
D isomer Dobutamine |
|
Definition
| α1 antagonist & potent β1 agonist |
|
|
Term
| Since Dobutamine comes as a racemic mixture of both L & D isomers, what is the overall effect of Dobutamine? |
|
Definition
|
|
Term
| When is dobutamine used clinically? |
|
Definition
| actue management of heart failure to improve cardiac output |
|
|
Term
Function
adrenergic antagonists |
|
Definition
| inhibit action of NE, Epi & other adrenergic agonists at receptor level => inhibits responses of effector organs |
|
|
Term
| What is the selectivity of the α adrenergic antagonists to prazosin, phenoxybenzamine, phentolamine, yohimbine? |
|
Definition
|
|
Term
|
Definition
| decrease in BP due to decrease in vascular resistance => reflex tachycardia & increase in cardiac output |
|
|
Term
| Which α receptor can exaggerate the effects of α antagonists? |
|
Definition
|
|
Term
| Why do α2 antagonists exaggurate α agonist effects? |
|
Definition
| enhanced NE in cardiac tissues => stimulation of β1 receptors |
|
|
Term
| How do α2 antagonists increase NE release in heart (& blood vessels)? |
|
Definition
| they "disinhibit" sympathetic drive to periphery => increased sympathetic outflow and NE release in heart & blood vessels |
|
|
Term
| What ate the 3 α antagonist groups? |
|
Definition
1) Haloalkylamines
2) Imidazolins
3) Qunazolins |
|
|
Term
What α antagonist type are phenoxybenzamine?
prazosin?
phentolamine? |
|
Definition
phenoxybenzamine: haloalkylamine
phentoalmine: imidazolin
prazosin: quanzolin |
|
|
Term
| Which type of α agonists are more popular clinically? |
|
Definition
|
|
Term
|
Definition
a noncompetitive irreversible α adrenergic antagonist.
It forms a covalent bond b/w α receptors & drug |
|
|
Term
| What are the "other" actions of phenoxybenzamine? |
|
Definition
| blocks neuronal & extraneuronal uptake of NE |
|
|
Term
| Why is phenoxybenzamine considered non-specific? |
|
Definition
| It blocks receptors for 5-HT, Ach, & histamine too |
|
|
Term
| What is the clinical use of phenoxybenzamine? |
|
Definition
management of Sx associated with pheochromocytoma & severe HTN
Use 1-3 weeks prior to operation to control exaggerated actions of catecholamines released from the tumor
Tx for peripheral vascular disease (Raynaud's syndrome) |
|
|
Term
|
Definition
| competitive reversive α antagonist |
|
|
Term
| How is phentolamine used clinically? |
|
Definition
HTN control in patients with pheochromocytoma
hypertensive crisis following abrupt withdrawl of clonidine or tyramine containing foods when on an MAO inhibitor |
|
|
Term
|
Definition
| slective antagonist of α1 (about 1000x greater affinity for α1 than α2) |
|
|
Term
| What is the clinical use for prazoin? |
|
Definition
HTN
congestive cardiac failure |
|
|
Term
| Why is prazoin used in congestive cardiac failure? |
|
Definition
| reduces preload & afterload |
|
|
Term
| What is the half life of prazoin? |
|
Definition
|
|
Term
| What is the duration of action of prazoin? |
|
Definition
|
|
Term
| What is the advantage of doxazoin over prazoin (newer α1 blocker)? |
|
Definition
| longer half life (10 hr) therefore longer duration of action (~20 hr) |
|
|
Term
| What are the 3 α1 subtypes? |
|
Definition
|
|
Term
| What are the 3 α3 subtypes? |
|
Definition
|
|
Term
| What are the most important adrenergic agents clinically? |
|
Definition
|
|
Term
| What 2 β antagonists are among the most perscribes Rx every year? |
|
Definition
|
|
Term
| What are β blockers used clinically for Tx of? |
|
Definition
HTN
angina
arrythmias
prevention of 2nd heart attack
MI
migranes
tremors
EtOH withdrawl
anxiet
glaucoma
etc. |
|
|
Term
| What synthetic β blocker is the classical prototype β antagonist that all others are compared to? |
|
Definition
|
|
Term
|
Definition
| selective β antagonist without any agonist activity |
|
|
Term
| Why is propranolol only used in times of sympathetic elevation (exercise/stress)? |
|
Definition
| it has little cardiovascular effect alone (compared to α antagonists), but has great effect in times of stress |
|
|
Term
|
Definition
| decrease HR & cardiac output (β1)
reduced sinus rate & slowed conduction
increased peripheral resistance (β2) => initial increase in BP (followed by normalization via vagus)
release of renin from juxtaglomerular apparatus (β1)
decrease peripheral manifestations of hyperthyroidism
reduce intraoccular pressure
anxiety management
prophylaxis of migranes |
|
|
Term
| What β blocker has complication when reducing intraoccular pressure in glaucoma and occular HTN? |
|
Definition
|
|
Term
| Why are β blockers used as anxiolytics? |
|
Definition
| anxiety is caused by increased activity of SS |
|
|
Term
MOA
β blocker prophylaxis of migranes |
|
Definition
| block CNS β receptors => vasodilation |
|
|
Term
| When should β blocker NOT be used (b/c the worsen the condition)? |
|
Definition
asthma
congestive heart failure
Raynaud's syndrome
diabetes |
|
|
Term
| What DDI is important to remember when dealing with β blockers? |
|
Definition
| β blockers + Ca2+ channel blockers = AV block |
|
|
Term
| Why must β blockers be withdrawn gradually after prolonged use? |
|
Definition
| To avoid withdrawl Sx, which include MI |
|
|
Term
| When can selective β blockers be non-selective? |
|
Definition
|
|
Term
| What 7 β blockers are non-selective (i.e. blocks both β1 & β2)? |
|
Definition
1) Propranolol
2) Carteolol
3) Levobunolol
4) Nadolol
5) Pindolol
6) Timolol
7) Penbutolol |
|
|
Term
| What is the only non-selevtive β blocker to be a full partial agonist? |
|
Definition
pindolol
(slight acitivity with carteolol, timolol, penbutolol) |
|
|
Term
| What is the only non-selective β blocker with membrane stabalizing capability? |
|
Definition
propranolol
(slight activity with pindolol) |
|
|
Term
| What are the 5 cardio selective β blockers (i.e. β1)? |
|
Definition
1) Acebutolol
2) Atenolol
3) Betaxolol
4) Esmolol
5) Metoprolol |
|
|
Term
| What is the only cardio-selective β blocker with slight partial agonist activity? |
|
Definition
|
|
Term
| What are the 2 cardio-selective β blockers with slight membrane stablilization? |
|
Definition
|
|
Term
|
Definition
| cardiospecific β blocker for β1 |
|
|
Term
|
Definition
decrease cardiac force of contraction & HR
vasodilation
decrease in peripheral resistance |
|
|
Term
| What is the classic α & β blocking agent? |
|
Definition
|
|
Term
| How does labetolol compare in potency to other α & β blockers? |
|
Definition
1/3 as potent as propranolol
1/10 as potent as phentolamine |
|
|
Term
| Is labetolol more selective for α or β adrenergic receptors? |
|
Definition
|
|
Term
| Is labetelol a selective or non-selective β blocker? |
|
Definition
|
|
Term
| Does labetolol have any partial agonist activity or membrane stabilization like other β blockers? |
|
Definition
|
|
Term
| What does membrane stabilization mean? |
|
Definition
| local anesthetic-like action |
|
|
Term
| What α receptor does labetelol have little affinity for? |
|
Definition
| pre-synaptic α2 receptors |
|
|
Term
| How does labetelol have cocaine-like action? |
|
Definition
| blocks NE neuronal uptake |
|
|
Term
|
Definition
| lower peripheral vascular resistance w/o major change of HR or CO (sum of effects of α & β blockers) |
|
|
Term
| When is labetelol used clinically? |
|
Definition
HTN
HTN w/ angina
preop management of patients with pheochromocytoma |
|
|
Term
|
Definition
|
|
