Muscarinic Receptor Agonist

Uses:

- opthalmic solution for rapid induction of miosis

- not used systemically due to ultra-short half-life due to AChE and plasma cholinesterase

Other:

- quaternary amine so limited CNS penetration/effects

- METHACHOLINE is predominantly a muscarinic agonist but is more resistant to hydrolysis by AChE but still has limited clinical use

Muscarinic receptor agonist

Uses:

1. stimulate tone and motility of GI tract - especially for post-op abdominal distention and gastric atony; occasionally used for treat congenital megacolon
2. stimulate urinary bladder motility - given post-op/ post-partum to treate urinary retention or inadequate emptying; also enhance detrussor muscle contraction after spinal cord injury 
3. oral treatment for xerostomia (dry mouth) - pilocarpine preferred but this drug has less diaphoresis 

Muscarinic receptor agonist

Uses:

1. Glaucoma - ocular administration produces miosis thus relieving intraocular pressure. Contraction of ciliary muscle causes spasm of accomodation

Pilocarpine

Muscarinic receptor agonist

Uses:

1. Glaucoma - topical muscarinic agonist lower intraocular pressure via contraction of the ciliary muscle facilitating aqueous humor outflow
2. Xerostomia - stimulates salivary secretion and treating dry mouth as a result of laryngeal surgery, head/neck radiation of Sjogren's syndrome

Reversible AChE inhibitors

Uses:

1. GI tract stimulator - stimulates GI tract motility esp the colon and stimulates gastric acid secretion
2. Glaucoma - produces miosis, reducing intraocular pressure but blocking accomodation reflex
3. Myasthenia gravis - autoimmune disorder destroying nicotinic (N_M) receptors at the neuromusclar junction
4. Neuromusclar blockade reversal - reverses effect of neuromuscular blockade used in surgery (tubocurarine) and restores muscle function; not able to restore depolarizing agent paralysis (succinylcholine)

Reversible AChE inhibitor

Uses:

1. GI tract stimulator - stimulates GI tract motility esp the colon and stimulates gastric acid secretion
2. Glaucoma - produces miosis, reducing intraocular pressure but blocking accomodation reflex
3. Myasthenia gravis - autoimmune disorder destroying nicotinic (N_M) receptors at the neuromusclar junction
4. Neuromusclar blockade reversal - reverses effect of neuromuscular blockade used in surgery (tubocurarine) and restores muscle function; not able to restore depolarizing agent paralysis (succinylcholine)

Reversible AChE inhibitor

Uses:

1. Reverse effect of centrally-acting muscarinic antagonists
2. reverse the sedative actions of diazepam

Reversible AChE inhibitor

Uses:

1. differential diagnosis of myasthenia gravis - IV administration rapidly and transiently enhances muscle contraction in patients with MG; no response to drug = no MG

Irreversible AChE inhibitors

Uses:

1. Glaucoma - used when other more conservative treatments are ineffective

Muscarinic receptor antagonists

Effects, uses:

1. Eye - blocks cholinergic regulation of iris sphincter muscle and ciliary muscles leading to mydriasis and cycloplegia respectively. Alpha adrenoceptor agonists preferred due to shorter duration of action
2. Respiratory tract - dries mucus membranes of respiratory tract and is used for older general anesthetics that elicit excessive bronchial secretions; also stops cilia 
3. Heart - high doses block vagal stimulation of M2 receptors on SA node --> tachycardia; conduction velocity increased helping correct AV block
4. GI tract - inhibits GI motility and reduces gastric secretion - seldom used due to side effects; can be used to treat IBD and reduce tone/motility of GI tract
5. Urinary tract - decrease tone and amplitude/frequency of ureter contractions thus decreasing intravesicular pressure and increasing capacity - seldom used due to other effects
6. Anti-AChE poisoning - large doses of drug are used to treat overdose/poisoning from AChE inhibitors, esp organophosphorous pesticides or nerve gases.

Muscarinic receptor antagonists

Uses:

1. Motion sickness - prophylactic; less effective in reversing motion sickness

Muscarinic receptor antagonist

1. COPD - reduces bronchoconstriction and secretions without compromising mucociliary function
2. Rhinorrhea - approved to treat runny nose associated with common cold

Muscarinic receptor antagonists

1. COPD - inhaled as dry powder with longer duration of action than ipratropium (~24hrs) thus allowing 1-day dosing and better compliance; less secretions and still has mucociliary action

Muscarinic receptor antagonist

1. GI ulcers - treats peptic ulcers by reducing gastric acid secretion  via inhibition of inhibition of autonomic ganglia(?); largely replaced by  H2 antagonists or PPIs

Muscarinic receptor antagonists

1. Urinary incontinence/overactive bladder - reduces bladder smooth muscle contractility

Muscarinic receptor antagonist

1. Overreactive bladder - used to decrease bladder contractility, and may also be used to relieve bladder spasm after urologic surgery

Nicotinic receptor agonists

1. No therapeutical effects but a strong toxicological profile
2. Autonomic ganglia - stimulates both SNS and PSNS leading to complicated and unpredictable effects; large doses can stimulate release of epi into bloodstream from adrenal medulla
3. Neuromuscular junction - can stimulate activity then produced depolarized block --> death via respiratory muscle paralysis

Nicotinic receptor agonist

1. partial agonist at CNS nAChR and helps reduce cravings for cigarettes along with decreasing pleasureable effects
2. smoking cessation aid

Ganglionic blocking agents

1. anti-hypertensive: no longer used because it has too wide of a range of target sites and better options now exist

Non-depolarizing neuromuscular blockers

1. paralytic derived from curare by competitively binding to AChR and block its firing by preventing ACh from binding to it

Non-depolarizing neuromuscular blockers

1. paralytic via AChR non-stimulatory competitive block
2. less potential for autonomic blockade making it essentially devoid of cardiovascular side effects
3. longer duration of action compared to tubocurarine and less potential for histamine release

Non-depolarizing neuromuscular blockers

1. least potent but fastest onset; high doses
2. high doses can produce antimuscarinic effects but little histamine release

Non-depolarizing neuromuscular blockers

1. Intermediate duration and slight tendency to release histamine
2. Cisatracurium has sam pharmacological profile but fewer side effects

Non-depolarizing neuromuscular blockers

1. short duration of action and is hydrolyzed rapidly by pseudocholinesterase - those with deficiency have prolonged duration

Depolarizing neuromuscular blockers

1. Combines with N_M receptor and initially depolarizes the cell causing contraction but further activation is prevented after inital depolarization
2. due to initial depolarization severe muscle contractions/fasciculations can occur if administered too rapidly
3. some potential for histamine release

Skeletal muscle relaxants

Uses:

1. joint disease pain, muscle spasms, anti-anxiety

Skeletal Muscle Relaxant

Uses:

1. Spasticity from SC lesions - MS or trauma, CN 5 & 9 neuralgias

Skeletal muscle relaxant

Uses:

1. spasticity from SC lesions - MS or trauma; malignant hyperthermia

AChE inhibitors used to treat Alzeheimers disease

Tacrine

Donepezil

Rivastigmine

Galantamine