Pharm PNS II Flashcards
What drugs are DIRECT ACTING ParaysympathoMIMETICS? (choline esters)
Bethanechol
What drugs are INDIRECT ACTING ParasympathoMIMETICS?
- Neostigmine
- Edrophonium
- Pyridostigmine
What drugs are DIRECT ACTING ParasympathoLYTICS?
- Atropine
- Glycopyrrolate
- Oxybutynin
- Propantheline
If a drug has Acetylcholine-like effects what changes will you see in the body?
- bradycardia (negative chronotropy)
- decreased blood pressure (negative inotropy + vasodilation)
- increase GI motility and secretion
- smooth muscle contraction in:
- bladder (micturition in contraction of detrusor muscle)
- uterus
- bronchioles (bronchoconstriction)
- iris (mitosis)
- increased secretions (salivation and lacrimal)
- convulsions (CNS)
- stimulation of autonomic ganglia and adrenal medulla
- skeletal muscle contraction
What is the mechanism of action for drugs that are parasympathomimetics and reversible anticholinesterases?
- competitive antagonism of acetylcholinesterase
- will compete with Acetylcholine (endogenous substance) for acetylcholinesterase which usually breaks it down
What does parasympathoLYTICS do?
they lyse the effect of acetylcholine and are also called anticholinergics. They are muscarinic antagonists.
What does parasympathoMIMETICS do?
They mimic the effect of acetylcholine and are muscarinic agonists.
What are atropine-like effects?
- tachycardia
- mydriasis (dilates pupil)
- dries secretions
- reduces salivation
- slows gut
- bronchodilator
- blurred vision (cycloplegia)
- difficulty with urination
If you have a dog under anesthesia and see you have sinus bradycardia. What main drug would you correct with?
Atropine
Which of the following is the treatment of choice for Myasthenia Gravis?
A. Pyridostigmine
B. Neostigmine
C. Edrophonium
D. Bethanechol
A. Pyridostigmine
Which of the following is used in the testing for Myasthenia Gravis?
A. Glycopyrrolate
B. Neostigmine
C. Edrophonium
D. Bethanechol
C. Edrophonium
Which of the following is a contraindications for the use of atropine?
A. Sinus bradycardia
B. 2nd degree AV block
C. Closed-angle glaucoma
D. Nausea
C. Closed-angle glaucoma
Compared with atropine, which of the following is true about glycopyrrolate?
A. Lasts longer than atropine
B. Crosses BBB
C. Antagonizes primarily nicotinic receptors
D. Does not treat bradycardia
A. Lasts longer than atropine
What are the mechanisms of action of Bethanechol?
- direct acting parasympathomimetic
- agonist of Acetylcholine
-
Directly stimulates contraction of the urinary bladder via the DETRUSOR MUSCLE
What are the clinical indications of Bethanechol?
- treatment of choice for detrusor muscle atony —> increases detrusor m. Contractility
- symptomatic tx plan for dysautonomia (degenerative disorder resulting in polyneuropathy)
- increases GI motility and can aid in tax of equine gastric ulcer syndrome (EGUS)
- reproduction —> stimulates uterine contraction (less common use)
What are the precautions with Bethanechol?
- SLUDD signs may be seen in higher doses
- can see life threatening cholinergic crisis is in the event of overdose/toxicity (severe bradycardia, bronchospasm)
What are the contraindications of Bethanechol?
- Problematic if patient has urethra obstruction or GI obstruction
- patient must have patent urethra and intact bladder wall
- caution with increased GI motility
What is seen in overdose with Bethanechol?
- excessive muscarinic effects like salivation, urination, defication
- in very high doses will see more life-threatening cholinergic signs (bradycardia, bronchospasm, etc)
What is the mechanism of action for Neostigmine?
- indirect acting parasympathoMIMETIC
- acetylcholinesterase antagonist
- relatively short onset (10-30 minutes)
- duration lasts about 4 hours
What are the clinical indications of Neostigmine?
- reversal agent of choice for reversal of competitive neuromuscular blockers (NMB)
- tx for rumen atony (initiate peristalsis)
- stimulate GI motility and increase bladder emptying
- may aid in the diagnosis and treatment of myasthenia gravis in dogs
What are the precaution for Neostigmine?
- SLUDD signs which may be more dramatic in patients with pre-existing high vagal tone
- watch in brachycephalic breeds, GI disease, concurrent medications, etc.
What is the mechanism of action of Neostigmine?
It is a competitive (reversible) antagonist of acetylcholinesterase
What is the onset and duration of Neostigmine?
It kicks in about 10-30 minutes and can last 4 hours
What are the clinical indications of Neostigmine?
- Reversal agent of choice for reversal of competitive neuromuscular blocks (NMB)
- tx for rumen atony by initiating peristalsis
- stimulate GI motility and increase bladder emptying
- aid in dx and tx of myasthenia gravis
What are some precautions for Neostigmine?
- SLUDD signs may be more dramatic with pre-existing vagal tone
- watch out for brachycephalic breeds, GI disease, concurrent medications
What are some contraindications with Neostigmine?
- peritonitis
- GI obstruction
- urinary tract obstruction
- in late pregnancy you risk abortion due to uterine contractions
- if you have the presence of other cholinesterase inhibitors then you risk SYNERGISM
What is the mechanism of action for Pyridostigmine?
It is a competitive (reversible) antagonist of acetylcholinesterase
What is the onset and duration of Pyridostigmine?
- onset –> 1 hour after oral dose (but faster if given IV)
- duration –> up to 8-12 hours (longer than Neostigmine)
What are the clinical indications of Pyridostigmine?
It is the treatment of choice for myasthenia gravis in dogs for long term maintenance therapy
What are some precautions and contraindications of Pyridostigmine?
- SLUDD signs seen with pre-existing high vagal tone
- dose-related cholinergic effects
- GI: nausea, vomiting, diarrhea, hyper salivation
- increase respiratory secretion, bronchospasm,
pulmonary edema
- bradycardia, tachycardia, cardiac arrest
- muscle cramps and weakness
What are the mechanisms of action for Edrophonium?
It is a competitive (reversible) acetylcholinesterase antagonist. IV injection is at 10 mg/mL.
What is the onset and duration of Edrophonium?
- onset –> very fast acting (within 1 minute)
- duration –> very short (lasts about 10 minutes)
What are the clinical indications of Edrophonium?
It is used for the Tension test which is used for myasthenia gravis. It is a reversal of non-depolarizing neuromuscular blocks (NMB) but not as commonly used as Neostigmine.
What are some precautions and contraindications of Edrophonium?
- SLUDD signs are usually mild
- less commonly but more severe cholinergic crisis (this is dose dependent)
Who has the longest duration of action?
A. Neostigmine
B. Pyridostigmine
C. Edrophonium
B. Pyridostigmine
Who has the shortest duration of action?
A. Neostigmine
B. Pyridostigmine
C. Edrophonium
C. Edrophonium
What are the mechanisms of action for Atropine sulfate?
- it is a competitive (reversible) antagonist of acetylcholine
- it is a tertiary compound that can cross the blood brain barrier (poorly @ therapeutic dose)
- injectable solution is more common and it will ionize in the GI tract
What are some clinical indications for Atropine sulfate?
- treatment of bradycardia/bradyarrythmias especially during anesthesia
- cardiac arrest (not in all CPR cases)
- reduces respiratory and GI secretions –> Xerostomia (dry mouth)
- treatment of acetylcholinesterase inhibitor toxicity (organophosphates and carbamates)
- treatment of cholinergic chrisis (due to anti cholinesterase overdose)
What are some precautions with Atropine sulfate?
- drops in heart rate seen initially after IV injection and then will see an increase rapidly
- may cause tachycardia or exacerbate tachyarrhythmias
- rabbits have endogenous atropinases (break down atropine) so it is not as effective and should use glycopyrrolate
What are some contraindications with Atropine sulfate?
- glaucoma with systemic and ophthalmic use
- tachycardia/tachyarrhythmias
- hypothermic bradycardia patients
- certain GI diseases, obstructive urinary tract, myasthenia gravis
What are the mechanisms of action of Glycopyrrolate?
It is a competitive (reversible) antagonist of acetylcholine. It is a quaternary compound that DOES NOT cross the blood brain barrier.
What is the onset and duration of action with Glycopyrrolate?
- onset –> slower( but IV is fast @ about 1 minute)
- duration –> longer than compared to atropine (most vagolytic effects last about 2-3 hours)
What are the clinical indications of Glycopyrrolate?
- same as atropine but slower kinetics may be more favorable depending on the situation
- can be used as a pre-med for anesthesia
- reduces respiratory and GI secretions
- can be used to reduced hypersialism (excessive salivation) which leads to sialocele (accumulation of saliva in surrounding tissue or glands)
- horses –> great reduction of cholinergic adverse effects of imidocarb
What are some precautions with Glycopyrrolate?
- same as for atropine
- less likely to cause CNS effects because it does not cross the blood brain barrier
- less arrythmogenic than atropine
- since duration of action is longer it may interfere with the ability to assess patient heart rate post-op
What are the mechanisms of action for Oxybutynin and Propantheline?
- competitive (reversible) antagonist of acetylcholine
- GI or urinary antispasmodic agents
- causes the relaxation of the detrusor muscle and allows the bladder to empty more easily
- Oxybutynin –> widely distributed and CAN cross the blood brain barrier
- Propantheline –> does NOT cross the blood brain barrier
What are the clinical indications of Oxybutynin and propantheline?
- MAIN USE –> treat detrusor muscle instability (hyperactive bladder) and urinary antispasmodic
- Propantheline can also be used to treat certain bradyarrythmias
What are some precautions and contraindications of propantheline and oxybutynin?
- potential to cause other parasympathetic signs (propantheline can stimulate HR)
- at normal therapeutic dose bladder and GI seem to be only organs affected
- avoid in glaucoma, tachycardia and ileus
