Drugs for General Anesthesia - NEET PG Anesthesia

Drugs used for general anesthesia are an important topic in the NEET PG exam because anesthesia is a critical component of many medical procedures. A thorough understanding of the topic is essential for any medical professional. 

In the exam, questions related to the pharmacology, mechanism of action, adverse effects, and clinical applications of anesthetic drugs are often asked, making it all the more to study for the NEET PG exam.

Let’s learn more about this important anesthesia topic for NEET PG exam preparation.

INHALATIONAL ANESTHETIC AGENTS

Commonly used inhalational agents

• Inorganic Gas 
  • N₂O: It is less potent, used as carrier gas
• Volatile liquids: More potent
  • Halothane
  • Isoflurane
  • Sevoflurane
  • Desflurane
• Volatile agents not in clinical use
  • Methoxyflurane: Most nephrotoxic
  • Enflurane: Causes epilepsy
• Inert gas
  • Xenon: Carrier gas, but due to high cost, currently not in use

PHARMACOKINETICS AND PHARMACODYNAMICS

	Properties of potent inhalation agent
Chemistry	Halothane	Isoflurane		Sevoflurane		Desflurane
	Halogenated Ethane	Halogenated Ethers
	Isoflurane and Desflurane are structural analogues Enflurane is isomer of isoflurane
Boiling point	50° C ± 2° C						Room Temp. 22° C
	TEC 2,3,4,7 or any other vaporizer can be used						Highest vapor pressure TEC 6 vaporizer is used
Color coding	Red		Purple		Yellow		Blue
MAC50	0.75		1.12		2		6

Important Information

• MAC: Minimal Alveolar concentration of the vapor / anesthetic agent to prevent movement (Motor Response) in 50% of subject in response to surgical stimulus.
  • ↑↑ MAC : Potency ↓↓
  • ↓↓ MAC : Potency ↑↑

Blood gas partition coefficient or blood gas solubility

	Halothane	Isoflurane	Sevoflurane	Desflurane
Blood gas partition coefficient	2.25	1.3	0.63	0.42 Fastest speed of induction and Recovery

• Blood gas partition coefficient tells about the
  • Speed of Induction
  • Speed of Recovery
• Low blood gas partition coefficient: Faster speed of induction and recovery (Vice Versa).

Important Information

• For induction we seldom use desflurane because of its irritant property: Causes Bronchospasm and Laryngospasm.
• Sevoflurane is inhalational induction agent of choice, has sweet smell
• Sevoflurane and Desflurane: Both good for day care surgery, since they give fast recovery.

Stability	Halothane	Isoflurane	Sevoflurane	Desflurane
	Most unstable Most metabolized Can cause autoimmune hepatitis Preservative Needed: Thymol (0.01%)	Stable	Stable	Most stable Very good Agent for the maintenance

Smell of Agents

Halothane	Isoflurane	Sevoflurane	Desflurane
Fruity smell Used both for induction & maintenance	Little bit irritant  Only used for maintenance	Sweet smell Induction & maintenance Inhalational induction agent of choice	Irritant (max) Maintenance
For maintenance isoflurane > sevoflurane

PHARMACODYNAMIC PROPERTIES

CNS Effects

Halothane	Isoflurane	Sevoflurane	Desflurane
↓ cerebral metabolic O2	↓ Cerebral metabolic O2	↓ Cerebral metabolic O2	↓ Cerebral metabolic O2
CBF increase (maximum) ↑↑↑ ICP maximum	CBF increase ↑ ICP	CBF increase ↑ ICP	CBF increase ↑ ICP
↓ EEG	↓ EEG	↓ EEG	↓ EEG

• Important Information
  • There is ↓ cerebral metabolic O₂ requirement in all.
    • Inhalational agent are uncouplers of brain, they dilate the cerebral blood vessel: ↑ Cerebral Blood Flow (CBF) because of intrinsic vasodilation of cerebral blood vessel
    • In IV Anesthetic Agent it is opposite, ↓ Cerebral Metabolic O₂:
      ↓ CBF.
• All inhalational Agent cause ↑ICP (intra cranial pressure).
  • Halothane not used for Neurosurgery, Rest of the inhalational agents can be used.
• Best Agent of Neurosurgery: Desflurane 
• 2^nd best agent for Neurosurgery: Isoflurane

Effects on CVS

Halothane	Isoflurane	Sevoflurane	Desflurane
Direct Myocardial Depressant  ↓ HR ↓ CO ↓ BP Sensitize Heart to the Arrhythmogenic effect of catecholamines. Contraindicated  for CVS surgery	Cardio stable ↓ Systemic Vascular Resistance For neurosurgery: Isoflurane > Sevoflurane
	Cause the Coronary steel phenomenon
	All 3 can be used for CVS surgery

Important Information

• Least cardio depressant: Desflurane > sevoflurane > isoflurane.
• Best agent for CVS surgery: Desflurane.
• Halothane not used for neurosurgery
• Desflurane is best agent for neurosurgery    
• Agent most commonly used for CVS surgery: Isoflurane because desflurane is not commonly available.
• Sevoflurane not used for prolonged hours.

Effects on Respiratory system

• All of the inhalational agents are respiratory depressants.
• Blunts hypoxic/ hypercapnic drive.
• All are bronchodilators.
  • Best bronchodilator: Halothane 
• Sevoflurane is also a very good bronchodilator, so mostly used in developed countries.

Effects on liver

Halothane	Isoflurane	Sevoflurane	Desflurane
Autoimmune hepatitis Disrupts dual blood flow of liver Bad for liver	All 3 can be used for Hepatic surgery.
Contraindicated for liver surgery	Good for liver surgery.  Best for liver transplant surgery.		Best for liver surgery.

Important Information

• For liver surgery Desflurane > isoflurane.

Effects on kidney 

Halothane	Isoflurane	Sevoflurane	Desflurane
No effect	No effect	Bioproduct of metabolism (Compound – A Nephrotoxic)	No effect

Components of GA

	Halothane	Isoflurane	Sevoflurane	Desflurane
LOC	Yes	Yes	Yes	Yes
LORR	Yes	Yes	Yes	Yes
Amnesia	Yes	Yes	Yes	Yes
Muscle Relaxation(membrane stabilizing effect)	Yes	Yes	Yes	Yes
Analgesia	No	No	No	No
Malignant hyperthermia	Unsafe	Unsafe	Unsafe	Unsafe

• Skeletal muscle relaxation: Desflurane>sevoflurane>isoflurane>halothane.
• All Inhalational agents provide good muscle relaxation but none of them provide analgesia.
• All of them can precipitate malignant hyperthermia

MALIGNANT HYPERTHERMIA

• Inhalational agents predisposes to this condition, but IV agents are safe in it.
• Pharmacogenetic Disease: AD form is expressed.

Drugs triggering 

1. SuccinylCholine 

• All halogenated Inhalational Agent 

2. Potent inhalational

• Lignocaine 

Mechanism 

• When a person having gene receives these drugs it gets activated and it stimulates SR which causes massive outflow of calcium inside the cell activating CGMP pathway and this increases the metabolism of our body by 2-3 times.

Clinical features 

• It presents with
  • Hypercarbia 
  • Tachycardia
  • Hyperthermia 
  • Increased BP
  • Increased HR
  • Arrhythmias 
• All occur due to hypermetabolism and result in cell lysis, and further cause myoglobinuria, acidosis, renal failure, hyperkalemia.

Management 

• Discontinue the triggering Agent. 
• Intravenous Dantrolene
  • Central Muscle Relaxant.
  • Stops release of Ca²⁺. 
  • Side Effects- Respiratory insufficiency and muscle weakness.
• Symptomatic Management
• Anesthesia safe in Malignant Hyperthermia: TIVA (Total Intravenous Anesthesia) 
  • Propofol: Agent of choice.

CARRIER GAS

N2O	Xenon
MAC: 104, least potent	MAC: 70, more potent than N2O
Blood gas solubility: 0.45	Blood gas solubility: 0.11-0.19 (fastest)
CVS unstable sympathetic stimulation	CVS stable
Not metabolically inert Peripheral neuropathy Megaloblastic anemia  Bone marrow depression	Metabolically inert
Environmental pollutant	Environment friendly
-	Expensive, not in clinical use

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