Centrally Acting Muscle Relaxants.pdf file

Centrally Acting Muscle Relaxants.pdf

1. Centrally Acting Muscle
Relaxants

2. CENTRALLY ACTING MUSCLE RELAXANTS
•These are drugs which reduce skeletal muscle tone by a
selective action in the cerebrospinal axis, without altering
consciousness.
•They selectively depress spinal and supra spinal poly synaptic
reflexes involved in the regulation of muscle tone.
•Polysynaptic pathways in the ascending reticular formation
which are involved in wakefulness are also depressed, though
to a smaller extent.

3. Cont..
•All centrally acting muscle relaxants cause sedation.
•They have no effect on neuromuscular transmission and on
muscle fibres but reduce decelebrate rigidity, upper motor
neuron spasticity and hyperreflexia.
•Note the differences between peripherally and centrally
acting muscle relaxants in the following table

4. Cont..

5. Cont..
Classification of Centrally Acting Muscle Relaxants.
•Mephenesin congeners: Mephenesin, Carisoprodol,
Chlozoxazone, Chlormezanone, Methocarbamol.
•Benzodiazepines: Diazepam, Trizolam and others.
•GABA derivative: Baclofen
•Central α2 agonist: Tizanidine

6. Cont..
Properties of Centrally Acting Muscle Relaxants.
•Mephenesin
–First drug to be discovered as a muscle relaxant.
–Modulates reflexes maintaining muscle tone.
–It is not used clinically because it causes gastric irritation,
and when administered IV it causes thrombophlebitis,
hemolysis and marked fall in BP.

7. Cont..
•Carisoprodol
–Has favorable muscle relaxant, sedative, analgesic
antipyretic, and anticholinergic properties.
–It is used in musculoskeletal disorders associated with
muscle spasm.
•Chlozoxazone
–Pharmacologically similar to mephenesin, has a longer
duration of action and is better tolerated orally.

8. Cont..
•Chlormezanone
–Has anti- anxiety and hypnotic actions and is used for
tension states associated with increased muscle tone.
•Methocarbamol
–Less sedative and longer acting than mephenesin.
–Orally used in reflex muscle spasm and chronic
neurological diseases.
–It can be given IV without producing thrombophlebitis and
hemolysis-used for orthopedic procedures and tetanus.

9. Cont..
•Diazepam
–A benzodiazepine (BDZ) which acts in the brain on specific
receptors, enhancing transmission by the inhibitory amino acid
neurotransmitter GABA.
–Muscle tone is reduced by supraspinal rather than spinal action.
–It has more sedative activity than muscle relaxation and
sedation limits the dose that can be used for muscle relaxation.
–Diazepam is particularly valuable in tetanus and spinal injuries.
–When combined with analgesics, it is useful for rheumatic
disorders associated with muscle spasm.

10. Cont..
•Baclofen
–Is a GABA
B receptor agonist which depresses both
polysynaptic and monosynaptic reflexes in the spinal cord.
–It does not produce muscle weakness like diazepam
because it does not affect chloride conductance.
–(BDZs facilitates the effect of GABA on GABA
A receptors
increasing chloride conductance while baclofen acts on
GABAB receptors, hyperpolarizing neurons by increasing K
+

conductance and altering Ca
2+
flux.).

11. Cont..
–It reduces spasticity in many neurological disorders like
multiple sclerosis, spinal injuries and flexor spasms.
–It is relatively in effective in stroke, cerebral palsy,
rheumatic and traumatic muscle spasms and Parkinsonism.

12. Cont..
• Tizanidine
–It is a new skeletal muscle relaxant which is a congener of
clonidine.
–It is a central α2-adrenergic agonist which inhibits the
release of excitatory amino acids e.g. aspartate in the
spinal interneurons while facilitating the inhibitory amino
acid neurotransmitter glycine.

13. Cont..
–It inhibits polysynaptic reflexes; reduce muscle tone and
frequency of muscle spasms without reducing muscle
strength.
–Efficacy similar to baclofen and diazepam has been noted
in multiple sclerosis, spinal injury and stroke with fewer
side effects.
–It is well absorbed and is administered as tablets of 2 and 4
mg.

14. Cont..
•Adverse Effects of Centrally Acting Muscle Relaxants
(CAMRs)
–Gastric irritation except for diazepam, Baclofen and
tizanidine.
–All CAMRs cause drowsiness and sedation.
–Baclofen can cause tachycardia, hypotension and rarely
visual and auditory hallucinations.
It can also cause ataxia and elevation of serum
transaminase.

15. Cont..
–Tizanidine may cause dry mouth, drowsiness, night time
insomnia and hallucinations.
Dose dependent elevation of liver enzymes has been noted.
–No consistent effect on BP has been noticed but should
still be avoided in patients receiving anti hypertensives,
especially clonidine.