Prepared By

Muhammad Nizam UddinM.Pharm

Jahangirnagar University

Musculoskeletal system is made up of the body's

Bones (the skeleton),

Muscles,

Cartilage,

Tendon (a tough band of fibrous connective tissue that usually connects muscle to bone and is capable of withstanding tension)

Ligaments (a tough band of fibrous connective tissue connect bone to bone)

Joints and

Other connective tissue (the tissue that supports and binds tissues and organs together)

MUSCULOSKELETAL SYSTEM

There are three types of muscles – Cardiac muscle

Skeletal muscle and

Smooth muscle

MUSCLES

Cardiac muscle is a type of involuntary striated muscle found in the walls of the heart, specifically the myocardium. Cardiac muscle cells are known as cardiac myocytes (or cardiomyocytes).

Skeletal muscle embedded with skeleton generally contracts voluntarily (via somatic nerve stimulation), although they can contract involuntarily through reflexes.

Smooth (or visceral) muscle, forming the muscle layers in the walls of the digestive tract, bladder, various ducts, arteries and veins, and other internal organs.

MUSCLES

Flexibility and rigidity is a very common phenomena of musculoskeletal system in human body. Neurotransmitters play the key role to mediate that.

Neurotransmitters are chemicals that are used to relay, amplify and modulate signals between a neuron and another cell.

NEUROTRANSMITTER

NEUROTRANSMITTER: EXCITATORY OR INHIBITORY

Some neurotransmitters are commonly described as "excitatory" or "inhibitory".

The effect on the postsynaptic cell depends entirely on the properties of the receptors. It so happens that for some neurotransmitters (for example, glutamate), the most important receptors all have excitatory effects: that is, they increase the probability that the target cell will fire an action potential.

For other neurotransmitters (such as GABA, glycine), the most important receptors all have inhibitory effects.

Action potential

An action potential is a very rapid change in membrane potential that occurs when a nerve cell membrane is stimulated.

Specifically, the membrane potential goes from the resting potential (typically -70 mV) to some positive value (typically about +30 mV) in a very short period of time (just a few milliseconds).

Action potential

Action potential

Action Potential causes opening of calcium channel in presynaptic nerve & then vesicle to open

Neurotransmitter released into synapse

Locks onto receptor molecule in postsynaptic membrane

NEUROTRANSMITTER RELEASE

NEURONAL TRANSMISSION

When neuronal transmission is impaired, hypertonicity, spasm and spasticity of muscle takes place.

• Hypertonicity is an increased tension of the muscles, meaning the muscle tone is abnormally rigid, hampering proper movement.

• Spasm is a sudden, involuntary contraction of a muscle, a group of muscles

• Spasticity is sustained muscle spasm or contractions or a condition in which certain muscles are continuously contracted.

Muscle relaxant is a drug which affects skeletal muscle function and decreases the muscle tone.

Muscle relaxants

Centrally acting muscle relaxant: Tolperisone, Baclofen

Direct acting muscle relaxant: Dantrolene

Baclofen

MODE OF ACTION

Baclofen is a GABA-B agonist which mimic the effect of GABA.

Baclofen inhibits both monosynaptic and polysynaptic reflexes in both pre & postsynaptic mechanism by stimulating the GABAB-receptors, which inhibits the release of glutamate and aspartate.

Moreover, Baclofen • Decreases calcium influx in presynaptic nerve• Increases the concentration of glycine, another

potent inhibitory neurotransmitter.

Baclofen also exerts an anti nociceptive effect by inhibiting substance P.

INDICATION

• Spasticity due to stroke, spinal cord injury

• Muscle spasm

• Muscular rigidity

• Low back pain

And

• Trigeminal neuralgia (Jaw and facial pain)

• Dysfunctional voiding (Urinary incontinence)

• Hiccup

Dosage and administration

Tolperisone Hydrochloride

MODE OF ACTION

Tolperisone suppresses mono- and poly-synaptic reflex transmission by pre- and post-synaptic mechanisms, especially in pathologically increased reflexes.

Tolperisone

• inhibits voltage-gated Ca2+ channels. So decreases neurtransmitter release.

• inhibits voltage-gated Na+ channels. Hyperpolarizaiton takes place.

Tolperisone also increases the peripheral circulation through vasodilatory action.

INDICATIONS

• Painful muscle spasm associated with disorders of the locomotor system: Low back pain, sciatica,

osteroarthritis, rheumatoid arthritis, spondylosis

• Muscle spasticity associated with neurologicalconditions: Stroke, spinal cord injury, multiple sclerosis,

cerebral palsy.

• Decreased peripheral circulation:As seen in atherosclerosis, Raynaud’s disease, and

intermittent claudication.

• Rehabilitation: Treatment after limb fractures followed by long-term fixation; post-operative therapy of

traumatological and orthopedic limb surgery; rehabilitation of hemiplegic patients.

DOSAGE AND ADMINISTRATION

Adults: The total daily dosage is 150-450mg, divided into 3 equal doses, according to the individual requirement andtolerance of the patient.

Children: 3 months to 6 years, 5-10 mg/kg/day divided into three doses; 6 to 14 years, 4-12 mg/kg/day divided into three doses.