What are the drugs for hyperhidrosis?
Describe eccrine sweat glands
Glands common on the soles of feet and forehead that secrete clear, odorless fluid for thermal regulation and receive post-ganglionic sympathetic innervation from Ach
Describe apocrine sweat glands
Glands common in the axillar and urogenital regions that secrete thick odorless fluid that is degraded by abcteria to produce stinkyness and receives post-gnalgionic sympathetic innervation from caetcholamines
What receptors are responsible for stimulating sweat production?
alpha 1 (localized) and M2/M3 (generalized effect)
Also note that alpha1 and alpha2 receptors are repsonsible for cutaneous vasoconstriction, but that vasodilation relies upon localized NO meidated effects, rather than a direct innervation from the ANS for body temp control
What are the effects of Ach on the body?
DUMBBELLS (diarrhea, urination, miosis/muscle weakness, bronchorrhea, bradycardia, emeiss, lacrimation, salivation/sweating)
How does a cholinergic agonist sitmulate secretions?
via icnreasing inracellular Ca2+ whihc then activates water and Cl-/K+ loss and results in cell shrinkage. The cell then udnergoes readjustment of potassium and chloride levels via pump processes
How does aluminum chloride (Drysol) work?
short-term occlusion of eccrine and apocrine sweat gland ducts (combines with keratin to produce fibrillar contraction of duct) with minimal systemic absorption
may cause skin irritation if skin is traumatized, wet, or recently shaved
How does Ach movement occur?
1) Ach is stored in pre-synpatic vesicles along with ATP and other co-transmitters
2) Action potential causing Ca2+ entering, resulting in fusion of Ach carrying vesicles with the cell membrane, and exocytosis (blocked by botulinum toxin)
3) Binding of Ach to post-synaptic nicotinic M receptors of G-couple muscarinic receptors
How does Ach vesicle release occur specifically?
SNARE proteins on the vesicle synapse to syntaxin and SNAP-25 (synaptobrevin, aka VAMP) on the membrane
Botulinum toxin cleaves SNARE
How does botulinum toxin work?
It binds to the cell membrane and is internalized by endocytosis and then requires cleavage into a heavy and a smaller light chain (the active form of the toin). The light chain binds to and thus inactivates the SNAP 25 protein.
Also blocks release of pain neuorpeptides such as substance P and CGRP)
How is Botox applied?
Uses of botox?
capable of causing muscular paralysis and blocks BOTH muscarinic and nictoinic receptors for uses such as cosmetic, migraine headaches, and muscle paralysis.
AEs of Botox?
-rarely respiratory arrest and death
-more commonly anti-cholinergic effects (blurred vision, dropping eyelids, etc.)
-contains albumin- allergy
Notes on Oxybutynin
anti-cholinergic drug used off-label for hyperhidrosis that CAN cross the BBB (glycopyrrolate and propantheline dont really cross the BBB)- this can cause sedation and delirium
Other drugs for sweating?
-Propanolol or centrally acting clonidine can reduce sympathetic tone and thuse sweating
-Diltiazem- blocks Ca2+ channels involved in secretion processes