Cholinergics / Anticholinergics Flashcards
Name 4 Muscarinic agonists
1) Acetylcholine (Miochol-E)
2) Bethanechol
3) Pilocarpine
- Systemic: Salagen
- Opthalmic: Isopto Carpine
4) Cevemiline
Name 4 reversible Cholinesterase inhibitors
1) Physostigmine
2) Neostigmine (Bloxiverz)
3) Pyridostigmine (Mestinon, Regonol)
4) Donepezil (Aricept)
Name 3 kinds of Irreversible Cholinesterase Inhibitors
Name two compounds in two of these categories
1) Echothiophate ( Phospholine Iodide)
2) Organophosphate insecticides
- Malathion
- Parathion
3) Nerve Agents
- Sarin
- VX
Name a cholinesterase reactivator
Pralidoxime ( Protopam Chloride)
Name a drug that blocks acetylcholine release
**Botulinum toxin ** (BOTOX)
Name 6 Muscarinic Antagonists
1) Atropine
- systemic: AtroPen
- opthalamic: IsoptoAtropine)
2) Scopolamine
3) Dicyclomine
4) Ipratropium
5) Tolterodine
6 ) Tropicamide
Name 4 Direct Acting Muscarinic Agonists
1) Acetylcholine
2) Bethanechol**
3) Pilocarpine** (systemic: Salagen , Opthalmic: IsoptoCarpine)
4) Cevimeline ** (Evoxac)
Name some physiological effects of direct acting muscarinic agonists
GI, Heart Rate, Blood Pressure, bladder, ocular, secretions
- Increased GI motility
- Decreased HR
- Decreased Blood Pressure
- decreased cardiac output
- direct vasodilation
- Contraction of bladder and relaxation of urinary sphincters
- Miosis and decreased intraocular pressure
- Stimulation of secretions
- salivation, lacrimation, GI secretions, sweating, etc.
Therapeutic uses of direct acting muscarinic agonists on Urinary and GI systems and some example medications
GI and Urinary applications (bethanechol)
- Stimulation of peristalsis and increased GI motility
- Formerly used to treat postoperative abdominal distention, gastric atony, adynamic ileus and GERD
- More efficacious therapies are now available
Treatment of urinary retention and inadequate emptying of the bladder
* Postoperative urinary retention
* Diabetic autonomic retinopathy
* Chronic hypotonic, myogenic or neurogenic bladder
Name some ocular therapeutic applications of direct acting Muscarinic Agonists
- Treatment of Glaucoma (carbachol and pilocarpine)
- Opthalmic surgery (induction of miosis)(acetylcholine, carbachol, pilocarpine)
Name some therapeutic uses of direct acting muscarinic agonists for salivary gland dysfunctions and some example medications
Pilocarpine and cevimeline
Xerostomia (dry mouth) due to:
- Head and neck radiation
- Sjorgen syndrome (autoimmune disorder where salivary and lacrimal secretions are compromised)
- They enhance salivary secretion and ease of swallowing
Name 8 adverse effects of direct acting Muscarinic Agonists
BP / HR / Lungs / GI / Urinary / Glandular / Salivary
Mainly the result of unwanted or excessive muscarinic stimulation
- Hypotension
- Bradycardia
- Bronchoconstriction
- Diarrhea
- Cramping
- Urinary incontinence
- Excessive sweating
- Salivation
Name contraindications of direct acting muscarinic agonists
Breathing / Cardiovascular / Stomach / bladder
- Asthma
- Cardiovascular
* Bradycardia
* Hypotension
* Vasomotor instability
* Coronary artery disease - Peptic ulcer disease
- Weakened smooth muscle of the bladder or GI tract (such as after bladder surgery or intestinal anastomosis)
- Urinary or intestinal obstruction
Acetylcholine: What is it used for, rate of metabolism?
Muscarinic Agonist
* Limited use to ophthalmic surgery where rapid miosis is necessary
* When it is administered systemically, it is very rapidly hydrolyzed by “pseudocholinesterase” in the plasma
Bethanechol: Structure, effect on nicotinic receptors and use?
Muscarinic Agonist
* Analog of acetylcholine that is resistant to rapid hydrolysis
* Direct muscarinic agonist with little effect at nicotinic receptors
* Used to stimulate GI motility and treat urinary retention
Pilocarpine: Uses
Muscarinic Agonist
* Used in the treatment of glaucoma and xerostomia due to poor salivary
secretion
Cevimeline: Therapeutic Uses
Muscarinic Agonist
* Used in the treatment of xerostomia due to poor salivary secretion
How do cholinesterase inhibitors work, and name 7 physiological effects
GI / Bladder / HR / BP / Secretions / Eye / Skeletal Muscle / Bronchial
The cholinesterase inhibitors act by preventing the breakdown
of acetylcholine in the synapse
Increased GI motility and secretion
Contraction of bladder and relaxation of sphincters
Bradycardia and hypotension
Increased secretions (salivation, lacrimation, sweating, etc…)
Decreased intraocular pressure
Stimulation of skeletal muscle (therapeutic doses) / paralysis of
skeletal muscle (toxic doses)
Bronchoconstriction
Cholinesterase Inhibitors: Therapeutic uses
Bladder / Neurodegenerative diseases
Treatment of paralytic ileus and atony of the bladder (neostigmine)
- Abdominal distention and acute colonic pseudo-obstruction from a
variety of medical and surgical causes
- Atony (lack of physiological tone) of the bladder detrusor muscle of the urinary bladder
Treatment of Alzheimer disease (donepezil)
- AD patients have reduced cerebral content of choline acetyltransferase (leads to decrease in acetylcholine synthesis and impaired cortical cholinergic function)
- Cholinesterase inhibitors increase cholinergic transmission by
inhibiting cholinesterase at the synaptic cleft and provide modest
symptomatic benefit in patients with AD
Cholinesterase Inhibitors Therapeutic Uses
neuromuscular
Treatment of myasthenia gravis (pyridostigmine) (neostigmine is
less commonly used)
Myasthenia gravis is an autoimmune neuromuscular disorder characterized by fluctuating motor weakness involving ocular, bulbar, limb, and/or respiratory muscles
What causes muscle weakness in Myasthenia gravis, and how do cholinesterase inhibitors help?
The weakness is due to an antibody-mediated, immunologic attack
directed at proteins in the postsynaptic membrane of the
neuromuscular junction (acetylcholine receptors or receptor-associated proteins)
Acetylcholinesterase inhibitors retard the degradation of ACh that
occurs by enzymatic hydrolysis in the neuromuscular junction, resulting in a prolonged effect of ACh
- Variable improvement in strength in patients with MG
- Pyridostigmine provides marke improvement in some patients and little or none in others
Name 2 drugs that can help treat glaucoma, and how they help. Why are they rarely used today?
1 Cholinergic agonist and 1 Cholinesterase Inhibitor
Pilocarpine: Cholinergic agonist
Echothiophate: Cholinesterase inhibitor
Work by contracting the ciliary muscle, these drugs put tension on the trabecular meshwork and increase the outflow of aqueous
humor through the canal of Schlemm
Rarely used today because:
- Ocular side effects such as fixed, small pupils, myopia, and increased subjective visual disturbance related to coexistent cataract
What are some drugs that can protect against poisoning?
Treatment of poisoning with atropine or other antimuscarinic
drugs (physostigmine)
Pyridostigmine is used by the military to protect personnel
against nerve agents used in chemical warfare
What are some adverse effects of Cholinesterase inhibitors
Toxic effects may be severe (cholinergic crisis) especially in
overdose situations (organophosphate insecticide poisoning or
nerve-gas poisoning)
SLUDGE (salivation, lacrimation, urination, defecation, GI
distress, emesis)
Skeletal muscle fasciculation followed by paralysis
Bradycardia, hypotension, shock
Severe miosis
CNS stimulation and seizures followed by coma
Cholinesterase Inhibitor Contraindications
Asthma
Cardiovascular
Bradycardia, hypotension, coronary artery disease
Peptic ulcer disease
Urinary or intestinal obstruction
How do you treat acute cholinesterase inhibitor poisoning?
Administer high doses of atropine (2-4 mg IV initially) followed by 2 mg IM every 10 minutes until symptoms disappear to block muscarinic receptors
Administer pralidoxime to reactivate enzyme (effective only with organophosphates)
Provide additional symptomatic treatment as needed.
Diazepam is useful for controlling seizures
Neostigmine and Pyridostigmine
Function / CNS / Uses
Reversible cholinesterase inhibitors
Quaternary ammonium compounds that don’t enter the CNS
Uses:
Treatment of myasthenia gravis (both are longer acting)
Neostigmine is used to treat paralytic ileus and atony of the bladder
Pyridostigmine is also used by the military to protect troops against nerve agents
used in chemical warfare
Donepezil
type / CNS / uses
Reversible cholinesterase inhibitor
Nonquaternary, so it can get into the CNS
Used in the treatment of mild to moderate Alzheimer disease
Physostigmine
Reversible cholinesterase inhibitor
Nonquaternary, so it can get into the CNS
Used in treating poisoning with atropine or other antimuscarinic agents
What is sarin / VX gas. Signs and symptoms, and how to treat?
Nerve Gases (sarin, VX)
Very potent and toxic, irreversible cholinesterase inhibitors
Just a few droplets of sarin can kill an adult
Signs and symptoms are typical for cholinesterase inhibitors
Treat poisoning with atropine and pralidoxime
What is pralidoxime?
Type / mechanism of action / uses
Cholinesterase reactivator
It chemically binds to the phosphate group that inhibits the enzyme and thereby regenerates the enzyme
Antidote for organophosphate poisoning
It must be used within 2 hours following exposure because the
phosphorylated enzyme changes to a form that can not be
regenerated
What is Botulinum Toxin
Type / Mechanism of Action / Toxicity and Treatment
Toxin produced by Clostridium botulinium
Humans usually are exposed by ingesting canned foods that were not processed properly
Toxin prevents the release of acetylcholine from nerve endings
It affects both the autonomic nerve endings (classic anticholinergic effects) and the neuromuscular junction (paralysis)
Treatment involves aggressive symptomatic support (especially of respiratory function) plus administration of antibodies to the toxin
Clinical Uses of Botulinum Toxin
Clinical uses as a locally injected neuromuscular blocker (sold under the brand name Botox)
Reduce the appearance of facial wrinkles
Excessive sweating (hyperhidrosis)
Overactive bladder
Lazy eye (an imbalance in the muscles responsible for positioning the eye)
Eye twitching
Prevention of chronic migraines
Name some physiologic effects of Muscarinic Antagonists
secretions, GI, bladder, lungs, pupils, HR, CNS
Drying of secretions (lacrimal, salivary, respiratory, GI, sweat, etc.)
Decrease tone and motility of GI tract
Relaxation of the bladder and urine retention
Bronchodilation
Mydriasis (dilation of pupil) with cycloplegia (loss of
accommodation) and pronounced increase in intraocular pressure
Increased heart rate
CNS
-Sedation and amnesia at low doses
- Excitation and seizures at toxic doses
- Some of the agents are quaternary salts that do not produce these CNS effects
Muscarinic Antagonists Therapeutic Uses
GI, Urology, Eyes, Poisoning, Cardiac
Treatment of GI disorders
Cramping, diarrhea, irritable bowel syndrome
Urology
Treatment of urinary incontinence
Ophthalmologic use as mydriatic agents
Do not use in patients with glaucoma
Antidote for poisoning with cholinesterase inhibitors or
muscarinic agonists (e.g. some types of mushroom poisoning)
Prevention of motion sickness (scopolamine)
Cardiac stimulation in emergency situations (atropine)
Name 6 adverse effects of muscarinic antagonists
Dry mouth
Dry, hot skin
Constipation
Urine retention
Visual disturbances, blurred vision, photophobia
CNS effects
Sedation, confusion, amnesia (especially in elderly patients)
Muscarinic Antagonist Contraindications
Glaucoma
Prostatic hypertrophy
Cardiovascular instability
Severe ulcerative colitis
Muscarinic Antagonist Contraindications
Glaucoma
Prostatic hypertrophy
Cardiovascular instability
Severe ulcerative colitis
Symptoms of Muscarinic antagonist Acute Poisoning
Anticholinergic syndrome
Symptoms include:
Dry, hot skin and hyperthermia
Severe mydriasis, blurring of vision, photophobia
CNS stimulation
Agitation, hallucinations, seizures progressing to coma and death
Cessation of GI motility (no bowel sounds)
Cardiovascular
Weak, rapid pulse, tachycardia and arrhythmias
Treatment for Muscarinic Acute Poisoning
Treatment:
Administration of physostigmine or other cholinesterase inhibitors
Benzodiazepines for the treatment of seizures
Ice baths to reduce hyperthermia
Keep patient in a dark, quiet area to prevent photophobia and
excitement
Atropine
type / clinical uses
Prototypical antimuscarinic agent
A naturally-occurring belladonna alkaloid found in the plant Deadly
Nightshade (Atropa belladonna) and Jimson weed
Clinical uses:
Bradycardia
Inhibition of salivation and secretions (preanesthesia)
Organophosphate or nerve agent poisoning
Scopolamine
type / structure / clinical use
Muscarinic Antagonist
A natural product found in the plant Hyoscyamus niger (Henbane)
Chemically similar to atropine
Clinical use:
Transdermal patch (Transderm Scop) is used for the prevention of motion- sickness and vertigo
Dicyclomine
clinical uses
Muscarinic Antagonist
Nonquaternary - enters CNS
Widely used as an intestinal antispasmodic for the treatment of
irritable bowel syndrome
Ipratropium
clinical use
Quaternary salt
Administered by inhalation for the treatment of asthma and COPD
Fewer systemic effects
Tolterodine
clinical use
Used to treat urinary incontinence
Tropicamide
Widely used to dilate the pupil for ophthalmologic examination
