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Intravenous Anesthetics

  1. Thiopentone sodium (a Barbiturate)
    Discovered by Water & Lundy 1934. It is ultra short acting barbiturates.
    1. Physical Properties
      1. Available as yellow amorphous powder
      2. H2S like smell
      3. PH = 10.5 (Highly alkaline solution)
      4. Prepared in nitrogen
      5. Preservative used is 6% anhydrous sodium carbonate (It increase its solubility)
      6. Used on 5% & 2.5% solutions compatible with normal saline and distill water, once reconstituted shelf life 2 weeks.
        2.5% → preferable - highly lipid soluble, if concentration more than 2.5% is used it causes pain on injection and incidence of venous thrombosis increased.
    2. Systemic Effects
      1. CNS: Unconsciousness is produced in one arm brain circulation time (15sec).
        Consciousness is regained in 10-15 min due to Redistribution of drug to viscera, muscle and fat.
        1. Sleep -↑stage 2, ↓ 3,4 and REM
        2. Anticonvulsant action - Those epileptic patients who are resistant to Benzodiazepine and phenytoin. require thiopentone.
        3. Decrease cerebral O2 consumption, so used for cerebral protection.
      2. Modes of cerebral protection:
        1. Hypothermia (Most effective against both global and focal ischemia)
        2. Barbiturates, etomidate, propofol, isoflurane
        3. Calcium channel blockers, nimodipine, nicardipine.
          MOA - GABA mediated, At high doses and directly potentiate Cl- conductance.
      3. Anti analgesic: It has a unique property. It increases pain at low doses.
      4. CVS:
        1. Causes hypotension esp. due to veno dilation cause decrease venous return.
        2. Also direct myocardial depressant.
      5. Respiratory system
        1. Inadequate depth laryngeal spasm
        2. Transient Apnea is very common
        3. Resp. depression at higher doses
      6. Eyes
        1. Reduces intraocular pressure at higher doses.
        2. Pupils - dilate initially then contract.
      7. Muscles:- Not a muscle relaxant
    3. ​​Pharmacokinetics
      1. Equilibrium between plasma and brain is achieved in 1 min.
      2. Elimination half - life - 10.3 hours
      3. Metabolism - liver
      4. 85% is bound to Albumin is plasma
      5. Dose : 3-5 mg/kg IV
    4. Complications
      1. Local
        1. Perivenous and intramuscular infiltration
          1. Can cause local necrosis of the area that can lead to ulceration
          2. Rx- prevention →
            • use 2.5% solution
            • Inject very slowly
            • Inject in incremental doses
          3. Rx  10 ml of 1% Lignocaine with 100 units of hyalase to be injected in that area.
        2. Intra-arterial injection - Patient c/o of severe burning pain down the injection site followed by pallor and cyanosis, ultimately leading to edema.
          1. Most commonly it occurs if injection is given at antecubital fossa.
          2. à because of its high alkalinity it gets precipitated in arterial pH leading to crystal formation which blocks the small arteries and induces vascular spasm.
Always use - 2.5% (because with 5% intra arterial complication incidence are more).
  1. Rx of Accidental intra arterial injection-
    1. Leave the needle at site
    2. Inject 500 units of heparin through this needle ( this will make the solution acidic and will prevent thrombus)
    3. Papaverine 40-80 mg in 20 ml of saline
    4. Tolazoline 5 ml or phenoxybenzamine 0.5 mg can also be used.
    5. If none of the above is available 5-10 ml of Xylocaine 1%
    6. Brachial plexus or stellate ganglion block
    7. Oral anticoagulants for 7-14 days.
  2. Systemic Complications : of Thiopentone
    1. Respiratory depression
    2. Cardiovascular depression
    3. Laryngeal spasm
    4. Hiccups
    5. Coughing
    6. Tachyphylaxis

Thiopentone is the drug is avoided in shock and hypotensive states. (AIIMS Nov 07)

  1. Contraindication
    1. Absolute -
      1. Porphyria thiopentone cause LMN paralysis in porphyria patients & even death.
      2. H/O thiopentone anaphylaxis.
    2. Relative -
      1. Hypotension
      2. Asthmatics
      3. Patient with fixed cardiovascular lesions who can’t Cardiac output like tight valvular
      4. stenosis. Heart block, Constrictive pericarditis
      5. Inflammatory conditions of oral cavity and neck where airway maintenance is difficult
      6. Dystrophia myotonica
      7. Familial periodic paralysis
  1. Methohexitone
    1. 2-3 times more potent than thiopentone
    2. Recovery quicker than thiopentone used as 1% solution
    3. Dose - 1.5 mg / kg elimination half life - 4 hrs
    4. It induces seizures
    5. Anesthetics of choice for ECT
    6. Myoclonus can occur
  2. Propofol (AIPG 08)
    • Available as 1% & 2%  milky white coloured solutions in soya bean oil so injection is painful.
    • (1% Xylocaine 2 ml is given along with it).
    • Content of propofol.
    1. ​​​​Alkyl phenol: 2, 6 diisopropyl phenol
    2. Emulsion containing
      1. 1% propofol
      2. 10% soybean oil (AIPG- 2008)
      3. 2.25% glycerol
      4. 1.2% egg phosphatide
      5. 0.005% disodium
      6. Edetate*/Metabisulfite
  • pH 7, milky white solution, pKa - 10.76
  • Compatible with dextrose
  1. Feature:
    1. Onset of action - 15 sec.
    2. Effect duration of unconsciousness- 2-8 min.
    3. Elimination half life - 2-3 hrs.
    4. Dose - 2 mg/kg.
  2. Mechanism of Action
    1. Binds of beta subunit of GABA -A receptor
    2. GABA - induced chloride current potentiated
    3. Decreased release of ACh in hippocampus & prefrontal lobe
    4. Direct depressant action on spinal neurons
    5. Decrease serotonin in area postrema (Anti emetic)
  3. CNS Effects propofol
    1. Hypnotic, sedative, amnesic
    2. Sense of well being (Choice in day care)
    3. Anticonvulsant
    4. Decrease ICP
    5. Decrease CMRO2
    6. Cerebral protective effects also
    7. Antiemetic
    8. NOT an analgesic (An Analgesic)
  4. Cvs effect-
    1. Peripheral vasodilatation more than thiopentone.
    2. Impairs normal arterial baroreflex response – no tachycardia, rather bradycardia is more common.
  5. Respiratory system
    1. Respiratory depressant
    2. Depression of upper airway reflexes
    3. Bronchodilator
    4. It lack airway irritation so particularly suitable for OPD surgery. (AIPG 08)
  1. Effects
    1. Apnea more common & long duration than thiopentone
    2. Hypotension is significant
    3. Recovery rapid than thiopentone
    4. Antiemetic
    5. Hallucinations, sexual fantasies.
  1. Propofol is i/v Anaesthetics of choice for:
    1. Day care surgery
    2. Sedation in ICU
    3. Malignant hyperthermia
    4. Neurosurgery
    5. Renal failure
    6. Porphyria
    7. For performing endoscopy
  2. Complications
    1. Pain on injection
      1. most notorious in causing pain on injection other drugs causing pain on injection –etomidate, 5% thiopentone.
      2. Reason – kallikrein pathway activated.
      3. How to reduce pain – mix with lignocaine (1ml per 10 ml of propofol)
        1. Larger vein should be used
        2. Lignocaine given 10 secs before.
    2. ​​Propofol Infusion Syndrome
      Particularly in Children.
      1. Failure of free fatty acid metabolism
      2. Hyperlipidemia Syndrome
      3. Acute cardiac failure
      4. Cardiomyopathy
      5. Skeletal myopathy
      6. Hepatomegaly
      7. Metabolic acidosis
      8. Hyperkalemia
      9. Pancreatitis in adults
  1. Etomidate
    1. Imidazolone derivative
    2. Acts through GABA receptor
    3. Rapid onset and metabolism
    4. Dose - 0.3 mg / kg
    5. CNS- cerebroprotective
    6. Most Cardiovascular stable – myocardial contractility unchanged (AIIMS May 09)
    7. Less resp. depression
    8. Side Effects
      1. Adrenal suppression- temporary inhibition of cortisol synthesis
      2. Highest incidence of nausea & vomiting (40%)
      3. Thrombophlebitis
      4. Painful injection
      5. Myoclonus 30- 60 %
    9. Anaesthetic of choice for
      1. MI patients
      2. Aneurysm surgery
  2. ​​Ketamine
    1. Synthesized by Stevens of Detroit & first used by Domino & Corsen. It can be given by oral, i/m, i/v intrathecal routes.
    2. Dissociative Anaesthesia.
    3. Causes profound analgesia.
    4. Sympathetic stimulation (excitement).

  1. Pharmacokinetics
    1. Onset of action - 60 sec. i.v, 10 min. I/M,
    2. Duration of action - 10-15 min. I/V, 20 - 30 min. I/M
    3. Dose - I/V - 1-2 mg/kg
    4. I/M - 5-10 mg/kg
    5. Metabolized to Nor ketamine
    6. t 1/2 - 2 to 3 hrs.
​​​
  1. Effects:
    1. CNS:- Strong analgesic
      1. ​Dissociative anaesthesia i.e cortical function & thalamus are inhibited & limbic system gets stimulated.
      2. Vivid dreaming, hallucination & emergence delirium.
      3. Increases I.C.T. so Contra indicated in head injuries.
  • Remember
    1. ​​Ketamine raises both systolic and diastolic blood pressures and is thus contraindicated in hypertension.
    2. Ketamine increases cerebral blood flow and intracranial pressure and is contraindicated in raised ICT.
    3. Ketamine raises intraocular tension and is thus contraindicated in glaucoma.
    4. Ketamine causes increases cerebral oxygen consumption (AIIMS Nov 2007).
  1. CVSStimulates + symph. system so  ↑BP ↑PR
    So i/v anaesthetic of choice for SHOCK patients.
  1. Resp.- Stimulates respiration, increases Bronchial secretions
    - Pharyngeal laryngeal reflexes are preserved so good for full stomach patients (although it dose not guarantee 100% protection).
  2. Eye  Increase i.o.t.
  3. Gut: Increase intragastric pressure, secretion.
  4. Muscle: muscle tone (Hypertonia), produces catalepsy.
    Non purposeful movements are seen.
  1. Side Effects
    1. Commonest is hallucination (40 - 50%), vivid dreaming, Emergence delirium (10-30%)
      To decreases hallucination agent of choice is Diazepam (also Opiates & thiopentone decrease hallucinations).
    2. increase muscle tone, catalepsy.
    3. increase pharyngeal, respiratory secretions so premedications with atropine is necessary.
    4. HT, tachycardia
    5. increase i.c.t., increase i.o.t., increase intragastric pressure
  2. Advantages & uses
    1. Can be used as sole anaesthetic for minor surgeries.
    2. Safest anaesthetic to be used at remote places & inexperienced hands (since it does not depress respiration).
    3. I/V anaesthetic of choice for shock patients (maintains BP).
    4. Preferred agent when patient is full stomach (preserves pharyngeal reflexes).
    5. Because of its analgesic properties good for burn dressings.
    6. Excellent for children (i/m can be given).
    7. For induction (but not the preferred agent).
  1. Benzodiazepines
    1. Diazepam
      1. Available as oil base preparation
      2. 98% bound to plasma proteins
      3. Highly acidic (Ph = 3.3)
      4. Onset of action 1-2 minutes.(When given i/v)
      5. t 1/2 - 30 - 60 hrs.
      6. Dose - 0.1 - 0.2 mg / kg for sedation
        0.3 - 0.5 mg / kg for induction
  1. Effects: CNS
    1. These are GABA facilitatory
    2. Mainly acts on RAS (in midbrain) & Amygdala (limbic system)
    3. No effects on cortex
    4. Anxiolytic
    5. Anterograde amnesia
    6. Not an analgesic
    7. Anticonvulsant
    8. Does not increase I.C.T.
  2. CVS: myocardial depression & decreases B.P only at high doses
  3. Resp.- Resp depression only at high doses
  4. Muscle: Muscle relaxation is seen
  1. Midazolam
    1. Water based preparation so injection is not painful
    2. t 1/2 - 2-3 hrs. so excellent for day care surgery.
    3. Dose -
      1. 0.1 mg / kg for sedation
      2. 0.2 - 0.3 mg / kg for induction
      3. 3 times more potent than diazepam
  2. ​​Lorazepam
    1. 5 times more potent than diazepam.
    2. Long duration of action.
  3. Flumazenil
    1. It is Benzodiazepine antagonist (AIPG - 2008)
    2. given in increments of 0.1 - 0.2 mg to a max. of 1 mg
    3. Drawback is that t 1/2 is 1-2 hrs. so there are high chances of re-sedation.
​​
  1. Neuroleptic Analgesia
    1. Droperidol (2.5 mg) + Fentanyl (0.05 mg) ratio 50:1
    2. S/E & pharmacology is of Phenothiazine & fentanyl
    3. Most common S/E - Hypotension (a blockade)
  2. Neuroleptic anaesthesia
    1. Droperidol + fentanyl + inhalational agent (esp. N2O)
  3. Althesin
    1. alphadione, steroidal agent
    2. non irritant, decrease B.P. and increase P.R.
    3. Bronchospasm, anaphylactoid reaction
  4. Propanidid
    1. Ultra short Acting, derivative of eugenol
    2. metabolized by pseudocholinesterase
    3. Rapid metabolism – short duration, Ester hydrolyses
    4. Hyperventilation followed by apnea.
    5. S/E: Severe hypersensitivity reactions.

Thiopentone sodium (a Barbiturate)

Discovered by Water & Lundy 1934. It is ultra short acting barbiturates
  1. Physical Properties
    1. Available as yellow amorphous powder
    2. H2S like smell
    3. PH = 10.5 (Highly alkaline solution)
    4. Prepared in nitrogen
    5. Preservative used is 6% anhydrous sodium carbonate (It increase its solubility) 
    6. Used on 5% & 2.5% solutions compatible with normal saline and distill water, once reconstituted shelf life 2 weeks
       
      2.5%  preferable - highly lipid soluble, if concentration more than 2.5% is used it causes pain on injection and incidence of venous thrombosis increased
  2. Systemic Effects
    1. CNS: Unconsciousness is produced in one arm brain circulation time (15sec).
       
      Consciousness is regained in 10-15 min due to REDISTRIBUTION of drug to viscera, muscle and fat.
      1. Sleep - stage 2,  3,4 and REM
      2. Anticonvulsant action - Those epileptic patients who are resistant to Benzodiazepine and phenytoin. require thiopentone
      3. Decrease cerebral O2 consumption, so used for cerebral protection.
Modes of cerebral protection:
  1. Hypothermia (Most effective against both global and focal ischemia)      
  2. Barbiturates, etomidate, propofol, isoflurane  
  3. Calcium channel blockers, nimodipine, nicardipine.
MOA - GABA mediated, At high doses and directly potentiate Cl- conductance
 
Anti analgesic: It has a unique property. It increases pain at low doses.
  1. CVS:
    1. i. Causes hypotension esp. due to veno dilation cause decrease venous return
    2. ii. Also direct myocardial depressant
  2. Respiratory system
    1. Inadequate depth laryngeal spasm
    2. Transient Apnea is very common
    3. Resp. depression at higher doses
  3. Eyes
    1. Reduces intraocular pressure at higher doses
    2. Pupils - dilate initially then contract
  4. Muscles :- Not a muscle relaxant
  1. Pharmacokinetics
    1. Equilibrium between plasma and brain is achieved in 1 min.
    2. Elimination half - life - 10.3 hours
    3. Metabolism - liver
    4. 85% is bound to Albumin is plasma
    5. Dose: 3-5 mg/kg IV
  2. Complications
    1. Local
      1. Perivenous and intramuscular infiltration
        • Can cause local necrosis of the area that can lead to ulceration
        • Rx- prevention →
           
          o use 2.5% solution
           
          o Inject very slowly
           
          o Inject in incremental doses
        • Rx 10 ml of 1% Lignocaine with 100 units of hyalase to be injected in that area
      2. Intra-arterial injection - Patient c/o of severe burning pain down the injection site followed by pallor and cyanosis, ultimately leading to edema
        • à because of its high alkalinity it gets precipitated in arterial pH leading to crystal formation which blocks the small arteries and induces vascular spasm.
           
          Rx of Accidental intra arterial injection-
          1. Leave the needle at site
          2. Inject 500 units of heparin through this needle ( this will make the solution acidic and will prevent thrombus)
          3. Papaverine 40-80 mg in 20 ml of saline
          4. Tolazoline 5 ml or phenoxybenzamine 0.5 mg can also be used.
          5. If none of the above is available 5-10 ml of Xylocaine 1%
          6. Brachial plexus or stellate ganglion block
          7. Oral anticoagulants for 7-14 days.
    2. Systemic Complications: of Thiopentone
      1. Respiratory depression
      2. Cardiovascular depression
      3. Laryngeal spasm
      4. Hiccups
      5. Coughing
      6. Tachyphylaxis
  3. Contraindication
    1. Absolute -
      1. Porphyria thiopentone cause LMN paralysis in porphyria patients & even death
      2. H/O thiopentone anaphylaxis
    2. Relative -
      1. shock
      2. Asthmatics

Methohexitone

  1. 2-3 times more potent than thiopentone
  2. Recovery quicker than thiopentone used as 1% solution
  3. Dose - 1.5 mg / kg elimination half life - 4 hrs
  4. It induces seizures
  5. Anesthetics of choice for ECT
  6. Myoclonus can occur

Propofol (AIPG 08)

  • Available as 1% & 2%  milky white coloured solutions in soya bean oil so injection is painful
  • (1% Xylocaine 2 ml is given along with it)
  • Content of propofol
    1. a. Alkyl phenol: 2, 6 diisopropyl phenol
    2. b. Emulsion containing  
      1. 1% propofol,
      2. 10% soybean oil (AIPG- 2008),  
      3. 2.25% glycerol
      4. 1.2% egg phosphatide
      5. 0.005% disodium  Edetate* / Metabisulfite
  • pH 7, milky white solution, pKa - 10.76
  • Compatible with dextrose
  1. Feature:
    1. Onset  of action - 15 sec
    2. Effect duration of unconsciousness- 2-8 min
    3. Elimination half life - 2-3 hrs.
    4. Dose - 2 mg / kg
  2. Mechanism of Action
    1. Binds of beta subunit of GABA -A receptor
    2. GABA - induced chloride current potentiated
    3. Decreased release of ACh in hippocampus & prefrontal lobe
    4. Direct depressant action on spinal neurons
    5. Decrease serotonin in area postrema (Anti emetic)
  3. CNS Effects propofol
    1. Hypnotic, sedative, amnesic
    2. Sense of well being (Choice in day care)
    3. Anticonvulsant
    4. Decrease ICP
    5. Decrease CMRO2
    6. Cerebral protective effects also
    7. Antiemetic
    8. NOT  an analgesic
  4. CVS effect-
    1. Peripheral vasodilatation more than thiopentone
    2. Impairs normal arterial baroreflex response – no tachycardia, rather bradycardia is more common.
  5. Respiratory system
    1. Respiratory depressant
    2. Depression of upper airway reflexes
    3. Bronchodilator
    4. It lack airway irritation so particularly suitable for OPD surgery. (AIPG 08)
  1. Effects
    1. Apnea more common & long duration than thiopentone
    2. Hypotension is significant
    3. Recovery rapid than thiopentone
    4. ANTIEMETIC
  1. Propofol is i / v Anaesthetics of choice for:
    1. Day care surgery
    2. Sedation in ICU
    3. thoracic surgery
    4. Malignant hyperthermia
    5. Neurosurgery
    6. Renal failure
    7. Porphyria
    8. For performing endoscopy  
  2. Complications;
    1. Pain on injection
      1. most notorious in causing pain on injection other drugs causing pain on injection – metomidate, 5% thiopentone        
      2. Reason  – kallikrein pathway activated
      3. How to reduce pain – mix with lignocaine (1ml per 10 ml of propofol)
        • Larger vein should be used
        • Lignocaine given 10 secs before.
    2. Propofol Infusion Syndrome
       
      Particularly in Children.
      1. Failure of free fatty acid metabolism
      2. Hyperlipidemia Syndrome
      3. Acute cardiac failure
      4. Cardiomyopathy
      5. Skeletal myopathy
      6. Hepatomegaly
      7. Metabolic acidosis
      8. Hyperkalemia
    3. Pancreatitis in adults

Etomidate

  1. Imidazolone derivative
  2. Acts through GABA receptor
  3. Rapid onset and metabolism (Rapid Redistribution)
  4. Dose - 0.3 mg / kg, Peak brain level – 1 min after iv injection, Clinical use- iv induction,  highly cardio stable
  5. CNS- cerebroprotective
    1. Decreased CBF
    2. Decreased CMRO2
    3. May activate seizure
  6. Most Cardiovascular stable – myocardial contractility unchanged (AIIMS May 09) Useful in cardiac compromise condition.
  7. Less resp. depression
  8. Stress free anesthesia
  9. High in PONV
  10. Side Effects      
    1. Adrenal suppression- temporary inhibition of cortisol synthesis
    2. Highest incidence of nausea & vomiting (40%)
    3. Thrombophlebitis
    4. Painful injection
    5. Myoclonus 30- 60 %
  11. Anaesthetic of choice for
    1. MI patients
    2. Aneurysm surgery

Ketamine

  1. Synthesized by Stevens of Detroit & first used by Domino & Corsen. It can be given by oral, i/m, i/v intrathecal routes.
  2. Dissociative Anaesthesia.
  3. Causes profound analgesia.
  4. Sympathetic stimulation (excitement).
  5. Pharmacokinetics
    1. Onset of action - 60 sec. i.v, 10 min. I/M, 
    2. Duration of action - 10-15 min. I/V,  20 - 30 min. I/M
    3. Metabolized to Nor ketamine       
    4. t 1/2 - 2 to 3 hrs.
Dosage:
  1. Induction, by intramuscular injection, Adult and Child 6.5–13 mg/kg (10 mg/kg usually produces 12–25 minutes of anaesthesia)
  2. Induction, by intravenous injection over at least 1 minute, Adult and Child 1–4.5 mg/kg (2 mg/kg usually produces 5–10 minutes of anaesthesia)
  3. Induction, by intravenous infusion of a solution containing 1 mg/ml, Adult and Child total induction dose 0.5–2 mg/kg; maintenance (using microdrip infusion), 10–45 micrograms/kg/minute, rate adjusted according to response
  4. Analgesia, by intramuscular injection, Adult and Child initially 4 mg/kg .
  1. Effects:
    1. CNS:- Strong analgesic
      1. ​Dissociative anaesthesia i.e cortical function & thalamus are inhibited & limbic system gets stimulated.
      2. Vivid dreaming, hallucination & emergence delirium.
      3. Increases I.C.T. so Contra indicated in head injuries.
Remember
  • ​​Ketamine raises both systolic and diastolic blood pressures and is thus contraindicated in hypertension.
  • Ketamine increases cerebral blood flow and intracranial pressure and is contraindicated in raised ICT.
  • Ketamine raises intraocular tension and is thus contraindicated in glaucoma.
  • Ketamine causes increases cerebral oxygen consumption (AIIMS Nov 2007).
  1. CVSStimulates + symph. system so  ↑BP ↑PR
     
    So i/v anaesthetic of choice for SHOCK patients.
  2. Resp.- Stimulates respiration, increases Bronchial secretions
     
    Pharyngeal laryngeal reflexes are preserved so good for full stomach patients
     
    (although it dose not guarantee 100% protection).
  3. Eye → Increase I.O.T.
  4. Gut: Increase intragastric pressure, secretion.
  5. Muscle: muscle tone (Hypertonia), produces catalepsy.
     
    Non purposeful movements are seen.
  1. Side Effects
    1. Commonest is hallucination (40 - 50%), vivid dreaming, Emergence delirium (10-30%)
      To decreases hallucination agent of choice is Diazepam (also Opiates & thiopentone decrease hallucinations).
    2. increase muscle tone, catalepsy.
    3. increase pharyngeal, respiratory secretions so premedications with atropine is necessary.
    4. HT, tachycardia
    5. increase i.c.t., increase i.o.t., increase intragastric pressure
  2. Advantages & uses
    1. Can be used as sole anaesthetic for minor surgeries.
    2. Safest anaesthetic to be used at remote places & inexperienced hands (since it does not depress respiration).
    3. I/V anaesthetic of choice for shock patients (maintains BP).
    4. Preferred agent when patient is full stomach (preserves pharyngeal reflexes).
    5. Because of its analgesic properties good for burn dressings.
    6. Excellent for children (i/m can be given).
    7. For induction (but not the preferred agent).
Contraindications:
  1. Thyrotoxicosis; 
  2. Hypertension (including pre-eclampsia); 
  3. History of cerebrovascular accident, 
  4. Cerebral trauma, 
  5. Intracerebral mass or haemorrhage or other cause of raised intracranial pressure; 
  6. Eye injury and increased intraocular pressure; 
  7. Psychiatric disorders, particularly hallucinations

Benzodiazepines

  1. ​​​Diazepam
    1. ​Available as oil base preparation
    2. 98% bound to plasma proteins
    3. Highly acidic (Ph = 3.3)
    4. Onset of action 1-2 minutes.(When given i/v)
    5. t 1/2 - 30 - 60 hrs.
    6. Dose - 0.1 - 0.2 mg / kg for  sedation
       
      0.3 - 0.5 mg / kg for induction
      1. Effects: CNS
        • ​These are GABA facilitatory
        • Mainly acts on RAS (in midbrain) & Amygdala (limbic system)
        • No effects on cortex
        • Anxiolytic
        • Anterograde amnesia
        • Not an analgesic
        • Anticonvulsant
        • Does not increase I.C.T.
      2. CVS: myocardial depression & decreases B.P only at high doses
      3. Resp.- Resp depression only at high doses
      4. Muscle: Muscle relaxation is seen
  2. Midazolam
    1. ​Water based preparation so injection is not painful
    2. t 1/2 - 2-3 hrs. so excellent for day care surgery.
    3. Dose -
      1. ​0.1 mg / kg for sedation
      2. 0.2 - 0.3 mg / kg for induction
      3. 3 times more potent than diazepam
  3. ​​Lorazepam
    1. ​5 times more potent than diazepam.
    2. Long duration of action.
  4. ​Flumazenil
    1. ​It is Benzodiazepine antagonist (AIPG - 2008)
    2. given in increments of 0.1 - 0.2 mg to a max. of 1 mg
    3. Drawback is that t 1/2 is 1-2 hrs. so there are high chances of re-sedation.

Dexmedetomodine

Dexmedetomidine has become the frequently used drugs in anaesthetic practice , along with routine anaesthetic drugs, due to its haemodynamic, sedative, anxiolytic, analgesic, neuroprotective and anaesthetic sparing effects.
  1. Advantages - minimal respiratory depression with cardioprotection, neuroprotection and renoprotection, thus making it useful at various situations including offsite procedures.
     
    α-1 to α-2 ratio of 1:1600 makes it a highly selective α-2 agonist compared to clonidine.
  2. Dose -
     
    intravenous doses varying from 0.25 to 1 mcg/kg
  3. side effects
    1. Bradycardia and hypotension are the major side effects.
    2. Bradycardia is attributed to reflex response for transient hypertension during initial part of infusion. Subsequent decrease in heart rate is due to decrease in central sympathetic outflow.
    3. Hypotension is attributed to decreased central sympathetic outflow.

Neuroleptic Analgesia

  1. Droperidol (2.5 mg) + Fentanyl (0.05 mg) ratio 50:1
  2. S/ E & pharmacology is of Phenothiazine & fentanyl
  3. Most common S/E - Hypotension (a blockade)

Neuroleptic Anaesthesia

  1. Droperidol + fentanyl + inhalational agent (esp. N2O)

Althesin

  1. alphadione, steroidal agent
  2. non irritant, decrease B.P. and increase P.R.
  3. Bronchospasm, anaphylactoid reaction

Propanidid

  1. Ultra short Acting, derivative of eugenol
  2. metabolized by pseudocholinesterase
  3. Rapid metabolism – short duration, Ester hydrolyses
  4. Hyperventilation followed by apnea.
  5. S / E : Severe hypersensitivity reactions

Opioid Anaesthesia

opioid receptor → 5 type μ, , δ, σ, ε


 
- Resp. depression (low ceiling)
  • Miosis (low ceiling)
  • Dysphoria
  • Hallucination
  • Dependence
δ (Delta) –
 
Analgesia (spinal level)
 
Respiratory depression
 
Constipation

σ (Sigma) –
 
Dysphoria
 
Hallucination
 
Tachycardia
 
HT

ε (Epsilon) –
 
Stress response
 
Acupuncture
 
Classification
 

Naturally occurring

Semisynthetic

Synthetic

Morphine

Codeine

Thebaine (non analgesic)

 

Heroin

Dihydromorphone

Oxymorphone

Pentamorphone

 

Butorphenol

Buprenorphine

Pentazocine

Pethidine (meperidine)

Fentanyl, Alfentanil,

Sufentanil

Tramadol

Methadone (Prevention of opioid withdrawal symptoms & Tt of chronic pain)

 

Pure Agonist highest propensity for

Agonist – Antagonist d

Pure antagonist

Morphine

Pethidine

Fentanyl / Alfentanil / Sufentanil / remifentanil

Pentazocine, Butorphenol, nalbuphine: all are κ receptor agonist, μ receptor antagonist

 

Buprenorphine: receptor partial agonist

 

Nalorphine

 

Dezocine

 

Meptazinol

Naloxone

 

Naltreoxone

 

Nalmefene

 

Opium Alkaloid:

 

Phenanthrens: Morphine codeine, thebaine

 

Benzylisoquinolines: papaverine, noscapine both are non analgesic

 
 
 
Mech. of action of opioids:
 
Supraspinal binding to receptor and activate pain control circuit that descend from the mid brain, via the rostroventral region of medulla to spinal cord dorsal horn.
 
Spinal – acts in substansia gelatinosa of dorsal horn cells to inhibits the release of excitatory transmitters substance P
 
Systemic effects of opioids (morphine as prototype)
  1. Cvs:
    1. Hypotension
    2. Shifting of blood from pulmonary to systemic circulation (i.e. why used in Rx of LVF)
    3. Bradycardia (except Pethidine & pentazocine which causes tachycardia)
  2. Respiration:
    1.  Resp. (both frequency & tidal volume)
    2. Resp. depression is cause of death in morphine poisoning
    3.  Hypoxic & hypercapnic drive
    4. Recurrence of resp. depression (biphasic)
       
      (Since i/v opioids are sequestered by stomach & reabsorbed)
       
      Airway & tracheal reflexes (sufentanil maximum)
    5. Bronchi  Histamine release can cause bronchoconstriction; but direct effect on bronchial muscle is dilatation
  3. Cns
    1.  i.c.t. so C/I in head injury (direct cerebral vasodilator)
    2. stimulates CTZ – nausea & vomiting (high doses antiemetic)
    3. Convulsions can occurs (more common with pethidine)
  4. Eye
    1. miosis (only central action)
  5. Muscle
    1. Muscle rigidity (max. alfentanil)
    2. Rigidity in thoracic muscles causes wooden chest syndrome
  6. Renal
    1. Relaxes UB  Retention
  7. git
    1.  Gut motility,  gastric emptying  constipation
       
      (No tolerance to constipation)
  8. Biliary tract
    1. Causes constriction of sphincter of oddi  biliary duct pressure

Dependence

 

Both physical & psychological

 

Tolerance:

 

Mainly pharmacodynamic, tolerance is seen with all actions except constipation & miosis. So addicits are chronically constipated and miotic.

 

Petidine (Mepridine)

  • Atropine like action (Tachycardia, mydriasis,dry mouth, less constipation, less biliary spasm, less urinary retension)
  • Metabolite norpethidine has analgesic property and seizure potential.
  • Potency 1/10
  • MAO inhbitior can cause fatal reaction
  • Used for treatment of shivering

Pentazocine (Fortwin)

  • Mianly acts on receptors at spinal level
  • Potency 1/3
  •  Symph. System casues tachycardia & BP
     
    So C/I in MI patients

BUPRENORPHINE

  • 25 times more potent than morphine
  • Has highest receptor binding potential
FENTANYL
  • Can be given i.v, i.m, transmucosal transdermal, epidural, intrathecal, sweetened lozenge on stick
  • Muscle rigidity
  • 100 times more potent than morphine
Alfentanil
  • Quick onset and short acting so opioid of choice for day care surgery
Sufentanil
  • Most potent (500 times)
  • Opioid of choice for inhibiting cardiovascular response to Laryngoscopy and intubation. Not yet available in India
Remifentanil
  • ultra short acting
  • Metabolized by non-specific esterases
  • Opoid of choice for hepatic and renal patients
  • Not recommended for spinal & epidural route.
Naloxone – opioid antagonist
 
Highest propensity to block μ receptors
 
Naloxone also antagonizes the action of
  • Diazepam
  • N2O
  • Barbiturates
  • Endogenous opioids

Other uses of naloxone

  1. Neonatal asphyxia if opioid is used during labour
  2. Δ of opioid dependence

Dose: 40-80 μg i/v to a max. of 400 μg

 

 Can be given intra-trachealy

 

S/E: HT, V.fibrillation, pulmonary edema, cardiac arrest

 

Naltrexone: long acting, orally active

 
 for supraspinal control of pain i.e activate decending inhibitory pain pathways.
 
Dynorphins  for spinal control pain
  • β Endorphins modulates nociception in stress
  • Enkephlins in acupuncture mediated analgesia
  1. Opioids compounds are frequently administered during anaesthesia to suppress autonomic responses to tracheal intubation and painful (noxious) surgical stimuli.
  2. Opioids anaesthetics used commonly are fentanyl, alfentanil, remifentanil, sufentanil.
  3. These drugs are potent opioids analgesics and are used i.v. ate beginning of painful surgical procedure.
  4. Fentanyl is frequently used with droperidol as neurolept analgesia, when N2O is also added it is called neurolept anaesthesia.
  5. Alfentanyl is opioids of choice for day care surgery
  6. Alfentanyl is used with propofol for total intravenous anaesthesia (TIVA)
  7. Sulfentanil is the most potent opioid.
  8. Order of potency (in decreasing order)-  Sunfentanil > Fentanyl = Remifentanil > Alfentanil. Sufentanil is the most potent opioids
  9. Remifentanil is shortest acting acting opioid due to its metabolism by plasma esterase  Dose reduction is not necessary in hepatic or renal disease
  10. Use of fentanyl, sufentanil and alfentanil during induction anaesthesia can prevent increase in IOT.
  11. Tone of chest muscles may increase with rapid fentanyl injection  All fentanyl cogneres can produce truncal rigidity on rapid i.v. injection

Rapid Sequence Induction

When anaesthesia is given for emergency surgery, it is called a “rapid sequence anaesthesia”. The patients have full stomach because there is no starvation for anaesthesia (it is an emergency surgery) and gastric emptying is delayed due to trauma, acute abdomen. Therefore, the objective of rapid sequence anaesthesia is to secure the airway rapidly and prevent aspiration of gastric contents.
  1. Procedure of rapid sequence has following steps:
  2. The patient is preoxygenated for full 3 minutes.
  3. Intravenous induction agent (thiopentone or propofol) is given
  4. Sellick’s maneuver (cricoids/pressure) is done to prevent aspiration.
  5. After ensuring the correct position of tube cricoids pressure is released and maintenance anaesthesia (N2O) 66%), O2% 33% & inhalational agent) is given. A non-depolarizing blocker is now added.
  6. Suxamethenium (succinylcholine) is given as it quickly relaxes the laryngeal muscles so that rapid intubation can be done.
Not done during rapid sequence anaesthesia:
  1. Manual ventilation before intubation is avoided as this inflates the stomach and encourages regurgitation and aspiration
  2. Premedications are not given.

Ambulatory (Outpatient/day care) Anaesthesia

Ambulatory or day care or outpatient anaesthesia means, patient comes on same day, gets operated and is discharged on same day. So the drugs used in outpatient anaesthesia are those which have short duration of action. Anaesthetic techniques and agents ideal for day care surgery are:-
 
Premedication
 
Usually premedication is not used. However in anxious patients, midazolam is the drug choice, which should be given 1-2 hours before the surgery with sip of water by oral route or 30 min. before surgery by im route. If patient is prone to nausea and vomiting, dolastron is the drug of choice. Ondansetron is an alternative.
 
Airway
 
Laryngeal mask airway is preferred over intubation
 
Intravenous anaesthetic
 
Intravenous route is the preferred method for induction. Propofol is the intravenous anaesthetic of choice for induction because of iths smooth induction and rapid recovery. Antiemetic action of propofol is also beneficial→use of propofol for induction or maintenance of anaesthesia is associated with a reduced incidence of post-operative nausea and vomiting.
 
Inhalational agents
 
Inhalational anaesthetics are preferred for the maintenance. Desflurane (1st choice) and sevoflurane (2nd choice) are the agents of choice. These agents are used along with N2O as N2O decreases the requirement of other anaesthetics hence fastening the recovery. Halothane and isoflurane have largely Been replaced by the less soluble desflurane and sevoflurane.
 
Muscle relaxants
 
Intermediate or short acting
 
Opioid analgesics
 
Fentanyl and its congeners




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