Intravenous Anesthetics

Pharmacology 6,924 Views

Commonly used for induction because of rapid onset of action. They act within seconds and produce unconsciousness.

There is no special delivery system required. I/V (bolus/infusion) given.

Barbiturates

Two drugs used are:

1. Thiopental

2. Thiopentone Sodium

Induction / Onset

When administered, produce anesthesia within seconds, even during first circulation through brain this state is produced.

Pharmacokinetics

a. Highly lipid soluble goes to the highly perfused organs; brain liver and kidneys. Afterwards to less perfused like muscles, fatty tissue and skin. Due to lipophilic nature, is redistributed to fatty tissues.

_b.T_1/2– 3 min / 12 hrs

As redistributed to fatty tissues, so has 2 half-lives, one 3-5 minutes, action of which remains for 10-15 minutes.

Drowsiness remains for 12-24 hours, due to redistribution.

c. Metabolism / Excretion

Elimination half-life is 12 hours, during which it is excreted out. Metabolized in liver and metabolites are excreted in urine.

Pharmacological Effects

1. CVS / Respiration

Depressant effect on CVS and respiratory system.

Decrease in cardiac output and blood pressure

2. CNS – metabolism

Decreased metabolism and cerebral blood flow, so beneficial in patients having increased intracranial pressure or with pressing lesion (tumor) or head injury.

3. Pain / muscle relaxation

It does not have good analgesic property and is not a good muscle relaxant, so along with it analgesic and muscle relaxant is administered.

Uses

Dental / Endoscopy / Circumcision/ Orthopedics / Dressings / Psychoanalysis

Used mostly for short surgical procedures like dental extractions, endoscopy, orthopedic, changing painful dressing, psychoanalysis bio psychiatrist leading to diagnosis of psychiatric problems and treatment.

Named ‘truth drug’ because patient specks many things under its influence.

Adverse effects

1. Laryngospasm (atropine is given before anesthesia, treatment is to give suxamethonium)

2. Shivering

3. Restlessness –during recovery

4. Injection site pain

5. Inadvertent injection –artery or vein causing necrosis, thrombosis or damage to nerves

6. Acute porphyria –known to precipitate in susceptible patients. Also seen with Thiopentone sodium.

Contraindications

Relative

CCF

Hypovolemia

Obstruction

Absolute

Porphyrias

Advantages	Disadvantages
Non irritant	Very short duration of action
Non explosive	Repeated doses accumulate
Easy administration	Insignificant analgesic action
Rapid and pleasant induction	Cannot be used alone as an anesthetic
Less incidence of nausea/ vomiting	Coughing, hiccough, laryngospasm, bronchospasm may develop during induction
Quiet respiration	Muscle relaxation is not adequate

Methohexital

Advantage:

1. Clearance –cleared out rapidly, with shorter half-life of 4 hours

2. Potency –3-5 times potent than Thiopentone sodium.

3. Central excitation –whenever excitatory focus providing seizure like activity (epileptic), used for ablation of foci.

Use – ECT (anti-seizure) generally antiseizure activity, so given during ECG

Propofol

Formulations

Available as different formulations:

Emulsion (Conventional) oily preparation

Ampofol has less lipid content

Fospropofol; water soluble/aqueous preparation –prodrug

Disadvantage of oily preparations is that once they are opened up for use, there are chances of bacterial growth.

Disadvantage of aqueous preparation is that they are more painful at injury site.

Pharmacokinetics

a. Onset / recovery– induction is within seconds (10-15 sec)

_{b. .}T_1/2– 2-8 / 30-60 min –has distributive half-life as well as elimination half life. Metabolism is ten times faster than Thiopentone sodium, so less hang over effects.

c. Metabolism / excretion –metabolized in liver, excreted as glucuronide and sulphate conjugation

Pharmacological Effects

1. CVS / Respiration

Depressive action on CVS and respiration. Much severe effect.

2. CNS (thiopental)

Decreases metabolic rate and cerebral blood flow.

3. Pain / Muscle relaxation

Not good muscle relaxant, with no analgesic property, supplemented analgesia and muscle relaxant are applied.

Uses

1. Advantages – post-op N/V

2. Used in ambulatory surgeries because propofol post–op volume is very less, so person feels much better earlier.

3. Also used for sedation, for which lesser dose is required. This sedation is for procedures like endoscopy or for prolonged periods in critically ill patients, e.g. on ventilators.

Adverse effects

1. CVS / respiration –highly depressive

2. Injection site (lignocaine) –pain in water soluble preparations, either mixture of lignocaine and propofol is given or lignocaine is administered before at site of administration.

3. Elevated lipid levels in blood (conventional) –lipid preparations if used for prolonged periods

4. Muscle movements –hypotonus and sometimes tremors

5. Children (respiratory infections) – when used for prolonged periods lead to acidosis

– neurological effects when withdrawn or discontinued

Etomidate

Pharmacokinetics

Onset / recovery –onset of action within seconds

T_1/2– biphasic distribution with two distributive half-lives – 3 min and 29 min –elimination half-life of 4-6 hrs.

Metabolism occurs in liver

Excretion –renal (78%) / biliary (22%)

Pharmacological Effects

1. CVS / Respiration –does not affect very much, either no or minimal, so used in patients having poor cardiovascular reserves

2. CNS / Pain (thiopental) –decrease in blood flow and metabolism. No effect on pain so combined with analgesic.

Use

Main use is in patients having poor cardiovascular reserves e.g. old or with IHD or cardiomyopathies.

Adverse effects

1. Injection site –pain, so lignocaine is used

2. Nausea / vomiting / restlessness / tremors

3. Steroidogenesis inhibition – cortisol

Inhibition of adrenocortical hormone formation by inhibitory beta hydroxylation esp. cortisol and when given for short periods, transient effect occurs. If given for prolonged period, this effect can be responsible for severe side effects like hypotension and electrolyte imbalance, oliguria, etc.

Ketamine

Ketamine is hallucinogenic drug, available as racemic mixture of S and R enantiomers.

S enantiomer is more potent with less side effects, still administered as racemic mixture.

Phencyclidine (PCP) congener

Mechanism of action

It blocks NMDA receptors in CNS, decreasing excitatory effects of glutamate, producing anesthesia.
It dissociates thalamus from limbic system, producing dissociative anesthesia.

Pharmacokinetics

Mostly given I/V; but also I/M; oral; rectal

It is highly lipid soluble, so has wide distribution; rapidly crosses blood brain barrier to enter brain.

Metabolism occurs in liver and excretion occurs in urine.

Pharmacological Effects

1. CNS

Different mechanism of action. It binds NMDA receptors and blocks them, so that glutamate (excitatory neurotransmitter) cannot bind.

Psychoactive drug, has been abused as hallucinogenic drug.

2. Cerebral BF / metabolism

Effects cerebral blood flow and intracranial pressure, causes increase in cerebral metabolism and increase in cerebral blood flow, leading to increased intracranial pressure, so should be avoided in patients of head injury or space occupying lesion.

3. CVS – stimulation (2-20 min)

Cardio stimulatory by two mechanisms:

a. Sympathetic stimulation

b. Prevents reuptake of norepinephrine from adrenergic terminals.

Cardio stimulatory effect peaks within 2-4 minutes and normalizes in around 12-20 minutes.

4. Respiratory – reflexes / bronchodilation

No effect on reflexes and does not abolish ventilator reflexes. Person respires spontaneously without outside assistance.

Another advantage is that it causes bronchodilation due to:

a. Sympathetic stimulation

b. Mild degree of direct bronchodilatory effect

Uses

1. Dissociative anesthesia – cataleptic state

In which patient experiences analgesia, catatonia, amnesia, hypnosis, eyes open but unresponsive to painful stimuli, respiring spontaneously, patient is disassociated from surroundings, appears awake but cannot perceive what is going on around him, so called dissociative anesthesia.

2. Analgesia

Good analgesia given for short surgical procedures, where complete loss of consciousness is not required like

a. Old age

old age, where poor cardiovascular reserves are present (cardio stimulatory action).

b. Children

Also commonly used in children

c. Hemodynamic stability

In patients with hemodynamic instability (septic shock, cardiogenic shock) or patients bleeding profusely.

d. Bronchodilation

Also useful for patients of chronic obstructive airway disorder, where bronchodilation has beneficial effect.

e. Topical – arthritic pain

Newer preparations of Ketamine are available for topical application for arthritic pain.

Adverse effects

1. CVS – IHD

As cardio stimulatory avoided in patients with ischemic heart disease

2. Emergence delirium – BZD

Seen during recovery. Patient experiences hallucinations, illusions and dream like state. This is due to very high lipid solubility. Ketamine dissolves in nervous tissue, when plasma levels are decreased, effects are still present.

To avoid this patient is administered benzodiazepines like diazepam or midazolam.

Advantages	Disadvantages
No sensitization of heart to catecholamines	pharyngeal/ laryngeal reflexes are not abolished
Rapid recovery	In over dosage depression of VMC, myocardium and respiration
No excitement during induction	Regurgitation due to relaxation of gastro esophageal sphincter
	Injection may cause necrosis, thrombophlebitis, nerve damage, vasospasm on intra – arterial injection (may lead to gangrene)
Effective by both i/v & i/m injection	No muscle relaxation
Anesthesia is accompanied by profound analgesia	Tends to raise intraocular, intra cranial blood pressures and heart rate
Can be used alone for minor surgery	Hallucinations, nightmares and delirium may last up to 24 hrs.
Does not produce vomiting, hypotension, bronchospasm	Cannot be used for surgery on larynx, pharynx, bronchi
Less respiratory complications due to less impairment of pharyngeal/ laryngeal reflexes	Poor in relieving visceral pain