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Lecture Three

Neuromuscular Agents

What are the three types of muscles that we have? Skeletal, Smooth, Cardiac
What are Skeletal muscles for? e.g. triceps. For outer body movement and posture
What are Smooth muscles for? they line tubing in [our body to help inner body movement
What are Cardiac muscles for? for movement of the circulation to stay alive.
What are the two main reasons for why you would want to promote muscle RELAXATION? To reduce hypertension/blood pressure. To make you not all rigid and contracted so you can move easily.
What are the two main reasons for why you would want to promote muscle contraction? To increase blood pressure/hypertension/ To decrease movement.
What are neuromuscular agents? * Drugs that target the neuromuscular junction (NMJ) to work to increase or decrease skeletal muscle contraction.
What is a NMJ? Stands for Neuromuscular junction. And it is the synapse between motor neuron and skeletal muscle. Its a nice, clean one to one synapse
There are three functional divisions of the PNS. In what two are the NMJ's in? * Motor (efferent) and Somatic (voluntary).
Are neuromuscular agents considered to be psychoactive drugs? No because they do not influence the brain
How would you promote Muscle contraction or relaxation? * By targeting the NMJ/synapse. This means that you will target the AHc system.
By targeting the NMJ, what system are you also targeting? The ACh system
What are the two receptors for ACh? Nicotinic and Muscarinic. Read over these
What does ACh do? Alters muscle tonicity
If you want muscles to contract you want as much ACh as possible to release. True or false? true. You want to keep lots of ACh in the middle of the synapse
How could you manipulate the cholerginic system to promote muscle contraction? * You would get as much ACh as possible to release and stay in the middle of the synapse.
In the lecture, lecturer used to example of members of the natural world that are neuromuscular agents that contract muscle. What are they? * The Black Widow spider and the Physostigma venerosum plant
Go over questions and answers for reading *
What is the name of the agent that contracts muscles, that is from the plant in the reading? Physostigmine
What is the mechanism of action for physostigmine? * AChE inhibitor
What is the site of action for Physostumines? * Neuromuscular junctions in the PNS. But this is not the only site. ACh can go everywhere in the body as there are receptors all over the PNS.
What is the mode of action for physostigmine? * Muscular tonicity/contraction.
There are Physostigmine derivatives that we use today. What are the ROA for Physostigmine itself? * INJECTION and oral
There are Physostigmine derivatives that we use today. What are the ROA for Neostigmine? * Injection and ORAL
There are Physostigmine derivatives that we use today. What are the ROA for Rivastigmine? * Oral and PATCH
What is good about the fact that Rivastigmine can be administered by patch? People with Allzheimers might forget to inject or take orally so patch is good for this
What are the main uses of Toxic AChE Inhibitors? Main use: Pesticides, insecticides, nerve gases
There are toxic AChE inhibitors which are very potent and can be volatile. What are the consequences of this? * A little if all you need for it to be very harmful/deadly. They can be inhaled which is annoying. Also can be absorbed through skin (transdermal) from weeds/crops. Kids dies orally as pesticide with AChE inhibitor was in food.
How could 'muscle contraction' be deadly? Because you can't breathe! It affects your diaphram muscles!
Toxic AChE inhibitor drugs are a common culprit in drug-related homocide, suicide and accidental death. Why? * Very accessible. Can get parathion and malathion from Mitre 10.
What is the mode of action of Toxic AChe Inhbitors? * AChE inhibitors
How can some AChE inhibitors be therapeutic and others lethal? * Has to do with the degree of inhibition. Not sure if whole answer??
Read over pill military use to prevents gas poisoning. *
What are the two reasons for wanting to promote muscle contraction? * Therapeutically to help with MG and glaucoma. Behaviourally - malisciously with toxic contraction.
Are drugs that contract muscles addictive? * No as they dont fele good.
To contract muscle you want to increase what? Cholinergic tone (amount of ACh in system) at the NMJ (sometimes you also want to do this in the brain)
What are the therapeutic reasons for promoting muscle RELAXATION? * To reduce severe muscular tension. To prep for surgery so can cut into relaxed abdomen muscle. To reduce spasticity of ALS, MS, cerebral palsy
What is the behavioural reason to promote muscle RELAXATION? * Aesthetically to relax face muscles e.g. botox.
How can promoting muscle RELAXATION be addictive? * Because aesthetically relaxing face muscles can be addictive behaviour.
To promote muscle RELAXATION what do you want to happen with ACh? Don't want ACh to be activated, want as little ACh as possible
There are four ways that agents can relax muscles. One is to antagonise the nACh receptor. What are the two examples of natural things that do this? * Snakes - cobra venom and krait venom. and strychmos toxifera plant
Cucare is an agent used to relax muscles. What is its mechanism of action? * ACh inhibitor??
What is the site of action for cucare? * NMJ in the PNS
What is the mode of action for cucare? * Paralysis
When hunters use cucare to kill animals does it kill them or just paralize them? ???!!!!
When hunters eat the animals that they have killed with cucare, wont they be affected by the drug too? No because, they cooked it so perhaps the heat breaks it down and denatures the chemical. Also its a pharmacokinetic so doesn't pass into blood, just stays in small intestine and then continues out.
Why would you want to promote muscle RELAXATION using curare derivitives? * - Therapeutic reasons for acute muscle tension, and to prepare for surgery. Maliciously to paralyse someone - kill them. Not addictively as no appeal, doesn't make you feel good.
What is the Mechanism of Action (MOA) for Botox? * It prevents vesicular release of ACh
What is the site of action for Botox? * Neuromuscular junction in the PNS
What is the Mode of Action for Botox? * Paralysis
Botox doesn't make you high, so why would anyone get addicted to it? * You become psychologically driven to repeat behaviour. Once you look young and have no wrinkles, you do not want the wrinkles to come back so get more botox to get rid of them.
Botox is a __________ drug * lifestyle
**Botox was initially developed to treat what? facial and eye spasm
**How long does the quick fix for wrinkles from Botox last? 1-4 months
**What is botox increasingly now used for? to control sweating
What are spasmolytics? Oral 'muscle relaxers' (note quotations as not technically a neuromuscular relaxer as they are a CNS depressant but also promote muscle relaxation)
Created by: alice476