Lecture 6: Intro to Cholinergic Drugs

Question 1

Where are M1, M3, and M5 receptors located, what G protein do they use, and what is their mechanism of action?

Answer 1

M1 - nerves, M3 - glands/SM/endothelium, M5 - CNS

• Gq GPCR
• IP3/DAG cascade

Question 2

Where are M2 and M4 receptors located, what G protein do they use, and what is their mechanism of action?

Answer 2

M2 - heart, nerves, smooth muscle

M4 - CNS

• Gi GPCR
• inhibition of cAMP production (M2 = K channel activation)

Question 3

Where are M3 and M2 predominantly found?

Answer 3

M3 - in most organs (SM)

M2 - predominates in the HEART (also SM)

Question 4

What 2 Direct Acting Cholingerics have both Nicotinic and Muscarinic actions?

Answer 4

Acetylcholine and Carbachol

Question 5

What 3 Directing Acting Cholinergics are charged and poorly absorbed? (BAM)

Answer 5

Bethanechol, Acetylcholine, Methacholine

Question 6

What 4 Direct Acting Cholinergics are uncharged and highly absorbed? (MP/NL)

Answer 6

Muscarinic: Muscarine, Pilocarpine

Nicotinic: Nicotine, Lobeline

Question 7

What 4 AChE Inhibitors are Charged (quaternary) and poorly absorbed? (NEEP)

What is the difference between the two types?

Answer 7

Neostigmine, Edrophonium, Echothiophate, Physiostigmine

Alcohols and Carbamic Acid Esters are reversible, but CAE’s are longer lasting

Question 8

What 4 AChE Inhibitors are Uncharged (tertiary) and highly absorbed? (PRGT)

Answer 8

Physostigmine, Rivastigmine, Galantamine, Tacrine

Question 9

Asthma, Hyperthyroidism, Coronary Insufficiency, and Acid-Peptic Disease are contraindications of what kind of drugs?

Answer 9

Muscarinic Drugs

Question 10

How is acute nicotinic poisoning treated?

Answer 10

atropine plus parenteral anticonvulsants (diazepam)

Question 11

What are Acetylcholine and Bethanechol approved for use in?

Answer 11

A: intraocular used during surgery (causes miosis)

B: selective urinary and GU stimulant
- treat patients with urinary retention/heartburn

Question 12

What is Carbachol approved for use in?

Answer 12

treatment for glaucoma or producing miosis during surgery/ophthalmic exams

Question 13

What are Cevimeline and Pilocarpine approved for use in?

Answer 13

C: oral; treat dry mouth (xerostomia) in pts with Sjogrens syndrome

P: xerostomia from Sjogrens/head and neck cancer

• topical use for miosis and glaucoma
• pure mAChR agonist

Question 14

What is Vernicline used for?

Answer 14

• partial agonist that binds to Nn (a4B2); approved for smoking cessation
• moderate, sustained release of dopamine to reduce cravings and withdrawal symptoms
• nausea is most common side-effect

Question 15

Why would indirect-acting cholinergic agonists be useful when treating a pt. with dementia (Alzheimers)

Answer 15

• pts with alzheimers have a lack of intact cholinergic neurons, so making sure agonists are not broken down would help keep those neurons bound

Question 16

How does AChE inhibitor toxicity manifest and what would you treat it with?

Answer 16

• SLUDGE symptoms and effects on NMJ (twitching and paralysis)
• use atropine and pralidoxime (AChE regenerator) to help stop poisoning

Question 17

What anticholinergic is used to treat motion sickness?

Answer 17

Scopolamine

Question 18

What anticholinergics (BTP) are used for the treatment of Parkinsons Disease?

Answer 18

• antagonists used to REDUCE TREMORS

- benztropine, trihexyphenidyl, procyclidine

Question 19

What anticholinergics are used in Anesthesia?

Answer 19

• ATROPINE (blocks vagal reflex via surgical manipulation)

- atropine or glycopyrrolate (GI) is paired with neostigmine to block parasympathetic effects

Question 20

When are anticholinergics used for ophthalmologic disorders and what two are commonly used? (HA)

Answer 20

• only used when cycloplegia/prolonged mydriasis is required (LASIK)
  
  • adrenergic agonists are short-lived, less adverse

use Homatropine and Atropine to prevent synechia formation in uveitis and iritis (iris adheres to lens/cornea)
- long acting, effects (above) linger

Question 21

What two anticholinergics are used to treat respiratory disorders such as asthma and COPD? (TI)

Answer 21

Ipratropium and Tiotropium

• inhalation antagonists
• Tiotropium has longer action (can be used once daily)

Question 22

Why is Oxybutynin not the BEST choice for bladder urgency treatment? What are 3 better options that could be used? (Dar/S/T)

Answer 22

• Oxybutynin is a M3 selective (good) by has side effects (dry mouth/dizziness, constipation, blurred vision)
• Darifenacin, Solifenacin, and Tolterodine are also M3 selective
  • have longer half-lives
  • reduced instance of constipation/xerostomia

Question 23

What drugs can be given to treat cholinergic poisoning? What is atropine not useful in treating?

Answer 23

• Atropine is a solid first choice for reducing mAChR stimulation, but has little effect at nAChR
• atropine can be paired with pralidoxime (AChE regenerator at NMJ) to inc. the breakdown of cholinergic agonists
• atropine NOT useful for cholinergic poisoning by Mushroom poisoning (vomit and nausea 6-12 hrs after ingestion –> hepatic/renal failure via amatoxins)

Question 24

What are common adverse reactions to anticholinergics?

What are 3 contraindications of anticholinergics?

Answer 24

• usually good for one system but can cause adverse effects in others (mydriasis/cycloplegia are adverse effects in GI reduction)
• high systemic conc. lead to block of parasympathetic function = blind as a bat, dry as a bone, red as a beet, hot as a hare, etc

CONTRA: glaucoma, prostatic hyperplasia, acid-peptic disease

Question 25

What are Ganglion-Blocking drugs (M) and how do they work?

Answer 25

• synthetic amines (Mecamylamine) used to competitively block ACh action at nACHrRs of both parasympathetic and sympathetic autonomic ganglia
• approved for use in Hypertension (overall there are better options so they are NOT used frequently)