tubocurarine

Action and Spectrum

Actions and Spectrum: 

Actions: 

Tubocurarine falls within the category of muscle relaxants, specifically classified as “competitive non-depolarizing neuromuscular blocking agents.” Referred to as “competitive neuromuscular blockers,” these drugs function within the peripheral nervous system, disrupting neuromuscular transmission by competing with the neurotransmitter acetylcholine. As a result, they diminish the response of acetylcholine receptors to subsequent nervous impulses. 

Spectrum: 

This medication is employed to induce muscle relaxation, excluding neuromuscular blocking agents. Its principal clinical and therapeutic application involves addressing muscle spasms and immobility linked to strains, sprains, and injuries to the back and, to a lesser extent, injuries to the neck. It is also used to treat a variety of clinical problems, including muscle spasms linked to illnesses like multiple sclerosis, which are conditions marked by hyperactivity of the skeletal muscles. 

Drug Interaction

Adverse Reaction

Frequency not defined 

Muscle weakness 

Rash 

Allergic reactions 

Hypotension 

Musculo-skeletal disorders 

Dyspnea 

Asthma 

Excessive release of histamine 

Reflex tachycardia 

Urticaria 

Reactions at the injection site 

Laryngospasm 

Bronchospasm 

Black Box Warning

Black Box Warning: 

Respiratory acidosis and hypokalemia amplify the blocking impact of tubocurarine, while respiratory alkalosis diminishes it. Individuals with myasthenia gravis exhibit heightened sensitivity to the blocking effects of nondepolarizing agents; consequently, the recommended dose should be significantly reduced. 

Contraindication / Caution

Contraindication/Caution: 

Contraindications 

• Hypersensitivity 

Cautions 

• Renal impairment 
• Dehydration 
• Altered pH of blood 
• Electrolyte imbalances 
• Hepatic impairment 
• Drug interactions 
• Pregnancy  
• Breastfeeding 

Pregnancy / Lactation

Pregnancy consideration:  

No data is available regarding the administration of the drug during pregnancy. 

Breastfeeding warnings:  

No data is available regarding the excretion of drug in breast milk. 

Pregnancy category: 

Category A: well-controlled and satisfactory studies show no risk to the fetus in the first or later trimester. 

Category B: there was no evidence of risk to the fetus in animal studies, and there were not enough studies on pregnant women. 

Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.    

Category D: adequate data with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits.    

Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women.    

Category N: No data is available for the drug under this category. 

Pharmacology

Pharmacology: 

Tubocurarine has been employed in anesthesia to achieve the required degree of muscle relaxation. Administered intravenously, its paralytic effects typically endure for approximately 20 minutes, with residual muscle weakness persisting for a few hours. Following administration, artificial ventilation becomes essential due to the paralysis of respiratory muscles. Tubocurarine has the tendency to reduce blood pressure by impeding transmission at the sympathetic ganglia. Additionally, it may induce bronchial constriction as it has the potential to release histamine in tissues. 

Pharmacodynamics: 

The plant alkaloid tubocurarine is a model for medications that block neuromuscular junctions, although it is not currently being used in clinical settings. It works as a long-acting, non-depolarizing blocker with a gradual onset. It functions as a competitive antagonist of acetylcholine (ACh) at nicotinic acetylcholine receptors (nAChR), blocking postsynaptic nAChRs to prevent the transmission of action potentials and, as a result, induce relaxation of skeletal muscle.

By using an anti-cholinesterase medication like neostigmine, one can reverse this kind of blockage and raise the relative concentration of ACh. Another neuromuscular blocking medication, atracurium, binds to the same location as ACh to stop the receptor-channel complex from being activated. 

Pharmacokinetics: 

Absorption 

The bioavailability is 100% 

The time to achieve peak effect is 2-5 minutes 

Distribution 

Protein-bound is 50% 

Vd is 0.2-0.4 L/kg 

Metabolism 

Approximately 1% of the tubocurarine dose is thought to undergo N-demethylation in the liver, and the resulting demethylated metabolite is also excreted in the bile. 

Elimination and Excretion 

The half-life is 1-3 hours 

The drug is excreted unchanged 43% in urine. 

Adminstartion

Administration: 

When tubocurarine is administered, it is typically delivered intravenously, meaning it is injected directly into the bloodstream. The specific dosage and rate of administration vary depending on the particular medical procedure, patient characteristics, and the desired level of muscle relaxation. The primary purpose of this drug is to induce temporary paralysis, aiding in specific medical interventions like facilitating intubation during surgery. 

Given the potential for side effects and complications associated with tubocurarine, including histamine release, hypotension, and prolonged muscle paralysis, its use demands careful consideration and monitoring. Healthcare professionals decide to use tubocurarine based on factors such as the patient’s medical condition, the nature of the procedure, and a comprehensive assessment of the associated risks and benefits. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: tubocurarine 

Pronounced: too-boh-KYUR-uh-reen 

Why do we use tubocurarine? 

Tubocurarine, derived from the bark of specific South American plants, particularly those within the Chondrodendron genus, is a neuromuscular blocking agent with a historical application as a skeletal muscle relaxant in surgical procedures. Its primary function is to induce muscle paralysis, proving beneficial in various medical scenarios, notably during surgery.

By blocking the nerve impulse transmission to the muscles, tubocurarine induces temporary paralysis of skeletal muscles, facilitating procedures like intubation, reducing muscle spasms, and aiding surgeons in their tasks. 

However, the utilization of tubocurarine has diminished over time due to the emergence of newer and safer neuromuscular blocking agents characterized by more predictable and controllable effects. Tubocurarine is associated with side effects and complications, including histamine release, hypotension, and prolonged muscle paralysis, contributing to its restricted use in contemporary medical practice.

Modern medicine tends to favor muscle relaxants with enhanced safety profiles and greater precision in controlling muscle relaxation. As always, the administration of such medications is conducted under the supervision and prescription of qualified healthcare professionals.