ANS Pharmacology Flashcards
What doe alpha1 receptors do?
Stimulate contraction of all smooth muscle
Vascular smooth muscle: vascoconstriction
Glandular smooth muscle: secretion
What do beta2 receptors do?
Relax smooth muscle: vasodilation
What do muscarinic receptors do?
Contract smooth muscle (different intracellular signal than alpha1 receptors)
ACh and muscarinic agonists given IV cause vasodilation due to release of nitric oxide (NO)
Compare parasympathetic vs sympathetic tone
Parasympathetic (rest and digest) Cholinergic Salivation, lacrimation Pupil constriction (myosis) Decrease in HR Urination, defecation Increased secretion and motility
Sympathetic (fight or flight) Adrenergic (anticholinergic) Cutaneous vasodilation Pupil dilation (mydriasis) Increase in HR Reduction/elimination of desire to urinate Decreased secretion and motility
83 year old female of nursing home presents with 2 month history of worsening urinary incontinence. 3 years ago, she presented with same symptoms which were managed with adult diapers and bladder training. She is exhibiting symptoms consistent with activation of which division of nervous system? What drug class will alleviate her symptoms? What is the most likely adverse effect of drug?
Parasympathetic nervous system
Muscarinic AChR antagonist (inhibits bladder contraction)
Constipation, dry mouth/eyes, dizziness, blurred vision
Describe anticholinergic agents for genitourinary disorders
mAChR antagonists provide symptomatic relief in treatment of urinary urgency caused by minor inflammatory bladder disorders
Agents with selectivity to M3 subtype are beneficial due to presence on bladder wall and sphincter smooth muscle
Oxybutynin is a prototype M3 antagonist but side effects (dry mouth/eyes, dizziness, constipation, blurred vision)
Darifenacin, solifenacin, tolterodine are selective for M3 subtype and have longer half-lives and reduced incidence of xerostomia and constipation
How does activation of mAChRs cause trigone and sphincter relaxation?
Activation of mAChRs on epithelial cells cause production and release of endothelium-derived relaxing factor (EDRF) aka NO
Stimulation of NO release can occur from ACh, vasoactive products, and physical stimuli
57 year old male smoker presents with daily cough and mild dyspnea on exertion with strenuous activity. Wheezing but no chest pain. COPD. Which agent is appropriate? Smoking cessation and inhaled tiotropium are prescribed. Adverse effects?
MAChR antagonist
Decreased mucus production (may lead to infection)
32 y/o female presents with intermittent attacks of headache, perspiration, palpitations, and anxiety. During these attacks, she feels like there is impending doom. These occur after exercise or drinking coffee. BP 165/98. Plasma fractionated free metanephrine test is positive and 24hr urine specimen support diagnosis of what? What will immediately reduce her blood pressure? An antagonist of what receptor will likely reduce her heart rate? If this selective antagonist (propranolol) is administered, what is expected? Why? Imaging shows large, right-sided inhomogeneous adrenal mass with a central area of low attenuation that represents hemorrhage or necrosis. If a centrally acting alpha-2 receptor agonist (clonidine) is administered to this patient, what is the most likely result? Why?
Pheochromocytoma
Alpha-1 antagonist
Beta-1
Worsening of hypertension (possible death)
Unopposed alpha stimulation (vasoconstriction)
No change in symptoms
Clonidine activates central presynaptic alpha2 receptors and suppresses release of catecholamines from neurons. However, no effect on catecholamine secretion from a pheochromocytoma
2 y/o female presents to ED after accidental overdose of antihistamines. Temp 102.5, pupils fixed and dilated. Heart rate 160 bpm (normal 120). Signs of delirium and marked cutaneous vasodilation upon PE. She is exhibiting symptoms of overactivity of which division of nervous system? The symptoms are most likely due to what? Stimulation of which receptor will correct the symptoms? What agent is appropriate?
Sympathetic nervous system
Inhibition of muscarinic acetylcholine receptors
Muscarinic acetylcholine receptor (mAChR)
Acetylcholinesterase inhibitor (indirect acting agonist)
46 y/o female complains of dry eyes and dry mouth for past 6 months and have worsened. She has to wake up in the night to drink water and has to drink water to help swallow food. She experiences feeling grit or sand in eyes on a daily basis. Which agent is most appropriate? Cevimeline is prescribed. Adverse effect? Concomitant condition would be exacerbated?
MAChR agonist
Diaphoresis
Asthma
29 y/o male presents to ED unconscious, with nonreactive, pinpoint pupils, massive oral foaming, and muscle fasciculations. Pants wet with urine and feces. Depression. What receptor is most likely involved? What agent was ingested?
Cholinergic
AChE inhibitor
What are the neurotransmitters and receptors for parasympathetics? Sympathetics?
Parasympathetics:
Neurotransmitters: ACh
Receptors: nAChR, mAChR
Sympathetics:
N: NE>Epi (DA); ACh
R: alpha, beta, nAChR, mAChR
Describe acronyms for symptoms of AChE (organophosphate) inhibitor toxicity
SLUDGE: salivation, lacrimation, urination, defection, gastrointestinal pain and gas, emesis
DUMBELS: defecation, urination, miosis, bronchorrhea/bronchospasm/bradycardia, emesis, lacrimation, salivation
Ingestion: GI symptoms occur first
Percutaneuous absorption: localized sweating and muscle fasciculations
Lipid-soluble agents: CNS involvement follows rapidly
What are cholinesterase regenerators?
Current antidotes for organophosphate exposure:
Parenteral atropine
Oxime (pralidoxime0
Benzodiazepine to alleviate convulsions
