Propofol ( dipprivan, recofol) dikemas dalam cairan emulsi lemak berwarna putih susu bersifat isotonic dengan pemekatan 1% ( 1 ml = 10 mg). Suntikan intravena sering menyebabkan nyeri, sehingga beberapa detik sebelumnya dapat diberikan lidokain 1-2 mg /kg intravena.
Dosis bolus untuk induksi 2-2.5 mg/kg, dosis rumatan untuk anesthesia intravena total 4-13 mg/kg per jam , atau 100 - 200 mcg/kgbb/menit dengan syringe pump dan dosis sedasi untuk perawatan intensif 0.2mg / kg atau 25 -50 mcg/kgbb/menit syringe pump. Pengenceran propofol hanya boleh dengan dextrose 5%. Pada manula dosis harus dikurangi, pada anak kurang dari 3 tahun dan pada wanita hamil tidak dianjurkan.
Sumber: http://www.pharmacology2000.com
Sumber: http://www.tbiomed.com
tambahan........
Propofol ( 2,6 – diisopropylphenol )
Merupakan derivat fenol yang banyak digunakan sebagai anastesia intravena dan lebih dikenal dengan nama dagang Diprivan. Pertama kali digunakan dalam praktek anestesi pada tahun 1977 sebagai obat induksi.
Propofol digunakan untuk induksi dan pemeliharaan dalam anastesia umum, pada pasien dewasa dan pasien anak – anak usia lebih dari 3 tahun. Mengandung lecitin, glycerol dan minyak soybean, sedangkan pertumbuhan kuman dihambat oleh adanya asam etilendiamintetraasetat atau sulfat, hal tersebut sangat tergantung pada pabrik pembuat obatnya. Obat ini dikemas dalam cairan emulsi lemak berwarna putih susu bersifat isotonik dengan kepekatan 1 % (1 ml = 10 mg).
Mekanisme kerja
Mekanisme kerjanya sampai saat ini masih kurang diketahui ,tapi diperkirakan efek primernya berlangsung di reseptor GABA – A (Gamma Amino Butired Acid).
Farmakokinetik
Digunakan secara intravena dan bersifat lipofilik dimana 98% terikat protein plasma, eliminasi dari obat ini terjadi di hepar menjadi suatu metabolit tidak aktif, waktu paruh propofol diperkirakan berkisar antara 2 – 24 jam. Namun dalam kenyataanya di klinis jauh lebih pendek karena propofol didistribusikan secara cepat ke jaringan tepi. Dosis induksi cepat menyebabkan sedasi ( rata – rata 30 – 45 detik ) dan kecepatan untuk pulih juga relatif singkat. Satu ampul 20ml mengandung propofol 10mg/ml. Popofol bersifat hipnotik murni tanpa disertai efek analgetik ataupun relaksasi otot.
Farmakodinamik
Pada sistem saraf pusat
Dosis induksi menyebabkan pasien tidak sadar, dimana dalam dosis yang kecil dapat menimbulkan efek sedasi, tanpa disetai efek analgetik, pada pemberian dosis induksi (2mg /kgBB) pemulihan kesadaran berlangsung cepat.
Pada sistem kardiovaskular
Dapat menyebakan depresi pada jantung dan pembuluh darah dimana tekanan dapat turun sekali disertai dengan peningkatan denyut nadi, pengaruh terhadap frekuensi jantung juga sangat minim.
Sistem pernafasan
Dapat menurunkan frekuensi pernafasan dan volume tidal, dalam beberapa kasus dapat menyebabkan henti nafas kebanyakan muncul pada pemberian diprivan
Dosis dan penggunaan
a) Induksi : 2,0 sampai 2.5 mg/kg IV.
b) Sedasi : 25 to 75 µg/kg/min dengan I.V infuse
c) Dosis pemeliharaan pada anastesi umum : 100 – 150 µg/kg/min IV (titrate to effect).
d) Turunkan dosis pada orang tua atau gangguan hemodinamik atau apabila digabung penggunaanya dengan obat anastesi yang lain.
e) Dapat dilarutkan dengan Dextrosa 5 % untuk mendapatkan konsentrasi yang minimal 0,2%
f) Profofol mendukung perkembangan bakteri, sehingga harus berada dalam lingkungan yang steril dan hindari profofol dalam kondisi sudah terbuka lebih dari 6 jam untuk mencegah kontaminasi dari bakteri.
Efek Samping
Dapat menyebabkan nyeri selama pemberian pada 50% sampai 75%. Nyeri ini bisa muncul akibat iritasi pembuluh darah vena, nyeri pada pemberian propofol dapat dihilangkan dengan menggunakan lidocain (0,5 mg/kg) dan jika mungkin dapat diberikan 1 sampai 2 menit dengan pemasangan torniquet pada bagian proksimal tempat suntikan, berikan secara I.V melaui vena yang besar. Gejala mual dan muntah juga sering sekali ditemui pada pasien setelah operasi menggunakan propofol. Propofol merupakan emulsi lemak sehingga pemberiannya harus hati – hati pada pasien dengan gangguan metabolisme lemak seperti hiperlipidemia dan pankreatitis.
FROM MORGAN
PROPOFOL
Mechanisms of Action
The mechanism by which propofol induces a state of general anesthesia may involve facilitation of inhibitory neurotransmission mediated by GABA.
Structure–Activity Relationships
Propofol (2,6-diisopropylphenol) consists of a phenol ring with two isopropyl groups attached (Figure 8–9). Altering the side-chain length of this alkylphenol influences potency, induction, and recovery characteristics. Propofol is not water soluble, but a 1% aqueous solution (10 mg/mL) is available for intravenous administration as an oil-in-water emulsion containing soybean oil, glycerol, and egg lecithin. A history of egg allergy does not necessarily contraindicate the use of propofol because most egg allergies involve a reaction to egg white (egg albumin), whereas egg lecithin is extracted from egg yolk. This formulation can cause pain during injection (less common in elderly patients) that can be decreased by prior injection of lidocaine or by mixing lidocaine with propofol prior to injection (2 mL of 1% lidocaine in 18 mL propofol). Other formulations of propofol (eg, 1% propofol in 16% polyoxyethylated castor oil) may decrease injection discomfort. Propofol formulations can support the growth of bacteria, so good sterile technique must be observed in preparation and handling, including cleaning the rubber stopper or ampule neck surface with an alcohol swab prior to opening it. Administration should be completed within 6 h of opening the ampule. Sepsis and death have been linked to contaminated propofol preparations. Current formulations of propofol contain 0.005% disodium edetate or 0.025% sodium metabisulfite to help retard the rate of growth of microorganisms; however, these are still not antimicrobially preserved products under United States Pharmacopeia standards.
Pharmacokinetics
ABSORPTION
Propofol is available only for intravenous administration for the induction of general anesthesia and for moderate to deep sedation (see Table 8–7).
DISTRIBUTION
The high lipid solubility of propofol results in an onset of action that is almost as rapid as that of thiopental (one-arm-to-brain circulation time). Awakening from a single bolus dose is also rapid due to a very short initial distribution half-life (2–8 min). Most investigators believe that recovery from propofol is more rapid and is accompanied by less hangover than recovery from methohexital, thiopental, or etomidate. This makes it a good agent for outpatient anesthesia. A lower induction dose is recommended in elderly patients because of their smaller Vd. Women may require a higher dose of propofol than men and appear to awaken faster.
BIOTRANSFORMATION
The clearance of propofol exceeds hepatic blood flow, implying the existence of extrahepatic metabolism. This exceptionally high clearance rate (10 times that of thiopental) probably contributes to relatively rapid recovery after a continuous infusion. Conjugation in the liver results in inactive metabolites that are eliminated by renal clearance. The pharmacokinetics of propofol do not appear to be affected by moderate cirrhosis. Use of propofol infusion for long-term sedation of children who are critically ill or young adult neurosurgical patients has been associated with cases of lipemia, metabolic acidosis, and death.
EXCRETION
Although metabolites of propofol are primarily excreted in the urine, chronic renal failure does not affect clearance of the parent drug.
Effects on Organ Systems
CARDIOVASCULAR
The major cardiovascular effect of propofol is a decrease in arterial blood pressure due to a drop in systemic vascular resistance (inhibition of sympathetic vasoconstrictor activity), cardiac contractility, and preload. Hypotension is more pronounced than with thiopental but is usually reversed by the stimulation accompanying laryngoscopy and intubation. Factors exacerbating the hypotension include large doses, rapid injection, and old age. Propofol markedly impairs the normal arterial baroreflex response to hypotension, particularly in conditions of normocarbia or hypocarbia. Rarely, a marked drop in preload may lead to a vagally mediated reflex bradycardia. Changes in heart rate and cardiac output are usually transient and insignificant in healthy patients but may be severe enough to lead to asystole, particularly in patients at the extremes of age, on negative chronotropic medications, or undergoing surgical procedures associated with the oculocardiac reflex (see Chapter 38). Patients with impaired ventricular function may experience a significant drop in cardiac output as a result of decreases in ventricular filling pressures and contractility. Although myocardial oxygen consumption and coronary blood flow decrease to a similar extent, coronary sinus lactate production increases in some patients. This indicates a regional mismatch between myocardial oxygen supply and demand.
RESPIRATORY
Like the barbiturates, propofol is a profound respiratory depressant that usually causes apnea following an induction dose. Even when used for conscious sedation in subanesthetic doses, propofol infusion inhibits hypoxic ventilatory drive and depresses the normal response to hypercarbia. As a result, only properly trained personnel should use this technique. Propofol-induced depression of upper airway reflexes exceeds that of thiopental and can prove helpful during intubation or laryngeal mask placement in the absence of paralysis. Although propofol can cause histamine release, induction with propofol is accompanied by a lower incidence of wheezing in asthmatic and nonasthmatic patients compared with barbiturates or etomidate and is not contraindicated in asthmatic patients.
CEREBRAL
Propofol decreases cerebral blood flow and intracranial pressure. In patients with elevated intracranial pressure, propofol can cause a critical reduction in CPP (< 50 mm Hg) unless steps are taken to support mean arterial blood pressure. Propofol and thiopental probably provide a similar degree of cerebral protection during focal ischemia. Unique to propofol are its antipruritic properties. Its antiemetic effects (requiring a blood propofol concentration of 200 ng/mL) make it a preferred drug for outpatient anesthesia. Induction is occasionally accompanied by excitatory phenomena such as muscle twitching, spontaneous movement, opisthotonus, or hiccupping possibly due to subcortical glycine antagonism. Although these reactions may occasionally mimic tonic–clonic seizures, propofol appears to have predominantly anticonvulsant properties (ie, burst suppression), has been successfully used to terminate status epilepticus, and may be safely administered to epileptic patients. Propofol decreases intraocular pressure. Tolerance does not develop after long-term propofol infusions. Drug Interactions Nondepolarizing neuromuscular blocking agents may be potentiated by previous formulations of propofol, which contained Cremophor. Newer formulations do not share this interaction. Fentanyl and alfentanil concentrations may be increased by concomitant administration of propofol. Some clinicians administer a small amount of midazolam (eg, 30 g/kg) prior to induction with propofol; they believe the combination produces synergistic effects (eg, faster onset and lower total dose requirements). However, this technique of "coinduction" has questionable efficacy.
Dosis bolus untuk induksi 2-2.5 mg/kg, dosis rumatan untuk anesthesia intravena total 4-13 mg/kg per jam , atau 100 - 200 mcg/kgbb/menit dengan syringe pump dan dosis sedasi untuk perawatan intensif 0.2mg / kg atau 25 -50 mcg/kgbb/menit syringe pump. Pengenceran propofol hanya boleh dengan dextrose 5%. Pada manula dosis harus dikurangi, pada anak kurang dari 3 tahun dan pada wanita hamil tidak dianjurkan.
Sumber: http://www.pharmacology2000.com
Sumber: http://www.tbiomed.comtambahan........
Propofol ( 2,6 – diisopropylphenol )
Merupakan derivat fenol yang banyak digunakan sebagai anastesia intravena dan lebih dikenal dengan nama dagang Diprivan. Pertama kali digunakan dalam praktek anestesi pada tahun 1977 sebagai obat induksi.
Propofol digunakan untuk induksi dan pemeliharaan dalam anastesia umum, pada pasien dewasa dan pasien anak – anak usia lebih dari 3 tahun. Mengandung lecitin, glycerol dan minyak soybean, sedangkan pertumbuhan kuman dihambat oleh adanya asam etilendiamintetraasetat atau sulfat, hal tersebut sangat tergantung pada pabrik pembuat obatnya. Obat ini dikemas dalam cairan emulsi lemak berwarna putih susu bersifat isotonik dengan kepekatan 1 % (1 ml = 10 mg).
Mekanisme kerja
Mekanisme kerjanya sampai saat ini masih kurang diketahui ,tapi diperkirakan efek primernya berlangsung di reseptor GABA – A (Gamma Amino Butired Acid).
Farmakokinetik
Digunakan secara intravena dan bersifat lipofilik dimana 98% terikat protein plasma, eliminasi dari obat ini terjadi di hepar menjadi suatu metabolit tidak aktif, waktu paruh propofol diperkirakan berkisar antara 2 – 24 jam. Namun dalam kenyataanya di klinis jauh lebih pendek karena propofol didistribusikan secara cepat ke jaringan tepi. Dosis induksi cepat menyebabkan sedasi ( rata – rata 30 – 45 detik ) dan kecepatan untuk pulih juga relatif singkat. Satu ampul 20ml mengandung propofol 10mg/ml. Popofol bersifat hipnotik murni tanpa disertai efek analgetik ataupun relaksasi otot.
Farmakodinamik
Pada sistem saraf pusat
Dosis induksi menyebabkan pasien tidak sadar, dimana dalam dosis yang kecil dapat menimbulkan efek sedasi, tanpa disetai efek analgetik, pada pemberian dosis induksi (2mg /kgBB) pemulihan kesadaran berlangsung cepat.
Pada sistem kardiovaskular
Dapat menyebakan depresi pada jantung dan pembuluh darah dimana tekanan dapat turun sekali disertai dengan peningkatan denyut nadi, pengaruh terhadap frekuensi jantung juga sangat minim.
Sistem pernafasan
Dapat menurunkan frekuensi pernafasan dan volume tidal, dalam beberapa kasus dapat menyebabkan henti nafas kebanyakan muncul pada pemberian diprivan
Dosis dan penggunaan
a) Induksi : 2,0 sampai 2.5 mg/kg IV.
b) Sedasi : 25 to 75 µg/kg/min dengan I.V infuse
c) Dosis pemeliharaan pada anastesi umum : 100 – 150 µg/kg/min IV (titrate to effect).
d) Turunkan dosis pada orang tua atau gangguan hemodinamik atau apabila digabung penggunaanya dengan obat anastesi yang lain.
e) Dapat dilarutkan dengan Dextrosa 5 % untuk mendapatkan konsentrasi yang minimal 0,2%
f) Profofol mendukung perkembangan bakteri, sehingga harus berada dalam lingkungan yang steril dan hindari profofol dalam kondisi sudah terbuka lebih dari 6 jam untuk mencegah kontaminasi dari bakteri.
Efek Samping
Dapat menyebabkan nyeri selama pemberian pada 50% sampai 75%. Nyeri ini bisa muncul akibat iritasi pembuluh darah vena, nyeri pada pemberian propofol dapat dihilangkan dengan menggunakan lidocain (0,5 mg/kg) dan jika mungkin dapat diberikan 1 sampai 2 menit dengan pemasangan torniquet pada bagian proksimal tempat suntikan, berikan secara I.V melaui vena yang besar. Gejala mual dan muntah juga sering sekali ditemui pada pasien setelah operasi menggunakan propofol. Propofol merupakan emulsi lemak sehingga pemberiannya harus hati – hati pada pasien dengan gangguan metabolisme lemak seperti hiperlipidemia dan pankreatitis.
FROM MORGAN
PROPOFOL
Mechanisms of Action
The mechanism by which propofol induces a state of general anesthesia may involve facilitation of inhibitory neurotransmission mediated by GABA.
Structure–Activity Relationships
Propofol (2,6-diisopropylphenol) consists of a phenol ring with two isopropyl groups attached (Figure 8–9). Altering the side-chain length of this alkylphenol influences potency, induction, and recovery characteristics. Propofol is not water soluble, but a 1% aqueous solution (10 mg/mL) is available for intravenous administration as an oil-in-water emulsion containing soybean oil, glycerol, and egg lecithin. A history of egg allergy does not necessarily contraindicate the use of propofol because most egg allergies involve a reaction to egg white (egg albumin), whereas egg lecithin is extracted from egg yolk. This formulation can cause pain during injection (less common in elderly patients) that can be decreased by prior injection of lidocaine or by mixing lidocaine with propofol prior to injection (2 mL of 1% lidocaine in 18 mL propofol). Other formulations of propofol (eg, 1% propofol in 16% polyoxyethylated castor oil) may decrease injection discomfort. Propofol formulations can support the growth of bacteria, so good sterile technique must be observed in preparation and handling, including cleaning the rubber stopper or ampule neck surface with an alcohol swab prior to opening it. Administration should be completed within 6 h of opening the ampule. Sepsis and death have been linked to contaminated propofol preparations. Current formulations of propofol contain 0.005% disodium edetate or 0.025% sodium metabisulfite to help retard the rate of growth of microorganisms; however, these are still not antimicrobially preserved products under United States Pharmacopeia standards.
Pharmacokinetics
ABSORPTION
Propofol is available only for intravenous administration for the induction of general anesthesia and for moderate to deep sedation (see Table 8–7).
DISTRIBUTION
The high lipid solubility of propofol results in an onset of action that is almost as rapid as that of thiopental (one-arm-to-brain circulation time). Awakening from a single bolus dose is also rapid due to a very short initial distribution half-life (2–8 min). Most investigators believe that recovery from propofol is more rapid and is accompanied by less hangover than recovery from methohexital, thiopental, or etomidate. This makes it a good agent for outpatient anesthesia. A lower induction dose is recommended in elderly patients because of their smaller Vd. Women may require a higher dose of propofol than men and appear to awaken faster.
BIOTRANSFORMATION
The clearance of propofol exceeds hepatic blood flow, implying the existence of extrahepatic metabolism. This exceptionally high clearance rate (10 times that of thiopental) probably contributes to relatively rapid recovery after a continuous infusion. Conjugation in the liver results in inactive metabolites that are eliminated by renal clearance. The pharmacokinetics of propofol do not appear to be affected by moderate cirrhosis. Use of propofol infusion for long-term sedation of children who are critically ill or young adult neurosurgical patients has been associated with cases of lipemia, metabolic acidosis, and death.
EXCRETION
Although metabolites of propofol are primarily excreted in the urine, chronic renal failure does not affect clearance of the parent drug.
Effects on Organ Systems
CARDIOVASCULAR
The major cardiovascular effect of propofol is a decrease in arterial blood pressure due to a drop in systemic vascular resistance (inhibition of sympathetic vasoconstrictor activity), cardiac contractility, and preload. Hypotension is more pronounced than with thiopental but is usually reversed by the stimulation accompanying laryngoscopy and intubation. Factors exacerbating the hypotension include large doses, rapid injection, and old age. Propofol markedly impairs the normal arterial baroreflex response to hypotension, particularly in conditions of normocarbia or hypocarbia. Rarely, a marked drop in preload may lead to a vagally mediated reflex bradycardia. Changes in heart rate and cardiac output are usually transient and insignificant in healthy patients but may be severe enough to lead to asystole, particularly in patients at the extremes of age, on negative chronotropic medications, or undergoing surgical procedures associated with the oculocardiac reflex (see Chapter 38). Patients with impaired ventricular function may experience a significant drop in cardiac output as a result of decreases in ventricular filling pressures and contractility. Although myocardial oxygen consumption and coronary blood flow decrease to a similar extent, coronary sinus lactate production increases in some patients. This indicates a regional mismatch between myocardial oxygen supply and demand.
RESPIRATORY
Like the barbiturates, propofol is a profound respiratory depressant that usually causes apnea following an induction dose. Even when used for conscious sedation in subanesthetic doses, propofol infusion inhibits hypoxic ventilatory drive and depresses the normal response to hypercarbia. As a result, only properly trained personnel should use this technique. Propofol-induced depression of upper airway reflexes exceeds that of thiopental and can prove helpful during intubation or laryngeal mask placement in the absence of paralysis. Although propofol can cause histamine release, induction with propofol is accompanied by a lower incidence of wheezing in asthmatic and nonasthmatic patients compared with barbiturates or etomidate and is not contraindicated in asthmatic patients.
CEREBRAL
Propofol decreases cerebral blood flow and intracranial pressure. In patients with elevated intracranial pressure, propofol can cause a critical reduction in CPP (< 50 mm Hg) unless steps are taken to support mean arterial blood pressure. Propofol and thiopental probably provide a similar degree of cerebral protection during focal ischemia. Unique to propofol are its antipruritic properties. Its antiemetic effects (requiring a blood propofol concentration of 200 ng/mL) make it a preferred drug for outpatient anesthesia. Induction is occasionally accompanied by excitatory phenomena such as muscle twitching, spontaneous movement, opisthotonus, or hiccupping possibly due to subcortical glycine antagonism. Although these reactions may occasionally mimic tonic–clonic seizures, propofol appears to have predominantly anticonvulsant properties (ie, burst suppression), has been successfully used to terminate status epilepticus, and may be safely administered to epileptic patients. Propofol decreases intraocular pressure. Tolerance does not develop after long-term propofol infusions. Drug Interactions Nondepolarizing neuromuscular blocking agents may be potentiated by previous formulations of propofol, which contained Cremophor. Newer formulations do not share this interaction. Fentanyl and alfentanil concentrations may be increased by concomitant administration of propofol. Some clinicians administer a small amount of midazolam (eg, 30 g/kg) prior to induction with propofol; they believe the combination produces synergistic effects (eg, faster onset and lower total dose requirements). However, this technique of "coinduction" has questionable efficacy.
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