autonomic drugs Flashcards
which components of sympathetic NS are innervated by cholinergic fibers?
adrenal medulla
sweat glands
which components of PNS have nicotinic receptors?
somatic skeletal mm
adrenal medulla
pre-synaptic neurons of autonomic NS
how do nicotinic receptors work?
ligand-gated Na/K channels
- Nn subtype in autonomic ganglia
- Nm subtype in NMJ
how do muscarinic receptors work?
GPCRs
which autonomic receptors are Gq coupled?
Quick! HAVe 1 M&M H1 alpha1 V1 M1 M3
which autonomic receptors are Gi coupled?
I’m 2 MAD
M2
A2
D2
which autonomic receptors are Gs coupled?
B1 B2 D1 H2 V2
what does Gq do?
activates PLC –> IP3 and DAG
- IP3 –> increased Ca influx –> smooth mm contraction
- DAG –> PKC activation
what does Gs do?
activates adenylyl cyclase –> cAMP increases
cAMP activates PKA –> increased Ca influx in heart, inhibition of myosin light chain kinase
what does Gi do?
inhibits adenylyl cyclase –> cAMP decreases, PKA deactivated
actions of alpha1?
Gq
vasoconstriction (skin, GI, renal, brain)
mydriasis
intestinal and bladder sphincter contraction
actions of alpha2?
Gi decreased sympathetic outflow decreased insulin, lipolysis increased platelet agg decreased aqueous humor production
actions of beta1?
Gs
inotropy, chronotropy
increased renin release (via JG cells)
increased lipolysis
actions of beta2?
Gs vasodilation bronchodilation increased lipolysis, insulin release uterine and ciliary mm relaxation increased aqueous humor production
actions of M1?
parasymp - Gq
acts on CNS, enteric NS
actions of M2?
parasymp - Gi
decreases HR and atrial contraction
actions of M3?
parasymp - Gq increases exocrine gland secretion increases gut peristalsis, bladder contraction bronchoconstriction miosis, accommodation
actions of D1?
Gs
relaxes renal vascular smooth mm
actions of D2?
Gi
brain transmitter release
actions of H1?
Gq increased nasal/bronchial mucus increased vascular permeability bronchoconstriction pruritus pain
actions of H2?
Gs
increased gastric acid secretion
actions of V1?
Gq
increased vasoconstriction
actions of V2?
Gs
collecting tubules - AQP insertion
hemocholinium MOA?
blocks choline entry into axon
vesamicol MOA?
blocks ACh entry into pre-synaptic vesicle
botox MOA?
blocks pre-synaptic release of ACh
AChE does what?
splits ACh into choline and acetate in synapse - terminates signal
metyrosine MOA?
blockes tyr –> DOPA conversion
reserpine MOA?
blocks dopa entry into pre-synaptic vesicles
bretylium, guanethidine MOA?
block NE release into synapse
amphetamine, ephedrine MOA?
stimulate NE release into synapse
cocaine, TCA, amphetamine MOA?
block NE reuptake into axon
how does NE regulate its own signal?
binds alpha2 receptor on pre-synaptic axon –> inhibits further release
bethanechol?
uses: ileus, urinary retention
MOA: activates bowel and bladder smooth mm
** resistant to AChE
carbachol?
uses: pupil constriction, glaucoma
MOA: same as ACh
methacholine?
uses: asthma dx challenge
MOA: stimulates airway muscarinic rctprs
pilocarpine?
uses: stimulates sweat, tears, saliva – use in open and closed angle glaucoma
MOA: contracts ciliary mm, pupillary sphincter
** resistant to AChE
drugs for Alzheimer?
AChE inhibitors!
donepezil
rivastigmine
galantamine
edrophonium?
used for dx of MG (historically)
very short acting AChE inhibitor
neostigmine?
AChE inhibitor
uses: ileus, urinary retention, MG, postop reversal of NMJ blockade
** no CNS penetration
physostigmine
AChE inhibitor
uses: anticholinergic toxicity
** crosses BBB - CNS effects
pyridostigmine?
AChE inhibitor
uses: MG (long-acting).
- increases mm strength
- no CNS penetration
what can you exacerbate when giving pts cholinomimetics?
COPD
asthma
peptic ulcers
DUMBBELSS?
cholinesterase inhibitor poisoning - irreversible inhib of AChE
e.g. parathion, malathion - farmers!
** give atropine + pralidoxime (regenerates AChE if early)
atropine, homatropine, tropicamide?
anticholinergic
used in eye –>
mydriasis
cycloplegia
benztropine?
anticholinergic
used in PD, acute dystonia
glycopyrrolate?
anticholinergic
parenteral –> preop to reduce airway secretions
oral –> drooling, peptic ulcer
hyoscyamine, dicyclomine?
anitcholinergic
used in IBS (antispasmodics)
ipratropium, tiotropium?
anticholinergic
used in COPD, asthma
oxybutynin, solifenacin, tolterodine?
anticholinergic
used in bladder spasms, urge urinary incontinence
scopolamine?
anticholinergic
used in motion sickness
atropine toxicity?
hot as a hare…
can cause acute angle closure glaucoma
urinary retention in BPH
hyperthermia in infants
jimson weed?
plant alkaloids –> mydriasis (atropine-like rxn)
“gardener’s pupil”
i ate a fugu/pufferfish! what’s going to happen to me?
tetrodotoxin poisoning (if improperly prepared) binds fast voltage gated Na channels in cardiac and nerve tissue --> depol prevented nausea, diarrhea, paresthesias, weakness, dizziness, hyporeflexia
** tx: supportive
i ate a barracuda/snapper/moray eel! what’s going to happen to me?
ciguatoxin poisoning
opens Na channels –> depol
sx similar to cholinergic poisoning
- temperature dysesthesia (cold feels hot, hot feels cold) is specific for this! WEIRD SHIT
- tx: supportive
i ate bonito/mackerel/mahimahi/tuna! what’s going to happen to me?
scombroid poisoning (if stored at warm temp): bacterial histidine decarboxylase converts histidine --> histamine acute burning sensation in mouth, flushing, erythema, urticaria, possible anaphylaxis
** tx: antihistmines; anti-anaphylactics as needed
albuterol, salmeterol?
beta2 > beta1
albuterol = acute asthma salmeterol = long term asthma, COPD
dobutamine?
beta 1 > beta 2, alpha
use in HF, stress testing
** inotropy > chronotropy
dopamine?
D1 = D2 > beta > alpha
use in unstable brady, HF, shock
** at high doses, alpha effects (inotropy, chronotropy) dominate
epinephrine?
beta > alpha
use in anaphylaxis, asthma, open angle glaucoma
- alpha effects dominate at high doses
- stronger at beta 2 than NE
isoproterenol?
beta1 = beta2
use in EP eval of tachyarrhythmias
** can worsen ischemia
NE?
alpha1 > alpha2 > beta1
use in hypoT
- decreases renal perfusion
- weaker at beta2 vs epinephrine
phenylephrine?
alpha1 > alpha2
use in hypoT, ocular procedure (causes mydriasis), rhinitis (decongestant)
amphetamine?
indirect general sympathomimetic
reuptake inhibitor
releases stored catecholamines
use in narcolepsy, obesity, ADHD
cocaine?
indirect general sympathomimetic
reuptake inhibitor
vasoconstriction, local anesthesia
** DON’T give BBs to cocaine users - risk of unopposed alpha1 –> extreme HTN
ephedrine?
indirect general sympathomimetic
releases stored catecholamines
use for nasal decongestion, urinary incontinence, hypoT
NE vs isoproterenol?
NE –> alpha1 –> increased sys and dia BP –> reflex bradycardia
isoproterenol –> beta2 –> vasodilation –> reflex (and beta1-mediated) tachycardia
clonidine?
alpha2 agonist - sympatholytic!
use in HTN urgency, ADHD, tourettes
- does not decrease renal blood flow
- toxicity: CNS depression, brady, hypoT, resp depression, miosis
alpha-methyldopa?
alpha2 agonist - sympatholytic!
use in preggos with HTN
** causes direct Coombs + hemolysis, SLE-like syndrome
phenoxybenzamine?
irreversible nonselective alpha blocker
use preop in pheo
** SEs: orthostatic hypoT, reflex tachy
phentolamine?
reversible nonselective alpha blocker
give to pts on MAOis who eat tyramine
** SEs: orthostatic hypoT, reflex tachy
prazosin, terazosin, etc?
alpha1 selective blocker
use in BPH with urinary sx, PTSD (prazosin), HTN (NOT tamsulosin)
** SEs: 1st dose orthostasis, dizziness, HA
mirtazapine?
alpha2 selective blocker
use in depression
** SEs: sedation, increased serum cholesterol, increased appetite
what happens when you give alpha blocker to pt on epi?
epi –> net BP increase
alpha blockade –> net BP decrease (because of unopposed beta 2 action)
what happens when you give alpha blocker to pt on phenylephrine?
phenylephrine –> net BP increase
alpha blockade –> suppression of phenylephrine effect without BP depression - no beta action
which BBs can you give for SVT?
metoprolol
esmolol
** decrease AV conduction
which BB can you give for glaucoma?
timolol
** decrease secretion of aqueous humor
BB toxicity?
impotence
CNS - sz, sedation, sleep alterations
dyslipidemia (metoprolol)
asthma/COPD exacerbation
** AVOID in cocaine users - risk of unopposed alpha –> HTN
which are the beta1 selective BBs?
from A to M: acebutolol atenolol betaxolol esmolol metoprolol
which are the nonselective BBs?
from N to Z nadolol pindolol propranolol timolol
which are the nonselective alpha and beta BBs?
carvedilol
lavetalol
nebivolol?
beta 1 blockade + beta3 stimulation –> NO synthase activation in vasculature
