Parasympathomimetics

Question 1

The three problems with ACh as a drug…

How have we solved this?

Answer 1

1. ineffective orally - it has a quaternary structure, its not lipid soluble
2. effects fleeting - seconds or minutes due to rapid hydrolysis
3. Widespread effects on injection

Made analogues

Question 2

Bethanechol

Answer 2

Beta methyl carbanchol

Absorbed P.O. despite quaternary structure
—just give a bigger dose

Used in post-partem or post-operative urinary retention; atony in GI tract
—sometimes after surgery you have to give the intestine a little kick to make it work

Question 3

Cevimeline from plant

Answer 3

Used to correct dryness of mouth and upper respiratory tract

After head and neck irradiation and in Sjogren’s syndrome to correct dryness

(^these people may have trouble swallowing so thats why we give Cevimeline; its stimulates M3)

Question 4

Muscarine

Answer 4

Alkaloid from mushroom (amanita muscarine)
–this is not used as a drug, but it is important historically, thats why we call these receptors muscarinic

Historically – 1907 Dixon noted parallel between effects of muscarine and those parasympathetic nerves

Question 5

Pilocarpine (also from plant)

Answer 5

Miotic in glaucoma

• -used to be widely used, but not as much anymore (now rarely)
• -used when pressure inside eye is increasing and need to bring the pressure down

Partial agonist, less headache

Relieves block of canal of Schlemm

IT ACTS FAST
-so its important even though not used frequently

Question 6

How is pilocarpine used in glaucoma?

Answer 6

used to constrict the pupil of the eye to decreased outflow and bring the pressure down

(constrict pupil –> pulls iris away from canal –> fluid drains out –> gets decreased pressure)

• -Intraocular pressure increased to 30-40 mmHg (in glaucoma) - normal is 20-25
• -The canal of schlemm is blocked

This drug is mustly used in those with narrow angle glaucoma patients that are waiting for surgery

Question 7

What are the two types of glaucoma?

Answer 7

1. Narrow angle

2. Wide angle

Question 8

What drugs are used with glaucoma

Answer 8

1. Beta blockers
2. Prostaglandins
3. Pilocarpine for narrow angle emergencies

1&2 act slower than 3
1&2 can take up to hours

Question 9

Precautions when using sympathomimetics

Answer 9

1. Asthma
   - -pilocarpine will stim muscarininc receptors in ariways –> bronchoconstrictors
2. Hyperthyroid
   - -excess receptors
   - -hypersensitive to the drug
   - -can get A.Fib

Question 10

M1

Answer 10

Brain

PIP2

Question 11

M2

Answer 11

Heart

Decreased cAMP

Question 12

M3

Answer 12

Smooth mm

PIP2