Autonomic Drugs Flashcards
Cholinomimetic agents (direct agonist): carbachol
clinical apps and action?
clinical apps: constricts pupil & relieves intraocular pressure in glaucoma
action: works just like acetylcholine; in fact it’s like a “carbon” copy
Cholinomimetic agents (direct agonists): Bethanechol
Clinical apps and action?
Clinical apps: postoperative ileus, neurogenic ileus, urinary retention
action: activates bowel and bladder smooth muscle; resistant to acetylcholinesterase
Cholinomimetic agents (direct agonist): Methacholine
clinical apps and action?
clinical apps: challenge test for diagnosis of asthma
action: stimulates muscarinic receptors in the airway when inhaled (increase bronchoconstriction)
Cholinomimetic agents (direct agonist): pilocarpine
clinical apps and action?
clinical apps: potent stimulator of sweat, tears, and saliva; open-angle and closed angle glaucoma
action: contracts ciliary muscle of eye (open-angle glaucoma); pupillary sphincter (closed-angle glaucoma); resistant to acetylcholinesterase
Cholinomimetic agents (indirect agonists by inhibiting achase): Donepezil, galantamine, rivastigmine
clinical apps and actions?
clinical apps: Alzheimer disease
actions: increase ach
Cholinomimetic agents (indirect agonists by inhibiting achase): edrophonium
clinical apps and actions?
clinical apps: historically used to diagnose myasthenia gravis (autoab against AchR); now myasthenia gravis is diagnosed by anti-AchR antibodies.
action: increase ach
Cholinomimetic agents (indirect agonists by inhibiting achase): Neostigmine
clinical apps and actions?
clinical apps: postop and neurogenic ileus and urinary retention, myasthenia gravis, reversal of NMJ blockade (postoperative) BUT no CNS penetration unlike physostigmine
actions: increase ACh
Cholinomimetic agents (indirect agonists by inhibiting achase): physostigmine
clinical apps and actions?
clinical apps: anticholinergic toxicity; does cross BBB
actions: increase Ach
Cholinomimetic agents (indirect agonists by inhibiting achase): pyridostigmine
clinical apps and actions?
clinical apps: myasthenia gravis (long acting); does not penetrate CNS
actions: increase ach, increase muscle strength
With all the cholinomimetic agents (direct and indirect), watch out for what types of symptoms and exacerbation of what types of underlying conditions?
cholinomimetics = SLUDGE (salivation, lacrimation, urination, defecation, gastric emptying, excitiation)
watch for exacerbation of COPD, asthma and peptic ulcer since cholinomimetics stimulate bronchial constriction and increase gastric secretions
List some insecticides (organophosphates, achase inhibitor by irreversible binding) and the symptoms assoc with the toxidrome. what’s the antidote?
marathion, parathion, nerve gas can all cause cholinesterase inhibitor poisoning (often seen in farmers)
symptoms are SLUDGE or DUMBBELSS
-defecation, urination, mydriasis, bradycardia, bronchospasms, excitation of skeletal muscle & CNS, lacrimation, salivation, sweating
antidote: atropine (competitive inhibitor) + pralidoxime (regenerates AchE if given early)
List the 3 muscarinic antagonists that target the eyes to produce mydriasis and cycloplegia (loss of accomodation)
- atropine
- tropicamide
- homatropine
List the muscarinic antagonist that targets the CNS to treat parkinson’s and acute dystonia
benztropine
List the muscarinic antagonist that targets GI, respiratory when given parenterally is used as a preop to reduce airway secretions and when given orally is for drooling and peptic ulcer.
glycopyrrolate
List the 2 muscarinic antagonists that are anti-spasmodics for treatment of irritable bowel syndrome
hyoscyamine, dicyclomine
List the 2 respiratory muscarinic antagonists used for COPD, asthma
ipratropium , tiotropium
List the 3 GU muscarinic antagonists used to reduce bladder spasms, and urge urinary incontinence (overactive bladder)
oxybutynin, solifenacin, tolterodine
List the anti-muscarinic agent that targets the CNS to treat motion sickness
scopolamine
What are some side effects of anti-muscarinic/anti-cholinergic (atropine) poisoning
“hot as a hare, dry as a bone, red as a beet, blind as a bat, mad as a hatter”
- hyperthermia and red b/c no ach stimulation of sweat glands so no sweating
- inhibition of secretions = dry
- rapid pulse
- cycloplegia and mydriasis
- confusion
Specifically, atropine poisoning can cause what in elderly, BPH, infants?
elderly: acute angle-closure glaucoma due to mydriasis
men with BPH: urinary retention
infants: hyperthermia
What is Jimson weed?
Gardener’s pupil (atropine-like effects) causing mydriasis
Atropine is a muscarinic antagonist used to treat bradycardia and for ophthalmic applications. Explain its effects on the eye, airway, stomach, gut, and bladder.
eye: mydriasis, cycloplegia
airway: decrease secretions
stomach: decrease acid secretion
gut: decrease motility
bladder: decrease urgency in cystitis
Ingestion of poorly prepared pufferfish can result in poisoning with what type of toxin? Explain mech that causes the toxicity and how to treat.
Tetrodotoxin
- binds to fast voltage-gated Na+ channels in cardiac and nervous tissue and prevent depolarization (blocks A.P without changing resting potential)
- causes nausea, diarrhea, paresthesias, weakness, dizziness, oss of reflexes
Treatment is supportive
Consuming reef fish (barracuda, snapper, moray eel) can cause ciguatera fish poisoning. What does ciguatoxin do mechanistically? What are some side effects? What’s the treatment?
Ciguatoxin opens Na+ channels causing depolarization. Symptoms can be confused with cholinergic toxicity (SLUDGE). Unique temperature-related dysesthesia (“cold feels hot, hot feels cold”)
Treatment is supportive
Consuming dark meat fish (bonito, mackerel, mahi mahi, tuna) that was improperly stored at warm temperature can cause scombroid poisoning. Bacterial histidine decarboxylase will convert histidine to histamine. Histamine is not degraded by cooking. What are some symptoms assoc with scombroid poisoning? How to treat?
acute-onset burning sensation of the mouth, flushing of face, erythema, urticaria, pruitus, headache. may cause anaphylaxis-like presentation (bronchospasm, angioedema, hypotension)
treat supportively with antihistamines, if needed, can give anti-anaphylactics
Scombroid poisoning is frequently misdiagnosed as?
Since it causes acute-onset burning sensation of the mouth, flushing of face, erythema, urticaria, pruitis, and headachle, scombroid poisoning is often misdiagnosed as allergy to fish.
sympathomimetics: albuterol, salmeterol (b2 > b1): What are they used for?
- b2 (Gs –> cAMP): bronchodilation, vasodilation, increase lipolysis, increase insulin release, decrease uterine tone, increase aqueous humor production, ciliary muscle relaxation
- b1 (Gs –> cAMP): increase HR, increase contractility , increase renin release, increase lipolysis
albuterol: acute asthma
salmeterol: long-term asthma or COPD control
sympathomimetics (direct): dobutamine (B1 > B2, alpha); What is it for?
B1: increase HR, contractility, increase renin release, increase lipolysis
B2: vasodilation, bronchodilation, increase lipolysis, increase insulin release, decrease uterine tone, ciliary muscle relaxation, increase aqueous humor production
a1: increase vascular sm contraction, pupilary dilator muscle contraction, increase intestinal and bladder sphincter contraction
a2: decrease symp outflow, decrease insulin release, decrease lipolysis, increase plt aggre, decrease aq humor production
dobutamine can be used for heart failure (inotropic > chronotropic), cardiac stress testing.
epinephrine (b > a effect). What can epinephrine be used for clinically?
anaphylaxis & asthma (due to its better b2 agonist effect than NE), open angle glaucoma
- alpha effects predominate at high doses
- stronger effect at b2 receptor than NE
Norepinephrine (a1 > a2 > b1) -what is it used for
hypotension by decreasing renal perfusion
Phenylephrine (a1 > a2 agonism). What 3 conditions can it be used for?
hypotension (vasoconstrictor), ocular procedures (mydriatic), rhinitis (decongestant)
amphetamine is an indirect general sympathetic agonist, reuptake inhibitor and causes release of stored catecholamines. What 3 conditions can it be used to treat? Also, in the case of amphetamine toxicity, what can you use to treat?
Amphetamine can be used for narcolepsy, obesity, ADHD
treatment for toxicity is to acidify urine with NH4Cl b/c amphetamine is basic.
Cocaine is an indirect general sympathetic agonist that is a reuptake inhibitor. It can cause vasoconstriction and local anesthesia (also can help with diagnosis of horner’s sydrome: ptosis, anhydrosis, miosis). In the case of cocaine intoxication, what should you NEVER give the pt? Why?
never give b-blockers because will leave alpha agonism activity unopposed, which means there will be a lot of vasoconstriction –> increased venous return –> increased blood pressure –> very bad HTN.
Ephedrine is an indirect general sympathetic agonist that releases stored catecholamines. What 3 conditions can it treat?
hypotension
nasal decongestation
urinary incontinence
Clonidine is an a2 agonist (sympatholytic). What can you use clonidine for? What are some side effects?
Clonidine is for hypertensive emergency (limited situations); does not decrease renal blood flow; ADHD, and tourette syndrome
toxicity: CNS depression, bradycardia, hypotension, respiratory depression, miosis (VERY SIMILIAR TO OPIOID TOXICITY)
a-methyldopa is an a2-agonist (sympatholytic) used for? What are some side effects?
hypertension in pregnancy b/c not teratogenic
side effects: lupus-like syndrome, direct coombs + hemolysis
Pheochromocytoma is a cancer of the adrenal medulla that causes sporadic releases of NE and epinephrine. What drug can be used preoperatively to prevent hypertensive crisis? What are some side effects of the drug?
Phenoxybenzamine (nonselective IRREVERSIBLE alpha blocker) w/ long-acting effects that will control NE (a1 > a2 > b1) alpha agonism effects (increase vasoconstriction –> increase BP).
Side effects: orthostatic hypotension, reflex tachycardia
Which alpha blocker can you give a patient on MAO inhibitors (MAO takes pride in shanghai: Tranylcypromine, Phenelzine, Isocarboxazid, Selegiline –> increase levels of amine NTs: NE, 5-HT, DA) and has been eating lots of wine & cheese (contain tyramine, also an amine), which will lead to hypertensive crisis?
Side effects of the drug?
Phentolamine (reversibe nonselective alpha blocker) will be given to ppl who are on MAOI + eat tyramine-containing food –> hypertensive crisis.
Side effects: orthostatic hypotension, reflex tachycardia
List the 4 selective a1-selective blockers (-osin ending). What can they be used to treat? Side effects?
- prazosin –> BPH, PTSD, HTN
- terazosin –> BPH
- doxazosin –> BPH + HTN
- tamsulosin –> BPH + HTN
Side effects: 1st dose orthostatic hypotension, dizziness, headache
List the a2 selective blocker that can be used for depression. What are 3 side effects?
Mirtazpine is an a2 blocker that can be prescribed for depression.
side effects: sedation, increase serum cholesterol, increase appetite
List the 5 B1 selective antagonists/blockers.
- acebutolol (partial agonist)
- atenolol
- betaxolol
- esmolol
- metoprolol
List the 4 nonselective beta blockers
nadolol
pindolol (partial agonist)
propranolol
timolol
List the 2 nonselective alpha AND beta blockers
carvedilol
labetalol
List the one beta blocker that combines cardiac-selective b1-adrenergic blockade w/ stimulation of B3 receptors (activate NO synthase in vasculature)
Nebivolol
Are beta blockers known to decrease mortality in MI and CHF?
YES
MI -metoprolol, carvedilol, bisoprolol decrease mortality
CHF
Non-selective or selective beta blockers can mask hypoglycemia in diabetes? How?
signs of hypoglycemia:
- neuroglycopenic: lack of glucose to brain: weakness, confusion, drowsiness, dizziness, syncope, difficulty speaking, blurry vision
- neurogenic: due to hypoglycemia-induced catecholamine release: adrenergic symptoms like diaphoresis, hunger, tingling, tremor, palpitations, chest pain, anxiety
*nonselective beta blockers can block sympathetic surge mainly due to b2 antagonism b/c b2 receptor activation is trigger for catecholamine-induced glycogenolysis
