Cholinergic Pharmacology

Question 1

Describe nicotinic receptors?

Answer 1

Ion channel
Ganglion on both SNS and PNS
Found in the skeletal muscle and the brain

Question 2

Describe muscarinic receptors?

Answer 2

G-protein mediated

Effector organs/tissues of parasympathetic

Question 3

What are important considerations for modulation of acetylcholine?

Answer 3

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)

Question 4

What is the overall goal of the PNS?

Answer 4

To protect you from chronic long term potential damage

Question 5

What is acetylcholine and what do it do?

Answer 5

As a drug is does not cross the blood brain barrier (no psycho effects)
It will activate all autonomic ganglia (sympathetic and parasympathetic)
It will activate skeletal muscle receptors (twitching followed by paralysis)
Typical effects of stimulating parasympathetic system (reduced heart rate, reduced blood pressure, increased saliva, fixed near focus, contracted pupils, diarrhea, intestinal cramping, plus sweating)
Way too much non-specific for systemic use (it’s only used during eye surgery because we can put it directly on the eye)

Question 6

What is pilocarpine?

Answer 6

Similar effects to ACh but can penetrate BBB (psycho effects)
Drug of choice for severe acute glaucoma (intraocular pressure) - causes immediate opening of drainage system of the eye
Also - fixed focus (from lens effect)

Question 7

What does acetylcholinesterase do (AChE)?

Answer 7

Degrades ACh in the synapse

Inhibition of AChE will thus increase activity of ACh in the synapse (cholinergic agonist effect)

Question 8

What is myasthenia gravis?

Answer 8

Autoimmune destruction of ACh receptors at neuromuscular junction
Drug which increase ACh activity can aid with symptoms (but not the underlying pathology)
Example: neostigmine

Question 9

What is alzheimer’s disease?

Answer 9

Reduction in activity, and then death of, cholinergic neutrons in the brain
Drugs which can increase ACh activity in the brain can therefore treat some symptoms of alzheimer’s disease, but not the underlying pathology

Question 10

What is neostigmine?

Answer 10

Acetylcholinersterase inhibitor
Stimulates bladder and GI tract (urinary bladder disease and constipation)
Aid symptoms of myasthenia graves (increases muscular strength and response)

Question 11

What is donepazil?

Answer 11

Acetylcholinesterase inhibtors
Aka aricept
Stimulates cholenergic neurons in brain - treat symptoms of Alzheimer’s disease

Question 12

What is atropine

Answer 12

Cholinergic antagonist (similar to sympathomimetic drugs)
Aka belladonna
Decreases cardiovascular response to PNS stimulation (heart rate increases, blood pressure rises)
Bronchodilation and decreased respiratory secretions (drying)
Antispasmodic effect on GI tract, other smooth muscles
Dilates pupils

Question 13

What is neocitran?

Answer 13

OTC cold medication
Has antihistamine: it’s “atropinic”, so it decreases PNS nerve activity. Side effect: sedation and drying, bladder it would relax wall, constrict sphincter, in the gut it would relax the wall, constrict the sphincters and decrease secretions
Has sympathomimetic increases sympathetic receptor activity, in the bladder is relaxes the wall, constricts sphincter, in the gut it relaxes the wall, constricts the sphincters and decreases secretions, and in the heart it will increase the heart rate and contractility and constrict the arterioles

Question 14

What are problems neocitran could possibly cause?

Answer 14

Cardiovascular: hypertension, myocardial infarction

GI/GU: constipation, urinary retention

Question 15

What is scopolamine?

Answer 15

Strong CNS effects
Most effective anti-nausea drug
Fairly specific

Question 16

What is tiotropium?

Answer 16

Derived from atropine
Inhaled bronchodilators (very long term effects)

Question 17

What are the overdose and side effects of cholinergic antagonists?

Answer 17

Eyes: “sandy eye” syndrome (eyes are so dry), loss of near vision
Mouth: dry, pasty saliva
Gut: No movement, but sustained acid, nausea, vomiting, constipation, pain
No sweat
Bladder: flaccid bladder, contracted sphincter
But none of this really matters because you’ll be paralyzed

Question 18

What is SLUDS?

Answer 18

Salivation, lacrimation, urination, defecation, sweat

All of this is shut off if you overdose on cholinergic antagonists

Question 19

What are other names for jimson weed?

Answer 19

Datura stramonium
Thornapple
Stinkweed
Locoweed

Question 20

What does jimson weed do?

Answer 20

It’s is the main ingredient of belladonna, alkaloids, atropine and scopolamine
It’s an anticholinergic: dry mouth, dilated pupils, high temperature (but reduced sweating), blurred vision
Red as a beet, dry as a bone, blind as a bat, mad as a hatter
High risk of poisoning

Question 21

What are the psychological effects of jimson weed?

Answer 21

Psychological effects: confusion, euphoria and delirium
Red as a beet, dry as a bone, blind as a bat, mad as a hatter
May experience seizures, intense visual or auditory hallucinations, or cardiac arrest
High risk of poisoning

Question 22

How is jimson weed used in traditional medicine?

Answer 22

Treat a variety of illnesses. Extracts are used in treating asthma, intestinal cramps, and both diarrhea and bed-wetting

Question 23

What are neuromuscular junction blockers?

Answer 23

NMJ blockers are used in surgery - reduces the amount of anesthesia needed and allows rapid recovery of sense
All are parenteral
They are either non-depolarizing or depolarizing. Because NMJ desensitizes, it causes paralysis in both cases

Question 24

What is the order of muscular paralysis by NMJ blockers?

Answer 24

Eyes, face, fingers, limbs, trunk and diaphragm

Recovery is in the opposite order

Question 25

What is an example of a non-depolarizing NMJ blocker?

Answer 25

Curare amazonian poison. It is no longer used

Question 26

What is an example of a polarizing NMJ blocker?

Answer 26

Succinylcholine. It is the only depolarizing NMJ used. Causing twitching and fasciculation at first (from depolarization) but then flaccid paralysis