Cholinergic Flashcards
Acetylcholine
- Approved for intraocular use during surgery and causes miosis (reduction in pupil size)
- Rarely given systemically
- Direct-acting cholinomimetics
- Choline esters
- permanently charged quarternary ammonium groups
- Hydrolyzed in the gastrointestinal tract and less active when given PO
Methacholine
- Administered by inhalation for the diagnosis of bronchial airway hyperreactivity in patients who do not have clinically apparent asthma
- Rarely used due to need for emergency resuscitation equipment, oxygen, and medications to treat severe bronchospasm (e.g., β2 adrenergic receptor agonists)
- direct acting
Bethanechol
- Can be used to treat patients with urinary retention and heartburn
- Selective mAChR agonist that primarily affects the urinary and GI tract
- Little cardiovascular stimulation
- May produce urinary tract infection if sphincter fails to relax
- direct acting
- choline ester
- permanently charged quarternary ammonium groups
- Hydrolyzed in the gastrointestinal tract and less active when given PO
Carbachol
- Nonspecific cholinergic agonist that is used for the treatment of glaucoma or to produce miosis during surgery or ophthalmic examination
- direct acting
- choline ester
- permanently charged quarternary ammonium groups
- Hydrolyzed in the gastrointestinal tract and less active when given PO
Cevimeline
- Oral tablet used to treat dry mouth (xerostomia) in patients with Sjögren’s syndrome
- Metabolized via P450 pathways and eliminated in urine
- direct acting
Pilocarpine
- Approved for xerostomia treatment in patients with Sjögren’s syndrome or head and neck cancer treatment related xerostomia (PO), miosis during ophthalmic procedures (topical), and for glaucoma (topical)
- Pure mAChR agonist
- Cholinoceptor alkaloid agents (uncharged tertiary amines)
- well absorbed
- direct acting
Varenicline
- FDA approved for smoking cessation
- Partial agonist that binds with high affinity and selectivity to α4β2 nicotinic acetylcholine receptors located in the brain to stimulate receptor-mediated activity, but at a substantially lower level than nicotine
- Stimulation and subsequent moderate, sustained release of mesolimbic dopamine are thought to reduce craving and withdrawal symptoms associated with smoking cessation (reward pathway)
- Greater than 90% eliminated in urine as unchanged drug
- Nausea is most common adverse effect; serious adverse effects include neuropsychiatric symptoms, including changes in behavior, agitation, depressed mood, suicidal ideation, and attempted and completed suicide
- Treatment comes with the following warning: If patients, their families, or caregivers notice agitation, depressed mood, or changes in behavior that are not typical for the patient or if the patient has suicidal thoughts or actions, the patient should stop taking varenicline and contact their healthcare professional.
- direct acting
Ambenonium
-Quaternary and charged AChE inhibitor
Donepezil
- AChE inhibitor
- lipid‐soluble,Cancrossbloodbrainbarrierandreadilyabsorbed
- organophosphates,tertiaryagent
- used to treat dementia (Alzheimer’s, Parkinson’s)
Echothiophate
- Organophosphate (Binding to AChE is covalent and irreversible)
- CHOLINESTERASE INHIBITOR
- not as lipid soluble in body do to its charge
- does not cross blood brain barrier
- Quaternary and charged
Edrophonium
- CHOLINESTERASE INHIBITOR
- Binding to AChE is noncovalent and reversible
- alcohol (quaternary ammonium group (positively charged)
- reverse the paralysis induced by neuromuscular blocking drugs during surgical anesthesia
- does not cross blood brain barrier
Galantamine
- AChE inhibitor
- Tertiary and uncharged
- lipid soluble, can pass blood brain barrier
- used to treat dementia (Parkinson’s, Alzheimer’s)
Neostigmine
- AChE inhibitor
- Carbamic acid ester (Binding to AChE is noncovalent and reversible )
- Quaternary and charged, relatively insoluble in lipids
- AChE inhibitors can reverse the paralysis induced by neuromuscular blocking drugs during surgical anesthesia
- paired with Atropineorglycopyrrolate toblockitsparasympatheticeffect
Physostigmine
- AChE inhibitor
- Carbamic acid ester
- Binding to AChE is noncovalent and reversible
- Tertiary and uncharged, well absorbed
- used to treat dementia (Parkinson’s, Alzheimer’s)
- used to treat Intoxication due to anticholinergic agents because it can pass blood brain barrier
Pyridostigmine
- AChE inhibitor
- Carbamic acid esters
- Binding to AChE is noncovalent and reversible
- Quaternary and charged (relatively insoluble in lipids)
- used as Prophylaxis for nerve agent poisoning and for myasthenia gravis
Rivastigmine
- AChE inhibitor
- Tertiary and uncharged
- used to treat dementia (Parkinson’s, Alzheimer’s)
Tacrine
- AChE inhibitor
- Tertiary and uncharged
- USED to be used to treat dementia but stopped due to liver toxicity
Scopolamine
- used to treat motion sickness
- antimuscarinic drug
- marked CNS effects producing drowsiness and amnesia (toxicdoses of scopolamine can cause excitement, agitation, hallucinations, and coma)
- Prior to inhalational anesthetics, which are less irritating to the airways, was useful in preoperative settings to limit increased airway secretions caused by irritant anesthetics
Atropine
-Antimuscarinic
-used to counter act toxicity of direct acting muscarinic and nicotinic stimulants and AChE inhibitors
-Atropine is a naturally occurring tertiary amine alkaloid ester found in the plant Atropa belladonna
-The half-life of atropine is 2 hours and 60% is excreted unchanged in the urine, The remaining 40% of atropine is transformed by hydrolysis and conjugation reactions (phase I and II) and is excreted in the urine
-used to produce sympathetic dilation of eye
-Pancreatic and intestinal secretions are mostly unaffected by atropine as these processes are primarily under hormonal rather than vagal control
-Atropine suppresses thermoregulatory sweating by inhibiting sympathetic cholinergic nerve fibers (there is no parasympathetic innervation of sweat glands)
-In children, ordinary doses of antimuscarinic agents may cause “atropine fever” (body temperature is elevated only if large doses are administered in adults)
-Atropine blocks vagal reflexes induced by surgical manipulation of visceral organs
-Prior to inhalational anesthetics, which are less irritating to the airways, was useful in preoperative settings to limit increased airway secretions caused by irritant anesthetics
-used to provide symptomatic relief in the treatment of urinary urgency caused by minor inflammatory bladder disorders
- first drug of choice for symptomatic bradycardia in an advanced cardiac life support
- Tertiary antimuscarinic agents (preferably atropine) are utilized to treat both CNS and peripheral effects of excessive stimulation of mAChRs due to cholinergic poisoning
- In life-threatening situations, as much as 1 gram of atropine per day may be required for as long as 1 month for full control of muscarinic excess
- Rapid-onset cholinergic poisoning caused by mushrooms is characterized entirely by signs of muscarinic excess within 15-30 minutes [e.g., nausea, vomiting, diarrhea, urinary
urgency, vasodilation, reflex tachycardia (occasionally bradycardia), sweating, salivation, and sometimes bronchoconstriction] and is adequately treated with atropine
-no use in delayed-onset mushroom poisoning, which is characterized by vomiting and nausea 6-12 hours after ingestion
- At high concentrations, atropine causes a block of all parasympathetic function
-Moderate to high doses of atropine in children and infants can cause death due to hyperthermic effects
-usedtopreventsynechia formationinuveitis andiritis (wheretheirisadherestoeitherthelensorthecornea)
Glycopyrrolate
- antimuscarinic
- paired with neostigmine to block parasympathetic effects during reversal of skeletal muscle relaxation
Homatropine
- antimuscarinic
- used to prevent synechia formation in uveitis and iritis (the iris adheres to either the lens or the cornea)
Tropicamide
- antimuscarinic
- used in ophthalmology
Ipratropium
- antimuscarinic
- quaternary amines are charged and elicit their antimuscarinic effects in the periphery
- used as an inhalational agent in the treatment of asthma and COPD and is currently a first-line therapy
Tiotropium
-inhalation antimuscarinic
-treats asthma and COPD
-has a longer bronchodilator action than
ipratropium (half life 120 hrs vs. 2 hrs) and can be dosed once daily (vs. 3-4 times/day)in patients with COPD
