Myorelaxing activity of Curare and its use in anesthesia
Tortone Francesca, Repetto Caterina
The term Curare is the phonetic transcription of the local word wurari, from the Carib language of the Macusi Indians of Guyana. It indicates a number of complex products of different botanic and geographical origins, but with the same pharmacological action.
Curare was used by natives of Central and South America to poison arrows of blowguns, used to hunt. In fact, it causes flaccid paralysis of the animal that dies suffocated but that can be eaten because the poison acts only by parenteral way. Only in more recent times Curare was used as war poison.
The making of Curare was done using species of the family of Menispermiaceae and Loganiaceae. Very often other products considered toxic were added to the mixture (snake liver, Capsicum anuum and others). The resulting solution was boiled and concentrated to the consistence of a soft extract.
The active ingredients of Curare are alkaloids of isochinolinic -type in Menispermiaceae, indolic-type in Loganiaceae; their activity, however, is identical. (Curares and timbos, poisons used in the Amazon, 2012.)
(De Castro P., Marsili D., Il curaro degli Indios dell'amazzonia da veleno a farmaco. Il ruolo di G.B. Marini Bettolo e dell'istituto superiore di sanità, Roma, De Vittoria srl, 2013.)
They act blocking the transmission of nerve impulses at the level of the endplate and are only active if administered by parenteral way. There is therefore a progressive paralysis of different muscles, up to the abdominal muscles and the diaphragm, for which there is respiratory arrest. The effect of Curare is reversible. In fact if the respiratory arrest is immediately prevented by artificial respiration, muscle function is resumed.
Of Curare is used only tubocurarine.
Synthetic molecules characterized by structural similarities with natural curare are currently preferred to it. They are used in surgery to:
- Facilitate tracheal intubation;
- Ensure muscular flaccid paralysis and prevents reflex movements and / or contractures of the patient during the surgery in order to facilitate the action of the surgeon;
- Facilitate artificial ventilation.
Pharmacological properties
Curare is an example of a non-depolarizing neuromuscolar relaxant that blocks the nicotinic acetylcholine receptor (nAChR), one of the two types of acetylcholine (ACh) receptors, at the neuromuscular junction. (Neuromuscular block, 2006.)
The main toxin of curare, d-tubocurarine, occupies the same position on the receptor as ACh with an equal or greater affinity, and elicits no response, making it a competitive antagonist. The antidote for curare poisoning is an acetylcholinesterase (AChE) inhibitor (anti-cholinesterase), such as physostigmine or neostigmine. By blocking ACh degradation, concentrations of AChE inhibitors increase ACh in the neuromuscular junction; the accumulated ACh will then correct for the effect of the curare by activating the receptors not blocked by toxin at a higher rate.
The time of onset varies from within one minute (for tubocurarine in intravenous administration, penetrating a larger vein), to between 15 and 25 minutes (for intramuscular administration, where the substance is applied in muscle tissue).
The speed of onset of curarization is affected by:
- Hemodynamic parameters:
- cardiac output;
- distance heart-skeletal muscle;
- blood flow of the muscle.
- Power of the molecule.
The duration of the action depends on the half-life. It is possible to divide curares by the lasting of their clinical action:
- Ultrashort
- Short
- Intermediate
- Long.
The elimination of curare is charged to the kidney and liver.
Different effects of curare were found between females and males, in particular it was noticed that, for the same administered dose, the effects are greater on the female. The reproductive cycle and hormonal status were not considered. The difference between male and females might be due to intrinsic gender-specific differences in recruitment and activation of neuromuscular junctions.(High gender - specific susceptibility to curare - a neuromuscolar blocking agent, 2013.)
Side effects
Tubocurarine induces hypotension likely due to interaction with other receptors and histamine release.
The neuromuscular blocking agents are contraindicated in cases of myasthenia gravis.
It has also effects on the release and reuptake of noradrenaline, on vagal stimulation and intragastric pressure.
Moreover, it can cause myalgia.
Anesthesia
To provide optimal operating conditions and facilitating intubation of the trachea, in modern anesthesia, neuromuscolar relaxants are very used. In the past, anesthesiologists used larger doses of the anesthetic agent, such as ether, chloroform or cyclopropane to achieve these aims. These methods were very dangerous and could be sometimes fatal.
Safer curare derivatives, such as rocuronium and atrachium, have superseded d-tubocurarine for anesthesia during surgery as better drugs are now available.
Modern anesthetists have at their disposal a variety of neuromuscolar relaxants for use in anesthesia. The use of neuromuscular blocking drugs carries with it a very small risk of anesthesia awareness.
Before the patient goes to sleep deeply and then is curarized and he is monitorized until he wakes up.
Management of curare poisoning
Curare poisoning can be managed by artificial respiration such as mouth-to-mouth resuscitation. In a study of 29 army volunteers that were paralyzed with curare, artificial respiration managed to keep an oxygen saturation of always above 85%, a level at which there is no evidence of altered state of consciousness. Yet, curare poisoning mimics the locked-in syndrome in that there is paralysis of every voluntarily controlled muscle in the body (including the eyes), making it practically impossible for the victim to confirm consciousness while paralyzed. But it’s important to say that curarized patient cannot breathe.
Spontaneous breathing is resumed after the end of the duration of action of curare, which is generally between 30 minutes to 8 hours, depending on the variant of the toxin and dosage. If available, the muscle paralysis can be reversed by administration of a cholinesterase inhibitor such as physostigmine.
Cardiac muscle is not directly affected by curare, but if more than four to six minutes has passed since respiratory cessation the cardiac muscle may stop functioning by oxygen-deprivation, making cardiopulmonary resuscitation including chest compressions necessary (for not to talk about the brain!!!).
Accidental poisoning by curare is very rare: its use is only hospital, an place equipped with everything you need (drugs, instruments and monitors ..) in order to adequately ventilate the patient.
Names
Curare is also known as Ampi, Woorari, Woorara, Woorali, Wourali, Wouralia, Ourare, Ourari, Urare, Urari, and Uirary.
