ANS Con't - Cholinergic Agonists Flashcards
Cholinergic agonists?
- not as many as adrenergic
- most are sympathomethic or sympathetic blocking
Nicotinic receptors
- Ion channel
– ganglion of both sympathetic and parasympathetic
– Skeletal muscle
Muscarinic receptors
- G-protein mediated
– Effector organs/tissues of parasympathetic
Difference b/t SNS & PNS
SNS:
pre - ACh
post - NE (ACh at sweat glands)
PNS
pre - ACh
post - ACh
The interesting case of sweat…
• Sweat glands are stimulated by the SYMPATHIC system BUT, most are CHOLINERGIC synapses
• So, when you activate the overall fight-or- flight system (sympathetic), you sweat
• BUT, if you use agonists to cholinergic synapses, you also sweat
Sweaty palms
• Sweat receptors on the palms (and only palms) are adrenergic
• Sweat receptors everywhere else are cholinergic (but remember, they’re still part of the sympathetic system)
(not on test)
Important considerations for modulation of acetylcholine (Ach):
1- ALL PREGANGLIONIC synapses (sympathetic and parasympathetic) are cholinergic. (Think of the non-specificity potential)
2- There are major PSYCHOLOGICAL effects caused by modulating Ach-possibly causing death (Think of drugs crossing the blood brain barrier)
3- SKELETAL MUSCLE works through Ach receptors (so think of paralysis potential)
Describe Acetylcholine
• As a drug, does not cross the BBB (no psycho effects)
• Will activate ALL autonomic ganglia (sympathetic and
parasympathetic)
• Will activate skeletal muscle receptors (twitching followed by paralysis)
• Typical effects of stimulating parasympathetic system (reduced HR, reduced BP, Increased saliva, fixed near focus, contracted pupils, diarrhea, intestinal cramping…plus, sweating*)
• WAY too non-specific for systemic use
• ONLY used for eye surgery
Describe Pilocarpine
• Similar effect to Ach BUT can penetrate BBB (psycho effects - so don’t want to much)
• Drug of choice for severe acute glaucoma (intraocular pressure)- causes immediate opening of drainage system of the eye
• Also- fixed focus (from lens effect)
Describe Acetylcholinesterase (AchE)
• Degrades Ach in the synapse
• Inhibition of AchE will thus INCREASE activity of Ach in the synapse (cholinergic agonist effect)
Describe Myasthenia Gravis
• Autoimmune destruction of Ach receptors at NMJ
• Drugs which increase Ach activity can aid symptoms (not underlying pathology)
Describe Alzheimer’s Disease
• Reduction in activity, and then death of, cholinergic neurons in brain.
• Drugs which can increase Ach activity in the brain can therefore treat some symptoms of AD, but not underlying pathology
List & describe Acetylcholinesterase Inhibitors
NEOSTIGMINE:
Stimulates the bladder and GI tract (urinary
bladder disease and constipation)
Aid symptoms of myasthenia gravis (increases muscular strength and response)
DONEPAZIL (Aricept)
Stimulates cholenergic neurons in brain- Treat symptoms of Alzheimer’s disease
Describe Cholinergic Antagonists
ATROPINE- BELLADONNA (BEAUTIFUL WOMAN)
Decreases cardiovascular response to parasympathetic stimulation. (HEART RATE INCREASES, BLOOD PRESSURE RISES) Bronchodilation and decreased respiratory secretions (DRYING)
ANTISPASMODIC effect on GI tract, other smooth muscles
DILATES pupils
OTC Cold Medication - NEOCITRAN
ANTIHISTAMINE - “atropinic” - DECREASE parasympathetic nerve activity
• side effect of antihistamine - sedation and drying (atropinic) • bladder (relax wall; constrict sphincter)
• gut (relax wall; constrict sphincters; decrease secretions)
SYMPATHOMIMETIC - INCREASE sympathetic receptor activity
• bladder (relax wall; constrict sphincter)
• gut (relax wall; constrict sphincters; decrease secretions)
• heart (increase heart rate / contractility; constrict arterioles)
Possible Problems?
- Cardiovascular (hypertension, MI)
- GI/GU (constipation, urinary retention)
