Cholinergic Agents & Parasympatholytic Actions

By: Richard Benedict S. Roxas, R.N, MD

November 25, 2010

AGONIST  Stimulation receptor MIMIC

ANTAGONIST  Opposite action of a receptor  LYTIC

Parasympathomimetic  Muscarinic Receptor

Parasympatholytic  Blocks/Inhibits Muscarinic Receptor

Neuromuscular Junction:

1. Presynaptic
- Vesicle (CONTAINING NEUTRANSMITTER) (Excitatory/Inhibitory)
- Calcium Voltage Gated Ion Channel - it only opens when the axon is energized (Electrical synaptic
event and that is -90mV)
- Synaptotagmin binding of calcium
- Docking Receptors (JAX)
- Presynaptic membrane  EXOCITOSIS  Release of NEUROTRANSMITTER
Events:
a. ACETYLCHOLINE FORMATION  trapped in vesicle

- Recycling : recycle CHOLINE

- Formation of Acetate  Mitochondria kreb Cycle
- Acetylcholine-O- Transferase  ACETYLCHOLINE
b. When it is Depolarized (-90mV) thru Electrical synapse from Axon
- Open CVGIO  Calcium entry
- Calcium + Synaptotagmin  Movement of Vesicle towards docking receptor (Jax)
c. Release
- Exocitosis aid of Calcium

2. Postsynaptic  This can be Target organ or Nerve

Events:
A. Receptor Activation (ACH  M,)
This is influenced by the following:
1. The surface area of the postsynaptic membrane increased and with burrow like feature.
a. The more deeper means more surface area, more muscarinic receptors (Acetylcholine
Receptors)
b. Less or flattened postsynaptic cleft  Will give you less binding sites for AcH
neurotransmitter, less stimulation of Muscarinic receptors
 2. The amount of exposure of the Acetylcholine (AcH) to the Acetylcholinesterase (AcHE)

a. If AcHE is increased  concentration of the AcH will be reduced  Reduce stimulation in

the target organ.
b. Decrease the level of concentration of the AcHE MORE AcH in the circulation inside the
junctional cleft.

Effects of AcH in various Organs:

a. Skeletal Muscle  Depolarize, Calcium release in the Sarcoplasmic reticulum /Sarcollema(storage

calcium) Troponin C binding Confirmational change in the Troponin-Tropomyosin complex
expose actin with the myosin head (ATPase enzyme cleaves ATP  ADP + Pi), Pi is source of
energy for the myosin head “COCKING”  MUSCLE SHORTING/Contraction.
b. Other organs: IP3 activation  DAG (Diacylglycerol  Releases Ca+)
c. HEART: K+ hyperpolarization  BRADYCARDIA
B. Degradation
a. ACETYLCHOLINESTERASE
- Hydrolyses the Acetylcholine  ACETATE+ CHOLINE
b. ACETATE  DEGRADE, CHOLINE  RECYCLE

Cholinergic Agents Agonistic Actions: Parasympathomimetic

1. Direct Acting
- Ach  1. Muscular Contraction/RIGIDITY  Ventilation, Pain, Mobility
- causes the stimulation of all Muscarinic receptors (M1-M4)

Critical Thinking: What will happen if the ACETYLCHOLINE LEVELS ARE KEPT IN HIGER LEVELS?
1. AcH is continual stimulating the postsynaptic cleft
a. N/V ? M1 receptor Dehydrate? Loss of HCl? Loss of Electrolytes?, Risk Aspirate?
b. Maglalaway? M3?  Aspirate?
c. Skeletal muscle  Muscular Spasm (RIGIDITY)
- Ventilation is affected prevents recoil  PaO2 is reduced, PaCO2 increased  ACIDOSIS
- Pain
- Immobility, compression  Reduced blood flow (Compressed blood vessel in muscle) 
Ischemia  (Cyanosis)
- Falls & safety
d. HCl in parietal secretion  Ulcer? Abdominal upset, GI bleeding, Aspirate /Chemical
Pneumonitis?
e. Relax LES  GERD?, Risk for Aspiration  Upper airway obstruction/Stridor, Respiratory
Distress Syndrome.
f. Pawisan?  muscarinic receptor activation  dehydrate?
g. Heart Failure?  M2 stimulation  CO reduction  Hypotension
h. Bronchoconstriction M3 stimulation  accumulation CO2  + H20 , carbonic anhydrase
enzyme,  pH reduction  Chemoreceptor activation  RR increased/ DOB
a. Wheeze  + sign for bronchoconstrion (RR, Pulse Oximeter, ABG)
 b. Crackes can be present only if hypersecretion in the goblet cells
i. MAGTAE?  Dehydration, Abdominal cramping, Messy?
j. Pupillary Constriction (MIOSIS)  Narrow angle glaucoma, Accomodation
k. Urinary Incontinence Dilated sphincters caused M3 activation

- Lets Discuss what will happen if AcH will be reduced?

a. Heart  Tachycardia (M2 not stimulated, B1 will become stimulated norepinephrine)
1. HPN
2. CHEST PAIN
3. ACS (acute coronary syndrome)
b. Bronchodilation
c. Constipation
e. Muscle weakness or Fatigability
d. Pupillary Dilation (Mydriasis)  Blurring of vision, Cycloplegic action
f. ANG MATA BA MAY MUSCLE? Rectus? Cillary Muscle, Super Oblique?
- FOR OCCULAR MOVEMENTS  Paralyzed or Weak muscle  EYE BALL ROLLING  Accidents
Vision  EYEBALLS MO PUMUPUNTA SA LIKOD  ASWANG
g. Sphincteric contraction in the ureter  Urinary Retention/ distention

2. Bethanicol For Urinary Retention

3. Pilocarpine  Pupillary Constriction (MIOSIS)  reduce IOP  ANTI-Glaucoma

2. Indirect Acting (REVERSIBLE)  ACHe Inhibitor (Myasthenia Gravis)

- Endrophonium

- Neostigmine

- Physiostigmine

- Pyridostigmine

ADD: Anti-Cholinergic Blocker to Reduce Side Effects:

ATROPINE SULFATE

0.5 mg
2.0 – 5.0 mg (Tachycardia, Dryness Mouth, Bronchodilation, Blurring Vison (mydriasis)
10mg (OVERDOSE: Delirium, COMA)

3. Indirect Acting (IRREVERSIBLE)

- Echothiophate

-Isoflurophate

4. Reactivation of Acetylcholinesterase
 - Pralidoxime (ANTIDOTE)

DOC: For insecticide poisoning

For AcHE inhibitors Toxicity

Steps in Acetylcholine Release

1. Synthesis

2. Uptake of Ca+ for Vesicular Migration

3. Release of Neurotransmitter

4.Binds to Postsynaptic cleft

5. Degradation by ACHE

6. Recycling

Anti-Muscarinic Agents : Target the Receptor (PARASYMPATHOLYTIC AGENTS) lowers or blocks action
AcH.

1. Atropine Sulfate

USES:

- Hyperperistaltic (Loose Bowel)

- Cholinergic Poisoning/Toxicity
- Dilation Pupils for OR prior Glaucoma Surgery
- Preop-medication
- Severe Asthma (Bronchodilating action)
- Urinary incontinence (NOT A DRUG OF CHOICE)

2. Ipratropium (COMBIVENT)  Anti Asthma (BRONCHODILATE, Reduce secretion)

3. Scopolamine (anti-motion sickness)