Halothane by Dr. Aram Shah

Presentation on Halothane

1. Halothane By: Aram A. Shah University of Sulaimani Faculty of medical sciences School of Medicine Department of Pharmacology

2. بسم الله الرحمن الرحيم Halothane is the only general inhalational, halogenated anesthetic agent, containing bromine. Long duration.

3. Hlaothane is an Inhalational General Anesthetic

4. General Anesthesia General anesthesia is a reversible state of central nervous system ( CNS) depression , causing loss of response to and perception of stimuli. For patients undergoing surgical or medical procedures, anesthesia provides five important benefits: • Sedation and reduced anxiety • Lack of awareness and amnesia • Skeletal muscle relaxation • Suppression of undesirable reflexes • Analgesia Because no single agent provides all desirable properties, several categories of drugs are combined to produce optimal anesthesia

5. Choosing Proper Anesthetic Status of organ systems Cardiovascular system: Anesthetic agents suppress cardiovascular function to varying degrees. This is an important consideration in patients with Heart and coronary artery diseases. Hypotension may develop during anesthesia, resulting in reduced perfusion pressure and ischemic injury to tissues. H alothane , sensitize the heart to arrhythmogenic effects of sympathomimetic agents. 2 . Respiratory system : Inhaled agents depress respiration but also act as bronchodilators, These effects may influence the ability to provide adequate ventilation and oxygenation during and after surgery.

6. 3. Liver and kidney: The liver and kidneys influence long-term distribution and clearance of drugs and are also target organs for toxic effects. 4. Nervous system: The presence of neurologic disorders ( for example , epilepsy, myasthenia gravis, neuromuscular disease, compromised cerebral circulation) influences the selection of anesthetic . 5. Pregnancy: Special precautions should be observed when anesthetics are administered during pregnancy. Effects on fetal organogenesis are a major concern in early pregnancy . Commonly, patients receive one or more of preanesthetic medications for preventing undesirable anesthetic effects.

7. STAGES OF ANESTHESIA A. Induction B. Maintenance of anesthesia C. Recovery D. Depth of anesthesia : Stage I—Analgesia : Stage II—Excitement : Stage III—Surgical anesthesia : Stage IV—Medullary paralysis:

8. Inhalational Anesthetics Inhaled gases are used primarily for maintenance of anesthesia after administration of an IV agent. Inhalational agents have very steep dose–response curves and very narrow therapeutic indices, so the difference in concentrations causing surgical anesthesia and severe cardiac and respiratory depression. No antagonists exist .

9. HALOTHANE Halothane is the prototype to which newer inhalation anesthetics are compared. When halothane was introduced, its rapid induction and quick recovery made it an anesthetic of choice. Due to adverse effects and the availability of other anesthetics with fewer complications , halothane has been replaced in most countries . ------------------------------------------------------------------------------------------ Chemical and Physical Properties Halogenated compound chemically: 2-bromo-2-chloro-1,1,1-tri fluoro ethane Volatile, so kept in sealed bottles Colorless , Pleasant odor , Non-irritant Non-explosive, Non-inflammable Light-sensitive Corrosive, Interaction – rubber and plastic tubing

10. Solubility in blood This is determined by a physical property of the anesthetic called the : blood/gas partition coefficient : Ratio of when the anesthetic is in equilibrium between the two phases.  

11. Potency Potency is defined(determined) quantitatively as the minimum alveolar concentration (MAC ), MAC : the minimum concentration of inhaled anesthetic needed to eliminate movement in 50% of subjects exposed to it. MAC is the median effective dose (ED50) of the anesthetic, expressed as the percentage of gas in a mixture required to achieve that effect. Numerically , MAC is small for potent anesthetics such as Halothane and large for less potent agents such as nitrous oxide .

12. Therapeutic uses Halothane is a potent anesthetic but a relatively weak analgesic. Thus, it is usually coadministered with nitrous oxide , opioids, or local anesthetics. It is a potent bronchodilator . Halothane relaxes both skeletal and uterine muscles and can be used in obstetrics when uterine relaxation is indicated. Halothane is not hepatotoxic in children (unlike its potential effect on adults). Combined with its pleasant odor , it is suitable in pediatrics for inhalation induction , although sevoflurane is now the agent of choice.

13. Pharmacokinetics Potent general anesthetic   MAC : 0.75% , thus lower MAC value, more drug potency.   Blood/Gas Partition Coefficient: 2.4 Produces a smooth and relatively rapid induction. Metabolism:   20-40% is metabolized in liver by oxidation, normally excreted in form of  trifluoroacetic acid.  Clearance: Around 60-80% is cleared out unchanged by lungs.

14. Mechanism of Action No specific receptor has been identified as the locus of general anesthetic action –generally-. It appears that a variety of molecular mechanisms may contribute to the activity of general anesthetics . Halothane activates  GABA A   ,   glycine receptors , 5-HT 3 and  twin-pore K +  channels . It antagonizes   NMDA receptor . It inhibits   nACh ( block excitatory postsynaptic currents of nicotinic receptors)  and  voltage-gated sodium channels . ----------------------------------------------------------------------------------------- At clinically effective concentrations, general anesthetics increase the sensitivity of the γ- aminobutyric acid ( GABA -A ) receptors to the inhibitory neurotransmitter GABA . This increases chloride ion influx and cause Hyperpolarization  Decrease Excitability  CNS Depression

15. GABA-A receptor

16. Disadvantages Weak analgesic (thus is usually coadministerd with N2O, opioids) Is a strong respiratory depressant Is a strong cardiovascular depressant ; halothane is vagomimetic and cause atropine-sensitive bradycardia . Cardiac arrhythmias : serious if hypercapnia develops due to hypoventilation and an increase in the plasma concentration of catecholamines (Sensitizes heart to catecholamines ) Hypotensive effect (Rx: phenylephrine recommended) Hepatotoxic : is oxidatively metabolized in the liver to tissue-toxic hydrocarbons (e.g., trifluroethanol and bromide ion ), could lead to hepatitis.

17. Disadvantages cont. Malignant hyperthermia : In a very small percentage of susceptible patients, a rare life-threatening condition. MH causes a drastic and uncontrolled increase in skeletal muscle oxidative metabolism, overwhelming the body’s capacity to supply oxygen, remove carbon dioxide, and regulate temperature, eventually leading to circulatory collapse and death if not treated immediately. Susceptibility to MH is often inherited as an autosomal dominant disorder . ----------------------------------------------------------------------------------------------- D antrolene is given as the anesthetic mixture is withdrawn, and measures are taken to rapidly cool the patient. Dantrolene blocks release of Ca2+ from the sarcoplasmic reticulum of muscle cells, reducing heat production and relaxing muscle tone.

18. Contraindications Liver dysfunction  History of unexplained jaundice or pyrexia after a previous exposure to halothane is an absolute contraindication to its future use in that patient. Halothane is contraindicated in patients with known, or suspected, genetic predisposition to malignant hyperthermia. Hypovolemic

19. References Lippincott Illustrated Reviews: Pharmacology, Sixth Edition Broad Review Series(BRS) Pharmacology, Sixth Edition www.Wikipedia.com www.Howmed.net www.Piramal.com www.RxList.com Dorland’s illustrated medical dictionary

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