Autonomic Drug Goals Flashcards
where are the cell bodies of parasympathetic neurons located and what are their trajectories
Preganglionic cell bodies: craniosacral nuclei
Trajectories: smooth muscle, cardiac muscle and glands
Describe the synthesis, storage, release, and degradation of acetylcholine.
synthesis: produced from pyruvic acid in the mitochondria and choline from the choline sodium transporter
stored in the presynaptic neuron vesicles and released via exocytosis into the presynaptic space
Degraded by acetylcholine esterase and recycled back through the choline sodium transporter
subtypes of cholinergic receptors, their anatomical locations, physiological response to ACH, and explain the differences in their signaling mechanisms.
M1 (Gq): mediates higher cognitive functions and stimulates the enteric nervous system
M2(Gi): decreases HR and atrial contractility
M3 (Gq): increases exocrine secretions, peristalsis, bronchoconstriction, miosis and increases insulin release (All faucets on)
when do you use direct AChR agonists?
Indirect Agonists?
Direct: alleviate neurogenic ileus, increased IP and miosis, produce secretions, bronchial challenge test(methacholine)
Indirect: treatment of myasthenia gravis, postop urinary retention
glaucoma, antidote for atropine, Alzheimer’s
when do you use AChR antagonists?
to increase HR/ AV conduction
decrease peristalsis/ secetions ad detrusr tone/ bladder contraction
bronchodilation
mydriasis/ impaired accomodation
decreased eocrine gland secretion
Describe the signs, symptoms, and principles of therapeutics of a patient with anticholinergic toxicity
treatment?
dry mouth
flushed skin
thirst
tachycardia
mydriasis
confusion/ agitation
Reverse with Physostigmine
Describe the signs, symptoms, and principles of therapeutics of a patient with excessive cholinergic stimulation
All faucets on!!!
similarly seen in organophosphate poisoning
Give Atropine for to block excessive muscarinics and Paralidoxime to regenerate cholinesterases
Compare and contrast the therapeutic uses, mechanism of action, adverse effects, contraindications, and drug interactions of type 5 phosphodiesterase inhibitors and Riociguat
MOA of Type5 PDE: increase cGMP to induce smooth muscle relaxation and vasodilation
Sildenafil: smooth muscle relaxation induces erection (Viagra) and pulmonary arterial HTN (Revatio)
Tadalafil: increased cGMP is used to vasodilate pulmonary vasculature in cases of pulmonary arterial HTN (Adcirca) and also improves BPH by increasing smooth muscle relaxation
Riociguat: increased cGMP is used to vasodilate pulmonary vasculature in cases of pulmonary arterial HTN
Avoid use with CYP3A4 inhibitors due to decreased clearance and avoid with Nitro to avoid hypotension an reflex tachycardia
where are the cell bodies of sympathetic neurons located and what are their trajectories
origin: thoracolumbar segments
targets: smooth muscle, cardiac muscle, and glands
neurotransmitters released by:
preganglionic sympathetic neurons
postganglionic sympathetic neurons
adrenal medulla.
Preganglionic sympathetic neurons: ACh
Postganglionic sympathetic neurons: Norepi in all but sweat glands, which use ACh
Adrenal Medulla: Norepinephrine
synthesis, storage, release, and the termination of action of dopamine, norepinephrine, and epinephrine.
autonomic and hormonal control of cardiovascular function and the RAAS system, respectively.
anatomical locations of Beta 2 AdR and the physiological response to stimulation
Location: smooth muscle, ciliary body of the eye, pancreatic beta cells, skeletal muscle and in the liver
Stimulation: vasodilation, bronchdilation, decreased peripheral vasodilation, increased lipolysis, increased insulin release, increased glycogenolysis, decreased uterine tone, increased aqueous humor production, increased cellular K+ uptake
Anatomical location of Beta 1 AdR and physiologic response to stimulation
Location: cardiac muscle and JG apparatus.
Stimulation: Increases, HR, contractility and conduction velocity in the heart and increases renin release in the kidney
Anatomical location of Alpha 1 AdR and physiologic response to stimulation
Location: vascular smooth muscle, pupillary dilator muscle of the eye, GI, blader, exocrine glands
Stimulation: increased vasoconstriction/PVR/preload, mydriasis, peristalsis, increased sphincter contraction in the bladder, ejaculation
anatomical locations of Alpha 2 AdR and the physiological response to stimulation
Location: blood vessels, eye, pancreatic islet cells, adipose tissue
Stimulation: decreased aqueous humor production, increased platelet aggregation,decreased insulin release, decreased lipolysis
Differentiate the second msgrs in alpha 1 ad beta 1 receptors
alpha 1= Gq
beta 1= Gs
indications and side effects for alpha 1 agonist
Indications:
- orthostatic hypotension/ autonomic insufficiency (Milodrine)
- Septic/ Neurogenic shock (Norepi)
- epistaxis/ rhinitis/ rosacea (Oxymetazoline)
- hypotension, rhinitis, allergic conjunctivitis, open-angle glaucoma, ischemic priapism: phenylephrine
Side effects
HTN, reflex bradycardia, piloerection, urinary retention. schemia / necrosis of distal dgits
indications and side effects of Alpha 2 agonists
Indications:
- HTN, ADHD, drug withdrawal: Clonidine
- HTN in pregnancy: Methyldopa
Side Effects:
CNS suppression, respiratory suppression, bradycardia, hypotension, miosis, rebound HTN, dry mouth
Methyldopa: autoimmune hemolytic anemia and SLE like syndrome
indications and side effects of Alpha 1 antagonists
Indications:
- HTN and BPH: Doxazosin, Terazosin
- BPH and urinary outflow obstruction: Tamsulosin, Alfuzosin, Silodosin
- HTN and PTSD nightmares: Prazosin
- Pheochromocytoma: Phenoxybenzamine, Phentolamine
Side Effects:
- peripheral edema, orthostatic hypotension, retrograde ejaculation, urinary frequency, intraoperative floppy iris syndrome
- nonselective antagonists: reflex tachycardia and vasodilation
indications and side effects of Beta 1 agonists
Indications:
- heart failure, shock, unstable bradycardia: Dobutamine
- bradycardia/ heart block, cardiac arrest from heart block when pacemaker therapy is unavailable: Isoproterenol
Side Effects:
Tachycardia, arrhythmias, can precipitate MI with CAD
indications and side effects of Beta 1 antagonists
Indications:
- CAD, compensated heart failure, ACS, Cardiac arrhythmias,
Side Effects:
bradycardia, bradyarrhythmia, torsades de pointes, worsened heart failure, orthostatic hypotension, CNS depression, hallucinations, high triglycerides, psoriasis
indications and side effects of Nonelective Beta 2 antagonists
Indications:
- an alternative to cardioselective beta blockers
Side Effects:
bronchoconstriction, erectile dysfunction, secondary Raynaud phenomenon, hyperglycemia in new-onset diabetes, weight gain, vasoconstriction in patients with PVD
