Midterm Chapter 5 Cholinergic Antagonist Flashcards
General term for AGENT THAT BIND TO CHOLINOCEPTORS and PREVENT THE EFFECT OF ACETYLCHOLINE and other cholinergic agonist
Cholinoceptor Antagonists
Selective blockers of Muscarinic receptors
Anticholinergic Agent
also known as “Antimuscarinic agent or “muscarinic receptor”
Anticholinergic Agent
affinity to muscarinic receptor but no intrinsic activity
anticholinergic Agent
also known as “hyoscyamine”
Atropine
Prototype of Antimuscarinic Drug
Atropine
Plant Source:
English Name- (Scientific Name)
deadly Nightshade- (SCIENTIFIC NAME)
Jamestown weed/jimsonweed.sacred datura/thorn apple- (SCIENTIFIC NAME)
local Source:
Talumpunay - (SCIENTIFIC NAME)
Plant Source:
English Name- (Scientific Name)
deadly Nightshade- (Atropa belladona)
Jamestown weed/jimsonweed.sacred datura/thorn apple-(Datura stramonium)
local Source:
Talumpunay - (Datura metel)
NOTE AND EXPLANATION!
MOA of Atropine:
Causes reversible (summountable(overcome)) blockade of cholinomimetic action at muscarinic receptor
In short:
its MOA it binding to muscarinic receptor thereby blocking the effects of acetylcholine and other cholinomimetic drug, mag bind lang siya, pero walang activation, walay dUMMBELLS mahitabo
….
ACTION OF ATROPINE:
Action last about ___ hours except when
Topically in the eye, where the action may last for _____
Action last about 4 hours except when
Topically in the eye, where the action may last for days
AFFECT OF ATROPINE IN SPECIFIC ORGAN
EYE
GASTROINTESTINAL TRACT
CARDIOVASCULAR SYSTEM
RESPIRATORY SYSTEM
GENITOURINARY TRACT
SWEAT GLANDS
CENTRAL NERVOUS SYSTYEM
NOTE ONLY!
EYE:
-Mydriasis
-cycloplegia
-cannot focus for near vision
-contraindicated in glaucoma
-Reduce lacrimation -“dry or sandy eyes”
…
an Italian term means “beautiful lady”
belladona
it means weaken contraction of the ciliary muscle
cycloplegia
it means to dilate pupil cosmetically and was name belladonna
Mydriasis
NOTE ONLY!
Gastrointestinal tract
-Xerostomia
-Pepsin, acid and mucin- reduce volume and amount
-antispasmodic
-decrease motility-intestinal paralysis
-now rarely used for peptic ulcer
-lomotil (r) = Atropine + diphenoxylate =treatment for Traveler’s Diarrhea and hypermotility treatment
…
NOTE ONLY!
Loperamide and Buscopan is also a anticholinergic drug
…
lomotil(r) is now reformulated and was name in today as…..
loperamide
it means dry mouth
Xerostomia
it means to relax muscle spasm and cramps
Antispasmodic
lomotil (r)= atropine + _________
diphenoxylate
NOTE ONLY!
Cardiovascular
-has little effect on Blood pressure
-Bradycardia- lowdose
-tachycardia-highdose
…..
Bradycardia low doses - has____ ____ beats per minutes
has less 60 BPM
Tachycardia high doses - has____ ____ beats per minutes
has exceed 100 BPM
Normal Heart rate
60-100 BPM
High dose effect of Atropine in Cardiovascular System?
Tachycardia
Low dose effect of Atropine in Cardiovascular System?
Bradycardia
Note Only!
Resperatory System-Atropine
-Bronchodilation
-Used in Asthmatic and COPD Patients
…
Respiratory System can cause ——-, in response to Atropine
Bronchodilation
Note Only!
GenitoUrinary Tract
-Relaxes smooth Muscles of the ureters and bladder wall
-Urinary retention
…
Inability to empty the bladder completely
Urinary retention
Note Only!
Sweat Glands
-Suppresses thermoregulatory sweating
-block the nerve signals that stimulates sweating
-“atropine fever”
-Hyperhidrosis(Apocrine glands)
…
It means excessive sweating
Hyperhidrosis
Sweat Glands:
Effect of atropine in infant and children at ordinary dose
Atropine fever
What does atropine does to sweat glands?
Supresses thermoregulatory sweating
In Sweating, Which gland does armfit and genital belong?
Apocrine gland
In Sweating, Which gland does the “all over the body” belong to?
Eccrine Gland
Note only!
Effect of Atropine in CNS:( Normal Dose)
- Minimal Stimulant on CNS
-Sedative effect, slower, longer lasting on the brain
…
Antidote for cholinergic agonist poisoning
Atropine
Antidote for atropic toxicity
Physostigmine
Two Contraindication of Atropine
-Glaucoma
-Prostatic Hyperplasia
Note Only!
Clinical Application of Atropine( Used for)
-Mydriatic and cycloplegic agent
-antispasmodic
-Treatment for bradycardia
-antisecretory agent used before surgery
-antidote for cholinergic agonist poisoning
….
Note Only!
Adverse effect of Atropine:(Side Effect)
-Dry Mouth
-Blurred vision
-Sandy Eye
-Tachycardia
-urinary retention
-Constipation
-CNS Effect
-….
Scopolamine is also known as..
Hyoscine
Greater action in CNS than atropine
Scopolamine
Plant Source of Scopolamine
Hyoscyamus niger
Anti Motion Sickness Drug
Scopolamine
Common brand of scopolamine
Buscopan (r)
Note Only!
Scopolamine = Buscopan(R)
-“Hyosine” =Hyoscyamus niger
-Greater action in CNS than Atropine
-Anti-Motion Sickness Drug
-Sedation/Sedative
-High Dose- Euphoria and susceptable to abuse
THERAPEUTIC USES:
-Motion sickness (Topical Patch -3days)
-Postoperative nausea and vomiting
..
Drugs for Respiratory Disorders:
IpraTROPIUM
TioTROPIUM
Longer bronchodilators Action (Once Daily)
Tiotronium
Synthetic Analog of Atropine
Ipratronium
Inhalation drug in Asthma and COPD
Ipratronium
Ipratronium and Tiotronium is an example of……
Relaxant of Bronchial Smooth Muscle (BRONCHODILATORS)
Other Antimuscarinic Drug
-Oxybutinin= Ditropan (R)
-Trospium
-DariFENACIN and SoliFENACIN
-TolTERODINE and FesoTERODINE
-Imipramine
-Propiverine
Relieve blader spasm after prostatectomy
Reducing involuntary voiding in patient with neurological disease
Oxybutinin
Brand name of oxybutinin
Ditropan (R)
Nonselective antagonist
Trospium
Also comparable to SE and efficacy of oxybutinin
Trospium
Advantage of once- Daily dosing
DariFENACIN and SoliFENACIN
Adult with urinary Incontinence
TolTERODINE and FesoTERODINE
Tricyclic Antidepressant
Imipramine
Strong Antimuscarinic Function
Imipramine
LONG been use to reduce incontenence in INTITUTIONAL ELDERLY PATIENTS
Imipramine
NEWER ANTIMUSCARINIC DRUG approved to reduce incontinence in elderly patients
PROpiverine
Note Only!
Basic & Clinical Pharmacology of the Ganglion-Blocking Drugs:
-Nicotine
-Tetraetylammonium (TEA)
-Hexamethonium (Hypertention)
-Decamethonium (Carbon 10)
-Mecamylamine
-Trimethaphan
…
COMPETITIVELY BLOCK the action of acetylcholine and similar agonists at nicotinic receptors of both parasympathetic and sympathetic autonomic ganglia
Ganglion- Blocking drug
More Positive Inside the Cell (Na+) (More Active) that causes CNS stimulant
Depolarization
•Low dose – depolarizes autonomic ganglia – stimulation
•High dose – ganglionic blockade – blood pressure falls and GIT & bladder musculature ceases
NICOTINE
Nicotine:
Effect: ganglionic blockade – blood pressure falls and GIT & bladder musculature ceases
High Dose
Nicotine:
Effect: depolarizes autonomic ganglia – stimulation
Low Dose
First to recognized (Ganglion Blocking Drug) but
VERY SHORT DURATION
Tetraethylammonium (TEA)
First drug effective for management of HYPERTENSION
Hexamethonium
DEVELOP TO IMPROVED and Extend absorption from GI due to Quarternary amine ganglion
Secondary Amine
Mecamylamine
DEVELOP AND INTRODUCED clinically First drug effective for management of HYPERTENSION
Hexamethonium
“C10” analog of hexamethonium
Decamethonium
Blocking compound were poorly and erratically absorbed after oral administration
Quarternary Amine ganglion
Nicotine patch to reduce smoking cravings
Mecamylamime
Depolarizing neuromuscular blocking agent
Decamethonium
SHORT ACTING ganglion blocker
Trimethaphan
Inactive orally, given via IV infusion
Trimethaphan
Hypertensive emergencies and dissecting aortic aneurysm
Trimethaphan
MOA: unknown MOA in CNS
Effects: Reduces vertigo, post-operative nausea
CA: Prevention of motion sickness and postoperative N & V
Scopolamine
MOA: competitive antagonist at M3 receptor
Effects: Reduces smooth muscle and secretory activity of the gut
CA: Irritable bowel syndrome, minor diarrhea
DICYCLOMINE (Bentyl®)
longer duration of action
HYOSCYAMINE
- similar to dicyclomine
GLYCOPYRROLATE
MOA: competitive antagonist at all M receptors
Effects: mydriasis and cycloplegia
CA: Retinal examination
CI: Glaucoma
ATROPINE
MOA: Competitive, non-selective antagonist at M receptors
Effects: Reduces/prevents bronchospasm
CA: Prevention & relief of acute episodes of bronchospasms
IPRATROPIUM (Atrovent)
MOA: non-selective muscarinic antagonist
Effects: Reduces detrusor smooth muscle tone, spasms
CA: Urge incontinence, post-operative spasms
OXYBUTININ (Ditropan®)
mandatory antidote for sever cholinesterase inhibitor poisoning
Atropine
MOA: very high affinity for phosphorus atom but does not enter CNS
Effects: Regenerates active AChE; can relieve skeletal muscle and plate block
CA: Usual antidote for early stage (48hrs) cholinesterase inhibitor poisoning
PRALIDOXIME (Protopam)
•Pralidoxime (PAM) and diacetylmonoxime (DAM) given IV
•not recommended for poisoning caused by carbamates
Cholinesterase Regenerator Compounds
(PAM) and (DAM) means
Pralidoxime (PAM) and diacetylmonoxime (DAM
characterized by early signs of muscarinic excess
Muschroom poisoning
- apparent within 30 mins to 2 hrs after ingestion
Rapid -Onset Type
apparent within 30 mins to 2 hrs after ingestion muschroom poisoning antidote?
Atropine
Delayed-onset - usually caused by
-Amanita phalloides,
-A virosa, -
Galerina autumnalis,
-G marginata
..
Mushroom Poisoning
Delayed-onset - usually caused by Amanita phalloides, A virosa, Galerina autumnalis, G marginata
- first symptoms: 6-12 hours after ingestion
- major toxicity involves hepatic and renal cellular injury
- Atropine is of no use in this form of mushroom poisoning
…
•Block cholinergic transmission between motor nerve endings & nicotinic receptors on the skeletal muscle
NEUROMUSCULAR BLOCKING AGENTS
NEUROMUSCULAR BLOCKING AGENTS TYPES
Nondepolarizing (competitive) blockers – antagonist
Depolarizing agents – agonist
Notes only!
NONDEPOLARIZING BLOCKERS:
•Curare
•Tubocurarine
•Atracurium Cisatracurium
•Pancuronium
•Rocuronium
•Vecuronium
…
Mechanism of Action
•Low dose – competitively block ACh at the nicotinic receptor (reversed by cholinesterase inhibitors, i.e. neostigmine)
– employed by anesthesiologist to shorten the duration and monitor the extent of NM blockade
High dose – block the ion channels of the motor endplate
– cannot be reversed by cholinesterase inhibitors
– results to complete blockade, thus the muscles do not respond to direct electrical stimulation anymore
Actions
Sequence of paralyzed muscles:
•Small, rapidly contracting muscles of the face and eyes are most susceptible
•Fingers, limbs, neck, trunk muscles, intercostal muscles
•Diaphragm
** recovery follows the reverse manner
Adverse Effects
•Pancuronium – increased heart rate
Drug Interactions
•Cholinesterase Inhibitors
•Halogenated hydrocarbon anesthetics
•Aminoglycoside antibiotics
•Calcium channel blockers
….
DEPOLARIZING AGENT
•Works by depolarizing the plasma membrane of the muscle fiber, similar to the action of ACh
•Resistant to degredation by AChE
•SUCCINYLCHOLINE – only depolarizing muscle relaxant in use today
…
Mechanism of Action
•Attaches to the nicotinic receptors and acts like ACh
Phase I - causes the opening of Na channel which results to depolarization of the receptor (transient twitching of the muscle or fasciculation)
Phase II – continuous depolarization gives way to gradual repolarization as the Na channel closes or is blocked (flaccid paralysis)
Actions
•Initially produces brief muscle fasciculations causing muscle soreness
•Respiratory muscles are paralyzed last
•DOA – extremely short due to pseudocholinesterase
Therapeutic Uses
•Useful for rapid endotracheal intubation required during induction of anesthesia
•Electroconvulsive shock treatment
Adverse Effects
•Malignant hyperthermia – antidote: Dantrolene
•Apnea
•Hyperkalemia
Malignant hyperthermia – antidote:——
Dantrolene
