PHTH1011 005 NMBJ & Antispastic Drugs - Williams.pdf

Drugs acting on the Skeletal Muscle Systems (1 Hr.) Professor M. Gossell-Williams Dept. of Basic Medical Sciences, Pharmacology & Pharmacy section Email: [email protected] Lecture objectives To discuss the pharmacology of some of drugs used to: 1. 2. 3. induce skeletal muscle paralysis i...

Drugs acting on the Skeletal Muscle Systems (1 Hr.) Professor M. Gossell-Williams Dept. of Basic Medical Sciences, Pharmacology & Pharmacy section Email: [email protected] Lecture objectives To discuss the pharmacology of some of drugs used to: 1. 2. 3. induce skeletal muscle paralysis increase muscle strength treat Spastic disorders https://www.youtube.com/watch?v=t9sjIByjw70 AP PROPAGATION How does AP pass from motor unit down the sarcolemma? Ach released stimulates Nicotinic Na+ channels AP Creates threshold potential stimulating voltage sensitive Na+ channels AP propagation FILL IN THE BLANKS: ARRIVAL OF AN ACTION POTENTIAL AT A QUIZZIZ.COM __________________________ NERVE RESULTS IN THE RELEASE OF THE NEUROTRANSMITTER CALLED, ______________________. THE NEUROTRANSMITTER TRAVELS IN THE CLEFT CAUSING THE DEVELOPMENT OF ENDPLATE POTENTIAL THROUGH THE STIMULATION OF ________________________ CHANNELS. THE DEPOLARISATION GETS PROPAGATED DOWN THE MUSCLE VIA ________________CHANNELS. THIS ACTION OF THE NEUROTRANSMITTER CAN BE TERMINATED BY THE ENZYME ____________________________ The DRUGS Non-Depolarizing MIVACURIUM Depolarizing SUCCINYLCHOLINE PANCURONIUM Competitive blockade of nicotinic receptor inhibiting the actions of Ach Persistent depolarization inhibiting the passage of action potential through voltage sodium channel CLINICAL APPLICATIONS To produce muscle relaxation during General anaesthesia Endotracheal intubation Chemistry Charged N groups Similarity to Ach Very polar agents Pharmacokinetics ROUTE: IM or IV Usually 0-3- 1mg/kg BW by IV ONSET: < 5 MINS Duration of action ULTRASHORT (5-10 MINS): SUCCINYLCHOLINE, MIVACURIUM LONG ACTING (30-120 MINS): PANCURONIUM Metabolism/Elimination SUCCINYLCHOLINE, MIVACURIUM: pseudocholinesterases PANCURONIUM: renal Adverse Drug Reactions MUSCLE FASCICULATION WITH SUCCINYLCHLOINE = POST OPERATIVE PAIN HISTAMINE RELEASE HYPERKALEMIA MALIGNANT WITH SUCCINYLCHOLINE HYPERTHERMIA WITH SUCCINYLCHOLINE Genetic disorder of skeletal muscle calcium regulation, resulting in uncontrolled skeletal muscle hypermetabolism SKELETAL MUSCLE RELAXANTS Clinical applications: to relieve the spasticity occurring with conditions such as cerebral palsy, multiple sclerosis, spinal cord injury, stroke. DANTROLENE o INHIBITS THE RELEASE OF CA2+ FROM SR. o PREVENTING SKELETAL MUSCLE EXCITATIONCONTRACTION COUPLING BALCLOFEN Agonist at GABA-B receptors in the spinal cord Action is at pre-synaptic and post-synaptic receptors to reduce motor neuron activation DIAZEPAM o GABA-A potentiation o At spinal cord and brain to decrease motor neuron activation 3/8/2024 http://accessphysiotherapy.mhmedical.com/data/Books/panu/panu_c033f005.gif 9 PHARMACOKINETICS Drug BACLOFEN Route M/E Notes O (good) (1-100 mg/bid) t ½ 3-4 h R most widely used DANTROLENE O t½ = 9h H ADRS: hepatotoxicrequires monitoring DIAZEPAM O (good) t1/2 = 60 h H IV Active metabolites Causes significant sedation 3/8/2024 1 0 PYRIDOSTIGMINE MOA: Reversible inhibition of acetylcholinesterase =accumulation of acetylcholine. Route: orally well absorbed Clinical applications: to improve muscle strength in patients with myasthenia gravis. Elimination: renal S/E: Salivation, anorexia, nausea and vomiting. Abdominal cramps and diarrhoea may occur. Muscle cramps, fasciculation and weakness, cholinergic crisis 3/8/2024