Neuromuscular blocking agents

What are muscle relaxants?

Drugs that affect muscle tone

What are the two major groups of muscle relaxants?

Neuromuscular blockers and spasmolytics

How do neuromuscular blockers act?

Interfere with transmission at neuromuscular end plate causing paralysis without CNS activity

What are neuromuscular blockers used for?

Adjuncts to general anesthesia

How do spasmolytics act?

Centrally and peripherally to reduce tone without loss of voluntary power

What are spasmolytics used for?

Chronic spastic conditions, acute spasms, tetanus, musculoskeletal pain

What is curare?

Mixture of alkaloids like tubocurarine used historically as poison and muscle relaxant

What is the site of action of neuromuscular blockers?

Neuromuscular junction of skeletal muscle fibers

What receptor is targeted by neuromuscular blockers?

Nicotinic NM cholinergic receptor

Neuromuscular blockers are analogues of which neurotransmitter?

Acetylcholine

What are the two classes of neuromuscular blockers?

Non‑depolarizing (competitive antagonists) and depolarizing (agonists)

Examples of non‑depolarizing blockers?

Tubocurarine, Pancuronium, Vecuronium, Rocuronium

Example of depolarizing blocker?

Succinylcholine (suxamethonium)

MOA of non‑depolarizing blockers?

Bind NM receptor, prevent ACh binding, block Na+ channel opening → flaccid paralysis

How can non‑depolarizing blockade be reversed?

By anticholinesterase drugs like neostigmine or ↑ACh concentration

Do non‑depolarizing blockers affect consciousness or pain?

No, only paralysis

Order of paralysis with non‑depolarizing blockers?

Eye muscles → facial muscles → limbs/pharynx → respiratory muscles

Onset and duration of tubocurarine?

Slow onset >5 min, long duration 1–2 hrs

ADRs of tubocurarine?

Hypotension, histamine release, bronchospasm

Onset and duration of pancuronium?

Intermediate onset 2–3 min, long duration

ADRs of pancuronium?

Tachycardia, less hypotension

Onset and duration of vecuronium?

Intermediate onset, intermediate duration 30–40 min

ADRs of vecuronium?

Minimal

Onset and duration of rocuronium?

Fast onset ~2 min, intermediate duration 30–40 min

ADRs of rocuronium?

Minimal

MOA of depolarizing blockers?

Bind NM receptor, open Na+ channels, cause depolarization → fasciculations then flaccid paralysis

Why does succinylcholine cause prolonged depolarization?

Not metabolized by AChE, dissociates slowly, keeps Na+ channels inactivated

Phases of succinylcholine action?

Phase I fasciculations, Phase II flaccid paralysis

How is succinylcholine metabolized?

By plasma pseudocholinesterase (butyrylcholinesterase)

Duration of succinylcholine action?

Short 5–8 min

Can anticholinesterases reverse succinylcholine?

No, they prolong its effect

Clinical uses of succinylcholine?

Intubation, laryngoscopy, bronchoscopy, laryngospasm, short orthopedic manipulations, adjunct to ECT

Clinical uses of non‑depolarizing blockers?

Prolonged surgery, muscle relaxation, assisted ventilation

ADR of succinylcholine: bradycardia mechanism?

Direct muscarinic receptor action on heart

How to prevent succinylcholine‑induced bradycardia?

Atropine

Why does succinylcholine cause postoperative pain?

Due to fasciculations correlating with pain severity

Why does succinylcholine cause hyperkalemia?

K+ release from damaged cells especially burns or trauma

Consequence of succinylcholine‑induced hyperkalemia?

Cardiac arrhythmias

Why does succinylcholine cause prolonged apnea?

Genetic deficiency or atypical pseudocholinesterase

What is malignant hyperthermia?

Rare autosomal dominant disorder triggered by succinylcholine + inhaled anesthetics

Pathophysiology of malignant hyperthermia?

Abnormal RyR → excessive Ca2+ release from SR → muscle contraction + heat

Symptoms of malignant hyperthermia?

Hyperthermia >40°C, tachycardia, tachypnea, acidosis, rigid muscles, rhabdomyolysis

Lab findings in malignant hyperthermia?

↑ CK, hyperkalemia

Treatment of malignant hyperthermia?

Dantrolene

Which drug shortens tubocurarine action?

Neostigmine

Which drug potentiates succinylcholine malignant hyperthermia risk?

Halothane

Which agents reduce effect of non‑depolarizing blockers?

Cholinesterase inhibitors like neostigmine

Which agents potentiate non‑depolarizing blockers?

Halothane, aminoglycosides, calcium channel blockers, benzodiazepines

Which agents potentiate depolarizing blockers?

Inhaled anesthetics like halothane

MOA of diazepam as spasmolytic?

Binds GABAA receptor, enhances GABA transmission → muscle relaxation without paralysis

Clinical uses of diazepam?

Spastic neurological diseases, tetanus, epilepsy, ECT, orthopedic manipulations, anxiety

What is baclofen?

GABA analogue activating GABAB receptors in spinal cord → depresses reflexes

Clinical use of baclofen?

Spasticity in MS or spinal cord lesions

What is tizanidine?

Central α2 agonist inhibiting excitatory amino acid release in spinal interneurons

Clinical uses of tizanidine?

Spastic neurological diseases, temporomandibular joint disorder

MOA of dantrolene?

Acts peripherally on RyR Ca2+ channels in SR, prevents Ca2+ release → muscle relaxation

Clinical uses of dantrolene?

Spastic syndromes, malignant hyperthermia, neuroleptic malignant syndrome

ADRs of dantrolene?

Severe muscle weakness, hepatotoxicity, sedation, respiratory depression, blurred vision

What are botulinum toxins?

Toxins from Clostridium botulinum (Botox, Dysport, Myobloc)

MOA of botulinum toxins?

Block ACh release → flaccid paralysis

Duration of botulinum toxin effect?

3–4 months

Route of administration of botulinum toxins?

Local IM or intradermal injection

ADRs of botulinum toxins?

Respiratory paralysis from spread, anaphylaxis

Clinical uses of botulinum toxins?

Strabismus, blepharospasm, cerebral palsy spasticity, stroke spasticity, hyperhidrosis, sialorrhea, cosmetic wrinkles

Difference in site of action between depolarizing and non‑depolarizing blockers?

Both act at NMJ

Difference in receptor target between depolarizing and non‑depolarizing blockers?

Both target NM cholinergic receptor

Difference in effect on ACh between depolarizing and non‑depolarizing blockers?

Non‑depolarizing are antagonists, depolarizing are agonists

Difference in Na+ channel action between depolarizing and non‑depolarizing blockers?

Non‑depolarizing prevent opening, depolarizing open channels

Difference in muscle AP between depolarizing and non‑depolarizing blockers?

Non‑depolarizing block depolarization, depolarizing cause depolarization

Difference in paralysis pattern between depolarizing and non‑depolarizing blockers?

Non‑depolarizing cause flaccid paralysis, depolarizing cause fasciculations then flaccid paralysis