PHRM 825: Pharmacologic Manipulations of the Cholinergic System Flashcards
What causes botulism and where is it present?
Bacterium clostridium botulinum; soil and water
How does clostridium botulinum cause botulism?
Inhibits release of Ach
What are symptoms of botulism?
- Weakness
- Trouble seeing
- Feeling tired
- Trouble speaking
- NOT NECESSARILY FEVER*
What is the most fatal symptom of neuropathy of the ANS?
Silent ischemic events (painless event)
What are 2 approaches to increase cholinergic stimulation?
Increase endogenous stimulation and use exogenous stimulation
What can reduce symptoms of neuropathic ANS disorders?
Cholinergic stimulation
Would an AchE inhibitor help botulism patients?
No. Patient’s don’t release Ach
What are the 2 types of cholinesterases?
Acetylcholinesterase (AchE) and plasmacholinesterase (Butyrylcholinesterase (BuChE)
Where is AchE located?
In nerve synapses
Where is butyrylcholinesterase (BuChE) located?
In plasma and many organs (liver, skin, GI tract, brain)
What does BuChE metabolize?
Succinylcholine
Where do acetylcholinesterase inhibitors bind?
The same site as acetylcholine
What are the 3 classes of AchE inhibitors?
Quaternary ammonium alcohols, carbamates, and organophosphates
What drug is a tertiary amine that can enter the CNS?
Physostigmine
What can physostigmine be used to treat?
glaucoma and Alzheimer’s disease, and atropine overdose
What is neostigmine used to treat?
myasthenia gravis, reversal of neuromuscular blockers and post-operative ileus
What is pyridostigmine use to treat?
myasthenia gravis, reversal of neuromuscular blockers and post-operative ileus
What is an irreversible, covalent binding AchE inhibitor?
Organophosphates
What are organophosphates used to treat?
Glaucoma (not commonly used)
What are symptoms of acetylcholinesterase inhibitor poisoning?
DUMBBELLSS (all of these are M3 except Bradycardia) -Diarrhea -Urination -Miosis -Bronchospasms -Bradycardia (M2) -Excitation of skeletal muscles and CNS -Lacrimation -Sweating -Salivation
What can be given to treat AchE “poisoning”?
Pralidoxime chloride (2-PAM) and/or Atropine
What drug is usually used for diagnosis of myasthenia gravis?
Edrophonium (tensilon)
Symptoms of myasthenia gravis
- Muscle weakness (visible in eye)
- Trouble chewing/swallowing
- Hard to talk/nasal sound
- Reduced facial expression
What causes myasthenia gravis?
Auto-antibodies that block nicotinic acetylcholine receptors at the postsynaptic neuromuscualr junction
What are the 2 cholinergic centers in the CNS?
- Nucleus Basalis of Meynert and medial septal nuclei (basal forebrain)
- Mesopontine tegmentum (brain stem)
What reversible AchE inhibitors are used in managing symptoms of Alzheimer’s Disease?
- Donepezil
- Rivastigmine
- Tacrine
- Galantamine
What was the first parasympathomimetic discovered?
Muscarine
Why is clinical use of muscarine not recommended?
It can cross the BBB and cause convulsions
What is methacholine used for?
To diagnose bronchial hyperreactivity in Asthma and COPD
How is open angle glaucoma treated?
M3 muscarinic agonist
How is closed angle glaucoma treated?
iridectomy; medical emergency
What muscarinic agonists are used to treat glaucoma?
Carbachol and pilocarpine
CNS effects are mainly mediated by what receptors?
M1
What are therapeutic effects of muscarinic agonists?
- Arousal and attention
- Improve cognitive function
Side effects of muscarinic agonists
Tremors and hypothermia
