Reading...
Play button
Play button
Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
91 Cards in this Set
- Front
- Back
|
Muscarinic Agonists
|
Choline esters
Acetylcholine ACH Carbachol car bac hol Bethanechol beth an e c hol Natural alkaloids Pilocarpine pilo car pine Muscarine |
|
|
Choline esters
|
Acetylcholine
Carbachol Bethanechol |
|
|
Natural alkaloids
|
Pilocarpine
Muscarine |
|
|
Cholinesterase Inhibitors and Reactivators
|
Reversible Inhibitors
Edrophonium Physostigmine Neostigmine Donepezil Irreversible Inhibitors Parathion (and other Organophosphates) Reactivators Pralidoxime |
|
|
Reversible Inhibitors
|
Edrophonium E drop hin i um
Physostigmine physo stig mine Neostigmine neo stig mine Donepezil don ep e zil |
|
|
Irreversible
Inhibitors |
Parathion
(and other Organophosphates) |
|
|
Reactivators
|
Pralidoxime
|
|
|
All choline esters and natural alkaloids activate
|
M1, M2 and M3 receptors
- Activation postsynaptic receptors = altered function effector organs - Activation presynaptic receptors = inhibits release neurotransmitters |
|
|
Acetylcholine acts on two types of receptors:
|
Nicotinic receptors.
Muscarinic receptors |
|
|
ACETYLCHOLINE:
|
HEART: M2 RECEPTORS
Decrease HR conduction contraction BLOOD VESSELS: M3 Vasodilation via the release of nitric oxide GIT: M1/M3 Increase tone and peristalsis. Increase secretion of GI & lacrimal gland. Relax sphincter (except LES contracted) URINARY BLADDER: M3 Contraction detrusor. Relaxation trigone and sphincter RESPIRATORY TRACT : Constriction bronchus Increases secretions EYE : spasm of accommodation via contraction ciliary muscle causing zonula to relax, allowing the lens to become more convex fixing for near objects |
|
|
Nicotinic action of Acetylcholine
|
Autonomic ganglia (Nn)
SNS & PSNS stimulated . Skeletal muscle (Nm) Contraction of fibers. |
|
|
DRUGS AFFECTING CHOLINERGIC TRANSMISSION
|
ANTICHOLINESTERASES - Neostigmine
INHIBITING CHOLINE CARRIER -Hemicholinium INHIBITION OF VESCICULAR STORAGE - Vesamicol INHIBITION OF RELEASE – Botulinium toxin |
|
|
CHOLINE ESTERS
|
Methacholine and Bethanechol have no nicotinic actions
Methacholine has prominent CVS action Carbachol and Bethanechol on GIT and Urinary bladder. Carbachol and Bethanechol are resistant to the hydrolysis by AchE |
|
|
Pilocarpine
|
stimulates only muscarinic receptors
Used in chronic simple glaucoma, acute congestive glaucoma and as miotic= excessive constriction of pupil |
|
|
Physostigmine
|
Natural alkaloid.
Tertiary amine. Oral absorption CNS action TX: -glaucoma -antidote to atropine poisoning. |
|
|
Neostigmine :
|
Synthetic
Quaternary amine =NO CNS action Poor oral absorption Prominent action on skeletal muscles Used in ileus, urinary retention, myasthenia gravis, reverses skeletal muscle paralysis |
|
|
USES OF CHOLINOMIMETIC DRUGS
|
Open / Wide angle glaucoma.
Miotics Myasthenia gravis Retention of urine Drug poisoning – Atropine, TCA. Alzheimer's disease – Donepezil, Galantamine, Rivastigmine, Tacrine |
|
|
Choline Esters
|
Ach
Carbachol (car ba chol) Bethanechol (beth an e chol) Increase Dumbells |
|
|
Choline Ester efects on: Heart
|
- S-A node:
decreased heart rate (M2-mediated opening of K+ channels) - Atria: decrease refractoriness, contractility no change/increase conduction, automaticity - A-V node: decrease conduction and automaticity; increase refractoriness - Ventricles: minimal direct effect on myocardial cells (postsynaptic M are few in ventricles); decrease NE release |
|
|
Choline Ester efects on: Vessels
|
-Generalized vasodilation (M3-mediated release of nitric oxide)
|
|
|
Choline Ester efects on: GI
|
- Increased tone, amplitude of contractions, peristaltic activity and secretions of GI tract.
- Relaxation of sphincters, likely from nicotinic stimulation of ganglionic peptidergic neurons. - Contraction of the lower esophageal sphincter. |
|
|
Choline Ester efects on: Endocrine Pancreas
|
- Mild stimulation of insulin secretion
|
|
|
Choline Ester efects on: GU
|
- Increased ureteral peristalsis.
- Contraction/ increased tone detrusor muscle (leads to decreased capacity of bladder). - Relaxation of trigone and internal sphincter of urethra - Erection in male. - Negligible effects on uterus. |
|
|
Choline Ester efects on: Respiratory
|
Bronchial smooth muscle contraction.
- Increased tracheobronchial secretions. via M3 receptor |
|
|
Choline Ester efects on: EYE
|
- Contraction of sphincter of iris (miosis).
- Increased secretion lacrimal glands. - Contraction of the ciliary muscle which leads to 1) Cyclospasm -lens curvature is increased -lens focus power is adjusted for near vision ciliary muscle can't relax, accommodation for far vision lost 2) Widening of spaces w/ in trabecular meshwork, facilitates aqueous humor outflow through Schlemm’s canal. |
|
|
Choline Ester efects on: Skin
|
- Increased secretion of sweat glands.
|
|
|
CHOLINE ESTERS BIOTRANSFORMATION
|
- ACH rapidly hydrolyzed by acetylcholinesterase and butyrylcholinesterase, are present in plasma and tissues.
- Carbachol and bethanechol resistant to hydrolysis by cholinesterases, so biotransformation is negligible |
|
|
CHOLINE ESTERS EXCRETION
|
the kidney
|
|
|
CHOLINE ESTERS ADMINISTRATION ROUTES
|
- Acetylcholine and carbachol: topical instillation on the conjunctiva.
- Bethanechol: PO, SC (IV or IM administration must be avoided) |
|
|
CHOLINE ESTERS effects on:
Heart Acetylcholine Carbachol Bethanechol |
- S-A node: decreased heart rate (M2-mediated opening of K+ channels)
- Atria: decrease refractoriness no change/increase conduction, automaticity; decrease contractility. - A-V node: decrease conduction and automaticity; increase refractoriness - Ventricles: minimal direct effect on myocardial cells decrease NE release *M2 recepters |
|
|
CHOLINE ESTERS effects on:
Vessels Acetylcholine Carbachol Bethanechol |
-Generalized vasodilation (M3-mediated release of nitric oxide)
|
|
|
CHOLINE ESTERS effects on:
GI Acetylcholine Carbachol Bethanechol |
- Increased:
tone, amplitude of contractions, peristaltic activity secretions of GI tract. - Relaxation of sphincters, likely from nicotinic stimulation of ganglionic peptidergic neurons. - Contraction of the lower esophageal sphincter. |
|
|
CHOLINE ESTERS effects on:
endocrine pancreas Acetylcholine Carbachol Bethanechol |
- Mild stimulation of insulin secretion.
|
|
|
CHOLINE ESTERS effects on:
GU Acetylcholine Carbachol Bethanechol |
- Increased ureteral peristalsis.
- Contraction detrusor muscle (leads to decreased capacity of bladder). - Relaxation of trigone and internal sphincter of urethra - Erection in male. - Negligible effects on the uterus. |
|
|
CHOLINE ESTERS effects on:
Respiratory system Acetylcholine Carbachol Bethanechol |
- Bronchial smooth muscle contraction.
- Increased tracheobronchial secretions. |
|
|
CHOLINE ESTERS effects on:
Eye Acetylcholine Carbachol Bethanechol |
- Increased secretion of lacrimal glands.
- Contraction of the sphincter of iris (miosis). - Contraction of the ciliary muscle which leads to 1) Cyclospasm -lens curvature is increased -lens focus power is adjusted for near vision. -Since the ciliary muscle cannot relax, accommodation for far vision is lost 2) Widening of the spaces within the trabecular meshwork, so facilitating aqueous humor outflow through the Schlemm’s canal |
|
|
CHOLINE ESTERS effects on:
Skin Acetylcholine Carbachol Bethanechol |
Increased secretion of sweat glands M3
|
|
|
CHOLINE ESTERS effects:
increase dumb bels Acetylcholine Carbachol Bethanechol |
Defication
Urination Miosis Bronchoconstriction Bradycardia Excititory CNS, skeletal muscle Lacrimation Salivaltion |
|
|
CHOLINE ESTERS ADVERSE EFFECTS
When given locally on the conjunctiva |
(Carbachol, acetylcholine) M3
- Visual difficulty: far vision + dim light. - Reddening, stinging and burning of conjunctiva. - Postoperative iritis. - Cataract - Retinal detachment (long-term use) |
|
|
CHOLINE ESTERS ADVERSE EFFECTS
When given systemically |
(Bethanechol) extream dumb bells
- Nausea and vomiting (via increased GI activity & stimulation M in CTZ), -abdominal pain, -diarrhea - Bronchospasm, cough - Sweating, lacrimation, salivation - Flushing and warmth of the skin - Urinary urgency - Hypotension |
|
|
CONTRAINDICATIONS AND PRECAUTIONS OF CHOLINE ESTERS
When given locally |
Iritis, cataract, previous history of retinal detachment.
|
|
|
PRECAUTIONS OF CHOLINE ESTERS
When given systemically |
if have respiratory, heart, GI, urinary, thyroid problems need to avoid giving choline esters
- Asthma, -COPD - Cardiac arrhythmias, -coronary artery disease, -myocardial disease, -hypotension. - Peptic ulcer disease, -GI obstruction, -irritable bowel disease, -inflammatory bowel disease, -peritonitis. - Urinary tract obstruction. - Hyperthyroidism. |
|
|
NATURAL ALKALOIDS
|
Pilocarpine pilo car pine
Muscarine activate only M1, M2 and M3 receptors |
|
|
NATURAL ALKALOIDS
Source and chemistry |
- Pilocarpine = tertiary amine in plants of genus Pilocarpus.
- Muscarine = quaternary ammonium compound c in mushrooms of genus Inocybe and Clitocybe |
|
|
NATURAL ALKALOIDS
Pharmacological effects |
- Peripheral effects like choline esters.
-Stimulation salivation & sweating - Central effects: arousal, excitation, headache, tremors -Pilocarpine enter CNS -muscarine can enter CNS, carried by active transport |
|
|
NATURAL ALKALOIDS
Adverse effects |
- Most adverse effects are similar to choline esters.
|
|
|
mycetism
|
- Poisoning produced by mushrooms
Symptoms from muscarine containing mushrooms develop within 30-60 minutes of ingestion and include: Dumb bels nausea and vomiting, headache visual disturbances, abdominal colic, bronchospasm, hypotension, tremors, confusion, convulsions coma skeletal muscle tone is not affected ** Inocybe species ** |
|
|
Pilocarpine
Therapeutic uses |
-open-angle glaucoma
-used orally in case of xerostomia due to radiation therapy or Sjogren’s syndrome -natural alkaloid |
|
|
CHOLINESTERASE REVERSIBLE INHIBITORS
|
Edrophonium
e drop ho nium Physostigmine phy so stig mine Neostigmine neo stig mine Donepezil done pe zil |
|
|
CHOLINESTERASE
Irreversible Inhibitors |
Parathion
Organophosphates |
|
|
CHOLINESTERASE
Reactivators |
Pralidoxime
is a cholinesterase regenerator tx. organophosphate poisioning |
|
|
Cholinesterase inhibitors can be:
|
a) Reversible:
carbamates (physostigmine and neostigmine) alcohols (edrophonium) others (donepezil) b) Irreversible: organophosphates (organophosphorus derivatives) |
|
|
CHOLINESTERASE INHIBITOR
Mechanism of action |
- Anti-ChE substrates for acetylcholinesterase and butyrylcholinesterase.
-affinity of enzymes for Anti-ChE is higher than for acetylcholine, therefore inhibit both enzymes. - most pharmacological effects Anti-ChE via inhibition acetylcholinesterase |
|
|
Mechanism of action Reversible inhibitors
|
a) Edrophonium prevents Ach access.
b) Carbamates undergo a two-step hydrolysis the carbamoylated enzyme is more resistant to hydrolysis and the second step is more prolonged (1-6 hours). c) some quaternary carbamates (i.e. neostigmine) directly activate nicotinic receptors at NMJ |
|
|
Mechanism of action Irreversible inhibitors
|
Organophosphates bind esteratic site.
-phosphorylated enzyme stable. -phosphorus-enzyme bond is strengthened by loss of a alkyl group = aging -return acetylcholinesterase activity depends on synthesis of new enzyme. |
|
|
CHOLINESTERASE INHIBITORS EFFECTS ON
CNS |
-increased alertness,
- stimulation various central activities. After high doses: confusion, ataxia, loss of reflexes, generalized convulsions, coma central respiratory paralysis. |
|
|
CHOLINESTERASE INHIBITORS
EFFECTS ON Eye, respiratory GI GU |
Parasympathetic is the predominant tone
increase dumb bels |
|
|
CHOLINESTERASE INHIBITORS
EFFECTS ON Cardiovascular system |
-stimulation SNS & PSNS ganglia
activation M3 vascular beds activation M2 heart release epinephrine from adrenal medulla bradycardia (but tachycardia can occur if signs of Nn activation prevail) |
|
|
CHOLINESTERASE INHIBITORS EFFECTS ON
Neuromuscular junction |
increased strength of contraction.
|
|
|
CHOLINESTERASE INHIBITORS
ABSORPTION |
Oral bioavailability:
a) good for tertiary amines(i.e. physostigmine) b) low for quaternary ammonium compounds (i.e. neostigmine, edrophonium) c) very good for organophosphates - Most organophosphates are well absorbed by all routes including the skin. |
|
|
CHOLINESTERASE INHIBITORS DISTRIBUTION
|
-Tertiary amines enter the CNS.
- Quaternary compounds peripheral tissues. -Organophosphates are distributed in all tissues. |
|
|
CHOLINESTERASE INHIBITORS BIOTRANSFORMATION
|
- Carbamates are hydrolyzed by plasma esterases.
paraoxonases: hydrolyze Organophosphates found in plasma and liver |
|
|
CHOLINESTERASE INHIBITORS EFFECTS ON
CNS |
-increased alertness
- stimulation various central activities. After high doses: confusion ataxia loss of reflexes generalized convulsions coma central respiratory paralysis |
|
|
CHOLINESTERASE INHIBITORS Adverse effects
|
same direct acting cholinomimetics.
fatigue, muscle cramps, fasciculations - When given locally for tx glaucoma, cataract adverse effect |
|
|
CHOLINESTERASE INHIBITORS Acute poisoning
|
- S & S via recptor activation of:
peripheral muscarinic, nicotinic central cholinergic - S & S apper rapidly -death due to: primary respiratory failure, secondary cardiovascular component -diagnose by cholinesterase activity in plasma and erythrocytes - The treatment always include: a) Maintenance of vital signs administration of oxygen b) Alleviation convulsion w/ diazepam c) Administration atropine d) Administration of cholinesterase reactivators (in case of poisoning by organophosphates) |
|
|
CHOLINESTERASE INHIBITORS
EFFECTS ON Eye, respiratory GI GU |
Parasympathetic is the predominant tone
increase dumb bels |
|
|
CHOLINESTERASE INHIBITORS
EFFECTS ON Cardiovascular system |
-stimulation SNS & PSNS ganglia
activatio M3 vascular beds activation M2 heart release epi adrenal medulla bradycardia (but tachycardia can occur if signs of Nn activation prevail) |
|
|
CHOLINESTERASE INHIBITORS EFFECTS ON
Neuromuscular junction |
increased strength of contraction.
|
|
|
CHOLINESTERASE INHIBITORS
ABSORPTION |
Oral bioavailability:
a) good for tertiary amines(i.e. physostigmine) b) low for quaternary ammonium compounds (i.e. neostigmine, edrophonium) c) very good for organophosphates - Most organophosphates are well absorbed by all routes including the skin. |
|
|
CHOLINESTERASE INHIBITORS DISTRIBUTION
|
-Tertiary amines enter the CNS.
- Quaternary compounds peripheral tissues. -Organophosphates are distributed in all tissues. |
|
|
CHOLINESTERASE INHIBITORS BIOTRANSFORMATION
|
- Carbamates are hydrolyzed by plasma esterases.
paraoxonases: hydrolyze Organophosphates found in plasma and liver |
|
|
CHOLINESTERASE INHIBITORS Adverse effects
|
same as direct acting cholinomimetics +
fatigue, muscle cramps, fasciculations - When given locally for tx glaucoma cataract = adverse effect |
|
|
CHOLINESTERASE INHIBITORS Acute poisoning
|
- S & S due to recptor activation of:
peripheral muscarinic, nicotinic central cholinergic - S & S apper rapidly -death due to: primary respiratory failure,secondary cardiovascular component -diagnose by cholinesterase activity in plasma & RBC - The treatment always include: a) Maintenance of vital signs administration of oxygen b) Alleviation convulsion with diazepam c) Administration of atropine d) Administration cholinesterase reactivators (in case of poisoning by organophosphates) |
|
|
POISONING BY CHOLINESTERASE INHIBITORS
Effects on organ systems |
Eye
Miosis, lacrimation, ocular pain, conjunctival congestion, ciliary spasm, brow ache, impaired vision. Respiratory system Rhinorrhea, increased salivary and bronchial secretions, laryngospasm, bronchospasm, paralysis of diaphragm and intercostal muscles, central respiratory depression. Skin Sweating, flushing and warmth of the skin. Skeletal muscle Fasciculation, weakness, paralysis. GI systems Nausea and vomiting, abdominal cramps, diarrhea, involuntary defecation and urination. Genitourinary system Involuntary urination, penile erection. Cardiovascular system Bradycardia, hypotension, cardiac arrhythmias. CNS Ataxia, slurred speech, loss of reflexes, generalized convulsions, coma. |
|
|
POISONING BY CHOLINESTERASE INHIBITORS
Effects on organ systems |
Eye
Miosis, lacrimation, ocular pain, conjunctival congestion, ciliary spasm, brow ache, impaired vision. Respiratory system Rhinorrhea, increased salivary and bronchial secretions, laryngospasm, bronchospasm, paralysis of diaphragm and intercostal muscles, central respiratory depression. Skin Sweating, flushing and warmth of the skin. Skeletal muscle Fasciculation, weakness, paralysis. GI systems Nausea and vomiting, abdominal cramps, diarrhea, involuntary defecation and urination. Genitourinary system Involuntary urination, penile erection. Cardiovascular system Bradycardia, hypotension, cardiac arrhythmias. CNS Ataxia, slurred speech, loss of reflexes, generalized convulsions, coma. |
|
|
THERAPEUTIC USES OF CHOLINERGIC DRUGS ON
eye |
pilocarpine, carbachol, physostigmine
Open-angle glaucoma: to reduce intraocular pressure |
|
|
THERAPEUTIC USES OF CHOLINERGIC DRUGS ON
eye |
pilocarpine, carbachol, physostigmine
Open-angle glaucoma: to reduce intraocular pressure |
|
|
THERAPEUTIC USES OF CHOLINERGIC DRUGS ON
neuromuscular system diagnosis: Myasthenia gravis |
- Edrophonium IV is used:
a) to confirm diagnosis: + test = brief improvement in muscular strength b)cholinergic crisis (further decrease in muscular strength) VS. myasthenic crisis (improved muscular strength). -treatment - Neostigmine, pyridostigmine, ambemonium (PO). - Atropine to control muscarinic effects. |
|
|
THERAPEUTIC USES OF CHOLINERGIC DRUGS ON
neuromuscular system diagnosis: Myasthenia gravis |
- Edrophonium IV is used:
a) to confirm diagnosis: + test = brief improvement in muscular strength b)cholinergic crisis (further decrease in muscular strength) VS. myasthenic crisis (improved muscular strength). -treatment - Neostigmine, pyridostigmine, ambemonium (PO). - Atropine to control muscarinic effects. |
|
|
pilocarpine,
bethanechol treat |
Xerostomia
|
|
|
pilocarpine,
bethanechol treat |
Xerostomia
|
|
|
THERAPEUTIC USES OF CHOLINERGIC DRUGS
other uses |
-counteract peripheral & central effects of poisoning by antimuscarinic drugs
-reverse paralysis induced by nondepolarizing neuromuscular relaxants, after surgery. |
|
|
THERAPEUTIC USES OF CHOLINERGIC DRUGS
other uses |
- counteract peripheral & central effects of poisoning by antimuscarinic drugs
- reverse paralysis induced by nondepolarizing neuromuscular relaxants, after surgery. |
|
|
bethanechol, neostigmine treat
|
-Postoperative nonobstructive ileus
-Postoperative and postpartum urinary retention -Neurogenic bladder |
|
|
bethanechol, neostigmine treat
|
-Postoperative nonobstructive ileus
-Postoperative and postpartum urinary retention -Neurogenic bladder |
|
|
Donepezil treat
|
selective inhibitor acetylcholinesterase in brain
little effect on peripheral acetylcholinesterase. slows deterioration cognitive function, improving performance in early stages AD, |
|
|
Donepezil treat
|
a selective inhibitor of acetylcholinesterase in brain
little effect on peripheral acetylcholinesterase. slows deterioration of cognitive function, improving performance in early stages AD |
|
|
cholinomimetics
-Carbachol -Pilocarpine -Physostigmine |
-Increased aqueous humor outflow
through Schlemm’s canal |
|
|
cholinomimetics
-Carbachol -Pilocarpine -Physostigmine |
-Increased aqueous humor outflow
through the Schlemm’s canal |
|
|
CONTRAINDICATIONS OF CHOLINESTERASE INHIBITORS
|
- Seizure disorder.
- Parkinson disease - GI and urinary tract obstruction, - inflammatory bowel disease, peritonitis. - Cholinergic crisis in the myasthenic patient. - Asthma, COPD. - Hypotension, cardiac arrhythmias, coronary artery disease, myocardial disease. - Peptic ulcer disease. - Hyperthyroidism. . |
|
|
CHOLINESTERASE INHIBITORS
therapeutic uses |
Poisoning by organophosphate insecticides
|
