Direct Cholinomimetics and indirect cholinomimetics Flashcards
What are direct cholinomimetics
Agonists at muscarinic cholinoreceptors and increase parasympathetic activity
Direct cholinomimetics work at muscarinic cholinoreceptors and thus have similar effects as stimulation of the ___ division
Parasympathetic
Examples of direct cholinomimetics
Bethanechol
Methacholine
Pilocarpine
Carbachol
What is bethanechol
Direct cholinomimetic agent used to induce bladder and GI smooth muscle contraction (motility)
What is bethanechol structurally similar to
Acetylcholine
How does bethanechol prevent urine retention and ileus
Stimulating smooth muscle motor activity
What is methacholine
Direct cholinomimetic , parasympathomimetic drug, used in the bronchial challenge test to help diagnose asthma
How is methacholine used for diagnosis of asthma with bronchial hypersensitivity
If asthma is less clinically apparent they are more sensitive to methacholine challenge, compared to normal patients
What is pilocarpine
Potent stimulator of sweat, tears, and saliva used for both open and closed angle glaucoma
What does pilocarpine do
Contractsciliary muscles of the eye (treat open angled glaucoma) and causes pupillary sphincter contraction (closed angle glaucoma).
How is pilocarpine administered
Ocular insert or as eyedrops
MOA of pilocarpine
Contract the ciliary muscle of the eye for open angle glaucoma and the pupillary sphincter for closed angle glaucoma.
What is pilocarpine resistant to
Acetylcholinesterase
Patients show __ after administration of pilocarpine
Miosis
What is carbachol
Cholinomimetic agent similar to ach
What is carbachol used for
Open angle glaucoma
Rare-closed angle glaucoma
How does carbachol help with open angle glaucoma
Helps relieve intraocular pressure and can be used to cause pupillary constriction
What is an indirect cholinomimetic
Decrease the action of the acetylcholinesterase enzyme (which works to break down acetylcholine)
What are indirect cholinomimetics also called
Anticholinesterases
What does indirect cholinomimetics lead to
Increased duration and action of the neurotransmitter acetylcholine
What indirect cholinomimetics don’t cross the BBB
Edrophonium, neostigmine and pyridostigmine
What are indirect cholinomimetics that that don’t cross the BBB used to treat
Myasthenia gravis
What is neostigmine used to treat
Ileus
What are the indirect cholinomimetics examples
Physostigmine Donepezil Ambenonium Neostigmine Pyridosstigmine Edrophonium Echothiophate Tacrine Rivastigmine Galantamine
Indirect cholinomimetics that cross the BBB care __ acting
Centrally
What is physostigmine used for
Atropine overdose and dementia
What is donepezil used for
Alzheimer’s
Describe endrophonium
Reversible acetylcholinesterase inhibitor, which prevents the breakdown of acetylcholine
How does edrophonium work
Competitively inhibiting acetylcholinesterase at the neuromuscular junction
Edrophonium is used to diagnose __ __
Myasthenia gravis
Describe the tensilon test
Myasthenia gravis can be diagnosed with edrophonium as patients immediately show decreased muscle weakness
What are pyridostigmine and neostigmine
Cholinomimetics or parasympathomimetics, which work to reversible inhibit acetylcholinesterase and do not cross the BBB
What do we use pyridostigmine and neostigmine treat
Myasthenia gravis
Neostigmine in addition to treating myasthenia gravis, treats what
Reverse neuromuscular blocking agents in anesthesia
Why are pyridostigmine and neostigmine used for long term treatment of myasthenia gravis
Improve muscle function by slowing the natural enzyme cholinesterase that degrades acetylcholine in the motor end plate; the neurotransmitter is therefore around longer to stimulate its receptor
What else can neostigmine used to also treat
Post operative and neurogenic ileus as well as in treating urinary retention
Physostigmine
More hydrophobic than other indirect cholinomimetics, and crosses the BBB
What is physostigmine used to treat
Atropine and anticholinergic drug overdoses
Physostigmine is helpful in inducing ___
Miosis
Leading to decreased intraocular pressure
What is donepezil
Acetylcholinesterase inhibitor which is used for treating Alzheimer’s disease
In Alzheimer’s ,patients have decreased ___ levels
Acetylcholine
How does donepezil treat Alzheimer’s
Centrally acting acetylcholinesterase inhibitors help increase the available amount of relative acetylcholine
What is pilocarpine (pilocar)
Direct cholinergic agonist that contracts the iris sphincter and ciliary muscle of the eyes
What indicates pilocarpine
Glaucoma and xerostomia (dry mouth)
Side effects of pilocarpine
Retinal detachment, decreased visual acuity and eye. Irritation, cholinergic side effects (bradycardia, bronchospasm, hypotension, and diarrhea)
Who should we not give pilocarpine to
Asthma and bradycardia
Because causes systemic effects
Pilocarpine is a direct acting cholinergic agonist that ___ aqueous blood flow
Increases
Pilocarpine mimics the effects of ____ and serves as a messenger between nerve cells and various organs throughout the body
Acetylcholine
What does pilocarpine , a parasympathomimetic agent stimulate
Cholinergic receptors and may lead to systemic effects such as bronchospasm or hypotension
Pilocarpine treacle intraocular pressure in patients with angle closure glaucoma. How
Contracts the iris sphincter of the eyes and causes pupil constriction or miosis
Pilocarpine contracts the ciliary muscle and focuses the lens for __ vision
Near
Indications for pilocarpine
Xerostomia
Glaucoma
How does pilocarpine treat xerostomia
Stimulates salivaryglands
What causes xerostomia
Meds, chemotherapy, or Sjögren’s syndrome
How does pilocarpine treat glaucoma (open angle)
Lowers IOP
Second line for open angle glaucoma
Contract ciliary muscles and widens to facilitate aqueous humor outflow
How does pilocarpine treat patients with glaucoma (closed angle)
Contraction of the iris sphincter pulls the iris from impeding aqueous humor outflow
Can treat acute cases of primary closed angle glaucoma
Side effects of pilocarpine
Detached retina
Decreased visual acuity
Eye irritation
Cholinergic effects
Why does pilocarpine cause detracted retina
Lens and vitreous to move forward and may create a retinal tear. Sustained contraction of the ciliary muscle may lead to retinal detachment
How does pilocarpine cause decreased visual acuity
Constricting pupils, may cause blurred vision and decreased visual acuity. Contraction of the ciliary muscle focuses the lens for near vision.
Why does pilocarpine cause eye irritation
Administered topically to the lower conjunctiva as a solution or gel.
What are the cholinergic effects of pilocarpine
Bradycardia, bronchospasm, hypotension, and hypersalivation , urinary urgency, diarrhea, and sweating.
What can be administered to reverse systemic toxicity caused by pilocarpine
Atropine
Who should you not give pilocarpine to
Asthma or bradycardia
Don’t want to worsen symptoms
Acetylcholinerase inhibitor poisoning /organophosphate toxicity/cholinergic overdose. Who is it seen in
Farmers , as organophosphate are commonly found in insecticides
What happens in acetylcholinesterase inhibitor poisoning
Irreversibly inhibit acetylcholinesterase
Antidotes to acetylcholinesterase inhibitor poisoning
Atropine and pralidoxime
Symptoms of acetylcholinesterase inhibitors
DUMBBELSS
Including excitation
Why get DUMBBELSS symptoms with acetylcholinesterase inhibitor poisoning
Massive discharge of the parasympathetic nervous system
Why get excitation with acetylcholinesterase inhibitor poisoning
CNS effects of cholinergic overdoes bc excitation of both CNS and muscle
What are acetylcholinesterase inhibitors
Drugs that inhibit the enzyme which breaks down acetylcholine
Antidotes to acetylcholinesterase inhibitor
Atropine and pralidoxime
How does atropine stop acetylcholinesterase inhibitor
Competitive antagonist of muscarinic acetylcholine receptors, which is why it is a great antidote
Why does pralidoxime antidote to acetylcholinesterase inhibitor
For organophosphate poisoning in conjunction with atropine
Binds to the site where an acetylcholinesterase inhibitor has attached, then regenerates the enzyme to allow it to function again and break down more acetylcholine at the synapse
