Cholinergic & Adnrenergic + NMJ, Anaesthetic Flashcards
Cholinergic & Adrenergic + NMJ, Anaesthetic
Direct-acting cholinomimetics : 4 choline esters (only 1 in the list)
Acetylcholine, Methacholine, Carbachol(B3), Bethanechol
Direct-acting cholinomimetics : 3 alkaloids (only 1 in the list)
Muscarine, Nicotine, Pilocarpine(B3)
Direct-acting cholinomimetics : 1 synthetic (not in the list)
Varenicline(not in the list)
About Acetylcholine(not in the list)
M and N, short half life, only use in opthalmology
About Methacholine(not in the list)
Non-selective, Methacholine provocation test, Challenge test for diagnosis of asthma(differential diagnosis of bronchial hyperactivity)
About Bethanechol(not in the list)
M, Oral, 30min-2hr, resistant to AChe, Non-obstructive ileus, Urinary retention
About Carbachol(B3)
M and N, Topical, resistant to AChe, Constricts pupil and relieves intraocular pressure in open-angle glaucoma
About Muscarine(not in the list)
M, Quatenary amine, Mushroom posion
About Nicotine(not in the list)
N, tertiary amine, plant-derived poison
About Pilocarpine(B3)
M, Oral, tertiary amine, 30-2hr, Glaucoma(eye drop), Xerostomia(sjogren syndrome)
About Varenicline(not in the list)
N partial agonist, smoking cessation
Indirect-acting cholinomimetics : acetylcholinesterase inhibitors : 6 carbamates
Neostigmine(B3), Pyridostigmine(B3), Physostigmine, Rivastigmine(B3), Galantamine(not in the list), Donepezil (not in the list)
Indirect-acting cholinomimetics : acetylcholinesterase inhibitors : 3 organophosphates (not in the list)
Malathion, Parathion, Sarin
Indirect-acting cholinomimetics : acetylcholinesterase inhibitors : 1 Alcohol
Edrophonium(B3)
AchE inhibitors poisoning (Muscarinic effects)
DUMBBELS D: Diarrhea U: Urination M: Miosis B: Bradycardia B: Bronchoconstriction E: Excitation(CNS, muscles) L: Lacrimation S: Secretion
About Neostigmine
Quaternary amine, 2-4 h, Myasthenia gravis, Non-obstructive ileus, Urinary retention
About Pyridostigmine
Quaternary amine, 3-6h, Myasthenia gravis
About Physostigmine
Tertiary amine, 0.5 2h, Antidote in atropine overdose (iv), Glaucoma treatment(topical)
About Rivastigmine, Galantamine, Donepezil
Tertiary amine, half life 70hr, Alzheimer disease(transdermal patch)
About Malathion, Parathion(not in the list)
Drug activation via P450 reaction (Malaoxon, Paraoxon) Insecticide
About Sarin(not in the list)
Rapid action, Nerve gas(lethal)
About Edrophonium(B3)
half life (5-10min), no CNS effect Diagnosis of Myasthenia gravis(improved muscle tone->positive diagnosis) Differential diagnosis (Tensilon test) : cholinergic crisis vs Myasthenia crisis
Indirect-acting cholinomimetics : acetylcholinesterase inhibitors : Competitive 2 drugs (only one in the list)
Edrophonium (B3), doenepezil (not in the list)
Indirect-acting cholinomimetics : acetylcholinesterase inhibitors : non competitive 4 drugs (1 not in the list)
Physostigmine (not in the list), Rivastigmine(B3), Neostigmine(B3), Pyridostigmine(B3)
Cholinoceptor blockers-cholinergic antagonists : 10 muscarinic antagonists (1 not in the list)
Atropine(B4), Cyclopentolate(B4), Scopolamine(B4), Butyl-scopolamine(B4), Procyclidine(B4, A34), Benztropine(not in the list), Solifenacin(B4), Oxybutynin(B4), Ipratropium(B4), Tiotropium(B4)
About Atropine(B4)
Non-selective, Alkaloid, Plant-derived, Tertiary amine, 2–4 h action Mydriatic and cycloplegic agent - ophthalmology Antispasmodic, antisecretory, antidiarrheal Reverasal of AV block Management of Bradyarrhthmia (iv) Antidote for Cholinesterase inhibitor toxicity
About Cytclopentolate(B4)
Non-selective, Mydriatic and cycloplegic agent (eyedrop)
About Scopolamine(B4)
Non-selective, Tertiary amine, Motion sickness (transdermal patch)
About Butyl-scopolamine(B4)
Non-selective, no CNS effects used to treat pain and discomfort caused by abdominal cramps, menstrual cramps, or other spasmodic activity in the digestive system
About Procyclidine(B4, A34), Benztropine(not in the list)
Non-selective, Tertiary amine, Oral, Parenteral Parkinson disease
About Solifenacin(B4), Oxybutynin(B4)
Modest selectivity for M3, Oral, Transdermal patch Urinary incontinence
About Ipratropium(B4)
Non-selective, inhaled, Bronchodilator for asthma/COPD - Side effects: dry mouth, cough
About Tiotropium(B4)
M3-selective, longer duration, inhaled Bronchodilator for asthma/COPD - Side effects: dry mouth, cough
Cholinoceptor blockers-cholinergic antagonists : 3 tertiary tropeins (2 in the list)
Atropine(B4), Scopolamine(B4), Benztropine (not in the list)
Cholinoceptor blockers-cholinergic antagonists : 4 synthetic drugs with tertiary amine
Procyclidin(A34, B4), Cyclopentolate(B4), Solifenacine(A35), Oxybutynin(A35)
Cholinoceptor blockers-cholinergic antagonists : 3 Quaternary tropeins
Butyl-scopolamine(A35, B4), Ipratropium(B4), Tiotropium (B4)
Adverse effects- Muscarinic antagonists
- Decreased secretions (salivary, bronchiolar, sweat) - Mydriasis, cycloplegia → blurred vision - Hyperthermia (with resulting vasodilation) - Tachycardia - CNS effects (sedation, hallucination) - Urinary retention - Constipation
Cholinesterase regenerators (not in the list)
Pralidoxime(2-PAM) Chemical antagonist of organophosphate Antidote for organophosphate poisoning
3 Drugs for pre-synaptic inhibition (one in the list)
Hemicholinium : Inhibits transport of choline into the nerve terminal Vesamicol : Inhibits transport of Ach into storage vesicles Botulinum toxin(B9) : Inhibits release of Ach-loaded vesicles (interfere with SNARE proteins), Blepharospasm, hyper-hydrosis, dystonia, Cosmetics
Botulinum toxin(B9)
Direct-acting muscle relaxants - Prevents synaptic exocytosis through inhibition of SNARE fusion proteins in presynaptic nerve terminals → flaccid paralysis - Direct injection into muscle - Duration of action 2-3 months - Upper and lower limb spasm due to cerebral palsy, multiple sclerosis - Cervical dystonia - Migraine - Overactive bladder - Hyperhidrosis - Cosmetics
2 Drugs for pre-synaptic stimulation (not in the list)
4-aminopyridine : K+-channel blocker → membrane depolarization → Ca2+ influx → release of Ach alpha-Latrotoxin : Creates pores along membrane → Ca2+ influx → release of Ach (Spider venom)
5 Direct-acting sympathomimetics (catecholamines)
Epinephrine, Norepinephrine, Dopamine, Isoprenaline (Isoproterenol), Dobutamine
About Epinephrine (B5)
α1, α2, β1, β2 Pharmacologically: - Parenteral administration only (no oral) - Short duration of action - No CNS entry Dose-dependent effects: - Low-dose: β1, β2 stimulation predominates (HR, SV, CO, pulse pressure ↑, TPR, BP ↓, bronchodilation) - High-dose: α1 stimulation predominates (TPR, BP ↑, reflex bradycardia) Pharmacological indications: - Cardiac arrest, complete heart block - Anaphylactic (distributive) shock - Hypotensive emergency - Adjunct to local anesthetics (reduce local blood flow) - Acute asthma attack Side effects: hypertension, arrhythmia, stroke, myocardial infarction, pulmonary edema
About Norepinephrine (B5)
α1, α2, β1 Pharmacologically: - Parenteral administration only (no oral) - Short duration of action - No CNS entry - Cardiac arrest, complete heart block - Hypotensive emergency - Adjunct to local anesthetics (reduce local blood flow) - Shock (cardiogenic, neurogenic, septic) Side effects: vasospasm, tissue necrosis, hypertension, arrhythmia, infarction
About Dopamine (B5)
D1, α1, α2, β1, β2 Pharmacologically: - Parenteral administration only (no oral) - Short duration of action - No CNS entry Dose-dependent effects: - Low-dose: D1 stimulation (renal perfusion↑) - Medium dose: β1 stimulation (cardiac stimulation) - High-dose: acts like epinephrine (loses selectivity) Pharmacological indications: - Shock (especially with renal failure) Side effects: arrhythmia
About Isoprenaline (Isoproterenol) (B5)
β1 = β2 - Parenteral administration - Cardiac arrest, complete heart block (IV) - Acute asthma attack (nebulizer)
About Dobutamine
β1 > β2 >>> (α1) - Parenteral administration - Cardiogenic shock - Acute heart failure - Cardiac stimulation in cardiac stress-test
7 α-agonists (non-catecholamines)
Phenylephrine, Oxymetazoline, Clonidine, Rilmenidine, Methyldopa, Brimonidine, Tizanidine
About Phenylephrine (B6)
α1-agonist - Not inactivated by COMT – longer duration of action compared to catecholamines - Oral, parenteral - Duration of action 15-60 min’ - Ophthalmologic use (mydriatic agent) - Decongestant - Hypotension treatment (TPR↑, mean BP↑) Side effects: reflex bradycardia, hypertension, stroke, MI, ischemic changes of mucus membrane
About Oxymetazoline (B6)
Local α1-agonist Systemic α2-agonist - Topical - Decongestant Side effects: hypotension due to α2 clonidine-like effect
About Clonidine (B6)
α2-agonist I2-agonist - Imidazole derivative → agonist for both imidazole receptor (I2) and α2 receptors - Oral or transdermal patch - Antihypertensive (pre-synaptic sympatholytic effect) - Attention-deficit hyperactivity disorders (ADHD) - Tourette’s syndrome - Alcohol/opiates withdrawal syndrome Side effects: sedation, dry mouth, severe rebound hypertension if suddenly stopped, drug-induced lupus
Rilmenidine (B6)
α2-agonist, I2-agonist -Imidazole derivative → agonist for both imidazole receptor (I2) and α2 receptors - Antihypertensive (pre-synaptic sympatholytic effect) Side effects: milder compared to clonidine
Methyldopa (B6)
α2-agonist, I2-agonist - Imidazole derivative → agonist for both imidazole receptor (I2) and α2 receptors - Antihypertensive (pre-synaptic sympatholytic effect) Side effects: sedation, drug-induced lupus
Brimonidine (not in the list)
α2-agonist - Topical (eye drops) - Glaucoma (aqueous humour production ↓)
Tizanidine (B9)
α2-agonist - Oral - Centrally-acting muscle relaxant
4 Release-inducing agents Displace stored catecholamines from nerve endings
Amphetamine, Methylphenidate, Tyramine, Ephedrine
Amphetamine (not in the list)
- Enter CNS - Resistant to metabolism by MAO - long duration of action - Attention-deficit hyperactivity disorders (ADHD) - Central nervous system disorders (narcolepsy) - Psychostimulant due to central release of DA, NE, 5-HT - Appetite suppression - Drug of abuse (high addiction liability) Side effects: seizures, aggression, insomnia, hypertension
Methylphenidate (not in the list)
- Amphetamine derivative - Attention-deficit hyperactivity disorders (ADHD) - Narcolepsy
Tyramine (not in the list)
- Oral bioavailability is limited due to rapid metabolism by MAO-A in gut and liver - MAO-A inhibition results in increased bioavailability, potential hypertensive crisis (“cheese effect”) - No clinical use - Found in fermented foods (red wine, cheese) - Psychoactive peripheral sympathomimetic effects
Ephedrine (B6)
- Plant-derived alkaloid - Oral bioavailability ↑, duration of action ↑ - Direct and indirect sympathomimetic effects - Stimulant, appetite suppressant, concentration aid - Decongestant - Treatment of hypotension associated with anaesthesia - Lower addiction liability than amphetamines
3 Reuptake inhibitors Increase the activity of neurotransmitters in the synapse by inhibiting their reuptake into the pre-synaptic nerve terminal
Cocaine, Atomoxetine, Modafinil
Cocaine (A5)
- Enter CNS - Inhibits both NET and DAT - Drug of abuse - Local anesthetic + vasoconstrictor Side effects: hypertension, coronary spasm, chest pain, acute MI, arrhythmias, seizures
Atomoxetine(not in the list)
- Selective NE reuptake inhibitor - Attention-deficit hyperactivity disorders (ADHD)
Modafinil (not in the list)
- Inhibits both NET and DAT - Improve wakefulness in narcolepsy and other conditions
3 MAO inhibitors Inhibit the metabolism of catecholamines by monoamine oxidase enzyme (MAO)
Tranylcypromine, Moclobemide, Selegiline
Tranylcypromine (not in the list)
Non-selective - Irreversible inhibitor - Antidepressant (no longer in clinical use)
Moclobemide (A29)
MAO-A selective - Reversible inhibitor - Antidepressant
Selegiline (A34)
MAO-B selective - Reversible inhibitor - Parkinson disease
Direct-acting sympatholytics – α adrenoreceptor antagonists : 2 Non-selective α-receptor antagonists (only 1 in the list)
Phentolamine(B7), Phenoxybenzamine (not in the list)
Phentolamine(B7)
non-selective - Reversible inhibition - Duration of action 2-4 h’ orally, 20-40 min’ parenterally - Pre-operative management of pheochromocytoma - Antidote in case of acute hypertension due to α-agonist overdose (cocaine, amphetamine, tyramine) Side effects: orthostatic hypotension with subsequent reflex tachycardia
Phenoxybenzamine (not in the list)
α non-selective - Irreversible, non-competitive inhibition (covalent binding to the receptor) - Duration of action up to 48 h’ - Pre-operative management of pheochromocytoma - Antidote in case of acute hypertension due to α-agonist overdose (cocaine, amphetamine, tyramine) Side effects: orthostatic hypotension with subsequent reflex tachycardia
Direct-acting sympatholytics – α adrenoreceptor antagonists : 5 Selective α-receptor antagonists (3 in the list)
Prazosin(B7), Doxazosin(B7), Tamsulosin(B7), Urapidil(not in the list), Mirtazapine(not in the list)
Prazosin(B7)
α1-selective - Oral - Duration of action 8-24 h’ - Hypertension - Benign prostatic hyperplasia (BPH) → relax the muscle of the prostate and bladder neck, which allows urine to flow more easily Side effects: orthostatic hypotension (mainly in first doses)
Prazosin(B7), Doxazosin(B7), Tamsulosin(B7)
α1-selective - Oral - Duration of action 8-24 h’ - Hypertension - Benign prostatic hyperplasia (BPH) → relax the muscle of the prostate and bladder neck, which allows urine to flow more easily Side effects: orthostatic hypotension (mainly in first doses)
Urapidil(not in the list)
α1 antagonist α2 weak agonist 5-HT weak agonist β antagonist - Oral - Hypertension, hypertensive crisis - Benign prostatic hyperplasia (BPH)
Mirtazapine(not in the list)
α2-selective - Oral - Antidepressant (inhibitory effect on pre-synaptic α2-receptors in CNS → increased release of NE and 5-HT)
Direct-acting sympatholytics – β adrenoreceptor antagonists : 4 Non-selective β-receptor antagonists
Propranolol(B8), Timolol(B8), Pindolol(B8), Sotalol(B8, B16)
Propranolol(B8)
β non-selective - Oral, parenteral - High lipid-solubility (freely enter CNS) - Duration 4-6 h’ - Local anesthetic effect (inhibit Na+ channels) - Angina (HR↓ → diastolic perfusion↑, O2 demand ↓) - Anti-arrhythmic class II (treatment and prophylaxis) - Hypertension - Thyrotoxicosis - Migraine (prophylaxis) - Essential tremor
Pindolol(B8)
β non-selective - Intrinsic sympathomimetic activity (ISA) - Local anesthetic effect (inhibit Na+ channels) - Hypertensive treatment in asthmatic/COPD patients - Should be avoided in HF
Timolol(B8)
β non-selective - Topical - Glaucoma (aqueous humor production ↓)
Sotalol(B8, B16)
β non-selective K+-channel antagonist - Oral - Duration if action 7 h’ - Anti-arrhythmic class III (ventricular arrhythmias, AF) - Side effects: dose-dependent Torsade-de-Pointes
Direct-acting sympatholytics – β adrenoreceptor antagonists : 5 Selective β-receptor antagonists (cardio-selective) (4 in the list)
Metoprolol(B8), Bisoprolol(B8), Nebivolol(B8), Esmolol(B8, B16), Acebutolol(Not in the list)
Metoprolol(B8)
β1-selective - Duration 6-9 h’ - Local anesthetic effect (inhibit Na+ channels) - Hypertension - Congestive heart failure (reduce mortality) - Angina pectoris - Anti-arrhythmic - Acute coronary syndrome (ACS)
Bisoprolol(B8)
β1-selective - Long duration of action (10-12 h’) - Hypertension - Congestive heart failure (reduce mortality) - Angina pectoris - Anti-arrhythmic - Acute coronary syndrome (ACS)
Nebivolol(B8)
β1-selective - NO-dependent vasodilating action - Hypertension - Congestive heart failure (reduce mortality) - Angina pectoris - Anti-arrhythmic - Acute coronary syndrome (ACS)
Esmolol(B8, B16)
β1-selective - IV - Short duration of action (∼10 min’) - Arrhythmias associated with thyroid-storm or perioperative (acute management) - Hypertensive emergencies
Acebutolol (Not in the list)
β1-selective - Intrinsic sympathomimetic activity (ISA) - Hypertensive treatment in asthmatic/COPD patients
Direct-acting sympatholytics – β adrenoreceptor antagonists : 2 Combined α and β receptors antagonists
Carvedilol(B7, B8), Labetalol (not in the list)
Carvedilol(B7, B8)
β1 β2 antagonist α1-antagonist - Oral, IV - Duration of action 5 h’ - Congestive heart failure (reduce mortality) - Hypertension - Hypertensive emergencies (IV)
Labetalol (not in the list)
β1 β2 antagonist α1-antagonist - Oral, IV - Duration of action 5 h’ - Congestive heart failure (reduce mortality) - Hypertension - Hypertensive emergencies (IV)
2 Indirect-acting sympatholytic (not in the list)
Metyrosine, Reserpine
Metyrosine(not in the list)
- Competitive inhibitor of tyrosine hydroxylase enzyme (rate-limiting step in endogenous catecholamine synthesis) - Reduces synthesis of dopamine, norepinephrine, and epinephrine - Pheochromocytoma
Reserpine(not in the list)
Inhibits uptake of norepinephrine into storage vesicles, resulting in depletion of catecholamines and serotonin from central and peripheral axon terminals - Antihypertensive - Antipsychotic - Huntington’s disease (adverse effects limit its clinical use)
Local Anesthetics : 3 amides
Lidocain(A5, B16), Articaine(A5), Bupivacaine (A5)
Lidocain(A5, B16)
- Topical use or injection (perineural, epidural, subarachnoid); rarely used IV - Hepatic metabolism via CYP450 - Duration of action 1-2 h’, with epinephrine 2-4 h’ - Short-duration, local surgical procedures (dental, ophthalmology, throat, urology, obstetrics) - Post-operative analgesia - Produce autonomic blockade in ischemic conditions - Side effects: excitation, seizures, vasodilation, hypotension, arrhythmias *Risk of drug-induced methemoglobinemia
Articaine(A5)
- Onset of action is the most rapid of all local anesthetics - Short-duration, local surgical procedures (dental, ophthalmology, throat, urology, obstetrics) - Post-operative analgesia - Produce autonomic blockade in ischemic conditions - Side effects: excitation, seizures, vasodilation, hypotension, arrhythmias *Risk of drug-induced methemoglobinemia
Bupivacaine (A5)
- Parenteral (usually not topical or IV) - Hepatic metabolism via CYP450 - Duration of action 3-6 h’ - Longer-duration, local surgical procedures - Side effects: CNS toxicity, cardiovascular collapse
Local Anesthetics : 3 Esters (1 in the list)
Procaine(not in the list), Tetracaine(not in the list), Cocaine(A5)
Procaine(not in the list)
- Parenteral (usually not topical or IV) - Metabolism by plasma cholinesterase (pseudocholinesterase) - Duration of action 30-60 min’, with epinephrine 60-90 min’ - Short-duration, local surgical procedures - Side effects: excitation, seizures, vasodilation, hypotension, arrhythmias
Tetracaine(not in the list)
- Duration of action 2-3 h’ - Used primarily for spinal anesthesia
Cocaine(A5)
- Intrinsic sympathomimetic effect due to its inhibition of norepinephrine reuptake into nerve terminals - Topical or parenteral - Metabolism by plasma cholinesterase (pseudocholinesterase) - Duration of action 1-2 h’ - Procedures requiring high surface activity and vasoconstriction - Drug of abuse - Side effects: CNS excitation (psychostimulant), convulsions, cardiac arrhythmias, hypertension, coronary vasospasm *except for cocaine, all local anesthetics are vasodilators
About Neuromuscular blocking agents
Act locally, at the level of the neuromuscular junction, to produce muscle paralysis 1. Non-depolarizing agents Competitive antagonists at skeletal muscle Ach nicotinic receptors (NM); parenteral administration Indications: - Prolonged relaxation for surgical procedures - Relaxation of respiratory muscles to facilitate mechanical ventilation in ICU patients - Epileptic seizure (convulsion) not responding to antiepileptics - Intoxication with certain drugs (theophylline, amphetamine) 2. Depolarizing agents - Agonist at skeletal muscle Ach nicotinic receptors (NM); may stimulate ganglionic nicotinic Ach receptor (NN) and cardiac muscarinic Ach receptors (M3) - Phase I → membrane depolarizes, resulting in an initial discharge that produces transient contraction (fasciculations/twitch), followed by flaccid paralysis - Phase II → membrane repolarizes, but receptor is desensitized to the effect of Ach (succinylcholine is still bound to the receptor)
Neuromuscular blocking agents : Non-depolarizing agents : 4 isoquinoline
D tubocurarine(B10), Atracurium(B10), Cisatracurium(B10), Mivacurium(B10)
D tubocurarine(B10)
isoquinoline Intermediate-acting (25-45 min’) Renal mechanism - Histamine release (hypotension) - Prolonged apnea (muscle weakness)
Atracurium(B10)
isoquinoline Intermediate-acting (25-45 min’) Spontaneous metabolism - Histamine release (hypotension) - Muscle spasm (muscle weakness)
Cisatracurium(B10)
isoquinoline Intermediate-acting (25-45 min’) Spontaneous metabolism - Histamine release (hypotension) - Prolonged apnea (muscle weakness)
Mivacurium(B10)
isoquinoline Short-acting (10-15 min’) Pseudocholinesterase (metabolism) - Histamine release (hypotension) - Prolonged apnea (muscle weakness)
Neuromuscular blocking agents : Non-depolarizing agents: 4 steroids (2 in the list)
Pancuronium(B10), Rocuronium(not in the list), Vecuronium(not in the list), Pipecuronium(B10)
Pancuronium(B10)
Long-acting (60-180 min’) Renal metabolism - M2-inhibition (tachycardia) - NE reuptake inhibition
Rocuronium(not in the list)
Intermediate-acting (25-45 min’) Hepatic metabolism - Prolonged apnea (muscle weakness)
Vecuronium(not in the list)
Intermediate-acting (25-45 min’) Hepatic metabolism - Prolonged apnea (muscle weakness)
Pipecuronium(B10)
Long acting (60 180 minutes) renal metabolism
Neuromuscular blocking agents : 1 depolarizing agents:
Succinylcholine(B10)
Succinylcholine(B10) (suxamethonium)
-Selective agonist of the Nm receptor receptor and the acetylcholinesterase does not metabolize it - Parenteral - Duration of action 5 min’ - Rapid metabolism by pseudocholinesterase in the blood then in liver - Surgical procedures where a rapid onset and brief duration is needed (intubation, endoscopy, ECT) - Side effects: arrhythmias(mainly bradycardia), hyperkalemia, transient increased intra-abdominal and intraocular pressure, postoperative muscle pain, Malignant hyperthermia (highlighted in the lecture)
About Spasmolytic agents
Act centrally, at the level of the CNS, to reduce abnormal muscle tone caused by neurologic/muscle end-plate disease (causing spasm and associated muscle pain). The goal is to reduce excessive skeletal muscle tone without reduction of strength; reduced muscle spasm results in reduction of pain and improved morbidity.
4 Spasmolytic agents
Diazepam(A25, A33,B9), Baclopen(B9), Tizanidine(B9), Tolperisone(B9)
Diazepam(A25, A33,B9)
GABAA agonist - Increases interneuron inhibition of primary motor afferents in spinal cord - Hepatic metabolism - Duration of action 12-24 h’ - Chronic spasm due to cerebral palsy, stroke, spinal cord injury - Acute spasm due to muscle injury - Side effects: CNS depressant actions, tolerance, dependent liability
Baclopen(B9)
GABAB agonist - Pre- and postsynaptic inhibition of motor output in the spinal cord - Oral, intrathecal - Spasm due to cerebral palsy, multiple sclerosis, stroke - Side effects: sedation, weakness,
Tizanidine(B9)
α2 agonist - Pre- and postsynaptic inhibition of reflex motor output in the spinal cord - Oral - Renal and hepatic elimination - Duration of action 3-6 h’ - Spasm due to multiple sclerosis, stroke, amyotrophic lateral sclerosis - Side effects: weakness, sedation, hypotension, hepatotoxicity (rare), rebound hypertension upon abrupt withdrawal
Tolperisone(B9)
- Poorly understood inhibition of muscle stretch reflex in spinal cord and brain stem → reduction of muscle reflexes - Mechanism involved inhibition of Na+ and Ca2+ channels - Oral - Acute spasm due to muscle injury - Not used in chronic spasm - Side effects: sedation, confusion, ocular effects, strong anti-muscarinic effect
2 Direct-acting muscle relaxants
Dantrolene(9), Botulinum toxin(B9)
Dantrolene(9)
- RyR1 antagonist → Blocks Ca2+-release channels in the sarcoplasmic reticulum of skeletal muscle → reduces actin-myosin interaction - IV, oral - Duration of action 4-6 h’ - Malignant hyperthermia (IV) - Spasm due to cerebral palsy, spinal cord injury, multiple sclerosis (oral) - Side effects: muscle weakness, hepatotoxicity
Botulinum toxin(B9)
- Prevents synaptic exocytosis through inhibition of SNARE fusion proteins in presynaptic nerve terminals → flaccid paralysis - Direct injection into muscle - Duration of action 2-3 months - Upper and lower limb spasm due to cerebral palsy, multiple sclerosis - Cervical dystonia - Migraine - Overactive bladder - Hyperhidrosis - Cosmetics
