Autonomic Nervous System 6-Anticholinergic Drugs
أ0م0د.وحدة بشير اليوزبكيObjectives
Nicotinic AntagonistsAntinicotinic agents
1- Ganglionic Blocking agents
2-Neuromuscular Blocking agents
Non Depolarizing competitive blocking agents
Depolarizing Non-competitive blocking agents
1- Ganglionic Blocking Agents
- Hexamethionin, mecamylamine and other ganglion-blockers were mainly used in the treatment of hypertension. - But unfortunately, the adverse effect of ganglion blocked are so severe (both sympathetic and parasympathetic divisions are blocked), so that patients are unable to tolerate long term treatment with them.1- Ganglionic Blocking agents
Trimethaphan - It is the only Ganglion-blocker still in clinical use. Its poorly lipid soluble. - Inactive orally and has a short half-life. - It is used IV to treat severe accelerated hypertension (malignant hypertension). Note: Because the ganglion-blocking agents interrupts sympathetic control of venous-pooling, so so these drugs cause postural hypotension.
2- Neuromuscular Blocking Drugs
- These drugs are important for producing complete sk-m relaxation in surgery, by specific blockade of the N-M junction. -They enable light level of anesthesia to be employed with adequate relaxation of the muscles of the abdomen and diaphragm. - They also relax the vocal cords and allow the passage of a tracheal tube. Note: - Patients who have received a M-relaxant should always have their respiration assisted or controlled until the drug have been inactivated or antagonized.Non Depolarizing Competitive N-M blocking agents
Action: - Drugs of this group cause N-M block by competing with Ach at the receptor site at the N-M junction so prevent depolarization of muscle cell membrane and inhibit muscle contraction so causing complete SK- M relaxation. PK: - Most non depolarizing agents have relatively long t1/2 ranging from 20 min to several hours. - These drugs are given parentally (by injection).Non Depolarizing Competitive N-M blocking agents
Tubocurarine - Is the prototype it produces a competitive block at the at the motor endplate of the muscle causing flaccid paralysis lasts 30-60 min. - Tubocurarine blocks autonomic ganglia and causes an initial transient drop in blood pressure & cause histamine release which may induce bronchospasm. Pancuronium, Atracurium are short acting non-depolarizing agents.Non Depolarizing Competitive N-M blocking agents
Note: The action of competitive N-M blocking drugs is antagonized by anticholinesterases, like Neostigmine which is usually given IV, and preceded by atropine to prevent the parasympathetic autonomic effect of Neostigmine (such as bradycardia and salivation).Depolarizing Non competitive N-M blocking agents
Suxamethonium (Succinylcholine) Mechanism of action: - It attaches to the nicotinic receptors and acts like Ach to depolarize the N-M junction. - Unlike acetylcholine, which is rapidly destroyed by Achesterase, the depolarizing agent persists at high concentrations in the synaptic cleft, remaining attached to the receptor for a relatively long time & providing a constant stimulation of the receptor. Initially this produces short-lasting muscle fasciculation, followed within a few minutes by muscle paralysis.Suxamethonium (succinylcholine)
- The drug does not produce a ganglionic block, except in high doses, although it does have weak histamine-releasing action. - Normally, the duration of action of succinylcholine is extremely short (Total paralysis last up to 4 min) - succinylcholine It is particularly used during anesthesia for brief procedures? such as tracheal intubations or electroconvulsive therapy (ECT).PK of Suxamethonium (succinylcholine)
PK of Suxamethonium (succinylcholine)- It is hydrolyzed by plasma pseudo cholinesterase and its persistence in the body is increased by : 1- Neostigmine, which inactivate that enzyme. 2- In patient with hepatic disease or severe malnutrition, whose plasma concentration of enzyme may be lower than normal. 3- Procaine also is destroyed by this enzyme and so by competing with suxamethonium for the enzyme, may prolong its action. 4- There are persons with hereditary defects in amount or kind of enzyme, who cannot destroy the drug as rapidly as normal, so paralysis (Apnea) then prologed for hours. - Here treatment consist of ventilation until recovery, and may need fresh blood transfusion.