autopharm 3 Flashcards
what kind of cholinergic receptor agonists are there/ categories?
direct acting
-nicotinic
-muscarinic
indirect acting
-quaternary alcohols (short acting)
-carbamates (intermediate acting)
what receptor subtype works at neuroeffector junctions (PNS)
Muscarinic receptors
hat receptor subtype works at ganglionic synapses?
nicotinic receptors
what kind of direct-acting cholinergic agonists are there? what drugs?
-muscarinic agonists
>Bethanechol chloride (generic, Duvoid®, Urecholine®)
>Pilocarpine (generic, Isopto Carpine®)
what do muscarinic agonists do ie. what is their general mechanism of action?
- mimics ACh at neuroeffector junctions of PNS
what kind of drug is Bethanechol chloride and what are generic names?
muscarinic agonist
Bethanechol chloride (generic, Duvoid®, Urecholine®)
what does Bethanechol chloride (generic, Duvoid®, Urecholine®) do? what are its uses and effects?
- Choline ester; resistant to cholinesterases
> prolongs actions - Stimulates urinary bladder
> promotes emptying of hypocontractile bladder - Contraindicated in GI or urinary tract obstruction
> If functional increase in urethral tone; pretreat with α blocker or skeletal muscle relaxant - SLUD syndrome possible; atropine (muscarinic blocker) is antidote
what type of drug is Pilocarpine and what is its generic name?
muscarinic agonist
Pilocarpine (generic, Isopto Carpine®)
what is the use of Pilocarpine (generic, Isopto Carpine®)? what are possible complications? How does it work with Keratoconjunctivitis sicca?
Constricts the pupil (miosis) and increases aqueous outflow
* May be used to treat glaucoma
* Causes irritation to the eye resulting in compliance issues
* Newer antiglaucoma agents used more commonly
Less use now as a tear stimulant in KCS (Keratoconjunctivitis sicca)
* Relies on having some function lacrimal tissue
* Largely replaced by cyclosporine for immune mediated KCS
* Can be used in neurogenic KCS where lack of neurogenic
input to lacrimal glands is the problem; directly stimulate muscarinic receptors on the gland to produce tears
what are the characteristics of indirect-acting cholinomimetic drugs? how do they work, generally, and what are the resulting effects? what is the mechanism?
- Anticholinesterase drugs ie. inhibitors of ACh metabolism
- Resultant effects similar to direct-acting cholinomimetics
- Normally ACh is rapidly degraded in synapse by acetylcholinesterase
> Very short half-life (T1/2= 40 μsec) - Anticholinesterase drugs block acetylcholinesterase > increase ACh in synapse
=>Muscarinic or nicotinic receptor stimulation can result
what type of drug is edrophonium? what is its generic name?
Indirect-acting cholinomimetic drugs
-Quaternary alcohol
* Edrophonium (generic, Tensilon®)
what is the mechanism of action for edrophonium? how does it work and what does it do? whata re notable characteristics?
- Bind reversibly to active site of cholinesterase
- Prevents access of cholinesterase to ACh > increase Ach levels in synapse
- Short duration of action (T1/2 of 2-10 min)
- Poor penetration into CNS due to charged polar molecule
- Available in injectable formulation
what type of drugs are Neostigmine and Pyridostigmine? what are their generic names?
Neostigmine (generic, Prostigmin®), Pyridostigmine (Mestinon®)
indirect-acting cholinomimetic drugs
>carbamate esters
what are Neostigmine (generic, Prostigmin®) and Pyridostigmine (Mestinon®)? how do they work and what do they do? what are some notable characteristics?
- Carbamylates active site of cholinesterase
- Carbamylated enzyme more resistant to hydration step
- Longer duration of action (T1/2=30-60 min)
- Poor CNS penetration
- Available in oral and injectable formulations
therapeutic uses for Neostigmine, Pyridostigmine
at neuromuscular junction, helps with Myasthenia gravis
main cause of myasthenia gravis and what can be done about it? what are clinical signs? How do we diagnose and how can we treat?
- Main cause is autoimmune disease > destruction of nicotinic receptors
> Clinical signs of weakness, fatigue, & swallowing difficulty (megaesophagus)
> Resembles neuromuscular blockade
Dx:
* Condition worsens with d-tubocurarine (N-M blocker)
* Edrophonium may be used to support diagnosis
* Demonstration of autoantibodies to the nicotinic receptor is confirmative
Rx:
* Neostigmine, pyridostigmine used in management of the condition
>increase strength of contraction
how do we reverse a neuromuscular blockade? what drugs can we use?
Edrophonium, Neostigmine
* Can be used to reverse nondepolarizing NMB drugs eg. d-Tubocurare following their use in surgical procedures
what drug can be used tharapeutically for paralytic ileus and rumen atony?
- Appears more commonly used in large intestinal motility
disorders - Neostigmine has been used with varying results
- Other prokinetic drugs are more appropriate but have limited data with use in cattle
what categories of cholinergic receptor antagonists are there?
antimuscarinic
-non-selective (all drugs)
antinicotinic
-ganglion blockers (limited use in veterinary medicine)
-neuromuscualr blockers
another name for muscarinic antagonists, and what is the mechanism?
parasympatholytic drugs
* Reversible blockade of ACh at muscarinic receptors by competitive binding
classes of antimuscarinic drugs and their basic mechanisms
- Tertiary Amines (able to penetrate CNS)
- Quaternary ammonium compounds (more limited to peripheral effects)
what kind of drug is atropine?
muscarinic antagonist - tertiary amine
what is atropine? what is it derived from and what is its basic mechanism of action? how can it be administered? what are its therapeutic uses?
- Prototype antimuscarinic drug
- Derived from Atropa belladonna (deadly nightshade)
- Lipid soluble and readily enters CNS
- Available for parenteral, topical & oral absorption
Therapeutic uses:
Ophthalmic uses as a mydriatic-cycloplegic
* Blocks pupillary constrictor muscle > pupil dilation (mydriasis) for ocular exam
* Blocks contraction of the ciliary muscle > reduces ciliary spasms with uveitis
* Tropicamide (generic, Mydriacyl®)
=> Limited to mydriasis > facilitates ocular examination
- Treatment of organophosphate poisoning
- Present in some calf scour preparations for oral administration
- Used also to treat some bradyarrythmias
what is Tropicamide (generic, Mydriacyl®)? use?
muscarinic antagonist, teriary amine
* Limited to mydriasis > facilitates ocular examination
what type of drug is oxybutynin? what are its uses? adverse effects?
muscarinic antagonist
-tertiary amine
- Relatively selective for bladder smooth muscle
- Used primarily for spastic bladder in dog and cat
- General caution when GI obstruction or infection
or ileus, or urinary tract obstruction present (risk vs benefits)
Adverse effects:
* Constipation
* Urine retention
what type of drugs are quaternary ammonium compounds and what are their CNS effects and why?
muscarinic antagonist
* Charged polar molecules can’t cross BBB readily > less CNS effects
what type of drug is Propantheline
Muscarinic Antagonists
Quaternary ammonium compound
what are the uses for Propantheline? what are possible adverse effects?
Propantheline (generic, Pro-Banthine®)
* Can be used for treatment of GI motility disorders
* Antidiarrheal effects
* Intestinal spasms and facilitate rectal exams in horses
* Also used to treat spastic (hypercontractile) bladder
* General caution in GI infections or obstruction or ileus, or obstruction of bladder
* Adverse effects possible: dry mouth, dry eyes, urinary retention, tachycardia, constipation (like atropine)
what type of drug is Ipratropium
Muscarinic Antagonists
Quaternary ammonium compound
what are the uses of Ipratropium? How do we administer?
Ipratropium (generic, Atrovent®)
* May be of benefit in bronchospasm associated with respiratory disorders; occasionally used in horses as adjunct therapy for lower airway disease and possibly chronic bronchitis in dogs, and asthma in cats
* Administered by nebulizer or metered dose inhaler
what type of drug is Hyoscine butylbromide?
Muscarinic Antagonists
Quaternary ammonium compound
what are the uses for Hyoscine butylbromide (Buscopan®)? adverse effects?
Hyoscine butylbromide (Buscopan®)
Antispasmodic approved for treatment of pain associated with GI motility disorders ie. colic in horses
* Tachycardia and reduced gastrointestinal motility are possible adverse effects
* Should not be used in horses intended for human food consumption
Potential for use in acute severe exacerbations of airway obstruction in horses with lower airway disease; immediate bronchodilator effects
* Possibly less potential for adverse effects compared to atropine
Please complete the following sentence from the choices given below. “In the sympathetic nervous system the ganglia are located ____________. Discharge of the parasympathetic nervous system is considered ____________”. (1 mark)
a. close to the end-organ; discrete
b. near the spinal cord; diffuse
c. near the spinal cord; discrete
d. close to the end-organ; diffuse
c. near the spinal cord; discrete
Which one of the following is matched correctly (1 mark)
a. phenylephrine: selective a2-receptor agonist
b. isoproterenol: mixed (a,b) adrenergic receptor
agonist
c. clenbuterol: selective b2-receptor agonist
d. norepinephrine: non-selective (b1, b2) beta receptor agonist
c. clenbuterol: selective b2-receptor agonist
- Edrophonium has a longer duration of action than does neostigmine (1 mark)
a. True b. False
b. False
Which one of the following statements regarding the autonomic nervous system (ANS) is most correct (1 mark)
a. The sympathetic nervous system (SNS) is essential for life
b. Acetylcholine is formed from tyrosine and choline
c. Most organs are innervated by either the PNS or SNS, but not both
d. The ANS contains the parasympathetic and sympathetic but not the somatic nervous systems
d. The ANS contains the parasympathetic and sympathetic but not the somatic nervous systems
All of the following are potential therapeutic uses for atropine, EXCEPT (1 mark)
a. mydriatic-cycloplegic
b. present in some calf scour preparations
c. hypocontractile bladder
d. treatment of organophosphate poisoning
c. hypocontractile bladder
