LEcture 2- cholinergic antagonists

Question 1

BELLADONNA ALKALOIDS

Answer 1

ATROPINE &; SCOPOLAMINE

Question 2

atropine comes from ?

Answer 2

Atropa belladonna (nightshade)
 Datura Stramonium (jimsonweed

Question 3

ATROPINE MOa/what kind of amine

Answer 3

Binds competitively to muscarinic receptors, preventing acetylcholine from binding. Tertiary amine. Both central and peripheral muscarinic blocker

Question 4

Atropine action on organs

Answer 4

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.

Question 5

Atropine clinical uses

Answer 5

Antisialogogue/increase heart rate/decrease AV block/ overdose of cholinergic drugs/alleviate the muscarinic side effects of anticholinesterase drugs

Question 6

atropine PK

Answer 6

Half life 4 hrs/meatbolised in the liver/excreated by the kidneys

Question 7

Atropine AE

Answer 7

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.

Question 8

SCOPOLAMINE

Answer 8

Another belladonna alkaloid; produces peripheral effects similar to atropine. Greater actions on CNS and longer duration of action.

Question 9

scopolamine

Answer 9

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

Question 10

scopolamine uses

Answer 10

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.

Question 11

QUATERNARY AMMONIUM MUSCARINIC ANTAGONISTS

Answer 11

IPRATROPIUM AND TIOTROPIUM and glycopyrrolate

Question 12

ipratropium uses

Answer 12

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.

Question 13

Tiotropium uses

Answer 13

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.

Question 14

TERTIARY AMINE MUSCARINIC ANTAGONISTS

Answer 14

HOMATROPINE AND TROPICAMIDE andBENZTROPINE AND TRIHEXYPHENIDY and tolterodine

Question 15

HOMATROPINE AND TROPICAMID

Answer 15

Particularly useful in ophthalmology. They produce mydriasis with cycloplegia. These agents are preferred to atropine because of their shorter duration of action

Question 16

BENZTROPINE AND TRIHEXYPHENIDY

Answer 16

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

Question 17

contraindications of antimuscarinic agents

Answer 17

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

Question 18

antagonism of nicotinic receptor

Answer 18

mecamylamine and hexamthonium

Question 19

antagonism of nicotinic recpeotr via prolonged depolarization

Answer 19

nicotine

Question 20

Arterioles and veins predominant tone/receptor type/effect of blockage

Answer 20

Sympathetic (adrenergic) 1 Vasodilation; hypotension

Question 21

Heart predominant tone/receptor type/effect of blockage

Answer 21

Parasympathetic (cholinergic) M2 Increase in heart rate

Question 22

Iris predominant tone/receptor type/effect of blockage

Answer 22

Parasympathetic (cholinergic) M3 Mydriasis

Question 23

ciliary muscle predominant tone/receptor type/effect of blockage

Answer 23

Parasympathetic (cholinergic) M3 Cycloplegia (focus for far vision)

Question 24

GI tract predominant tone/receptor type/effect of blockage

Answer 24

Parasympathetic (cholinergic) M3 Reduced tone and motility; constipation; decreased secretions

Question 25

urinary bladder predominant tone/receptor type/effect of blockage

Answer 25

Parasympathetic (cholinergic) M3 Urinary retention

Question 26

Salivary gland predominant tone/receptor type/effect of blockage

Answer 26

Parasympathetic (cholinergic) M3 Xerostomia

Question 27

Sweat gland predominant tone/receptor type/effect of blockage

Answer 27

Sympathetic (cholinergic) M3 Anhydrosis

CHOLINERGIC EVEN THOUGH IT IS Sympathetic

Question 28

NEUROMUSCULAR BLOCKERS

Answer 28

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

Question 29

competitive non depolarizing blocker at neuromuscular junction

Answer 29

tubocurarine

Question 30

depolarizing m\NMJ blocker

Answer 30

succinylcholine

Question 31

succinylcholine pk

Answer 31

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).

Question 32

succinylcholine AE

Answer 32

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.

Question 33

Succinylcholine Uses

Answer 33

Useful when rapid endotracheal intubation is needed. Also used during ECT

Question 34

INHIBITORS OF ACETYLCHOLINE SYNTHESIS

Answer 34

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

Question 35

INHIBITORS OF ACETYLCHOLINE STORAGE

Answer 35

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.

Question 36

INHIBITORS OF ACETYLCHOLINE RELEAS MOA /AE

Answer 36

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

Question 37

Tubocurarine PK/AE

Answer 37

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.

Question 38

define atropine flush

Answer 38

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.

Question 39

antisialogogue

Answer 39

reducing secreations of respiratory tract

Question 40

inhibitors of ACH synthesis

Answer 40

hemicholinium-3 –> blocks CHT needed to bring choline in the neuron
for research only

Question 41

inhibitors of ACH storage

Answer 41

vesamicol–>blocks VAChT (antiporter that bring ach into the vesicle ) for researches only

Question 42

inhibitors of ACH release

Answer 42

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)