3 - Muscarinic Agonists Flashcards
Diabetic autonomic neuropathy may _______
and affect _____
precede other complications
affect one or more organs
Mechanisms of neuropathy
Metabolic nerve damage
neurovascular insufficiency
AI damage
Neurohormonal growth factor deficiency
Clinically, the most important form of autonomic neuropathy
Caradiovascuar
Common in patients with liver disease
Autonomic (mainly VAGAL) dysfunction
Exaggerated by alcohol abuse
Advanced chronic liver disease is characterized by…
Peripheral arterial vasodilation
Increased plasma catecholamine concentrataions
Botulism toxin MOA
cleaves SNAP-25 in the SNARE complex
Inhibiting release of Ach in vesicles
Hyperthyroidism mimics ___________
hyperadrenergic state
Hyperthyroidism heart rate is __ and ___
irregular and fast
Treat with Beta blockers
Hyperthyroidism-related tachycardia is a contraindication for ____________
Muscarinic agonists (even though they decrease CO)
Can induce atrial fibrillation
Graves disease etiology
AI disease against TSH receptor –> activation
Crosstalk between Thyroid and Adrenal
Adrenal gland activation produces GC’s
GCs inhibit enzyme that converts T4 into active T3
Effect of reduced body weight
Lower T3 and Sy ANS
Heightened PSy
Hyperthyroidism causes _________ of adrenergic receptors
Desensitization
Hypothyroidism causes _________ of adrenergic receptors
Sensitization
Undiagnosed Hypothyroidism most common in women
iodine deficiency
Hashimotos thyroiditis symptoms
Cold, dry skin, hair loss, slowed heart rate
Cholinergic stimulation can reduce…
symptoms of neuropathic ANS disorders
Effects of cholinergic stimulation
Increase of ureteral peristalsis BP increase Increased GI tone Bronchoconstriction + mucus secretion Increase glandular activity Miosis, drainage of anterior chamber
Types of drugs that increase cholinergic stimulation
AchEI’s
Muscarinic agents
Muscarine was the first _______
Problem/sides?
parasympathomimetic
Can cross BBB and cause convulsions
Direct acting Cholinergic recepor agonists are ______
Esters
Examples of direct cholinergic agonists
Ach
Bethanechol
Carbachol
Methacholine
What causes the polarity of direct receptor agonists?
Due to the polarity of direct agonists, they have…
The quaternary ammonium
limited CNS distribution and GI absorption
Carbachol acts on which receptors
mAchR + nAchR
Methacholine acts on which receptors
All, but mostly mAchR
“M”uscarinic for “M”ethacholine
Risk with nAchR activity
Systemic fatal OD
–> nicotinic receptors son diaphragm and IC’s
(still low risk d/t polarity)
Ocular use for muscarinic agents
Treatment for glaucoma
reduces intra-ocular pressure
Mechanisms for glaucoma
Overproduction of humor
Drainage canal blockage
Which type of glaucoma is the emergency?
Closed angle
canal of schlemm occluded between iris and corneal/scleral layer
Endothelial cells with ____ secete aq. humor
B2-AR
____ blocks B2AR in the endothelial cells of the eye
Timolol
blocks without miosis or loss of accommodation
Muscarinic agonsts for the treatment of glaucoma
Carbachol
Pilocarpine
Carbachol is a ____
PK?
Full agonist, longer acting
2-5 minute onset, can last 24h if intra-ocuar
Pilocarpiine is a ____
MOA?
Partial agonist (less headache) relieves Canal of Schlemm blockage
Sides for pilocarpine
Sweating, salivation, diarrhea, mucus secretion
Miosis (blurred vision, impaired night vision)
Reduced BBB function (can enter CNS and cause epilepsy at higher doses!)
Bethanecatechol use
Urinary retention
Post-op ileus (GI atony)
Avoid bethanecatechol use in
bladder outlet obstruction (stones, BPH, tumor)
Bethanecatechol MOA
muscarinic selective, doesnt bind to nicotinic
resistant to AchE
Cevimelie and pilocarpine uses
Xerostomia
After head/neck radiation
Sjogrens
Nicotinic agonists for cessation
Nicotine (full agonist, protonated at acidic pH)
Varenicline (partial agonist of a4B2 nicotonic receptor, blocks nicotine from binding at the same time)
Sides for Nicotine
Irritation at site, tachycaridia/arrhythmia, dyspnea
Sides for Varenicline
GiT related
Dream stuff
Varenicline reduces ________
effects of withdrawal