Cholinoceptor-Blocking Drugs By M.H.Farjoo M.D. , Ph.D.Shahid Beheshti University of Medical Science
Cholinoceptor-Blocking Drugs Introduction Classification Organ Effects & Clinical Applications Antimuscarinic Antinicotinic Intoxication Drug Pictures
Schematic diagram comparing some anatomic andneurotransmitter features of autonomic and somatic motornerves. Only the primary transmitter substances are shown.Parasympathetic ganglia are not shown because most areof vessels Smooth muscle residing in skeletal musclein or near the wall of the organ innervated. Cholinergicnerves are shown in blue; noradrenergic in red; anddopaminergic in green. Note that some sympatheticpostganglionic fibers release acetylcholine or dopaminerather than norepinephrine. The adrenal medulla, amodified sympathetic ganglion, receives sympatheticpreganglionic fibers and releases epinephrine andnorepinephrine into the blood. ACh, acetylcholine; D,dopamine; Epi, epinephrine; M, muscarinic receptors; N,nicotinic receptors; NE, norepinephrine.
General effects ofParasympatheticstimulation:
General effects ofanticholinergic Drugs:
Introduction Antimuscarinic agents block exogenous muscarinic stimulants better than the effects of parasympathetic (Vagal) nerve activity. The non polar antimuscarinic drugs are used for their effects on the eye or the CNS.M.H.Farjoo
Introduction Cont,d Atropine & Scopolamine (hyoscine) are highly selective for muscarinic receptors. Tissues most sensitive to atropine are the salivary, bronchial, and sweat glands. Many antihistaminic, antipsychotic and antidepressant drugs have similar structures and antimuscarinic effects.M.H.Farjoo
Atropine (oxygen at  is missing)Scopolamine (oxygen present).
Effects of atropine on various organs. Salivation is the mostsensitive to atropine and accommodation is the least.
Effects of atropine on salivary flow.The parasympathomimetic effect is attributed to blockade ofprejunctional inhibitory muscarinic receptors.
Antimuscarinic Organ Effects & Clinical Applications CNS Eye Cardiovascular System Respiratory System Gastrointestinal Tract Genitourinary Tract Sweat Glands Cholinergic PoisoningM.H.Farjoo
CNS Scopolamine rapidly enters the CNS and has greater effects than other antimuscarinic drugs. Scopolamine produces drowsiness and amnesia in sensitive individuals. In toxic doses, scopolamine can cause excitement, agitation, hallucinations, and coma.M.H.Farjoo
CNS Cont,d Motion sickness involves muscarinic transmission. Scopolamine is effective in preventing or reversing these disturbances. Useful doses by any route cause marked sedation and dry mouth. Benztropine is sometimes used for parkinson treatment.M.H.Farjoo
Effects of topical scopolamine drops on pupildiameter and accommodation.
Eye Antimuscarinic drugs cause mydriasis and cycloplegia which impairs accommodation for near vision. Long acting antimuscarinic drugs should never be used for mydriasis unless cycloplegia or prolonged action is required. Scopolamine effect on the iris and ciliary muscle persist for 72 hours. Cyclopentolate (Cyclogyl) and Tropicamide (Mydriacyl) are short acting mydriatics.M.H.Farjoo
Eye Cont,d Homatropine is very valuable to prevent synechia (adhesion) formation in uveitis and iritis. Large doses of antimuscarinic drugs may cause dry or "sandy" eyes. Antimuscarinic drugs are contraindicated in patients with glaucoma, especially angle- closure glaucoma.M.H.Farjoo
Effects of atropine on heart rate.The parasympathomimetic effect is attributed to blockade ofprejunctional inhibitory muscarinic receptors.
Cardiovascular System Atropine causes tachycardia by blockade of vagal slowing. In toxic concentrations, intraventricular conduction block may occur. All vessels contain muscarinic vasodilating receptors and are blocked by antimuscarinic drugs.M.H.Farjoo
Cardiovascular System Cont,d Vasovagal attack may accompany the pain of MI and depress SA / AV node and impair cardiac output. Atropine is useful in this situation.M.H.Farjoo Hamedan Medicine Faculty
Respiratory System Atropine can cause some bronchodilation and reduce secretion. The effect is more significant in patients with airway disease. Antimuscarinic drugs are used prior to inhalant anesthetics to reduce secretions in the trachea.M.H.Farjoo
Respiratory System Cont,d Ipratropium an analog of atropine, is used as an inhalational drug in asthma. Patients with COPD benefit from ipratropium and tiotropium.M.H.Farjoo
Gastrointestinal Tract The walls of the viscera are relaxed, and propulsive movements are diminished. Intestinal "paralysis“ is temporary; ENS reestablishes peristalsis after 1-3 days of antimuscarinic therapy. Secretion of gastric acid is not very sensitive to atropine like drugs.M.H.Farjoo
Gastrointestinal Tract Cont,d Many anticholinergics are used for hypermotility syndromes. Antimuscarinic agents can provide some relief in the treatment of travelers diarrhea. Since the antimuscarinic drugs slow gastric emptying, they may increase symptoms in patients with gastric ulcer.M.H.Farjoo
Genitourinary Tract Atropine can precipitate urinary retention in prostatic hyperplasia. Oxybutynin, is used to relieve bladder spasm after prostatectomy. It is also valuable in reducing involuntary voiding in patients with neurologic disease. Antimuscarinic agents are used to relieve the pain in urolithiasis but their usefulness is debatable.M.H.Farjoo
Sweat Glands Thermoregulatory sweat glands innervated by sympathetic cholinergic fibers are suppressed by atropine. In infants and children even ordinary doses may cause "atropine fever."M.H.Farjoo
Cholinergic Poisoning For direct acting cholinergic poisoning an antimuscarinic drug is used. For indirect acting cholinergic poisoning a cholinesterase regenerator may also be added. Nicotinic effects of cholinergic poisoning can not be reversed. Both the nicotinic agonists and antagonists cause blockade of transmission.M.H.Farjoo
Cholinergic Poisoning Cont,d To reverse the muscarinic effects, a non polar antimuscarinic (atropine) treats both the central and peripheral effects. The acute effects of an anticholinesterase agent lasts for 24-48 hours or longer. Atropine may be required for as long as 1 month for chronic effects of cholinergic poisoning.M.H.Farjoo
Cholinergic Poisoning Cont,d Cholinesterase regenerators are most effective for the enzyme in neuromuscular junctions. Pralidoxime is not recommended for poisoning by carbamate inhibitors. Pretreatment with reversible enzyme inhibitors prevents binding of the irreversible organophosphate inhibitors. In this case simultaneous use of atropine is required to control muscarinic excess.M.H.Farjoo
Cholinergic Poisoning Cont,d Some mushrooms cause rapid poisoning of the muscarinic excess type. Atropine is an effective treatment. The initial symptoms usually include nausea and vomiting. The major toxicity is hepatic and renal cellular injury by Amatoxins that inhibit RNA polymerase.M.H.Farjoo
Antinicotinic Organ Effect & Clinical Applications Nicotine and acetylcholine (with an AChE inhibitor) cause depolarization blockade. Blockade can be surmounted by increasing the concentration of an agonist (acetylcholine).M.H.Farjoo
Antinicotinic Organ Effect & Clinical Applications Cont,d Eye The ganglion-blocking drugs cause cycloplegia because the ciliary muscle receives primarily parasympathetic fibers. Ganglionic blockade causes dilation of the pupil because parasympathetic tone dominates this tissue.M.H.Farjoo
Antinicotinic Organ Effect & Clinical Applications Cont,d Cardiovascular system Blood vessels receive chiefly sympathetic fibers so ganglionic blockers decrease vascular tone. Gastrointestinal tract Motility is profoundly inhibited, and constipation can be marked.M.H.Farjoo
Antinicotinic Organ Effect & Clinical Applications Cont,d Trimethaphan is used in the treatment of hypertensive emergencies and dissecting aortic aneurysm. It is also used for controlled hypotension in neurosurgery to reduce bleeding.M.H.Farjoo
Intoxication Atropine is a remarkably safe drug in adults but a highly dangerous drug when overdose occurs in children. Symptomatic treatment may require temperature control with cooling blankets and seizure control with diazepam.M.H.Farjoo
Intoxication Cont,d Poisoning by polar antimuscarinic drugs is associated with marked orthostatic hypotension. In very severe cases a quaternary cholinesterase inhibitor such as neostigmine reverses the antimuscarinic effects. Control of hypotension may require the administration of a sympathomimetic drug such as phenylephrine.M.H.Farjoo