INTRAVENOUS ANAESTHETIC AGENTS DRUGS.pptx

Intravenous Anesthetic agents

1. INTRAVENOUS ANAESTHETIC AGENTS

2. INTRODUTION/ DEFINITION THE IDEAL I.V AGENT-PROPERTIES CLASSIFICATION GENERAL USE COMMONLY USED AGENTS CONCLUSION OUTLINE

3. Intravenous Anaesthetic agents are drugs which when given in clinical doses depresses the CNS in one or few arm – brain circulation. Includes- Sedatives Tranquilizers Hypnotic agents Commonly used to induce anaesthesia and/or for maintenance Usually produce rapid, smoother induction compared with inhalational agents. INTRODUCTION AND DEFINITION

4. Ideal iv anaesthetic induction agent do NOT exist Hence, the continued search for new drugs Desirable properties of an Ideal iv agent include: Soluble and stable in solution Provide smooth and rapid induction of /recovery from anaesthesia No pain or excitation on injection No emergence phenomenon No emetic effect Produces minimal/no CVS and respiratory depression No histamine release or anaphylactic reaction No irritant effect and sequalae if injected inadvertently into an artery or extravascularly The Ideal IV Anaesthetic agent

5. A. Rapidly Acting (1 o ) Induction agents Barbiturates Methohexital Thiopental Thiamylal Alkyl phenols Propofol Imidazole Compounds Etomidate Steroids Eltanolol- obsolete Althesin - obsolete Eugenols Propanidid- withdrawn from market Classification

6. B. Slower Acting (basal narcotic) agents Phencyclidine derivatives ketamine Benzodiazepines Diazepam Midazolam. Large dose Opioids Fentanyl Alfentanil Sufentanil

7. Induction agents Total IntraVenous Anaesthesia- TIVA- Induction/Maintenance of anaesthesia ICU Sedation Supplement to Regional Anaesthesia Anticonvulsant Brain protection Electroconvulsive therapy esp methoexithal prefered to propofol Wada test to locate dominant cerebrum General uses

8. Thiopentone Ketamine Propofol Others –less in use eg. Midazolam, Fentanyl, etc. Commonly Used agents and their clinical relevance

9. Most commonly used iv induction agent A thiobarbiturate Physical properties: Yellow powder, soluble in water with PH of 10.8, PKa of 7.6 Solution not stable for >24 hrs after reconstitution in water to a 2.5% Best prepared fresh Mode of Action Act 1 ly at synapses by depressing post-synaptic sensitivity to neurotransmitters and inhibit pre-synaptic neurotransmitter release Administration- Dose- iv route – 3-7 mg/kg Onset time- one arm-brain circulation time DOA- 5-15 mins, Repeated doses effect is cummulative Other route- rectally, onset time is within 15 mins Thiopentone

10. Systemic Effects CVS- ↓CO (By 20%), ↓PVR →Hypotension Resp. S- depresses centre, ± apnoea. Reduces resp centre’s response to CO 2 . Histamine release may lead to bronchospasm CNS- depressed→ hypnosis. Anticonvulsant, ↓ CBF, ICP, IOP Skin- erythematous rash around neck and chest, sometimes Metabolism Liver- main site, @ rate of 10-15% per Hr. 30% remain in body after 24 hrs. Inactive metabolites excreted mainly in the urine, 0.5% excreted unchanged Thiopentone is not removed by dialysis Thiopentone

11. Contra-indications Severe hypotension or shock Previous anaphylaxis Acute intermittent porphyria Acute bronchial asthma Extravascular inj→ severe pain Inadvertent intra-arterial inj→arterial spasm, thrombosis→gangrene of eg the hand Rx: leave needle in the artery, Flush with saline, Inj procaine to relieve spasm, Keep the hand warm, elevate it, ± anticoagulant therapy Thiopentone

12. Widely used as TIVA in developing countries A phencyclidine derivative Enjoys wider use in children cos of less post-anaesth effects Available as colorless solution- 1%, 5% soln. Precipitates if mixed with thiopentone Main action- Dissociative anaesth (combination of profound analgesia with superficial sleep ie light hypnosis). Gag, eye lash reflexes are preserved MOA- non-competitive antagonist of NMDA receptor. Modulates opioid muscarinic receptor activity Administration- im dose- 5-10 mg/Kg, onset time within 5 mins, DOA of 10-20 mins Iv dose- 1-2 mg/Kg, onset time within 1 min, DOA of 5-10 mins Other routes- orally, intrathecally, rectally, nasally Ketamine

13. Systemic Effects: CVS- ↑SBP,DBP, ↑PR,→↑CO RS- mild stimulation, with preservation of airway reflexes but aspiration still possible. Bronchodilatation. CNS- ↑CBF, CMR, IOP. Amnesia, Analgesia. State of Dissociative Anaesthesia. GIT- ↑mucous secretions including salivation, ↑Post-op. nausea and vomitting. Others- ↑ uterine tone.↑ Ad,and Norad, circ. Levels Metabolism- occurs in Liver. Metabolites excreted in urine Clinical importance- Good CVS and RS stability Potent Analgesic effect Both im and iv admin. Can be used as sole anaesthetic agent, TIVA, for many types of surgery Ketamine

14. Disadvantages- Slower induction time Slower recovery Poor muscle relaxation Unpleasant dreams, hallucinations, emergence delirium are problems, but can be reduced by premedication with diazepam, midazolam, lorazepam Contra-indications- Hypertension Psychiatric disturbance Ketamine

15. Relatively new iv anaesth. A phenol derivative- 2,6-diisopropylphenol Presented as white oil-in-water amulsion containing 1% (ie. 10 mg/ml, common) or 2% propofol in soyabean, purified egg phosphatide, and sodium hydroxide. No preservative, good culture medium for bacteria Main action- hypnotic Uses- Induction and maintenance of GA Sedation in ICU or during regional anaesth. Rx of refractory N,V in pts receiving chemotherapy Rx of status epilepticus For optimal insertion of LMA Propofol

16. Administration- For induction- iv bolus 1.5-2.5 mg/Kg, with onset time of 30 secs, DOA 10 mins after a single dose For maintenance- infusion of 4-12 mg/Kg/hr For Children- ↑ the doses above by 50% for induction, and by 25-50% for maintenance Pt recover rapidly without hangover effect Effects- CVS- ↓BP,↓SVR→↓CO by 20%, without reflex increase in HR. Attenuates haemodynamic response to laryngoscopy Rapid bolus injection may cause bradycardia and asystole RS- apnoea with rapid bolus, suppression of laryngeal reflexes, depresses ventilatory response to hypercarbia and hypoxia. Bronchodilatation. Propofol

17. CNS- smooth, rapid induction with rapid and clear-headed recovery. - ↓ ICP, CPP, CMRO 2 GIT- intrinsic anti-emetic ppties Others- free radical scavenger, Long term use may lead to hypertriglycerdaemia, and ↑ mortality esp in children in ICU Causes pain on injection, may be reduced by- Addition of Lidocaine, cooling the drug, or use of large veins Metabolism- mainly in Liver to inactive glucuronide.+ other extra hepatic clearance. Metabolites, and small unchanged form excreted in urine Renal and Hepatic dx have NO clinically significant effect on metabolism Contraindications- Shock, untreated hypovolaemia, hypotension pts Propofol

18. A water soluble imidazobenzodiazepine Highly protein bound, 97% Presentation- clear, colourless soln Main actions Hypnosis- iv induction Sedation Anxiolysis Anterograde amnesia Anticonvulsant Muscular relaxation Administration Premedication/sedation: im/iv dose- 0.05-0.1 mg/kg 30mins pre-induction Induction dose: iv- 0.2-0.3 mg/kg onset time within 2-3 mins, DOA 10-15 mins (varies) Other routes- intrathecal, epidural, oral (sweetened/flavoured) Midazolam

19. Effects- CVS- ↓BP,↓SVR, but reflex ↑PR lesser than propofol, thiopentone, hence produces relatively stable haemodynamics RS- impairs resp. response to hypercapnoea, resp depression, apnoea may occur CNS- ↓CBF, ↓CMRO 2 →↓ICP- brain protection against ischaemia Metabolism- occur in Liver, excreted in urine - termination of action of single dose is due to re-distribution from brain to periph t/s. Midazolam