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Newer Drugs in Anaesthesia
Pradnya Kulkarni*
New designer drugs, novel routes of
administration of old and new drugs and advanced delivery systems is a future of anaesthesia.
Anaesthesia is on the verge of a major evolution that will involve newer, more specific and better anaesthetic agents and newer safer, precise and probably simpler techniques to deliver these agents.
Why do we need new drugs? We need new drugs because our target is to achieve zero morbidity and mortality from anaesthesia.We need safer anaesthetic agents to achieve this goal. We hope that newer anaesthetic agents will make anaesthesia experience absolutely safe and pleasant for the patients and less stressful for the anaesthesia provider.
In the past anaesthetic agents were discovered by chance or accident but now extensive research is needed to find out more potent and receptor specific anaesthesia drugs. Over recent years an increasing knowledge of the mode of drug action and receptor sites has improved our ability to design new drugs. These are the ‘modern designer drugs’. Development of Remifentanil is an excellent example of such designer drugs.
Following are some of the forthcoming attractions in anaesthesia, some may become indispensable, some may not even reach hands of practicing anaesthetists and some may not have genuine cost effective benefits to gain place in routine anaesthesia practice.
An extremely short summary is given below for quick review. Interested readers can get more information through references
Premedication: dexmeditomedine
Induction: xenon
Muscle relaxants: cisatracurium
Anaesthesia maintenance: dexme-ditomedine and xenon.
Analgesics: dexmeditomedine, Remi-fentanil
Reversal agent: Sugammadex
Regional/local anaesthetics: Dexme-ditomedine, Levobupivacaine, Ropivacaine, local anaesthetic formulations.
Fluid management: adenosine triphosphate, flurocarbons, haemoglobin solutions.
Dexmeditomedine : It is a potent alpha 2 agonist which can be used as an anxiolytic, to improve intraoperative haemodynamic stability, to decrease intraoperative hypnotic requirement and as an analgesic. Only available in parenteral form. Currently extensively used in veterinary practice. Very promising drug, after all we are evolved from them.
Xenon : Inert gas. Have all the properties of ideal anaesthetic agent. Use may be possible with new physioflex machine. Can not be used with conventional anaesthesia machines due to its high density. Environment friendly as it is trace gas. Future unpredictable as cost is phenomenally high. appx 2000 $ / lit. Oh!
Remifentanil: Mu opiate receptor agonist with ultrarapid clearance and effect of action which is independent of excretory organ function. No epidural use. Ultra short action has become a disadvantage as another narcotic is used for control of post operative pain. Why use two?
Cisatracurium: less laudnosine produced. Fewer side effects like histamine release, bronchospasm, and hypotension compared to atracurium. Recovery from block is independent of renal and hepatic function.
Ropivacaine: long acting local anaesthetic with less cardiac and central nervous system toxicity than bupivacaine. Lesser tendency to cause motor block can not be used in paediatric age group (< 12 yrs). Can not be combined with adrenaline. Use with caution in liver failure. Not yet approved for spinal anaesthesia. Data for long duration epidural infusion not available.
Levobupivacaine: the S(—) enantiomer of levobupivacaine with less cardiovascular and CNS toxicity. Slightly longer sensory block but otherwise similar to parent bupivacaine.
A.T.P.: The energy currency inside all cells. Profound extra cellular effects both by itself and through its metabolite adenosine. A wealth of new uses may be just round the corner.
Sugammadex: It is a gamma cyclodextrine designed to chelate or encapsulate rocuronium. This chelation is very rapid full recovery from neuromuscular blockade caused by rocuronium can be achieved in less than 3 mins irrespective of time of administration of rocironium. No muscarinic side effects. It reverses only rocuronium. So do we use only rocuronium in future?
Flurocarbon emulsion: Perflurocarbon emulsions are the agents with potential for ensuring oxygenation during marked haemodilution; under research. Many hurdles to pass before it can be used.
Hb solutions: There are many unresolved questions regarding its metabolism, potential toxicity, and brief duration of action (less than 24 hrs). A source of great hope as concern over blood transfusion is growing.
Novel routes of administration of drugs
Noninvasive routes are gaining fast popularity. In noninvasive route transdermal delivery is an important concept. Advantages being decreasing dosage frequency increased convenience / compliance and maintenance of blood levels with fewer fluctuations. A number of transdermal patches are available; few commonly used are nitroglycerine, fentanyl, scopolamine, nicotine, clonidine, diclofenac, etc. Rectal, transnasal and sublingual routes are also being researched with old and new drugs.
Delivery systems
In recent past intermittent bolus doses of I.V. anaesthetic agents are replaced by constant infusions to some extent. In future pharmacological advances will stimulate changes in anaesthesia delivery technology so much that anaesthesia equipment may be virtually unrecognizable to present day practitioners. Inhalational anaesthetics will slowly fade out. Recent arrivals are computer controlled I.V. syringe pumps. These pumps are set to obtain a specific target concentration of medication at the effector site. The target controlled infusion pump—TCI pump. In this form of drug delivery the goal is to maintain constant concentration (level) of drug in a specific pharmacological compartment. These pumps are controlled by mathematical models based on pharmacokinetic and pharmacodynamic properties. In future synergism of anaesthetic agents will be exploited to ensure maximum drug effect with minimum adverse effects. Multidimensional models may be available to calculate the synergism between many anaesthetic agents and suggest appropriate combinations of target concentration. The target guided anaesthesia machines. These models along with advanced depth of anaesthesia monitors will make it possible the precise time of awakening."
Are all new drugs better?
Many drugs in recent past were developed to eliminate the side effects of some of frequently used agents but had to be withdrawn from practice due to their other unacceptable/ dangerous side effects. E.g.:
Rapacuronium bromide – developed as substitute for succinyl choline (scoline) in the setting of rapid sequence induction. It was withdrawn from market in less than 2 years due to its dangerous side effect bronchospasm which was life threatening in some cases. Rofecoxib withdrawn due to dangerous cardiovascular side effects. Cleofol: the clear propofol marketed as vegetarian formulation of propofol has lost out due to severe pain on injection and severe thrombophlebitis.
Newer drugs: Can we afford them?
Cost is a major concern especially in country like India. We can not ignore the phenomenal cost of some of the agents available and some in pipeline e.g. xenon. Anaesthesiologist are facing great challenge in making decisions as no definitive guidelines are available about cost benefit ratio of new and old drugs. Many a times choices are influenced by financial consideration rather than merits of patient's conditions. Pharmacoeconomics is extremely dynamic. Sometimes cost of agents falls with extensive use. Then our attitude may have been penny wise and pound foolish. Cost of drugs forms fraction of total cost of treatment. Then is it that we know cost of everything but value of nothing.
References
1. W Bosseau Murray. The future of anaesthesia delivery. From art based science to science based art. American Society of Anaesthesiologist 2004: 68.
2. Stockall C. New drugs in anaesthesia: can we afford them? Canadian J Anaesthesia Vol 45. R95 to 105.
3. Sing Sanjay. Xenon: consultant cardiac anaesthetist Suraksha hospital Calcutta.
4. Henderson F, Kenny GN. University Department of Anaesthesia. Glasgow Royal Infirmary. U.K. Ann Acad Med Singapore 1999; 28 (3) : 434-9. |
