Download Free Medical Anticholinergic Drug PowerPoint Presentation

Anticholinergic Drug PowerPoint Presentation

DOWNLOAD MEDICAL POWERPOINT PRESENTATION

About This Presentation

Description : Check out this medical presentation on Pharmacology, which is titled "Anticholinergic drugs", to know about the anticholinergic drugs, ganglion blocking agents and neuromuscular blocking agents.

Tags : Pharmacology, Anticholinergic drugs, ganglion blocking agents, neuromuscular blocking agents

Published on : Jul 18, 2021 | Views : 3730 | Downloads : 12

Shareable Url :

Embed Code :

Comment

Transcript

Slide 1-

Medical University of Sofia, Faculty of Medicine Department of Pharmacology and Toxicology ANTICHOLINERGIC DRUGS, GANGLION BLOCKING AGENTS AND NEUROMUSCULAR BLOCKING AGENTS Assoc. Prof. I. Lambev E-mail: itlambev@mail.bg
Slide 2-

ANTICHOLINERGIC DRUGS (Muscarinic Receptor Antagonist, Parasympatholytics, Cholinolytics Atropine-like Drugs) Atropine, the prototype drug of this class, is a highly selective blocking agent for pre and postmuscarinic receptors, but some of its synthetic derivatives have significant nicotinic blocking proparty as well.
Slide 3-

Presynaptic receptors in adrenergic synapse and their role in the regulative negative and positive feedback Atropine (-)
Slide 4-

Atropine (-)
Slide 5-

50 100 150 200 A B C D 1 min Atropine blocks M-effects of ACh Blood pressure [mm Hg] ACh 2 mcg i.v. ACh 50 mcg ACh 50 mcg ACh 5 mg M- effect M- effect N- effect Atropine 2 mg i.v. ACh
Slide 6-

Tropane alkaloids Atropine Atropa belladonna L. (Deadly night shade) Cura bulgara (Ivan Raev) Scopolamine (Hyoscine) Solanine (in potatoes)
Slide 7-

Datura stramonium L. Hyoscyamus niger L. Jimson weed Henbane
Slide 8-

Carl von Linné (1707–1778) – binominal system (genus and species). 7700 plants!!! (Mr Flower Power)
Slide 9-

Action of atropine CNS. Atropine has an overall stimulant action. Its sti- mulant effects are not appreciable at low doses which produce peripheral effects because of restricted entry into the brain. Hyoscine produces central depressant effects even at low doses. Atropine stimulates many medullar centers – vagal, respiratory, and vasоmotor. By blocking the relative cholinergic overactivity in basal ganglia, it suppresses tremor and rigidity in parkinsonism. High doses cause cortical excitation, rest- lessness, disorientation, hallucinations, and delirium followed by respiratory depression and coma.
Slide 10-

CVS. Atropine causes tachycardia, due to blockade of M2-receptors on SA node through which vagal tone decreases HR. The tachycardia is more marked in young adults than in children and the elderly. Atropine shortens the refractory period of AV conduction, especially if it has been depressed by high vagal tone. Atropine does not influence BP. It blocks the vasodepressor action of cholinergic agonists. Eye. Topical instillation of atropine (0.1%) causes mydriasis, abolition of light reflex, and cycloplegia, lasting 7–10 days. This results in photophobia and blurring of near vision. The intraocular tension rises, specially in narrow angle glaucoma, but conventional systemic doses produce minor ocular effects.
Slide 11-

Autonomic control of pupil (A) and site of action of mydriatics (B) and miotics (C)
Slide 12-

Smooth muscles. All visceral smooth muscles with parasympathetic inervation are relaxed (M3-blokade). Tone and amplitude of GIT are reduced. Spasm may be reduced, constipation may occur. Peristalsis is only incompletely suppressed because it is primarily regulated by local reflexes and other neurotransmitters (serotonin, encephalin, etc.). Atropine causes bronchodilation and reduced airway resistance, especially in asthma patients. Inflammatory mediators (histamine, PGs, and kinins) increase vagal activity in addition to their direct action on bronchial muscle and glands. Atropine attenuates their action by antagonizing the reflex vagal component.It has a relaxant action on the ureter and urinary bladder. Urinary retention can occur in older men with prostatic hyperplasia.
Slide 13-

Glands. Atropine decreases sweat, salivary, tracheo- bronchial, and lacrimal secretion (M3-blockade). Skin and eyes become dry, talking, and swallowing my be very difficult. Atropine decreases less the secretion of acid and pep- sin and more of the mucus in the stomach. Body temperature. Rise in body temperature occurs at higher doses, and is due to both inhibition of sweating as well as stimulation of the temperature regulating centre in the hypothalamus. Children are highly susceptible.
Slide 14-

Local anaesthetic action. Atropine has a mild anaesthetic action on the cornea. The sensitivity of different organs and tissues to atropine varies and can be graded as (Tripathy, 2003): saliva, sweat, bronchial secretion > eye > bronchial muscles > heart > intestinal and bladder smooth muscles > gastric glands and gastric smooth muscles
Slide 15-

Pharmacokinetics Atropine and hyoscine are rapidly absorbed from GIT. Applied to the eyes they penetrate the cornea. Passage across BBB is somewhat restricted. 50% of atropine is metabolized in the liver and excreted unchanged in urine. It has t1/2 3–4 h. Hyoscine is more completely metabolized and has better BBB penetration. Some rabbits have a specific atropine esterase which degrades atropine very rapidly.
Slide 16-

Unwanted effects: Dry mouth, difficulty in swallowing and talking; dry, flushed, and hot skin (especially over the face and neck); fever; difficulty in micturition; a scarlet rash may appear; dilated pupils, photophobia, blurring of near vision; palpitation; excitement, psychotic behavior, ataxia, delirium, hallucinations; hypotension, weak and rapid pulse, cardiovascular collapse with respiratory depression; convulsion and coma (in very high doses). Diagnosis: 1 mg neostigmine s.c. fails to induce typical M-effects. Treatment: Gastric lavage with tannic acid (KMnO4 is ineffective in oxidation of atropine). The patient must be kept in a dark quiet room. Galantamine or physo- stigmine (1-3 mg s.c./i.v.), diazepam against convulsion.
Slide 17-

Natural alkaloids: Atropine (spasmolytic, mydriatic), Hyoscine (Scopolamine), Scopoderm® TTS (antiemetic) 2. Semisynthetic derivatives Mydriatics: Homatropine GI spasmolytics: Hyoscine butyl bromide (Buscolysin®) 3. Synthetic compounds GI spasmolytics: Oxyphenonium Antiulcus drugs: Pirenzepine (M1-blockers) Antiasthmatics: Ipratropium and Tiotropium Antidisurics: Flavoxate, Oxybutynyne, Trospium Mydriatics: Tropicamide Antiparkinsonian (central M-cholinolytics): Benztropine, Biperiden, Trihexyphenidyl ANTICHOLINERGIC DRUGS
Slide 18-

Central М-cholinolytics: Biperiden Trihexyphenidyl They remove tremor and hypersa- livation. Atropine-like side effects! Indications: Drug induced (e.g. neuroleptics) parkinsonism Spastic paralysis Atropa belladonna L.
Slide 19-

Homatropine Tropicamide
Slide 20-

Primarily, the site of bronchodilation action of inhaled β2-adrenergic agonists is mainly the bronchiolar smooth muscle. Atropinic drugs cause bronchodilation by blocking cholinergic constrictor tone, act primarily in large airways. Anticholinergics in asthma Ipratropium Tiotropium
Slide 21-

ppt slide no 21 content not found
Slide 22-

Main interactions of anticholinergic drugs Absorption of more drugs is slowed because atropine delays gastric emptying. As a result the dose of levodopa, needed to control parkinsonism may have to be increased. But the extent of digoxin, and tetracyclines absorption may be increased. Antacids interfere with the absorption of anticholinergics. Antihistaminics, tricyclic antidepressants, pheno- thiazines, pethidine, etc. have anticholinergic property: additive side effects with atropinic drugs are possible. MAO inhibitors interfere with the metabolism of central antiparkinsonian drugs (biperiden and others): delirium may occur.
Slide 23-

Ganglion blocking agents - many side effecs - out of date
Slide 24-

Skeletal muscle relaxants act peripherally at neuromuscular junction. According to their action they are divided into the following groups. Nondepolarizing (competitive) agents or curare-like drugs Depolarizing (hyperdepolarazing) agents NEUROMUSCULAR BLOCKING AGENTS
Slide 25-

ppt slide no 25 content not found
Slide 26-

NEUROMUSCULAR BLOCKING AGENTS (1) Nondepolarizing (competitive) agents Long acting: d-Tubocurarine, Pancuronium, Doxacurium, Pipecuronium Intermediate acting: Atracurium, Vecuronium Short acting: Mivacurium (2) Depolarizing agents Suxamethonium (Succinylcholine) Decamethonium (C-10)
Slide 27-

Competitive (curare-like) blocking agents N+ (14 Å) N+ GI resorption BBB
Slide 28-

Curare is plant extract from Chondrodendron tomentosum, Strychnos toxifera etc. It is used by South America tribals as arrow poison for game hunting. The animals got pa- ralyzed even if not killed by the arrow. Muscle paralyzing active principles of curare are alkaloids tubocurarine, toxiferine etc.
Slide 29-

Strychnos toxifera Chondrodendron tomentosum The South Americam lianas
Slide 30-

The competitive blockers have affinity for the nicotinic (NM) cholinoceptors at the muscle end-plate, but no intrinsic activity. The NM-receptor is a macroprotein with 5 subunits, which are arranged like a rosette surrounding the Na+ channel. The two alpha subunits carry two ACh binding sites with nega- tively charged groups which combine with the cationic group of ACh and open Na+ channel.
Slide 31-

Competitive (nondepolarizing) block Most of the competitive blockers have two or more quarternary N+ atoms which provide the necessary attraction to the same site, but the bulk of the antagonist molecule does not allow conformational changes in the subunits needed for opening the channel. Competitive blockers generally have thick bulky molecules and were termed Pachycurare by Bovet (1951). ACh esterase released from motor nerve endings is not able to combine with its NM-receptors to generate end-plate potential (EPP).
Slide 32-

N+: quarter- nary N-atom
Slide 33-

Depolarizing block Succinylcholine (SCh) and decamethonium have affinity as well as submaximal intrinsic activity at the NM-cholinoceptors. They depolarize muscle end- plates by opening Na+ channels (just as ACh does) and initially produce twitching and fascilations. These drugs do not dissociate rapidly from the receptor, induce prolonged partial depolarization of the region around muscle end-plate, and inactivation of Na+ channels. Depolarizing agents also have two quaternary N+ atoms but their molecule is long, slender, and flexible. They are termed Leptocurare by Bovet (1951).
Slide 34-

Depolarizing agents produce dual mechanism neuro- muscular blockade which can be divided in two phases: Phase I block. It is rapid in onset, results from persistent depolarization of muscular end-plate and has features of depolarization blockade. Phase II block. It is slow in onset and results from desensitation of the NM-receptor to ACh. It superficially resembles block produced by tubocurarine. Effects of neuromuscular blocking drugs Skeletal muscles. Intravenous injection of competitive blockers rapidly produces muscle weakness, followed by flaccid paralysis. Small fast response muscles (fingers, extraocular) are affected first. Paralysis spreads to hands, feet, arm, leg, neck, face, trunk,
Slide 35-

intercostal muscles, diaphragm, and respiration stops. Recovery occurs in the reverse sequence: diaphragmatic contractions resume first. Depolarizing agents produce fasciculations , lasting few seconds before inducing flaccid paralysis, but fasciculations are not prominent in well anaesthetized patients. The action of SCh develops very rapidly. Apnoea occurs within 45–90 sec, but lasts only 2–5 min and recovery is rapid. Autonomic ganglia. Competitive blockers can produce some degree of ganglionic blockade. SCh as an ago- nist of N-receptors may cause ganglionic stimulation. Histamine release with hypotension and broncho- spasm can cause tubocurarine from the mast cells. This does not involve the immune system.
Slide 36-

CVS. Tubocurarine produces significant fall in BP and sometimes – tachycardia (due to vagal ganglionic blockade). SCh initially produces bradycar- dia due to activation of vagal ganglia, followed by tachycardia and rise in BP, due to stimulation of sympathetic ganglia. GIT. The ganglion blocking action of competitive agents may enhance postoperative paralytic ileus after abdominal operations. Pharmacokinetics All neuromuscular blockers are quaternary compounds. They are not absorbed in GIT, do not cross placental, and BBB. The unchanged drug is excreted in urine, and bile.
Slide 37-

Indications The most important use of neuromuscular blockers is as adjuvant drugs to general anaesthesia. Surgical procedures are performed more safely and rapidly. SCh is rapidly hydrolyzed by plasma pseudocholin- esterase to succinylmonocholine and then to succinic acid and choline (the action lasts 3–5 min). Some patients (1:3000) have genetically determined abnormality (low affinity for SCh) or deficiency of pseudocholin- esterase. In these patients SCh causes dominant phase II blockade, resulting in muscle paralysis and apnoea, lasting hours. In this case the intubation of the patient must be continuous until full recovery.
Slide 38-

The competitive neuromuscular blockers are particularly helpful in abdominal and thoracic surgery, intubation and endoscopies, orthopedic procedures. SCh is employed for brief procedures, e.g. endotracheal intubation, laryngoscopy, bronchoscopy, esophagoscopy, reduction of fractures, and dislocations. SCh is mostly used to avoid convulsions and trauma from electroconvulsive therapy. In severe cases of tetanus and status epilepticus, which are not controlled by diazepam or other anticonvulsive drugs, competitive neuromuscular blockers are used.
Slide 39-

Main drug interactions There is in vitro incompatibility between SCh and thiopental (thiopentone). General anaestetics, aminoglysides (gentamicin, etc.) and hypokalemic diuretics potentiate competitive blockers. Anti-ChEs (galantamine, neostigmine) and amino- pyridine (Pymadine®) reverse the action of competitive neuromuscular blockers. SCh potentiates malignant hyperthermia, produced by halothane. SCh has not any antagonists. Calcium channel blockers potentiate both depolarizing and nondepolarizing neuromuscular blockers. Sympathomimetics (adrenaine, etc.) reduce the competitive block by increasing ACh release.
Slide 40-

Depolarizing agents
Slide 41-

Action of succinylcholine (suxamethonium) Toxicity Cardiac arrhythmias Prolonged apnoea Malignant hyperthermia (which needs treatment with directly acting muscle relaxant Dantrolene i.v.)