The document discusses ideal properties of intravenous anesthetics and summarizes the pharmacokinetics and pharmacodynamics of several commonly used IV anesthetics including barbiturates, propofol, etomidate, ketamine, benzodiazepines, and dexmedetomidine. It outlines desirable traits such as rapid onset and offset of action, minimal cardiovascular and respiratory depression, and lack of adverse effects. Each drug's mechanism of action, dosing, metabolism, indications, contraindications, and side effects are briefly described.

1. Intraveous anestheticsDr.Hussam Alsharani Dr.Osama IbrahimAnesthesia resident Assistant professorAnesthesia d. KKUH Anesthesia d. KKUH

2. Ideal IV anesthetics:1-Drug compatibility (water solubility) and stability in solution.2-lake pain on injection , veno irritation , and local tissue damage.3-low potential to release histamine.4-rabid and smooth onset of action without excitatory activity.5-rabid metabolism to inactive metabolites.6-a steep dose to minimize titratability and tissue accumulation.7-lake of acute cardiovascular and respiratory depression.8-decrease in cerebral metabolism and intracranial pressure.9-rabid and smooth return to consciousness .10-abcense of post operative nausea , vomiting, amnesia , psychoimetic reaction , dizziness , headache , and prolonged sedation.

4. Pharmacokinetics:Anesthesia is produced by diffusion of drug from arterial blood across the blood brain barrier in to the brain which regulated by the following factors:-protein binding: unbound drug is free to cross BBB.-blood flow to the brain.-extracellular PH and Pka of the drug: nonionized.-solubility of the drug in lipid and water: high lipid solubility enhances transfer in to the brain.-speed of injection.

6. Barbiturates (Thiopental):-available as sodium salts (yellowish powder).-bitter taste + smell of garlic.-solution of thiobarbiturates are stable for 2 weeks.-ph of solution of thiopental (2.5%) is 9.-does not cause pain on injection.-metabolized in liver to hydroxythiopental and carboxylic acid.-produce anesthesia in less than 30 sec after iv injection.-induction dose: 3-5 mg/kg in adults 5-6 mg/kg in children 6-8 mg/kg in infants-recovery after 10 min

7. -produce decrease in CPF there by lowering ICP.-widely used to improve brain relaxation during neurosurgery and to improve cerebral infusion pressure after acute brain injury-It cause dose dependent anticonvulsant activity.-dose dependent respiratory depression.-it cause decrease in cardiac output and ABP.-early absence in eyelidreflex.

8. -tissue necrosis: median nerve damage may be occur after extravenous injection in the antecubital fossa if perivenous injection occurred the needle should be left in place and injection of hyaloronidase.-intra-arterial injection: pt usually complains of burning pain + intense in this case: -stop injection. -leave needle in artery. -administrate papaverine 20 mg. -heparin should be given iv and orally. -stellate ganglion or brachial plexus block may reduce arterial spasm.

11. Propofol:-(2,6-dispropylphenol).-pain on injection 32-67% of patients.-t1/2 is 1-8 min (Barash 2009).-elimination half time 2-24 min.-metabolized in liver to sulfate and glucuronic acid which are eliminated by kidney.-extra hepatic rout of elimination by lungs.-anesthesia is induced in 20-40 sec after iv administration.-we can monitor the onset by loss of verbal contact.-induction dose 1.5 – 2.5 mg/kg.-children require bigger dose.-euphoria effect.

12. -propofol decrease CPF and ICP.-excitatory motor activity without EEG changes.-dose and concentration dependent cardiovascular depression.-dose dependent respiratory depression with apnea.-antiemetic effects (10-20 mg to treat nausea and emesis in the early post operative period.-antidopamenergic which lead to euphoria.-it decrease the pruritus produced by spinal opioids.-agent of choice in malignant hyperthermia suspictable pt.-Propofol syndrome : after high dose infusion of propofol for long time – myocardial failure – metabolic acidosis – rabdomyolysis.

13. Propofol has no effect on bronchial muscle tone and laryngospasm is particularly uncommon .The suppression of laryngeal reflex and low incidence of coughing or laryngospasm when a laryngeal mask airway (LMA) is introduced , and propofol is regarded by most anesthetists as the drug of choice for induction of anesthesia when LMA is to be used.

15. Etomidate:-carboxylated imidazole.-ph 6.9 , pain on injection , venoirritation.-induction dose : 0.2-0.3 mg/kg.-involuntary myoclonic movement are common at induction.-metabolism in liver.-it decrease CPF and ICP.-inhibitory effect on adrenocortical synthetic function (5-8 h after single use)-inhibit platelet function.-minimal cardiorespiratory depression .-does not induce histamine release.-high incidence of post op nausea and emesis .

16. Absolute contraindication: -airway obstruction. -prophyria. -adrenal impairment. -long term infusion in ICU (increase infection and mortality).

18. Kitamine:-Arylcyclohexylamine.-water soluble compound.-potent anesthetics and analgesic properties +amnesia .-metabolized by liver to norkitamine which excreted by kidney.-elimination half life 2-4 h .-dose dependent CNS depression + stimulation of limbic s.-induction dose: 1-2 mg/kg IV. 4-8mg/kg IM.-duration of action: 10-20min –full orientation require more 60 – 90 min

19. -high incidence of psychomimetic reactions (namely , hallucination , nightmares , altered short term memory , and cognition).-ketamine increase CPF and ICP .-bronchodilatory activity - minimal respiratory depression.-increase oral secretion.-cardiovascular stimulation + increase peripheral resistant.-not recommended in severe coronary artery disease.-increase pulmonary artery pressure (contraindicated in poor right ventricular reserve.

20. Indications: -high risk pt: shocked patients. -pediatric anesthesia. -difficult locations: site of accidents. -developing countries: where anesthetic equipment and trained staff in short supply.

21. Benzodiazepines:-medazolam , lorazepam , diazepam and antagonist flumazenil.-metabolized in liver , excreted by kidney.-short acting: midazolam - flumazenil.-intermediate: diazepam.-long acting: lorazepam.-only midazolam can given by continuous infusion.-all benzodiazepines produce: anxiolytic, anterograde amnesia, sedative, hypnotic, anticonvulsant, and spinally mediated muscle relaxant properties.

22. -dose dependent respiratory depression.-it depress the swallowing reflex and depress upper airway reflex activity.-produce decrease in systemic vascular resistant and blood pressure in large doses.-specific antagonist :flumazenil

23. Dexmedetomidine:-alpha 2 adreno receptor agonist.-approved by FDA for the short term less than 24 h sedation of the mechanically ventilated pt in ICU.-unique type of sedation-analgesia with less respiratory depression + amnestic affect .-it produce hypotension and bradycardia more than diazepines.-infusion rate 0.2-0.6 mcg/kg/h.-improve post op pain control after major surgery.-slower onset and offset than propofol , sedation like midazolam. -high cost.

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