Muscle Relaxants Flashcards
What are muscle relaxants?
All muscle relaxants act to reduce skeletal muscle tone ( how much it is contracted, high muscle tone means high contraction, low muscle town means more relaxed).
Although it is skeletal muscle that is affected, it can me altered by targeting both the CNS as well as the periphery.
What are centrally acting muscle relaxants?
Used to relieve chronic muscle spasticity associated with a range of conditions.
They work on the CNS.
Often used to treat symptoms such as anxiety,inflammation, pain or trauma that is being caused by inappropriate contraction.
What is muscle spasticity?
It is a tightness or stiffness in the muscle, which may include paralysis.
It is normally caused by the loss of inhibition in motor neurons, causing excessive contraction.
It can also lead to hyperreflexia, where responses are overactive leading to twitching/spasms.
What is the difference between muscle relaxants which act on the CNS and those that act on the muscle directly, compared to those that act at the neuromuscular junction?
Drugs that act on the CNS are there to alleviate muscle spasticity, as are those that affect the muscle directly.
Drugs that act on the neuromuscular junction cause complete flaccidity, meaning that there can be no contraction, the muscle is completely relaxed. This is not particularly useful if the drug is being used to relieve a particular problem such as inflammation, which is causing inappropriate contraction causing pain, as it will completely remove the ability to move.
What are some examples of important Muscle relaxants that target the CNS?
Baclofen and diazepam(mostly anti anxiety).
Both of these drugs help to facilitate the GABA pathway.
What is the specific action of Baclofen and its side effects?
Baclofen helps to facilitate the GABA pathway as it is an agonist of the GABA receptor.
GABA is an inhibitory neurotransmitter, so by activating it, there is a reductions in the levels of other neurotransmitters released.
It works in the spinal chord by inhibiting excitation of the motor neurons, which limits the drive for contraction in the muscle.
Because of this it decreases the number and severity of muscle spasms, which reduced pain.
Most commonly used for patients who are paraplegic( loss of use of lower limbs) or quadriplegic ( loss of lower limbs and torso as well as arms) which is due to spinal cord lesions, such as those days caused by trauma or MS.
There is possible interaction with other medications that depress the CNS, causing increased depression.
Th main side effect is drowsiness, and there are less association with dependence with this drug.
What is the specific action of diazepam and its side effects?
Diazepam affects the GABA pathway by binding to the gaba receptor, and making it more receptive to GABA. This is important because it only increases the affect of GABA present, it is not an agonist, so without the presence of GABA it does not itself alter the pathway.
There is possible interaction when used with other drugs that depress the CNS, and can cause drowsiness. There is also the additional concern of addition when taking benzodiazepines.
How does the GABA receptor function?
The GABAa receptor is linked to LG chloride channels, so when activating there is an influx of chloride, which is a negatively charged ion, so the inside of the cell is hyper polarised- it will take longer for an action potential to occur because it will take longer to reach its threshold potential.
GABAb is similar but is linked by GPCR to potassium channels. They also hyper polarise the cell by allowing potassium to leave the cell.
What is the most common peripherally acting muscle relaxant and why is it interesting?
Dantrolene sodium is the drug of choice to treat spasticity as it effects only the muscle and not the CNS, so there is limited CNS side effects. However in practice it is not used often because of how long it can take to see a benefit.
It still has the potential to affect the CNS, and the most likely side effect is drowsiness.
How do peripherally acting muscle relaxants work?
It inhibits the ryanodine receptors in the skeletal muscle. When these are activated, they release calcium from the sarcoplasmic reticulum into the sarcoplasm, where it binds to troponin, and moves it so that actin/ myosin interaction can occur. This causes contraction. By inhibiting the receptor, there is less release of calcium, which means less contraction can occur.
What conditions could a peripheral muscle relaxant be used to treat?
Can theoretically be used to treat any spasticity, but is particularly effective in cerebral palsy, MS, spinal cord injury or stroke.
Dantrolene can also be used to help reduce post anaesthesia malignant hyperthermia.
What are the drug interaction cautions for peripherally acting muscle relaxants?
As with CNS muscle relaxants, combination with a CNS relaxant can cause further depression, resulting in sedation, lack of coordination and respiratory depression.
What counselling should be given to patients taking CNS or peripheral muscle relaxants?
May cause drowsiness and could affect driving and coordination
Alcohol effects will be enhanced, take together only with care.
What are the two types of neuromuscular blocking drugs?
Non-depolarising
Depolarising
What are non depolarising muscle relaxants?
There can be sub divided into Aminosteroids and Benzylisquinolinium, but it is suitable to know how they work in general.
All variations which have slight differences in specificities, and duration of action but all similar. They are all competitive reversible antagonists of the nicotinic cholinergic receptor on skeletal muscle.
Because they are competitive rather than depolarising, a block can be reversed by increasing the availability of actylcholine. So for example, anticholinesterases such as neostigmine, can reverse the inhibition by reducing the breakdown of actylcholine by acetylcholinesterases.
