Centrally acting smr

Centrally acting smr

1. Centrally acting muscle Relaxants Dr. Johan

2. Muscle Relaxants Learning objectives: what is a muscle relaxant Various types of centrally acting muscle relaxants How do they act Where they can be used

3. Definition  Muscle relaxant is a drug which affects skeletal muscle function and decreases the muscle tone. It may be used to alleviate symptoms such as muscle spasms, sprains & pain Muscle relaxants are of two major therapeutic groups: neuromuscular blockers and  spasmolytics

4. Spasmolytics Spasmolytics are used to alleviate musculoskeletal pain, spasms and to reduce spasticity in a variety of neurological conditions. They are of three types Centrally acting Directly acting Miscellaneous

5. Can you tell what is spasm and what is spasticity

6. Mechanism of centrally acting drugs Spasmolytic agents generally work by either enhancing the level of inhibition, or reducing the level of excitation. Inhibition is enhanced by mimicking or enhancing the actions of endogenous inhibitory substances, such as gamma- Aminobutyric acid (GABA). GABA is the chief inhibitory neurotransmitter in the mammalian central nervous system. In humans, GABA is directly responsible for the regulation of muscle tone.

7. Individual centrally acting drugs Diazepam Facilitating the action of - aminobutyric acid (GABA) Acts at all GABA A synapses Useful in muscle spasms of any origin sedation limits use Tizanidine - Alpha2 adrenoceptor agonist reinforces both pre and post synaptic inhibition in the cord also inhibits nociceptive transmission in the spinal dorsal horn ADR: Drowsiness, hypotension, dry mouth

8. Baclofen GABA B agonist Induce hyperpolarization  serve as presynaptic inhibitory function Toxicity: drowsiness, seizure activity Intrathecal administration effective in sever spasticity.

9. Other centrally acting drugs used for local muscle spasm Carisoprodol Chlorophenesin Chlorzoxone Cyclobezaprine Metaxalone Methocarbamol orphenadrine Most of them act as sedative at level of the spinal cord or brain stem The main therapeutic use is in relief of acute temporary muscle spasm cause by Local trauma or strain

10. DANTROLENE- directly acting SMR Prevents calcium release from the sarcoplasmic reticulum through the ryanodine receptors (RyR1) channel. Used orally reduces spasticity in UMN disorders, hemiplegia , paraplegia, cerebral palsy and multiple sclerosis. ADR: generalized muscle weakness, sedation and occasionally hepatitis.

11. Malignant hyperthermia Triggered by GAs and Sch Sudden and prolonged release of calcium with massive muscle contraction, lactic acid production and increased body temperature. Prompt treatment by cooling the body and bicarbonate infusion for correcting acidosis is essential IV dantrolene is the drug of choice to reduce calcium load

12. Miscellaneous BOTULINUM TOXIN (BOTOX) Mechanism of Action: blocks release of ACh in the neuromuscular junction Indications: spasticity, hyperhidrosis (excess sweating), reduce facial lines and wrinkles Administration: subdermal injection Localized muscle paralysis occurs, so lines and wrinkles are less apparent Effects lasts weeks to months

13. Other spasmolytics Gabapentin – antiepileptic drug GABA B receptor agonist multiple sclerosis Progabide - a GABA A and GABA B agonist Glycine – inhibitory aminoacid neurotransmitter given orally and readily cross the BBB. Tried in ALS and myotonia congenita .

14. Idrocilamide and Riluzole – newer drugs – amyotrophic lateral sclerosis – through inhibition of glutaminergic transmission in the CNS Thiocolchicoside & Tolperisone – GABA A receptor agonist used in painful spasm, mainly LBA & sports injuries.

15. Thank you