Cholinergic Antagonists Flashcards
This set of cards will discuss cholinergic antagonists or muscarinic receptor antagonists. What is the action of these drugs?
Block muscarinic receptors
-they do not block nicotinic receptors
The first drug to discuss is Atropine (belladonna alkaloid), what is the action of this drug?
–Binds competitively to muscarinic receptors, preventing acetylcholine from binding
Each card will go through the effects of atropine on the various parts of the body. First is the eye
Mydriasis; unresponsiveness to light
Cycloplegia: paralysis of the ciliary muscle of the eye
-in patients with glaucoma intraocular pressure may rise
What are the effects of atropine on the GI system?
–reduction in gastric motility
but HCl production is not affected
not effective in promoting healing of peptic ulcers
What are the effects of atropine on the urinary system?
Decreases hypermotility of the urinary bladder
What are the effects of atropine on the cardiovascular system?
- atria of the heart of richly innervated by parasympathetic nerve fibers, and the SA node is therefore sensitive to muscarinic receptor blockade
- -blockage of atrial M2 receptors and therefore tachycardia
What is atropine flush?
At toxic doses and in normal doses in some patients, antimuscarinic agents cause cutaneous vasodilation, esp in the upper portion of the body
–this is called atropine flush
What are the effects of atropine on secretions?
salivary, sweat, and lachrymal glands are blocked,
–inhibition of sweat glands may cause high body temp
What is the use for atropine?
when excessive muscarinic effects are life threatening or are producing symptoms severe enough to call for muscarinic blockade
examples on next cards
What are some examples when atropine use is needed?
- Antisialogogue, prior to surgery, when reduction of secretions of the resp tract are needed
- Increase HR or decrease AV block
- Antidote for overdose of cholinergic drugs
- Antidote for rapid type of mushroom poisoning due to the presence of the alkaloid muscarine
- To alleviate the muscarinic side effects of anticholinesterase drugs
What are the pharmokinetics for atropine?
Readily absorbed, partially metabolized by liver, eliminated primarily in the urine
What are the adverse effects of atropine use?
- dry mouth, blurred vision, sandy eyes, tachycardia and constipation
- effects on CNS: restlessness, confusion, hallucinations, delirium, which may progress to depression
- In older individuals, the use of atropine to induce mydriasis and cycloplegia is considered to risky since it may exacerbate an attack of glaucoma in someone with a latent condition
The next muscarinic receptor antagonist (belladonna alkaloid) is scopolamine, what are its actions?
- -Greater actions on CNS and longer duration of action than atropine
- -one of the most effective anti-motion sickness drugs
- -side effect: blocks short term memory (often used in anesthesic procedures)
- -low doses produces sedation but high doses produces excitement
What are some uses for scopolamine (muscarinic antagonist)?
- –mydriasis and cycloplegia in diagnostic procedures
- -prevention of n/v associated with motion sickness
The next muscarinic receptor antagonist are ipratropium and tiotropium, what are their uses?
–used as inhalational drugs in the tx of COPD
Next up muscarinic receptor antagonist are homatropine, cyclopentolate and tropicamide, what is the primary use of these drugs?
Produce mydriasis with cycloplegia
–preferred to atropine because of their shorter duration of action
Next muscarinic receptor antagonist are benztropine and trihexyphenidyl, what is the primary use of these drugs?
–used to tx parkinsonism and the extrapyramidal effects of antipsychotic drugs
Next muscarinic receptor antagonist is glycopyrrolate, what is the use of this drug?
Inhibits GI motility
–also used parenterally to prevent bradycardia during surgical procedures
Finally the last muscarinic receptor antagonist is tolterodine, what is the use of this drug?
–reduce bladder spasms and urge urinary incontinence
for overactive bladder
There are some general contraindications of antimuscarinic agents, what are these?
- patients with angle closure glaucoma
- patients with prostatic hypertrophy — decrease detrusor contraction and increase the risk of urinary retention
- used with caution in the elderly
- low to medium levels of muscarinic blockage can cause bradycardia and sedation
- high levels of muscarinic blockage can cause tachycardia, CNS hyperexcition with delirium, hallucinations, and seizures
- Adverse effects: blurred vision, dry mouth, ileus, urinary retention, flushing and fever, agitation and tachycardia
Moving on to nicotinic receptor antagonists, what is the action of these drugs?
Ganglion blockers that block the action of ACh at the nicotinic receptors of both parasympathetic and sympathetic autonomic ganglia
Ganglion blockage may occur by what mechanisms?
- -Prolonged depolarization: Nicotine, a ganglion stimulant, can block ganglia after initial stimulation by this mechanism
- -Antagonism of Nicotinic Receptors: Mecamylamine, trimethaphan and hexamethonium act this way
Sympathetic (Adrenergic) is the predominant tone at what site?
Arterioles
Veins
Parasympathetic (cholinergic) is the predominant tone at what site?
Heart Iris Ciliary Muscle GI tract Urinary bladder Salivary glands
Sympathetic but cholinergic is the predominant tone site where?
Sweat glands
Moving on to Neuromuscular blockers, what is the action of these drugs?
Block cholinergic transmission between motor nerve endings and the nicotinic receptors on the neuromuscular end plate of skeletal muscle.
–used during surgery to produce complete muscle relaxation
There are two classes of neuromuscular blockers, the first class is nondepolarizing (Competitive) blockers, what is the primary drug for this?
Tubocurarine
- -compete with ACh for the receptors and ultimately prevent binding of ACh – this prevents depolarization of muscle cell membrane and inhibits muscular contraction
- used during anaesthesia during surgery to relax skeletal muscle
The action of nondepolarizing competitive blockers is overcome by what?
Increasing concentration of ACh in synaptic cleft with cholinesterase inhibitors such as neostigmine or edrophonium
–make sure you give atropine in addition to prevent bradycardia
The second class of neuromuscular blockers are depolarizing blockers like succinylcholine, what is the action of this drug?
- -binds to nicotinic receptors and acts like ACh to cause depolarization of the end plate
- -this spreads and depolarizes adjacent membranes, causing generalized disorganized contraction of muscle motor units
- -this drug is not metabolized effectively at the synapse therefore the membrane remains depolarized and unresponsive to additional impulses — flaccid paralysis results
What are the pharmacokinetics of succinylcholine?
–extremely brief duration of action and rapid onset (1-1.5 minutes)
What is the use of succinylcholine?
Rapid endotracheal intubation
What are the adverse effects of succinylcholine?
Malignant hyperthermia — caused by stimulus elicited excessive release of Ca2+ from the SR.
- -one of the main causes of death due to anesthesia
- -most of the incidents arise form the combination of succinylcholine and an halogenated anesthetic
- -tx with dantrolene, which blocks release of calcium from SR
What is an inhibitor of ACh synthesis?
Hemicholinium-3: blocks the high affinity transporter for choline and thus prevents the uptake of choline
–used as a research tool
What drug is an inhibitor of ACh storage?
Vesamicol: blocks the ACh-H+ antiporter that is used to transport ACh into vesicles
–used as a research tool
Finally, lets touch on a very popular drug that inhibits ACh release, botulinum toxin, which is a protein produced by Clostridium botulinum. What is the action of the toxin?
A potent neurotoxin that prevents synaptic vesicle fusion with the axon terminal membrane, thus inhibiting ACh release.
Injected locally into muscles, botulinum is used in the tx of several diseases associated with increased muscle tone, such as?
Torticollis Achalasia Strabismus Blepharospasm Focal Dystonias
