LEcture 2- cholinergic antagonists Flashcards
BELLADONNA ALKALOIDS
ATROPINE &; SCOPOLAMINE
atropine comes from ?
Atropa belladonna (nightshade) Datura Stramonium (jimsonweed
ATROPINE MOa/what kind of amine
Binds competitively to muscarinic receptors, preventing acetylcholine from binding. Tertiary amine. Both central and peripheral muscarinic blocker
Atropine action on organs
ACTIONS
Eye: mydriasis; unresponsiveness to light. Cycloplegia. In patients with glaucoma intraocular pressure may rise dangerously.
GI: can be used as antispasmodic. Gastric motility is reduced, but HCl production is not affected: not effective in promoting healing of peptic ulcer.
Urinary System: Decreases hypermotility of urinary bladder.
Cardiovascular: The atria of the heart are richly innervated by parasympathetic nerve fibers, and the SA node is therefore sensitive to muscarinic receptor blockade. The effect of moderate to high therapeutic doses is a blockade of atrial M2 receptors and tachycardia. NOTE: Lower doses of atropine often result in initial bradycardia before the effects of atrial M2 receptor blockade become manifest. This effect is due to blockade of presynaptic muscarinic M2 receptors on vagal postganglionic fibers that normally inhibit acetylcholine release in the sinus node.
At toxic doses, and in some individuals at normal doses, antimuscarinic agents cause cutaneous vasodilation, especially in the upper portion of the body. This is called ‘atropine flush’. The mechanism is unknown.
Secretions: salivary, sweat and lachrymal glands are blocked. Inhibition of sweat glands may cause high body temperature.
Atropine clinical uses
Antisialogogue/increase heart rate/decrease AV block/ overdose of cholinergic drugs/alleviate the muscarinic side effects of anticholinesterase drugs
atropine PK
Half life 4 hrs/meatbolised in the liver/excreated by the kidneys
Atropine AE
Dry mouth, blurred vision, sandy eyes, tachycardia, constipation. • Effects on CNS: restlessness, confusion, hallucinations, delirium, which may progress to depression, collapse of the circulatory and respiratory systems and death.
LD140218 3
• In older individuals, the use of atropine to induce mydriasis and cycloplegia is considered too risky since it may exacerbate an attack of glaucoma in someone with a latent condition.
SCOPOLAMINE
Another belladonna alkaloid; produces peripheral effects similar to atropine. Greater actions on CNS and longer duration of action.
scopolamine
ACTIONS
• One of the most effective anti-motion sickness drugs available. Can be administered through the transdermal route. • Unusual effect: blocks short-term memory. • In contrast to atropine, it produces sedation; at higher doses can produce excitement
scopolamine uses
USES
• For mydriasis and cycloplegia in diagnostic procedures. • For some pre- and postoperative states when a mydriatic and cycloplegic is needed in treatment of iridocyclitis. • For prevention of nausea and vomiting associated with motion sickness.
QUATERNARY AMMONIUM MUSCARINIC ANTAGONISTS
IPRATROPIUM AND TIOTROPIUM and glycopyrrolate
ipratropium uses
QUATERNARY AMMONIUM MUSCARINIC ANTAGONISTS
uses
Ipratropium and tiotropium are used as inhalational drugs in the treatment of chronic obstructive pulmonary disease (COPD).
They are also used as inhalational drugs in asthma.
Tiotropium uses
Quaternary ammonium muscarinic antagonist
Ipratropium and tiotropium are used as inhalational drugs in the treatment of chronic obstructive pulmonary disease (COPD).
They are also used as inhalational drugs in asthma.
TERTIARY AMINE MUSCARINIC ANTAGONISTS
HOMATROPINE AND TROPICAMIDE andBENZTROPINE AND TRIHEXYPHENIDY and tolterodine
HOMATROPINE AND TROPICAMID
Particularly useful in ophthalmology. They produce mydriasis with cycloplegia. These agents are preferred to atropine because of their shorter duration of action
BENZTROPINE AND TRIHEXYPHENIDY
TERTIARY AMINE MUSCARINIC ANTAGONISTS
uses
Tertiary-amine muscarinic antagonists gain access to the CNS and are therefore the anticholinergic drugs used to treat parkinsonism and the extrapyramidal effects of antipsychotic drugs. Specific agents used primarily for these conditions include benztropine and trihexyphenidyl
contraindications of antimuscarinic agents
Antimuscarinic drugs are contraindicated in patients with angle-closure glaucoma. • Antimuscarinics should be used with caution in patients with prostatic hypertrophy: antimuscarinics decrease detrusor contraction and increase the risk of urinary retention; this risk may be even greater in patients with increased urethral resistance. • Antimuscarinics should also be used with caution in the elderly. • Depending on the dose, antimuscarinic agents may cause bradycardia and sedation at low-to-medium levels of muscarinic blockade, and tachycardia and CNS hyperexcitation with delirium, hallucinations, and seizures at higher levels of blockade. • Other adverse effects may include blurred vision (cycloplegia and mydriasis), dry mouth, ileus, urinary retention, flushing and fever, agitation, and tachycardia
antagonism of nicotinic receptor
mecamylamine and hexamthonium
antagonism of nicotinic recpeotr via prolonged depolarization
nicotine
Arterioles and veins predominant tone/receptor type/effect of blockage
Sympathetic (adrenergic) 1 Vasodilation; hypotension
Heart predominant tone/receptor type/effect of blockage
Parasympathetic (cholinergic) M2 Increase in heart rate
Iris predominant tone/receptor type/effect of blockage
Parasympathetic (cholinergic) M3 Mydriasis
ciliary muscle predominant tone/receptor type/effect of blockage
Parasympathetic (cholinergic) M3 Cycloplegia (focus for far vision)
GI tract predominant tone/receptor type/effect of blockage
Parasympathetic (cholinergic) M3 Reduced tone and motility; constipation; decreased secretions
urinary bladder predominant tone/receptor type/effect of blockage
Parasympathetic (cholinergic) M3 Urinary retention
Salivary gland predominant tone/receptor type/effect of blockage
Parasympathetic (cholinergic) M3 Xerostomia
Sweat gland predominant tone/receptor type/effect of blockage
Sympathetic (cholinergic) M3 Anhydrosis
CHOLINERGIC EVEN THOUGH IT IS Sympathetic
NEUROMUSCULAR BLOCKERS
Block cholinergic transmission between motor nerve endings and the nicotinic receptors on the neuromuscular end-plate of skeletal muscle. Structural analogs of acetylcholine. Two classes: competitive antagonists (nondepolarizing) and agonists (depolarizing). Used during surgery to produce complete muscle relaxation
competitive non depolarizing blocker at neuromuscular junction
tubocurarine
depolarizing m\NMJ blocker
succinylcholine
succinylcholine pk
Given IV by continuous infusion. Rapidly hydrolysed by plasma cholinesterase. Extremely brief duration of action (5-10 min) and rapid onset (1-1.5 min).
succinylcholine AE
Malignant hyperthermia: autosomal dominant disorder of skeletal muscle. 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 from the combination of succinylcholine and an halogenated anesthetic. Treated with dantrolene, which blocks release of calcium from SR, reducing heat production and relaxing muscle tone.
Succinylcholine Uses
Useful when rapid endotracheal intubation is needed. Also used during ECT
INHIBITORS OF ACETYLCHOLINE SYNTHESIS
HEMICHOLINIUM-3
Hemicholinium-3 blocks the high-affinity transporter for choline, and thus prevents the uptake of choline required for ACh synthesis. Only used as a research tool
INHIBITORS OF ACETYLCHOLINE STORAGE
Vesamicol blocks the ACh-H+ antiporter that is used to transport ACh into vesicles, thereby preventing the storage of ACh. Only used as a research tool.
INHIBITORS OF ACETYLCHOLINE RELEAS MOA /AE
BOTULINUM TOXIN
• Protein produced by the anaerobic bacillus Clostridium botulinum. • Botulinum toxin, a potent neurotoxin, prevents synaptic vesicle fusion with the axon terminal membrane, thus inhibiting acetylcholine release. • Injected locally into muscles, it is used in the treatment of several diseases associated with increased muscle tone, such as torticollis, achalasia, strabismus, blepharospasm, and other focal dystonias. • Botulinum toxin is also approved for cosmetic treatment of facial wrinkles, and is being increasingly used to treat various headache and pain syndromes
Tubocurarine PK/AE
PHARMACOKINETICS
Given IV. Oral absorption is minimal. Penetrate membranes very poorly. Don’t cross blood-brain barrier.
ADVERSE
Autonomic effects: some agents are moderate blockers of muscarinic receptors. Histamine release: tubocurarine may cause histamine release.
define atropine flush
At toxic doses, and in some individuals at normal doses, antimuscarinic agents cause cutaneous vasodilation, especially in the upper portion of the body. This is called ‘atropine flush’. The mechanism is unknown.
antisialogogue
reducing secreations of respiratory tract
inhibitors of ACH synthesis
hemicholinium-3 –> blocks CHT needed to bring choline in the neuron
for research only
inhibitors of ACH storage
vesamicol–>blocks VAChT (antiporter that bring ach into the vesicle ) for researches only
inhibitors of ACH release
botulinium toxin released by clostridium botulinium
used for muscle spasm treatment ans wrinkle removal
prevents fusion of vesicle to the membrane by cleaving synaptobrevin (no formation of SNARE complex)
