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Onset of symptoms is rapid Nicotinic receptors desensitize very quickly (w/in seconds) Initial: salivations, nausea, vomiting, abdominal pain, diarrhea, loss of urine and feces, cold sweat, tachypnea, tachycardia, disturbed hearing and vision, headache, dizziness, mental confustion, marked weakness Progress to --> faintness and prostration, falling of BP, weak, irregular and rapid pulse, difficulty in breathing, tremors, convulsions --> death from respiratory failure within minutes
Acute OD of antimuscarinic How would death occur?
Think 3 C's Convulsions, Coma, Cardiac *for this to occur it can be quaternary compound...must be tertiary so that it crosses BBB Death due to respiratory failure, may follow after a period of ciculatory collapse and coma In cases of serious poisioning, symptoms and signs appear within 30-60 minutes and may last 2-7 days
Anti-muscarinic effect of respiratory system
bronchial smooth muscle relaxation decreased secretions decreased mucociliary clearance
Anti-muscarinic effect of skin 4a .
decreased secretion of sweat glands (atropine fever) 4b .
Anti-muscarinic effect on Eye 5a .
relax sphincter of iris --> mydriasis relax ciliary muscle --> cycloplegia (hinders outflow of aqueous humor through Schlemm canal) decreased secretion of lacrimal glands Atropine given locally can last for 3 days or more 5b .
Anti-muscarinic effect on Genitourinary system 6a .
relax pelvis. ureters decrease ureteral peristalsis relax detrusor 6b . calyces.
Anti-muscarinic effect on GI 7a .
decrease gastric secretion decrease tone. amplitude of contractions. peristaltic activity and secretions of intestinal tract relax LES mild relaxation of gallbladder and bile ducts 7b .
Antimuscarinic therapeutic dose on CV vessels? High dose? 8a .
can cause "dilitation" = atropine flush high doses --> dilitation of cutaneous blood vessels (atropine flush) 8b ..therapeutic dose --> negligible effects on circulation in kids..
Atropine Scopolamine Homatropine Darifenacin Benzotropine 9a .
Tertiary Amine (enters CNS) Anti-muscarinic drugs *Actually. atropine and scopolamine are natural alkaloids found in several plants (jimsonweed. deadly nightshade) 9b .
Biotransformation Exretion Half-lives Anti-muscarinic drugs 10a .
50% atropine and 90% scopolamine are metabolized by liver 60% atropine excreted by kidney Atropine/scopolamine = 3 hour half life Glycopyrrolate = 10 hours 10b .
Carbachol Cholinesterase inhibitors Succinylcholine Glycopyrrolate Ipratropium Tubocurarine 11a .
Drugs with significant ganglionic activity as side effects 11b .
Darifenacin what class of drug is it? which receptor does it have the highest affinity for? 12a .
tertiary amine M3 12b .Anti-muscarinic .
Diarrhea Sialorrhea Motion sickness prevention and treatment (scopolamine) Urinary system Renal colic. biliary colic. choroiditis Gastrointestinal system Irritable bowel syndrome Abdominal colic. enuresis Urge incontinence Respiratory system Preoperative use Bronchial asthma and chronic obstructive pulmonary disease (ipratropium) Cardiovascular system Cardiopulmonary resuscitation Sinus or nodal bradycardia A-V block Preoperative use 13a .Eye For funduscopic examination For measurements of refractive errors Iritis. iridocyclitis.
.Therapeutic uses of antimuscarinic drugs again.. 13b . Poisoning by AchE inhibitors or by certain mushrooms containing muscarine.just think logically about each one ALSO: Central nervous system Parkinson's disease (Trihexyphenidyl) Other uses To counteract the parasympathomimetic effects of neostigmine in myasthenic patients.
Ganglionic stimulant drug 14a .
Nicotine 14b .
Give 5adjectives for features of poisinoning with anti-cholinergics 15a .
RED = vasodilation HOT = vasodilation and hyperthermia DRY = reduced sweating. fluid intake & dehydration BLIND = cycloplegia and mydriasis MAD = delirum 15b . salivation.
Glaucoma Prostatic hypertrophy Urinary tract obstruction Gastrointestinal tract obstruction Adynamic ileus Gastric ulcer Severe infectious diarrhea Reflux esophagitis Ulcerative colitis. Crohn' disease (toxic megacolon can ensue) Tachyarrhythmias Coronary artery disease. cardiac failure Hyperthyroidism Children Elderly 16a .
List of contraindications and precautions of antimuscarinic drugs just think about what is going on with each and think logically why you wouldnt want to give anti-muscarinic 16b .
Glycopyrrolate Ipratropium 17a .
Quaternary ammonium compounds (no CNS) Anti-muscarinic drugs 17b .
Half life of nictoine 18a .
2 hours 18b .
KAPLAN FACT Someone on Atropine can develop what in heart/ekg 19a .
QT interval) (Torsa De Pointes) --> cardiac toxicity Treat torsa de pointes with Mg!!! 19b .Tachycardia (ventricular) (Inc. QRS) (Inc.
KAPLAN FACT What are some other categories of drugs that have anti-cholinergic side effects 20a .
Antihistamines Tricyclic anti-depressants Anti-psychotics Qunidine Amantadine Meperidine (opiate) 20b .
KAPLAN FACT: Tropicamide 21a .
Anti-muscarinic drug used topically eye drops --> shorter dilation of eye preferred over Atropine b/c of shorter half-life 21b .
Lets Play a game: What branch of ANS provides the predominant tone? and what would happen if i used a ganglionic blocker Heart Arterioles Veins Iris Ciliary Muscle GI Tract Urinary bladder Exocrine glands Ejection Ejaculation 22a .
decr CO Iris --> PNS --> Mydriasis Ciliary Muscle --> PNS --> cycloplegia GI Tract --> PNS--> constipation.Heart --> PNS --> Tachycardia Arterioles --> SNS --> vasodilation. venous pooling. gas accumulation Urinary bladder --> PNS --> urinary retention Exocrine --> SNS --> anhydrosis Ejection --> PNS --> impaired Ejaculation --> SNS --> impaired 22b . orthostatic hypotension Veins --> SNS --> vasodilation.
Mecamylamine 23a .
Ganglionic blocking drugs 23b .
Moderate dose of nicotine given Effect on GI? High dose? 24a .
nausea.anorexia. vomiting stimulation of peristalsis and secretions Toxic doses --> paralytic ileus 24b .
Moderate dose of nicotine? high dose? effect on Respiratory 25a .
stimulation of respiration bronchoconstriction and increased secretions Toxic --> apnea 25b .
Moderate doses of nicotine given: What affect on CV system? How bout high/toxic doses? 26a .
Increase CO and HR Constriction of skin and splnachnic vessels Dilation of muscular vessels Increased BP Toxic --> cardiovascular collapse 26b .
Name as many antimuscarinic drugs as you can 27a .
Atropine (natural) Scopolamine (natural) Homatropine (3) Darifenacin (3) Benzotropine (3) Glycopyrrolate (4) Ipratropium (4) 27b .
Pharmacologic paralysis of accomodation with the use of atropine works restoring visual acuity in children with _________? 28a .
lazy eye (which occurs in 50% of kids with esotropia/strabismus/squint Atropine eyedrops blur the healthy eye at near vision and force fixation of the amblyopic eye 28b .Amblyopia .
Pharmacological Effects of Nicotine on CNS 29a .
tremors. convlusions 29b .stimulate Renshaw cells (inhibitory interneurons of LMNs) stimulate or depress reticular formation direct and reflex stimulation of respiratory and vasomotor centers reflex stimulation of the emetic center direct stimulation of the chemoreceptor trigger zone stimulation of ADH secretion Mild Stimulation of attention and memory sedative-anxiolytic activity generalized stimulation of cerebrospinal axis which leads to hyperreflexia.
SCOPOLAMINE uses 30a .
(tertiary amine) Used for motion sickness opthalmology sedation and short-term memory block (anterograde amnesia) 30b .
So if i give someone an antimuscarinic drug: how would an intermediate dose affect their CNS? How about a high dose? 31a .
restlessness. Central stimulation followed by depression (coma) 31b . drowsiness. irritability. dreamless sleep depression of vestibular function reduction of parksonian tremor and rigidity High dose amnesia. sedation. delirium. hallucinations.Intermediate: mild central vagal stimulation fatigue. disorientation. malaise.
.what are signs and symptoms in each of the different organs 32a .Someone has been poisoned by a antimuscarinic drug..
eye --> mydriasis. delirium. difficulty swallowing. dyspnea. respiratory depression skin --> dry. absence of bowel sounds. palpitations. dryness respiratory --> trouble speaking. paralytic ileus Urinary systems --> difficulty in micturition CV --> tachycardia. coma 32b . arrhythmia CNS --> fatigue. generalized convulsions. blurring of near vision. thirst. hallucinations. restlessness. ataxia. headache. hot and red skin GI systems --> dryness of mouth.
Stimulation of sweat glands miosis induction of mixed function oxidases increased platelet aggregation and blood coagulability loss of body wt increased hand tremors paralysis of skeletal muscle 33a .
Nicotine effects 33b .
this antimuscarinic drug is used to treat parkinson's 34a .
Benztropine (tertiary amine) 34b .
This ganglionic blocker May be used to treat Tourette's syndrome 35a .
Mecamylamine 35b .
This ganglionic blocking dug is a secondary amine taken orally 36a .
Mecamylyamine 36b .
IV only 37a .This is a short acting ganglion blocker.
Trimethaphan 37b .
This is the prototype ganglionic blocking drug 38a .
Hexamethonium (quaternary ammonium) 38b .
This Quaternary antimuscarinic drug is primarily used to treat bronchospastic disorders like asthma/copd 39a .
.just decreases amount 39b ..Ipratropium *wont change mucus viscosity.
and visceral hypermotility and spasms 40a . sedation.This Quaternary antimuscarinic drug is used to treat CV disorders.
Glycopyrrolate 40b .
..This teriary amine anti-muscarinic is Used to treat neurogenic bladder and urinary urge incontinence Recall which receptors are involved. 41a .
Darifenacin M3 in detrussor --> increases motility and tone M3 in trigone/sphincter --> relaxaton
True or false Atropine's affinity for Muscarinic Receptors does not change among the different types (M1,M2,M3)
True so does Scopolamine High affinity for M1, M2 and M3
Urinary system effects if given nicotine 43a .
decreased diuresis contraction of detrusor muscle relaxation of trigone and internal sphincter of urethra 43b .
What effect does an antimuscarinic have on the SA-Node at low doses? intermediate doses? antimuscarin on atria? av node? ventricles? 44a .
Low --> decrease heart rate Intermediate --> tachycardia atira --> increase automaticity and contractility av node --> increase conduction and automaticity. decrease in refrractoriness ventricles --> minimal direct effects on myocardial cells 44b .
What is a ganglionic blocking drug 45a .
Mecamylamine Trimethaphan Hexamethonium 45b .
What is the antidote of Atropine OD 46a .
Physostigamine (tertiamy amine .crosses CNS) this is acetylcholinesterase inhibitor 46b .
Where are nictonic receptors located? 47a .
and pain receports 47b . aortic arch. skin/ tongue/lung...autonomic ganglia nmj presynaptic nerve terminals adrenal medulla cns Nictonie also stimulates sensory receptors of carotid bodies.
Which of the following would have the highest affinity for a nicotinic receptor? atropine ipratropium darifenacin 48a .
Ipratropium (also Glycopyrrolate) Think quaternary compounds All 3 are anti-muscarinic 48b .
Which organs are sensitive to high dose atrophine 49a .
ciliary muscle 49b . sphincter muscle of eye. and bladder smooth muscle gastric glands CNS (excitation) Heart.Intestinal. bronchial.
Which organs are sensitive to intermediate dose atrophine 50a .
salivary and sweat glands 50b .Heart (M2 receptors) Sphincter muscle of iris Ciliary Muscle CNS (depression) lacrimal.
Which organs are sensitive to low dose atropine? 51a .
Heart (M2 autoreceptors on parasympathetic terminals). salivary and sweat glands 51b . lacrimal.
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