Propofol |

Propofol

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Propofol Listen to Audio mechanism of action structure-activity relationships pharmacokinetics effects on organ systems drug interactions MECHANISM OF ACTION -may involve facilitation of GABA mediated inhibitory neurotransmitters STRUCTURE-ACTIVITY RELATIONSHIPS 2,6-diisopropylphenol consist two isopropyl groups attached to a phenol ring -potency, induction and recovery charecteristics are affected by altering the side-chain length on the alkylphenol of propofol -packages as 1% aqueous solution PHARMACOKINETICS Absorption -only available for intravenous administration -induction of general anesthesia Distribution -rapid onset due to high lipid solubility -onset nearly as rapid as thiopental with a one arm-to-brain time -short initial redistribution time of about 2-8 minutes leads to rapid awakening after a single bolus -good anesthetic agent for outpatient services due to less hangover sensation compared with thiopental and etomidate -elderly patients: may require a smaller induction dose due to a smaller Vd -female patients: may require a larger dose than males and may have a more rapid awakening Biotransformation -conjugation of propofol in the liver results in inactive metabolites which are then to be eliminated by renal clearance -extrahepatic metabolism is implicated due to the clearance of propofol exceeding the hepatic blood flow -very high clearance rate of propofol allows for a rapid recovery even after a continous infusion Excretion -primarily renal excretion of metabolites of propofol in the urine -chronic renal failure does not appear to affect the clearance of propofol Pharmacodynamics Effects on Organ Systems Central nervous system -decreases CBF -decreases ICP -patients with increased ICP, propofol may cause a critical reduction of CePP < 50 mmHg due to a decrease in MAP -may provide cerebral protection in focal ischemia of the brain similar to barbiturates -antiemetic and antipruritic properties of propofol provide good charecteristics for outpatient based anesthesia -anticonvulsant properties -may be associated with an excitatory phenomena during induction (ex. muscle twitching, spontaneous movement, hiccuping) -subcortical glycine antagonism may be the cause of hiccuping associated with propofol induction Cardiovascular system -decrease in mean arterial blood pressure -decrease in systemic vascular resistance SVR -decrease in preload -decrease in myocardial contractility -hypotension generally more profound with propofol than with thiopental -inhibits normal function of baroreceptors in response to decreased MAP, therefore leads to lack of reflex tachycardia Decreased cardiac output and perhaps even bradycardia may be more associated in the following patients: -extremes of age -negative chronotropic medications taken by patient -procedures involved with oculocardiac reflex Factors exacerbating hypotension associated with propofol induction include: -large doses of propofol -rapid injection of propofol -old age Respiratory system -profound respiratory depressant -generally causes apnea during induction doses of general anesthesia -decreased hypoxic ventilatory drive even with subanesthetic doses during an infusion for conscious sedation -associated with less wheezing in both asthmatic and nonasthmatic patients with induction doses of propofol compared to thiopental

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