Lecture 6: Intro to Cholinergic Drugs Flashcards
Where are M1, M3, and M5 receptors located, what G protein do they use, and what is their mechanism of action?
M1 - nerves, M3 - glands/SM/endothelium, M5 - CNS
- Gq GPCR
- IP3/DAG cascade
Where are M2 and M4 receptors located, what G protein do they use, and what is their mechanism of action?
M2 - heart, nerves, smooth muscle
M4 - CNS
- Gi GPCR
- inhibition of cAMP production (M2 = K channel activation)
Where are M3 and M2 predominantly found?
M3 - in most organs (SM)
M2 - predominates in the HEART (also SM)
What 2 Direct Acting Cholingerics have both Nicotinic and Muscarinic actions?
Acetylcholine and Carbachol
What 3 Directing Acting Cholinergics are charged and poorly absorbed? (BAM)
Bethanechol, Acetylcholine, Methacholine
What 4 Direct Acting Cholinergics are uncharged and highly absorbed? (MP/NL)
Muscarinic: Muscarine, Pilocarpine
Nicotinic: Nicotine, Lobeline
What 4 AChE Inhibitors are Charged (quaternary) and poorly absorbed? (NEEP)
What is the difference between the two types?
Neostigmine, Edrophonium, Echothiophate, Physiostigmine
Alcohols and Carbamic Acid Esters are reversible, but CAE’s are longer lasting
What 4 AChE Inhibitors are Uncharged (tertiary) and highly absorbed? (PRGT)
Physostigmine, Rivastigmine, Galantamine, Tacrine
Asthma, Hyperthyroidism, Coronary Insufficiency, and Acid-Peptic Disease are contraindications of what kind of drugs?
Muscarinic Drugs
How is acute nicotinic poisoning treated?
atropine plus parenteral anticonvulsants (diazepam)
What are Acetylcholine and Bethanechol approved for use in?
A: intraocular used during surgery (causes miosis)
B: selective urinary and GU stimulant
- treat patients with urinary retention/heartburn
What is Carbachol approved for use in?
treatment for glaucoma or producing miosis during surgery/ophthalmic exams
What are Cevimeline and Pilocarpine approved for use in?
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
What is Vernicline used for?
- 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
Why would indirect-acting cholinergic agonists be useful when treating a pt. with dementia (Alzheimers)
- pts with alzheimers have a lack of intact cholinergic neurons, so making sure agonists are not broken down would help keep those neurons bound
How does AChE inhibitor toxicity manifest and what would you treat it with?
- SLUDGE symptoms and effects on NMJ (twitching and paralysis)
- use atropine and pralidoxime (AChE regenerator) to help stop poisoning
What anticholinergic is used to treat motion sickness?
Scopolamine
What anticholinergics (BTP) are used for the treatment of Parkinsons Disease?
- antagonists used to REDUCE TREMORS
- benztropine, trihexyphenidyl, procyclidine
What anticholinergics are used in Anesthesia?
- ATROPINE (blocks vagal reflex via surgical manipulation)
- atropine or glycopyrrolate (GI) is paired with neostigmine to block parasympathetic effects
When are anticholinergics used for ophthalmologic disorders and what two are commonly used? (HA)
- 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
What two anticholinergics are used to treat respiratory disorders such as asthma and COPD? (TI)
Ipratropium and Tiotropium
- inhalation antagonists
- Tiotropium has longer action (can be used once daily)
Why is Oxybutynin not the BEST choice for bladder urgency treatment? What are 3 better options that could be used? (Dar/S/T)
- 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
What drugs can be given to treat cholinergic poisoning? What is atropine not useful in treating?
- 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)
What are common adverse reactions to anticholinergics?
What are 3 contraindications of anticholinergics?
- 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
What are Ganglion-Blocking drugs (M) and how do they work?
- 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)
