Cholinergic Agonists And Antagonists Flashcards
What are the types of cholinergic agonists ?
Direct acting: bind to and activates muscuranic or nicotinic receptors
Indirect acting: inhibit acetylcholinesterase
Summarize direct acting cholinergic agonists
- some are selective fir the muscuranic or nicotinic receptors
- many have effects on both receptors
- Most therapeutically useful drugs preferentially activate muscuranic drugs
What are the cardiovascular effects of direct acting effects of ACh?
Direct effects of acetylcholine
- vasodilation (M3 effect)
- Decrease in cardiac ratev(M2 effect)
- Decrease in rate of conduction in the SA and AV nodes (M2 effect)
- Decrease in force of contraction (M2 effect)
Some of the direct effects can be obscured by barireceotor reflexes
What are cardiovascular effects of acetylcholine IV injections?
- IV injection of a small dose of acetylcholine produces a fall in blood pressure due to vasodilation (M3 effect) usually accompanied by reflex tachycardia
- larger doses of acetylcholine cause vasodilation, a fall in blood pressure (M3 effect) and bradychardia (M2 effect)
What are the effects of vasculature(endothelial cells)?
Effects of acetylcholine: release of NO and vasodilation
Decrease in BP
What is the effect of acetylcholine on eye iris?
Miosis
What is the effect of acetylcholine on ciliary muscle?
Accommodation of lens to near vision
What is the effect of acetylcholine on salivary/ sweat/ lacrimal glands?
Increased secretions
What is the effect of acetylcholine on bronchi?
Constriction
What is the effect of acetylcholine on the heart?
Decreased, heart rate and conduction velocity
What is the effect of acetylcholine on the GI tract?
Increased tone & peristaltic activity; relaxation of sphincters
What is the effect of acetylcholine on the urinary bladder?
Contraction of detrusor muscle; relaxation of sphincter
What happens to acetylcholine in large doses if muscuranic effects are blocked by muscuranic antagonists (atropine)?
Fir thus reason, drugs like atropine produce nicotinic effects at large doses
Vasoconstriction and increase in blood pressure
These effects are due to stimulation of sympathetic ganglia and release of epinephrine from the adrenal medulla
What are the choline esters?
- Acetylcholine
- Methanecnoline
- Bethanechol
What are choline esters?
Choline esters are quartenary ammonium
- Poorly absorbed and poorly distributed into the CNS
- They differ in their susceptibility to hydrolysis by cholinesterase
- Acetylcholine is very rapidly hydrolyzed
- Methanecholine and Bethanechol are more resistant to hydrolysis by cholinesterase
What are the acetylcholine?
Muscuranic and nicotinic agonist
Uses: used to obtain miosis after delivery of the lens in cataract surgery and other procedures where rapid miosis is required
What is Bethanechol?
Muscuranic agonist
Uses:
- Postoperative urinary retention
- Antony of the urinary bladder
What is methanechol?
Muscuranic agonist
Uses: diagnosis of bronchial airway hyperactivity in subjects who do not have clinically appearent asthma
What are the natural alkaloids?
- pilocarpine
- nicotine
What is pilocarpine?
- Partial Muscuranic agonist
- tertiary amine
- Stable to hydrolysis by acetylcholinesterase
Uses:
- Glaucoma
- Treatment of dry mouth due to radiotherapy fir cancer of head and neck
What are the adverse effects of muscuranic agonists ?
The adverse eff3crs mimic the effects of generalized cholinergic stimulation:
-Sweating
- Salivation
- Flushing
- Low blood pressure
- Nausea
- Abdominal pain
- Diarrhea
- Bronchospasm
What is nicotine?
Tertiary amine
- Agonist at nicotinic receptors
- Depending on the dose, nicotine depolarizes autonomic ganglia, resulting first in stimulation and then in paralysis
What are the actions of nicotine?
Low dose: ganglionic stimulation by depolarization
The response resembles simulataneous discharge of both parasympathetic and sympathetic nervous systems
High dose: ganglionic blockade and neuromuscular blockade
What are the uses of nicotine?
-Smoking cessation therapy
What are the indirect-acting cholinergic agents(anticholinesterases)?
- Edrophonium
- Carbamates
- Physostigmine, neostigmine, pyridostigmine
- Orangophosphates
- Malathion, sarin
What is the mechanism of action of anticholinesterase?
Cholinesterase inhibitors, act by inhibiting acetylcholinesterase: they increase concentration of endogenous acetylcholine
What is the mechanism of action 9f edrophonium?
Binds reversibly to the active site of the enzyme. This inhibition is short .
What is the mechanism of action of carbamates?
Form a covalent bond with the enzyme
What is the mechanism of action of orangophosphates?
Phosphorylate the enzyme. The covalent bond formed is extremely stable and hydrolyzes very slowly
Summarize organ system effects of the anticholinesterases
- Antivholinesterases amplify the action of endogenous acetylcholine
- Therefore their effects are similar (but not always identical) to the effects of the direct-acting cholinomimmetic agents
What are the special effects of cholinesterase inhibitors?
Cardiovascular system: in. The vascular smooth muscle cholinesterase inhibitirs gave minimal effects because most vascular beds lack cholinergic innervation
Neuromuscular junction: cholinesterase inhibitors increase strength of contraction
- Useful to reverse action of nomdepolarizing neuromuscular blockers
- Useful in myasthenia Gravis
What are the properties of edrophonium?
Quaternary ammonium
-doesn’t enter CNS
Uses: diagnosis of myasthenia Gravis : edrophonium IV leads to rapid increase in muscle strength
Used to reverse the neuromuscular block produced by nom-depolarizing muscular blockers
What are the properties of physostigmine?
Tertiary amine
-can enter and stimulate CNS
Uses: treatment of overdoses of anti cholinergic drugs
What are the properties of neostigmine?
- Quatenary ammonium
- Doesn’t enter CNS
Uses:
- Urinary retention
- Reversal of effects of non-depolarizing neuromuscular blockers after surgery
- treatment of myasthenia Gravis
What are the properties of pyridistigmine ?
Quatenary ammonium
-Doesn’t enter CNSZ
Uses:
-treatment of myasthenia Gravis
What are orangophosphates?
- synthetic compounds
- many are extremely toxic
Give examples of orangophosphates that are also insecticides
Malathion
Sarin- among the most potent synthetic toxic agents known
What are the belladonna alkaloids?
Atropine & scopolamine
What is atropine?
- prototype of Muscuranic antagonists
- reversible competitive antagonist at muscuranic receptors
- Tertiary amine: both central and peripheral Muscuranic blocker
What are the actions of atropine?
Eye: mydriasis & cycloplegia (M3 blockade )
GI: reduces gastric motility (M3 blocksde)
Urinary system: decreases hypermotility of urinary bladder (M3 blocksde )
CV system: Moderate to high therapeutic doses cause tachycardia (Atrial M2 blockade)
Secretions: Salicary, sweat and lacrimal glands are blocked. Inhibitions of sweat glands may cause high body temperature (M3 blockade)
What are the uses of atropine?
- antidote for cholinergic agonists
- to block respiratory tract secretions prior to surgery
What are the adverse effects of atropine?
- dry mouth, blurred vision, sandy eyes, tachycardia, constipation, urinary retention
- effects on CNS: rest,Essenes, confusion, hallucinations, delirium
What are the uses of scopolamine?
Prevention of motion sickness
What are the synthetic and semisynthetic muscuran8c antagonists?
- Quatenary ammonium Muscuranic antagonists
- Tertiary amine Muscuranic antagonists
What is an example of a Quatenary ammonium Muscuranic antagonists?
Ipratropium
-used in the treatment of chronic obstructive pulmonary disease and asthma
Give an example of a tertiary amine Muscuranic antagonist
Tropocamide
- used as myristic fir fundus copy
- Produces mydriasis with cycloplegia
What are the contraindications of using antimuscuranic agents?
- contraindicated in patients with angle-closure glaucoma
- Should be used with caution in patients with prostatic hypertrophy and in the elderly
How May ganglion blocking occur?
Occurs by
-By prolonged depolarization example: nicotine
Or
-By antagonism of nicotinic receptors. Example:hexamethonium
What are the uses of ganglion blockers?
Hexamethonium was used fir hypertension in the past
Due to their adverse effects ganglion blockers have been replaced by superior anti hypertensive agents
What are the Pharmological uses of ganglion blockers ?
Effects of ganglion-blockers can be predicted by a knowledge of which division kf the autonomic nervous system exercises DOMINANT CONTROL of various organs
The effect of the ganglion blockers is to remove the dominant control
What are the types of neuromuscular blockers ?
- competitive antagonists (nondepolarizing blockers)
- agonists (depolarizing blockers)
Explain an example of non depolarizing neuromuscular blockers
Tubocurarine is the prototype
Mechanism of action: competitive antagonists
Uses: as adjuvant in anaesthsia during surgery to relax skeletal muscle
Give an example of depolaarizing neuromuscular blockers
Mechanism of action: succinylcholine binds to the nicotinic receptor and depolarizipes the junction. Pers8sts in the synaptic cleft, stimulating the receptor: receptor desensitizes
-this leads to the flaccid paralysis
Uses:
-rapid endotracheal intubation
-ECT
What drugs act presynaotically ?
Inhibitors of acetylcholine release
What is the effect of the botulinum toxin?
- injected locally into muscles for treatment 8f several s8seases involving muscle spasms
- Also approved for cosmetic treatment of facial wrinkles
