Pharmacology - ANTICHOLINERGIC & NEUROMUSCULAR BLOCKING AGENTS (MADE EASY)

in this video I'm going to cover cholinergic antagonists so let's get right into it cholinergic antagonists can be divided into three groups first antimuscarinic agents second ganglionic blockers third neuromuscular blockers so let's start with antimuscarinic agents also known as anticholinergic drugs these agents block primarily muscarinic receptors thus causing inhibition of muscarinic functions one of the most well known medications that belongs to this group is Atropine Atropine's primary sites of actions are the following eye GI tract heart salivary sweat and lacrimal glands now antimuscarinic activity of Atropine in the eye results in relaxation of ciliary muscle which causes dilation of the pupil also known as mydriasis inability to focus visually also known as cycloplegia and unresponsiveness to light so ophthalmic preparations of Atropine are used before an eye exam or eye surgery as well as to treat certain inflammatory conditions of the eye however because of its long duration of action other antimuscarinic agents such as Cyclopentolate and Tropicamide are preferred over Atropine while Cyclopentolate and Tropicamide can produce mydriasis that lasts for hours Atropine's effects can last for days another feature of Atropine is that it blocks M3 receptors in GI tract which results in reduction of GI motility from stomach to colon this translates into prolonged gastric emptying and lengthen intestinal transit time at higher doses Atropine can also effectively block M2 receptors on the SA node and AV node which produces tachycardia heart rate may increase by as much as 30 to 40 beats per minute lastly by blocking muscarinic receptors on salivary sweat and lacrimal glands Atropine produces dry mouth dry skin and ultimately causes body temperature to rise the next very well-known medication in the antimuscarinic group is Scopolamine so Scopolamine unlike Atropine has a much greater effect on the CNS as well as longer duration of action for that reason Scopolamine is one of the most effective medications used for prevention of motion sickness and post-operative nausea and vomiting it is available in a patch formulation that provides effects lasting up to three days another medications in the antimuscarinic group that I want to talk about are Ipratropium and Tiotropium Ipratropium and Tiotropium block muscarinic acetylcholine receptors without specificity for subtypes this results in decreased contractility of smooth muscle in the lungs which in turn leads to bronchodilation and reduction of mucus secretion Tiotropium and Ipratropium are administered by inhalation for maintenance treatment of bronchospasms in patients with COPD Ipratropium also comes in a nasal spray formulation which is often used for treatment of rhinorrhea which is runny nose the main difference between Ipratropium and Tiotropium is their duration of action Tiotropium is a long-acting agent that is dosed once daily while Ipratropium is a short-acting agent that typically requires up to four times daily dosing another medications that belong to this group are used for treatment of overreactive bladder these include Tolterodine Darifenacin Solifenacin Oxybutynin Trospium and Fesoterodine these agents have varying selectivity for the M3 receptor which is the main receptor involved in bladder function however the overall efficacy among all of these is very similar last but not least I wanted to briefly mention two muscarinic blockers Benztropine and Trihexyphenidyl which through their ability to suppress central cholinergic activity were found to be very beneficial in treatment of Parkinson-like disorders now before we move on to the next group I wanted to make sure everyone watching this video remembers their ABCDs which will help us to remember anticholinergic adverse effects where A stands for agitation B stands for blurred vision C stands for constipation and confusion D stands for dry mouth and S stands for stasis of urine and sweating now we can move on to the second group of cholinergic antagonists which are ganglionic blockers the main agent in this group is Nicotine which is a main component of cigarette smoke although Nicotine is a cholinergic agonist it is also considered a functional antagonist because of its ability to stimulate and then block cholinergic function so Nicotine acts on the nicotinic receptors of both parasympathetic and sympathetic autonomic ganglia effects of Nicotine result from increased release of neurotransmitters such as dopamine serotonin and norepinephrine just to name a few Nicotine is a nonselective it stimulates and later depresses autonomic ganglia for example Nicotine stimulates CNS which at high enough doses can lead to convulsions and then it depresses CNS which can lead to respiratory paralysis also by stimulating adrenal medulla and sympathetic ganglia nicotine increases blood pressure and heart rate but at higher doses it can cause blood pressure to fall in GI system nicotine increases the motility which can lead to nausea and vomiting last but not least use of Nicotine in any form can cause addiction due to CNS stimulation that produces increased alertness and surge of well-being overall other than to help people quit smoking Nicotine is not very useful in clinical practice now let's switch gears and let's talk about neuromuscular blockers neuromuscular blocking agents simply block the cholinergic transmission between motor nerve endings and nicotinic receptors on the skeletal muscle so if we zoom in on this part where nerve ending meets the skeletal muscle fiber you would see these nicotinic receptors to which acetylcholine can bind and induce their opening opening of these channels let's sodium ions to enter the muscle fiber and trigger muscular action potential the potential travels first along the surface of sarcolemma which is the excitable membrane that surrounds those cylindrical structures known as myofibrils then the action potential travels through T-tubule system which penetrates into the fiber and then the arrival of action potential causes calcium to be released from the sarcoplasmic reticulum which finally leads to muscle contraction now let's see all these steps in action so action potential causes release of acetylcholine channels open sodium goes in triggers another action potential calcium gets released and muscle contracts it's that easy now neuromuscular blocking agents work at this junction here by interacting with these nicotinic acetylcholine receptors we can divide these agents into two groups first nondepolarizing agents and second depolarizing agents for all of you who need a quick review of membrane depolarization I strongly encourage you to watch my short three-minute video about action potential so let's talk about nondepolarizing agents first these agents are competitive antagonists they bind to acetylcholine receptors but they don't induce ion channel opening what that means is that they prevent depolarization of the muscle cell membrane and thus effectively inhibit muscle contraction in clinical practice these agents are used to facilitate mechanical ventilation and tracheal intubation as well as to increase muscle relaxation during surgery which allows for lower doses of general anesthetics generally speaking nondepolarizing agents are not absorbed from GI and that's why must be injected usually intravenously time to onset of action is rapid usually less than two minutes once administered these agents paralyze small fast contracting muscle first that is eyes face fingers then larger muscles of neck trunk and limbs and lastly diaphragm on the other hand these muscles recover in the reverse manner that is diaphragm first then limbs trunk and so on and so forth the choice of an agent typically depends on the desired onset and duration of the muscle relaxation and just a side note a clinical duration of these agents is a time measured from administration to recovery of 25% of baseline muscle strength now some of the most widely used agents in this group are the following Cisatracurium which has clinical duration of about 90 minutes Pancuronium which also has clinical duration of about 90 minutes Rocuronium with clinical duration of about 40 minutes Vecuronium which also has clinical duration of about 40 minutes and lastly Atracurium with 40 minute clinical duration as well now when it comes to side-effects Atracurium causes histamine release which results in fall in blood pressure flushing and bronchoconstriction it also has toxic metabolite called laudanosine which can provoke seizures especially in patients with impaired renal function this is why Atracurium has been largely replaced by its isomer Cisatracurium which fortunately is much less likely to produce the same adverse effects because its metabolism is independent of hepatic or renal function therefore Cisatracurium is often used in patients with multi-organ failure now Vecuronium and Rocuronium are metabolized by liver so their action may be prolonged in patients with hepatic dysfunction but overall there are safe and have minimal side effects lastly Pancuronium is excreted unchanged in urine and one of its main side effects is increase in heart rate now let's move on to depolarizing agents so depolarizing agents act as acetylcholine receptor agonists they mimic the acetylcholine however they are much more resistant to degradation by acetylcholinesterase and therefore produce persistent depolarization now the only depolarizing agent that's still used in clinical practice is Succinylcholine so Succinylcholine binds to the nicotinic receptor and unlike the nondepolarizing agents it actually causes the sodium channel to open which results in membrane depolarization now because Succinylcholine is resistant to acetylcholinesterase it causes prolonged depolarization which leads to a transient fasciculations and finally flaccid paralysis this is referred to as phase-1 block now eventually sodium channel closes and membrane repolarizes however due to continued stimulation by Succinylcholine the receptor becomes desensitized to acetylcholine thus preventing formation of further action potentials this is referred to as phase-2 block now Succinylcholine has a rapid onset of action and therefore is commonly used to facilitate rapid sequence endotracheal intubation in critically ill patients it's also sometimes used to provide adequate muscle relaxation during electroconvulsive therapy following intravenous administration Succinylcholine causes complete muscle relaxation within one minute the effects typically last up to ten minutes due to rapid redistribution and hydrolysis by plasma pseudocholinesterase and that brings us to adverse effects in patients deficient in plasma pseudocholinesterase or patients who have genetic variation of this enzyme Succinylcholine can lead to prolonged apnea next prolonged depolarization caused by Succinylcholine leads to continued flow of potassium into the extracellular fluid which can result in hyperkalemia now in patients with normal potassium levels this is usually not a big issue however in those with elevated potassium levels for example due to burns or large tissue damage Succinylcholine can cause serious EKG changes and even in severe cases asystole lastly in genetically susceptible patients Succinylcholine can trigger rare and potentially fatal condition called malignant hyperthermia symptoms of malignant hyperthermia include severe muscle contractions and dangerously high body temperature that can reach as high as 43 degrees Celsius and with that I wanted to thank you for watching and I hope you enjoyed this video

Channel: Speed Pharmacology

Views: 632,378

Rating: 4.9265871 out of 5

Keywords: antimuscarinic, neuromuscular blockers, anticholinergic, neuromuscular blocking agents, cholinergic antagonist, anticholinergic drugs, depolarizing neuromuscular blockers, atropine mechanism of action, atropine pharmacology, succinylcholine mechanism of action, ganglionic, succinylcholine, atropine, nondepolarizing, neuromuscular, cholinergic and anticholinergic drugs, depolarizing, skeletal muscle relaxants pharmacology, blockers, muscle relaxants pharmacology, agents, cholinergic drugs

Id: cp_CZpCBVpk

Length: 14min 20sec (860 seconds)

Published: Sun May 22 2016