Myorelaxants Flashcards
Why do we use Central Muscle Relaxants?
- They have a relative specific depressant action on CNS causing decreased motor activity or paralysis of voluntary muscles without loss of consciousness
- using them at therpeutic dose they do not inhibit other functions of CNS
- many of CNS inhibitory drugs demonstrates weaker or stronger muscle relaxants effect, Eg: Phenotiazines < Opioids < Alpha2-agonist < Anaesthetics
- central myorelaxants can potentiate the effect of anaesthetics drugs and combinations
- they are also used to contro certain spasmodic and painful disorders of skeletal (spinal) muscles.
Name the different Central Muscle Relaxants drugs:
- Guaiphensesin
- Baclophen
- Carisoprodol
- Methocarbamol
Guaiphenesin:
- Indications, pharmacokinetics
Indications:
- horses, cattle, sheep: to adjunct anaesthesia
- dogs: strichnine poisoning (in pass)
Pharmacokinetics:
- onset and elimination of action is fast, 2-4 and 60-80 min
- large distribution, crosses placenta barrier
- metabolism: conjugation with glucuronide -> excration with urine
Guaiphenesin:
- Effect
- it is a spinal interneuronal blocking agent: it blocks polysunaptic but not monosynaptic reflexes
- exact mechanism is unknown
- it is effective against convulsion caused by strychnine, tetanus, but inactive in picrotoxin and leptazol induced colvulsions
- it paralyses limb muscles, whils respiratory muscles are generelly unaffected
- the consciousness is retained: sedatives must be applied (alpha2-agonist, opioids, ketamine)
Secondary effect:
- expectorant
Guaiphenesin:
- side-effects
- mild, at therapeutic dose slight decrease of arterial blood pressure
- only large doses causes respiratory depression
- ut causes haemolysis (concentration dependent), preferred 5% solution with 5% dectrose
Baclopen:
- effect, safety and indications
Effect:
- acts as agonist at GABAb receptors in the brain and spinal cord, resulting in hyperplarization of neurons due to increased K+ ion conductance
- also inhibitos neural funcion presynaptically, by reducing Ca2+ ion influx, and thereby reducing the release of excitatory neurotransmitters in both the brain and spinal cord.
- it may also reduce pain in patients by inhibiting the release of Substance P in the spinal cord
Safety: Large therapeutic index
- Clinical signs of toxicosis are vomitting, ataxia, and vocalization or disorientation
- life-threatening signs are respiratory arrest, and seizures
Indications: 1-2 mg/kg Orally TID
- spasms of skeletal muscles, rigidity, spinal cord injury and pain caused by injuries
- Baclophen has also been used extralabel in dogs to treat urinary retention by reducing urethral resistance.
-
Carisoprodol:
(scutamin C tabl)
- usefull against various types of pain (wheter or not related to muscle spasm) because of its analgesic-sparing (potentiating) effect of opioid analgesics)
- inactive in convulsion caused by strychnine
- is available by itself or mixed with Aspirine and in one preparation along with Codeine and Caffeine as well
Methocarbamol:
(Frexolan tabl)
- acts on the internuncial neurons of the spinal cord
- reduces skeletal muscle hyperactivity alteration in muscle tone
Peripheral muscle relaxant drugs:
- classes of neuromuscular blocking agents
- Depolarizing neuromuscular blocking agents (succinylcholine)
- Competitive (non-depolarizing) neuromuscular blocking agents (prototype: d-tubocurarine/curare)
Uses of neuromuscular blocking agents:
By intravenous or systemic administration:
- adjuvant in surgical anaesthesia t obtain relaxation of skeletal muscle
- “balanced” anesthesia, TIVA - to minimize anaesthetic use without compromising analgesia
- to assist in intubation (esp. succinylcholine)
- corneal or retinal surgeries to obtain relaxation of extraocular muscles (cisatracurium)
- therapy of spastic disorders
By topical administration:
- mydriasis in birds (eg. vecuronium)
Depolarizing neuromuscular blocking agents and its mechanism:
Succinylcholine (suxamethodnium) - twp ACh molecules
Mechanism:
- stimulate opening of nicotinic ACh receptor channel and produce depolarization of the cell membrane
- Succinylcholine persist at the neuroeffector junction and activates the nicotinic receptor channels continouusly, which results in inactivation of voltage-gated sodium channels so that they cannot reopen to support further action potenitals (= “depolarizing blockade”)
Succinylcholine (Sucamethonium) chloride:
- IV rapid (onset within 1min) and short-lasting block (app. 10min) –> Phase 1 block
- used to facilitate intubation (humans); used illegally in bow hunting or “euthanasia”
- In an emergency can be given IM, but slower and less predictable action
- can cause bradycardia (atropine can prevent!), hyperkalaemia, increased intra-ocular and intragstric pressure, anaphylaxis or malignant hyperhermia in geneticaaly predisposed subjects
- dogs, cattle, sheep sensitive
- horses and pigs less sensitive
Depolarizing angents termination of action:
metabolised by plasma pseudocholinesterase and liver
Depolarizing agents effect on skeletal muscle:
- fasciculation - “muscle twitch”
- weakness
- paralysis
Depolarizing agents effect on cardiovascular system:
- increased blood pressure, increased or decreased heart rate (due to stimulation of parasymp. and/or sympathetic ganglia)
- bradycardia occurs after repeated use more frequently (atropine)
Depolarizing agents actitvity is enhanced or potentiated by?
- neostigmine and organiphosphates (cholinesterase inhibitors)
- isoflurane
Undesirable side effects of Depolarizing agents:
- muscle fasciculation, hyperkalaemia (important in patient with congestive heart failure)
- phase 2 block (following repolarisation of the membrane cannot easily be depolarized again because it is desentizied) -> neostigmine can partly control
- may trigger malignatn hyperthermia in genetically susceptible patients (dyspnea, treor and stiffness, extreme hyperthermia, and rapid postmortem rigor mortis)
- muscarinic action at high doses
Advantages of Depolarizing agents:
short duration of action, little histamine release
Competitive - nondepolarizing-neuromuscular blocking agents:
mechanism
Selectively antagonize nicotinic receptors, thus preventing endogenous ACh binding and subsequent muscle cell depolarization
(= “Nondepolarizing blockade”)
Competitive neuromuscular blocking agents:
Benzylisoquinoline group: metablism in blood plasma, Histamine release
- d-tobocurarine
- atracurium
- cisatracurium
- mivacurium
Aminosteroid group: Metabolism in liver, no histamine release
- pancuronium
- vecuronium
- rocuronium
Others:
- gallamine
Classification of the Competitive neuromuscular blocking agents based on their duration of action:
Ultra short duration:
- Gantacurium
Short duration:
- Micavurium - Chandonium
Intermedia duration:
- Atracurium - Cisatracurium
- Faxadinium - Rocuronium - Vecuronium
Long duration:
- Doxacurium - Dimethyltubocurarine
- Pancuronium - Pipecuronium
- Laudexium - Gallamine
Effect of competative blockers on cardiovascular system:
- decreased blood pressure - due to histamine release (benzylisoquinolines)
- increased heart rate (baroreceptor reflex)
- coagulability of blood decreased (due to release of heparin from mast cells)
Competitive neuromuscular blocking agents - long acting:
- d-tubocurarine (BI) - slight hypotension and tachycardia; histamine release (problem in asthma), excretion via urine (in kidney disease delayed). Long acting. Limited use.
- Gallamine (O): tachycardia and hypertension; no HA release (only in very large doses). Long acting. Crosses placental barrier. Frequently used in human surgery
- Pancuronium (AS): long acting. Slight tachycardia and hypertension. metabolism in the liver, elimination via urine. liver and kidney disease prolongs its effect
Competitive neuromuscular blocking agents list the different Benzylisoquinolines:
- Atracurium (BI)
- Cisatracurium (BI)
Atracurium:
Competitive neuromuscular blocking agents
intermediate-acting
safe in liver and kidney disease (metabolism in plasma):
- bradycardia may occur during surgical manipulations, esp. opthalmologic, or laparoscopy (treat with atropine or glycopyrrolate)
- precipitates in alkaline pH
- can cause histamine release at higher doses
probably most used in vet.med
Cisatracurium and Mivacurium:
Competitive neuromuscular blocking agents:
Cisatracurium:
- R-cis isomer of atracurium. 3x potentcy; immediate onset of action;
- intermediate action
. metabolism in plasma
- used in opthalmologic surgeries
Mivacurium:
- short acting, succinylcholine alternative developed for human use
- Histamine release
- hypotension can occur
- metabolism in plasma (esterases)
Competitive neuromuscular blocking agents, list the different Aminosteroids:
- Rocuronium (AS)
- Vecuronium (AS)
Rocuronium
Competitive neuromuscular blocking agents: aminosteroids
- due to very fast onset of action is a succinylcholine alternative developed for human use
- intermediate-acting
- metabolism in liver
- excretion with bile
- lack of cardiovascular or histamine-releasing effects but may cause anaphylactic reaction quite frequently
Vecuronium:
Competitive neuromuscular blocking agents: aminosteroids
- intermediate acting
- lack of cardiovascular or histamine releasing effects
- drug choice when cardiovascular stability is required
- metabolism in the liver
- excretion with bile and urine
- causes mydriasis in birds
Antagnoized effect on cometitive blockers:
action antagonized by:
- cholinesterase inhibitors (neostgmine, pyridostigmine, endrophonium)
- tetanic stimulation (a 50-Hz electrical stimulation given for 5sek)
The muscarinic side effect of neostigmine has to be controlled with Atropine
