Miosis

Diaphoresis & Flushing

Salivation

Nausea and Abdominal pain

↓BP & HR

Bronchospasm

Diarrhea

Urinary urgency

Direct Acting Cholinergic Agonists

(3 mechanisms and examples)

1. Choline Esters
• ACh
• Methacholine
• Bethanechol
• Carbachol
2. Plant alkaloids
• Pilocarpine
3. Other
• Cevimeline

Direct acting cholinergic agonist

↓ HR + CO (by dec. SA firing)

M3 ->NO -> vasodilation

Salivation + Int secretions + GIm + urination

Ciliary ms contraction + pupillae sphincter ms contraction -> miosis

Tx: No use (AChE is fast)

Methacholine

R: Muscarinic

M: dec. HR + CO via dec. SA firing

Bronchoconstriction

Tx: Dx of Asthma

SE: Lightheadedness, Headaches, Pruritus

Bethanechol

R: Strong muscarinic

M: Inc. GIm + tone

GU -> +detrussor ms, -trigone, -sphincter -> inc. urination

Tx: inc. GI/GU (post-op, post-partum, Rx related)

SE: General cholinergic adverse effects (seperate card)

- Atropine --> reverse CVS and Resp effects

Carbachol

R: Muscarinic and Nicotinic

M: +ganglin --> 1st stimulate then represses CVS/GIS

Release Epi from A. Medulla (N receptor)

Eye - miosis + accommodation

Tx: Glaucoma (pupillary contraction -> intraocular P dec.)

Miosis during Sx

SE: Diffused Nicotinic action (so no systemic)

Topical -> dec. or no SE

A plant alkaloid (direct acting)

R: Muscarinic agonist

M: Eye - miosis - contraction of ciliary ms (dec. Pio)

- inc. Aq Humor draining

Secretogogue - inc. secretion (sweat, saliva, tears)

Tx: Glaucoma

inc. Pio (Rx of choice)

myodriasis from atropine

xerostomia from radiation

Sjorgen's syndrome

SE: CNS disturbances, inc. pSNS effects (atropine to dec.)

Indirect acting cholinergic agonists

- Reversible AChE inhibitors

1. Edrophonium
2. Physostigmine
3. Neostigmine
4. Pyridostigmine
5. Ambenoium
6. Tacrine
7. Donepezil
8. Rivastigmine
9. Galantamine

Indirect acting cholinergic agonists

- Irreversible AChE inhibitors

1. Echothiophate
2. Isoflurophate

Short acting AChE I

Reversibly inhibits AChE - acts on the periphary

Dx of MG

Antidote to Tubocurarine

Cholinergic Crisis

Intmed acting AChE I

M:Stimulate N&M  in ANS, NMJ and the CNS

Tx:Bowel/Bladder atony, Glaucoma, Treatment of MG

Rx of Choice: antidote to anticholinergic Rx overdose with CNS effects (Atropine)

SE: CNS effects, dec. HR, Skeletal Ms Paralysis

Intmed acting AChE I

M: Rev inhibits AChE --> gr8er effect on Sk ms; contracts before paralyzing

Tx: for Post-op abd distension & urinary retention

MG, Antidote for Tubocurarine

SE: generalized cholinergic effects, skeletal ms paralysis

Intmed actinG AChE

M: Rev inhibits AChE

Tx: chronic managing MG

SE: Generalized chol effects

Galatamine

Tacrine

Donepezil

Rivastigmine

Intmed AChEI

M: Rev inhibits AChE in the CNS

Tx: 1st line for Alzheimer Dz

SE: GI distress; Hepatotoxicity (tacrine)

Irreversible AChE I

Covalent bind to AChE - phosphorylation - perma inactive

Tx: NONE!

SE: Generalized cholinergic effect

ms weakness and cramps

CNS problems (depression, agitation, convulsoins, confusions, delirium, coma)

Resp paralysis

Irreversible but safe AChEI

M: Generalized cholinergic effect, intense Miosis

Tx: Glaucoma - topical solution on eye

- no longer used cuz of cataracts!

SE: Paralysis of motor function --> resp paralysis

General cholinergic stimulation

Cataracts

Blind as a bat - mad as a hatter - red as a beet - hot as hell - Dry as a bone - bowel and bladder lose their tone

Mydriasis

Confusion

Tachycardia

Blurred vision

Dry mouth/eyes

Constipation

Urinary retention

Atropine

Scopolomine

Pirenzepine

COPD: Ipatropium & Piatropium

Refractive error: Tropicamide & Cyclopentalate

Parkinson's: Trihexypheniyl, Benztropine & Amantadine

Overactive bladder: Darifenacin, Fesoterodine, Oxybutinin, Trospium

binds to M receptors

Action:

Greatest inhibitory effects on bronchial tissue & secretion of sweat and saliva

Eye: mydriasis, unresponsiveness to light, cycloplegia, inc. IOP

GI: antispasmodic (withtout much effect on acid)

Bladder: urinary retention

CV: inc. HR at high dose

dec. secretion from salivary, lacrimal and sweat glands

Tx: Mydraisis for ophthalmologic sx, antidote for cholinergic agonists, preop resp tract secretoin blockade, Acute symptomatic bradycardia

SE: attach of eye pain in glaucoma pts, general effec of a muscarinic block, CNS (restless, confusion, hallucination), problesm with body temp regulation (inhibits sweat glands)

Binds M receptors

Action: Strong CNS action - sedation at therapeutic doses, excitation and euphoria at high doses

Blocks short term memory

Tx: Drug of choice - motion sickness

Block short term memory with anesthesia

SE: General effects of a muscarinic block

CNS effects: restlessness, confusion, hallucination

M1 receptor antagonist

Action: decrease stomach acid secretion

Tx: PUD

SE: general effect of a M-block

Anti-muscarinics used in COPD?

and their action, tx, and SE?

Iprotropium & Tiotropium

Action: Bronchodilation

Tx: COPD (and asthma) maintenance treatment (inhalers)

SE: Gen effects of a M-block

Tropicamide & Cyclopentolate

Action: Mydriasis & Cycloplegia

Tx: Ophthalmic solution

SE: Eye pain in glaucoma pts

(Too Bloody Active)

Trihexyphenydyl

Benztropine

Amantadine

Tx: Parkinson's Dz - tremors and rigidity

parkinsonian syndromes

SE: general effects of muscarinic block

(Far Too Overactive Diuretics)

Action: Lower intravasc pressure, inc. bladder capacity, dec. frequency of bladder contractions

Tx: Overactive urinary bladder

SE: general effects of a M-block

- Act on the N receptors at the ganglion

- both pS and SNS

(NOT USED TX) eg: Nicotine

block the entire output of the ANS:

• preferentially block the predominant input
• eg:
• blood vessels: sym is blocked --> vasodil
• GI: pS is blocked --> atony
• Heart: pS is blocked --> inc. HR
• Eyes: pS is blocked --> cycloplegia, xerostomia

1. Surgical anethesia - reduce the need for deeper anesthesia
2. Orthopedic procedures
3. reduce the risk in electroshock therapy
4. facilitate tracheal intubation (+ anesthetics)
5. adjunct in control of ventilation (reduce chest wall resistance)

1. Competitive (non-depolarizing)

- Structure different from ACh

- competitive ACh antagonist at N receptors - low dose blocks reversed by inc. [ACh] --> AChEI - (neostigmine, edrophonium)

- use IV, not metabolized, dose <=> duration of relaxant needed

eg: D-tubocurarine

2. Depolarizing

- structure resembles ACh

- binds and activate the N receptors for a prolonged period

-

eg: Succinylcholine

Short acting:

Mivacurium

Intmed acting:

Vecuronium,    Atracuronium,    Rocuronium

Long acting: (Dont Move Please Dont Contract)

D-tubocurarine

Metocurine

Pancuronium

Doxacurium

Cisatracurium

Adverse effects of competitive NMJ blockers

(and which Rx causes it)

Ganglionic block (dec. BP inc. HR)

- Tubocurarine

- Metocurine

Vagal block (vagonium block)

- Pancuronium

- Rocuronium

Histamine release (bronchospasm, hypotension, inc. bronchial salivary secretions, flusing)

- Atracurium

- Mivacurium

- Tubocurarine

Seizures

- Atracurium only

Cholinesterase inh. (physostigmine, pyridostigmine)

- Tx dose: reverse action

- high dose: ACh increase too high and cause depol block

Halogenated Hydrocarbon Anesthetics (Halothane)

- senstitize NMJ to blockers

Aminoglycoside Abx (gentamicyn, tobramycin)

- inhibits ACh release of nerves (dec. competition)

Ca channel blockers (amlodipine, diltiazem)

- block ca channels --> dec. ACh release

Succinylcholine

Only depolarizing NMJ blocker used Txly

- Injected IV

- similar stucture to ACh

- not metabolized by AChE

- prolonged action on receptors

- Metabolized by Butyrylcholinesterase (pseudocholinesterase)

--> variation of BuChE in pt can lead to dangerous prolongation of the NMJ block

1. Hyperkalemia - rapid K release from intracells
• consequences: rhbdomyolysis, cardiac arrest
• contraindications: soft tissue trauma, burns, ocular lacerations, spinal cord injuries, ms dystrophies
2. Apnea - def in BuChE
• diaphragm paralysis and slow metab
3. inc. IOP, inc. intragrastric P
4. postop myalgias (muscle pain)
5. Malignant hyperthermia
• Inc. Ca release from SR in SkMs - contracture, heat production, inc. ms metab, metab acidosis, tachyK, hyperthermia
• tx: IV dantrolene (blocks Ca release)

1. beta-receptor antagonists

- dec. aq humour production

- timolol,levobunolol

2. alpha-2 receptor agonist

- dec. aq humour production

- Alpraclonidine, brimonidine

3. Muscarinic agonists

- inc. aq flow

- Pilocarpine, carbachol, AChEI(physostigmine, echothiphosphate, isoflurophate)

4. Prostaglandin PGF2α analogues - 1st line

- inc. aq humour outflow

- Latanoprost, Travopost

5. Carbonic anhydrase inhibitors

- dec. aq prodcution

- dorzolamide, brinzolamide