Pharm- Autonomic Drugs Flashcards
Describe nicotinic receptors
these ACh receptors are ligand-gated Na/K channels
Two types: NN found on autonomic ganglia and NM found on neuromuscular junctions
Describe muscarinic receptors
ACh receptors that are G protein-coupled receptors that usually act through 2nd messengers
5 subtypes: M1-M5
Describe the a1 receptor
Gq coupled to produced vascular smooth muscle contraction, increased pupillary dilator muscle contraction (mydriasis), and intestinal and bladder sphincter muscle contraction
Describe the a2 receptor
Gi coupled receptor to produce decreased sympathetic outflow, decreased insulin release, decreased lipolysis, decreased aqueous humor production, and increased platelet aggregation
Describe the B1 receptor
Gs coupled receptor to produce increased HR, contractility, increased renin release, and increased lipolysis
Describe the B2 receptor
Gs coupled receptor to produce vasodilation, bronchodilation, increased lipolysis, increased insulin release, decreased uterine tone (tocolysis), ciliary muscle relaxation, and increased aqeuous humor production
Describe the M1 receptor
Gq coupled receptor to modulate the CNS and enteric nervous system
Describe the M2 receptor
Gi coupled receptor to porduce decreased HR and atrial contractility
Describe the M3 receptor
Gq coupled receptor to produce:
increased exocrine gland secretions (e.g. lacrimal, salivary, gastric acid), increased gut peristalsis, increased bladder contraction, bronchoconstriction, increased papillary sphincter muscle contraction (miosis), ciliary muscle contraction (accommodation)
Describe the D1 receptor
Gs coupled receptor to relax renal vascular smooth muscle
Describe the D2 receptor
Gi coupled receptor to modulate NTM release in the brain
Describe the H1 receptor
Gq coupled receptor to produce nasal and bronchial mucus production, increased vascular permeability, pruritis, pain, and contraction of the bronchioles
Describe the H2 receptor
Gs coupled receptor to increased gastric acid secretion
Describe the V1 receptor
Gq coupled receptor to increased vascular smooth muscle cotnraction
Describe the V2 receptor
Gs coupled to increase H2O permeability and reabsorption in the collecting tubules of the kidney
What are the autonomic receptors coupled to Gq?
H1, a1, V1, M1
M3
What are the autonomic receptors coupled to Gs?
B1, B2, D1,
H2, V2
What are the autonomic receptors coupled to Gi?
M2, a2, D2
What are the main cholinergic agonists?
Bethanechol
Carbachol
Methacholine
Pilocarpine
What are the main uses of Bethanechol?
Postoperative ileus, neurogenic ileus and urinary retention that works by activating the bowel and bladder smooth muscle (resistant to AChE)
What are the main uses of Carbachol?
Constriction of the pupil and relieving intraocular pressure in glaucoma
What are the main uses of Methacholine?
challenge test for asthma that stimulates muscarinic receptors in airways when inhaled
What are the main uses of Pilocarpine?
Potent stimulator of sweat, tears, and saliver for open angle glaucoma
What are the anti-AChEs (indirect cholinergic agonists)?
Donepeil, Rivastigmine, Galantamine
Edrophonium
Nesostigmine
Physostigmine
Pyridostigmine
What are the main uses of Donepeil, Rivastigmine, Galantamine?
Alzheimer tx
What are the main uses of Edrophonium?
Diagnosis of myasthenia gravia (Extremely short acting) but it is now more commonly diagnosed via anti-AChR Ab test
How might cholinesterase inhibitor poisoning present (commonly due to organophosphates seen in insecticides- usually seen in farmers)?
DUMBBELSS
Diarrhea, Urination, Miosis, Bronchospasm
Bradycardia, Excitation of skeletal muscle and CNS
Lacrimation, Sweating, and Salivation
What is the antidote for cholinesterase toxicity?
Atropine and Pralidoxime (regenerates AChE if given daily)
What is a major use of Pyridogstigmine?
Increases ACh for tx of Myasthenia gravis
What is a major use of physostigmine?
atropine overdose
What are the major muscarinic antagonists?
Atrophin, homatropine, tropicamide (prouces mydriasis and cycloplegia)
Benztropine (Parkinson disease tx)
Glycopyrrolate (drooling, peptic ulcer)
Hyoscyamine, Dicyclomine (Antispasmodics for IBS)
Ipratropium, tiotropium (COPD, asthma)
Scopolamine (Motion sickness)
What are oxybutynin, Solifenacin, and Tolerodine?
Muscarinic antagonists that reduce bladder spasms and urge urinary incontinence in tx of overactive bladder
What are the main physiologic outcomes of atropine (muscarinic antagonist) use?
Pupil dilation and cycloplegia
decreased airway secretions
decreased stomach secretions
decreased gut motility
decreased urgency in cystitis
What are the AEs of atropine?
elevated body temp due to decreased sweating
rapid pulse, dry mouth, dry skin
cycloplegia
constipation
can cause acute angle-closure glaucoma in elderly
disorientation
What is Tetrodotoxin?
Highly potent toxin found in pufferfish that binds fast voltage-gated N+ channels in cardiac and nerve tissue preventing depolarization (blocks AP with changing resting potential), resulting in symptoms of nauseas, diarrhea, wekaness, dizziness, loss of reflexes, and paresthesias
Tx: supportive
What is Ciguatoxin?
Toxin released during ingestion of reef rish (e.g. barracuda, snapper, moray ell) that causes ciuatera fish poisoning by opening Na+ channels causing depolarization
How does ciguatoxin poisoning present?
Symptoms often confused with cholinergic poisoning and include:
Temp-related dysesthesia (e.g. cold feels hot, hot feels cold) is the classic finding
Tx is supportive
What causes SCOMBROID poisoning?
Caused by consumption of dark-meat fish such as bonito, mahi-mahi, and tuna) that is improperly stored at warm temps
How does c present?
Acute-onset of burning sensation of the mouth, flushing of the face, erythema, urticaria, pruritis, and HA
May cause anaphylaxis like presentation with bronchospasm, angioedema, and hypotension (frequently misdiagnpsed as fish allergy)
What mediates scrombroid poisoning?
Bacterial histidine decarboxylase converts histidine to histamine which is not degraded by cooking (tx with antihistamines if needed)
What receptors does albuterol and salmeterol act on?
B2 > B1
What are the uses of albuterol and salmeterol?
albuterol for asthma
salmeterol for long-term asthma or COPD control
What receptors does Dobutamine bind to?
B1 > B2,a for tx of heart failure (inotropic > chronotropic) and cardiac stress testing
What receptors does Dopamine bind to?
D1=D2 > B > a for tx of unstable bradycardia, HF, shock (inotropic and chronotropic a effects predominate at high doses)
What receptors does Epi bind to?
B > a for tx of anaphylaxis, asthma, open-angle glaucoma (a effects predominate at high doses)
Significantly stronger effect at B2 receptor than nor
What receptors does Isoproterenol bind to?
B1 = B2 for tx of eelectrophysoiologic evaluation of tachyarrhyhtmias (can worsen ischemia)
What receptors does Nor bind to?
a1 > a2 > B1 for tx of hypotension (but decreases renal perfusion)
Note about the tx of cocaine overdose:
Never give BBs if suspected because it can lead to unopposed a1 activation and extreme HTN
Note about Nor and Iso
Nor increases systolic and diastolic pressures as a result of a1-mediated vasoconstriction, which increases MAP and leads to reflex bradycardia
Iso has little a effect but causes B2-mediated vasodilation, resulting in decreased MAP and increased heart rate through B1 and reflex activity
What are the uses of clonidine?
a2- agonist used for HTN crisis (does not decrease renal blood flow)
ADHD and Tourette Syndrome (only if they are both present)- if only ADHD- use a stimulant, and use an antipsychotic for Tourettes only
What are some nonselective a-blockers and their applications?
Phenoxybenzamine for pheochromocytoma (preoperatively) to prevent catecholamine crisis
Phentolamine (reversible)- for tx of those on MAOIs who eat tyramine foods
How would MAP change if you have epi followed by an a-blocker?
How would MAP change if you have phenylephrine followed by an a-blocker?
MAP would increased after giving phenylephrine but only return to baseline after the a-blocker because phenylephrine has no B activity (pure a-agonist)
What are the B1-selective BBs?
A to M
Acebutolol, atenolol, betaxolol, Esmolol, Metoprolol
What are the nonselective BBs?
N to Z
Nadolol, Pindolol, Propranolol, Timolol
