Week 12 ANS Flashcards
You can stimulate the parasympathetic NS w/drugs that act as an agonist to _______ receptors, or inhibit _____________ enzyme.
nicotinic receptors
acetylcholinesterase enzyme
describe nicotinic receptors
- “nicotinic cholinergic receptors”
- in sympathetic ganglia & skeletal mm., nicotine mimics stimulatory actions of Ach
- vs. muscarinic which act in smooth mm. & glands via muscarine stimulation
- ligand-gated ion channels
describe nicotinic receptors
- “nicotinic cholinergic receptors”
- in sympathetic ganglia & skeletal mm., nicotine mimics stimulatory actions of Ach
- vs. muscarinic which act in smooth mm. & glands via muscarine stimulation
- ligand-gated ion channels (do not use 2nd messengers)
- signal for muscular contraction upon a chemical stimulus
- triggered by binding of Ach & nicotine
Which adrenergic receptors (a, b1, b2) affect vascular system?
alpha
Alpha-adrenoceptor agonists (α-agonists) bind to α-receptors on vascular smooth muscle and induce smooth contraction and vasoconstriction, thus mimicking the effects of sympathetic adrenergic nerve activation to the blood vessels.
Which adrenergic receptors (a, b1, b2) affect heart?
beta 1
antagonists increase cardiac output
Which adrenergic receptors (a, b1, b2) affect lungs?
beta 2
agonists cause smooth mm relaxation
what side effects would you expect from a substance that blocks b2 receptors?
- respiratory problems (bronchospasm)
- however no isolated b2 blocker is used clinically
- b1 antagonists are also b2 blockers => CV depression, nausea, diarrhea, diabetes, etc)
what is the difference between miosis and mydriasis?
mydriasis: pupil dilation
miosis: pupil contraction
Which adrenergic receptors (a, b1, b2) affect heart?
beta 1
antagonists increase cardiac output
remember: 1 heart
Which adrenergic receptors (a, b1, b2) affect lungs?
beta 2
agonists cause smooth mm relaxation
remember: 2 lungs
what autonomic receptors do you want to target for asthma
beta 2
want agonists
what autonomic receptors do you want to target for BPH
a1
want antagonists
what autonomic receptors do you want to target for urinary incontinence
muscarine
want antagonists
what autonomic receptors do you want to target for glaucoma
muscarine - agonist
b1 - antagonist
s/e assoc. with b1 antagonists
hypotension fatigue nausea diarrhea diabetes erectile dysfunction bronchospasm decreased circulation insomnia
s/e assoc. with b2 agonists
insomnia
anxiety
tremors
CV sxs
s/e assoc. with a1 agonists
rebound congestion
freq. application causes ischemia
s/e assoc. with a1 antagonists
retrograde ejaculation
s/e assoc. with a2 antagonist
fatigue
dry mouth
s/e assoc. with muscarinic receptor agonists
muscarine, pilocarpine, Ach
- increased secretions (saliva, urine, lacrimation, defecation), mitosis,smooth mm contraction & peristalsis (Cramping)
What is the difference between epinephrine & ephedra with regards to how long it remains active in the body?
- epinephrine: short T1/2 (MAO & COMT enzymes)
- ephedra: more intense reaction, longer acting
How does an a2 agonist lower BP?
- a2 receptors located in brain
- SE: inhibits NE release by negative feedback
what are b1 blockers used to treat? what is the most common side effect?
- tx: heart problems & glaucoma
- s/e: decreased heart function, fatigue, dizziness
what are b2 agonists used to treat? what is the most common side effect?
- asthma, pulmonary conditions
- s/e: insomnia, anxiety, tremors, CV problems
what are a1 blockers used to treat? what is the most common side effect?
- tx: BPH, HTN
- s/e: retrograde ejaculation
what are s/e of cholinesterase inhibitors? what would you use it to treat?
- dementia of Alzheimer’s
- s/e: SLUDGE
salivation/lacrimation/urination/defecation/GI upset/emesis)
if someone was poisoned with a nerve gas or a mushroom was causing severe GI distress (vomiting, diarrhea), what class of drugs could help?
anticholinergics
e.g. atropine, oxybutynin, tolterodine
what class of drugs decrease nocturnal melatonin levels & decrease HDL cholesterol & elevate blood sugar?
b1 blockers
what receptors do confine and curare target? agonist or antagonist?
- conine: nicotinic early agonist, and late antagonist
- curare: nicotinic antagonist
epinephrine binds to which receptors?
adrenergic
muscarinic
nicotinic
adrenergic
alpha & beta
(not selective - binds to all)
indications for administering epinephrine?
anaphylaxis
sepsis (can cause BP to drop)
cardiac arrest
asthma - when other drugs ineffective or unavailable
MOA of ephedrine?
- releases stored NE from storage vesicles
- directly stimulates both alpha & beta receptors
compare epinephrine & norepinephrine
The actions of epinephrine and norepinephrine are generally similar, although they differ from each other in certain of their effects. Norepinephrine constricts almost all blood vessels, while epinephrine causes constriction in many networks of minute blood vessels but dilates the blood vessels in the skeletal muscles and the liver. Both hormones increase the rate and force of contraction of the heart, thus increasing the output of blood from the heart and increasing the blood pressure. The hormones also have important metabolic actions. Epinephrine stimulates the breakdown of glycogen to glucose in the liver, which results in the raising of the level of blood sugar. Both hormones increase the level of circulating free fatty acids.
indications for ephedra/pseudoephedrine/synephrine?
asthma
sinusitis
weight loss
allergies
MOA of caffeine?
- inhibits adenosine receptors = increases release of catecholamines
- inhibits phosphodiesterase enzyme (increases cAMP)
MOA of caffeine?
- inhibits adenosine receptors = increases release of catecholamines
- inhibits phosphodiesterase enzyme (increases cAMP; cAMP is inactivated by phosphodiesterase) => results of epinephrine are sustained
- coffee doesn’t bind to adrenergic receptors, it just prevents the breakdown of the signal
what sympathetic effects does cAMP result in?
- relaxation of smooth mm
- enhanced contractility of cardiac mm
- glycogenolysis
- lipolysis
caffeine inhibits which enzyme?
phosphodiesterase
which breaks down cAMP
what is the MOA of a1 agonist as a decongestant?
a1 agonist = vasoconstriction
topical application avoids systemic s/e
what do a-agonists do?
Alpha-adrenoceptor agonists (α-agonists) bind to α-receptors on vascular smooth muscle and induce smooth contraction and vasoconstriction, thus mimicking the effects of sympathetic adrenergic nerve activation to the blood vessels.
what is the difference between a1 and a2 receptors?
α1-adrenoceptors are the predominant α-receptor located on vascular smooth muscle.
α2-adrenoceptors located on the sympathetic nerve terminals that inhibit the release of norepinephrine and therefore act as a feedback mechanism for modulating the release of norepinephrine.
what is the MOA of a2 agonist as an antihypertensive?
α2-adrenoceptors located on the sympathetic nerve terminals that inhibit the release of norepinephrine and therefore act as a feedback mechanism for modulating the release of norepinephrine.
a2 agonists decrease release of EP/ND
what is the MOA of a1 agonist as a decongestant?
a1 agonist = vasoconstriction
sympathoMIMETIC
topical application avoids systemic s/e
what is the MOA of a2 agonist as an antihypertensive?
α2-adrenoceptors located on the sympathetic nerve terminals that inhibit the release of norepinephrine and therefore act as a feedback mechanism for modulating the release of norepinephrine.
a2 agonists decrease release of EP/ND
sympathoLYTIC
what is the MOA of a1 antagonist as an antihypertensive or as tx for BPH?
sympathoLYTIC
- vasodilator
- relax smooth mm & sphincters (prostate & bladder)
which class of adrenergic drugs end in "-zosin"? which ends in "-zoline"?
zosin: alpha blockers
zoline: alpha agonist
describe beta blockers in general
Beta-blockers are drugs that bind to beta-adrenoceptors and thereby block the binding of norepinephrine and epinephrine to these receptors. This inhibits normal sympathetic effects that act through these receptors. Therefore, beta-blockers are sympatholytic drugs. Some beta-blockers, when they bind to the beta-adrenoceptor, partially activate the receptor while preventing norepinephrine from binding to the receptor. These partial agonists therefore provide some “background” of sympathetic activity while preventing normal and enhanced sympathetic activity.
describe beta blockers in general
Beta-blockers are drugs that bind to beta-adrenoceptors and thereby block the binding of norepinephrine and epinephrine to these receptors. This inhibits normal sympathetic effects that act through these receptors. Therefore, beta-blockers are sympatholytic drugs. Some beta-blockers, when they bind to the beta-adrenoceptor, partially activate the receptor while preventing norepinephrine from binding to the receptor. These partial agonists therefore provide some “background” of sympathetic activity while preventing normal and enhanced sympathetic activity.
Beta-blockers prevent the normal ligand (norepinephrine or epinephrine) from binding to the beta-adrenoceptor by competing for the binding site.
blood vessels have b1 or b2 receptors?
b2
heart has predominantly which beta receptor type? b1 or b2?
b1
heart has predominantly which beta receptor type? b1 or b2?
b1
Compared to their effects in the heart, beta-blockers have relatively little vascular effect because β2-adrenoceptors have only a small modulatory role on basal vascular tone. Nevertheless, blockade of β2-adrenoceptors is associated with a small degree of vasoconstriction in many vascular beds. This occurs because beta-blockers remove a small β2-adrenoceptor vasodilator influence that is normally opposing the more dominant alpha-adrenoceptor mediated vasoconstrictor influence.
b1 blockers MOA in cardiac arrhythmias, angina pectoris, HTN, glaucoma (topical)
- b1 receptor antagonist
- selectively block EP/NE from binding to b-receptors
- physiological effects: decrease CO, decrease HR, decrease BP (unclear)
what effect do b1 blockers have on sleep?
insomnia - decreases nocturnal melatonin levels
b2 agonists are indicated for tx in which 2 conditions?
asthma
pulmonary conditions
b2 adrenergic receptors react with with hormone/NT?
adrenaline (epinephrine)
what is the action of b2 receptors?
- smooth mm relaxation (uterus, GI tract [decreases motility], seminal tract, bronchi)
- dilation of blood vessels
- increase mass & contraction speed of striated muscle [fight/flight]
- glycogenolysis (produce fuel)
side effects of b2 agonists?
(less common w/inhalers) insomnia anxiety tremors CV symptoms
name 6 effects that stimulation of the parasympathetic NS has?
pupil constriction (myosis)
bronchoconstriction
decrease HR & force
increase gastric peristalsis & digestion
increase secretions (tears, sweat, saliva, bile)
allows for urination
Ach binds to which 2 receptors?
nicotinic
muscarinic
where are muscarinic receptors located in the body?
- target organs of PNS (heart, lungs, glands, organs)
- CNS (involved in reward & neuroplasticity)
where are nicotinic receptors located in the body?
- autonomic ganglions (sympathetic & PNS)
- neuromuscular junction: somatic NS
