Transcript SEDACION EN PACIENTES CON ERC

SEDACION EN PACIENTES
CON ERC
Francisco José de la Prada Alvarez
Servicio de Nefrología
Hospital Universitario Son Dureta
Ansiedad.
Dolor
Delirio
Disnea
Parálisis
Fármaco
Sedación
Hiponósis Amnesia
Analgesia
Benzodiacepinas
+
+
+
-
Haloperidol
+
+*
+*
-
Ketamina
-
-
+
+
Opioides
-
-
-
+
Propofol
+**
+
+*
-
*mínimo efecto
**solo a bajas dosis
Analgésicos:
– Fentanilo.
– Hidromorphina.
– Sulfato de morfina.
Anestésicos:
– Ketamina.
– Propofol.
Neurolépticos:
– Haloperidol.
Sedantes-Hipnóticos:
– Benzodiacepinas:
Diacepam
Lorazepam
Midazolam
– Barbitúricos:
Tiopental
Methohexital
Jacobi, J, Fraser, GL, Coursin, DB, et al. Clinical practice guidelines for the sustained use of
sedatives and analgesics in the critically ill adult. Crit Care Med 2002; 30:119
Benzodiacepinas
Mecanismo de acción:
– Unión a receptores específicos del complejo del receptor de
GABA en el SNC, favoreciendo la unión y el efecto de este
neurotransmisor inhibitorio de la excitabilidad neuronal.
(incrementa la permeabilidad al Cl de la membrana neuronal,
hiperpolarizando la membrana, estabilizandola y haciéndola
menos excitable.
Acciones:
– Sedantes a bajas dosis.
– A altas dosis:
Anticonvulsivantes
Sedantes.
Amnésicos.
Depresores cardio y respiratorio.
Principal problema:
– Tolerancia.
Benzodiacepinas
Todos tienen la misma eficacia a dosis
equipotentes. Las diferencias dependen de la
afinidad por el receptor, lipofilia y la cinética de
eliminación.
Afinidad:
– Lorazepam: mayor afinidad y mayor potencia
– Midazolam y Diazepam: menos afinidad y potencia
Lipofilia:
– Midazolam y Diazepam: los más lipofílicos (pasan
BHE, rápido inicio de acción, acumulación en los
tejidos grasos)
Cinética de eliminación:
Benzodiacepinas
Diazepam
Reducción oxidativa (Se
afecta por edad,
disfunción hepática e
interacciones
farmacológicas)
Gran volumen de distribución.
Bajo metabolismo hepático.
Metabolitos activos (diametildiazepam
y oxazepam) que se elimina via renal.
Propilenglicol (hiperosmolaridad y
acidosis metabólica con osmol gap
elevado)
Midazolam
Reducción oxidativa (Se
afecta por edad,
disfunción hepática e
interacciones
farmacológicas)
Corta vida media.
Gran volumen de distribución
Metabolito activo (alfahidroximidazolam)
Lorazepam
Glucoroconjugación
Bajo metabolismo hepático.
Metabolitos inactivos.
Propilenglicol (hiperosmolaridad y
acidosis metabólica con osmol gap
elevado).
Se afecta por la ERC.
N03AE-Benzodiacepinas
NOMBRE
GENÉRICO
PRESENTACIÓN
VÍA
NOMBRE
COMERCIAL
Clobazam
Comp 10 mg
Comp 20 mg
OR
OR
Noiafren
Clonazepam
Amp 1 mg/2 ml
Comp 0,5 mg
Comp 2 mg
Gts 2,5 mg/ml (1)
IM, IV
OR
OR
OR
Rivotril
Diazepam
Amp 10 mg/2 ml
Comp 5 mg
Comp 10 mg
Microenema 5 mg
IM, IV Valium,
Diazepam
Nota 1: 1 gota=0,1 mg
REC
Stesolid
Diazepam
DOSING: ADULTS — Note: Oral absorption is more reliable than I.M.
Anticonvulsant (acute treatment): Rectal gel: 0.2 mg/kg. Note: Dosage
should be rounded upward to the next available dose, 2.5, 5, 7.5, 10, 12.5,
15, 17.5, and 20 mg/dose; dose may be repeated in 4-12 hours if needed;
do not use for more than 5 episodes per month or more than one episode
every 5 days.
Anxiety/sedation/skeletal muscle relaxation:
– Oral: 2-10 mg 2-4 times/day
– I.M., I.V.: 2-10 mg, may repeat in 3-4 hours if needed
Sedation in the ICU patient: I.V.: 0.03-0.1 mg/kg every 30 minutes to 6
hours
Status epilepticus: I.V.: 5-10 mg every 10-20 minutes, up to 30 mg in an 8hour period; may repeat in 2-4 hours if necessary
Rapid tranquilization of agitated patient (administer every 30-60
minutes): Oral: 5-10 mg; average total dose for tranquilization:
20-60 mg
Diazepam
DOSING: PEDIATRIC
Conscious sedation for procedures:
Oral:
Children: 0.2-0.3 mg/kg (maximum dose: 10 mg) 45-60 minutes prior to procedure
Adolescents: 10 mg
I.V.: Adolescents: 5 mg; may repeat with 2.5 mg if needed
Febrile seizure prophylaxis: Oral: Children: 1 mg/kg/day divided every 8 hours; initiate therapy at first sign of fever
and continue for 24 hours after fever is gone
Sedation or muscle relaxation or anxiety:
Oral: Children: 0.12-0.8 mg/kg/day in divided doses every 6-8 hours
I.M., I.V.: Children: 0.04-0.3 mg/kg/dose every 2-4 hours to a maximum of 0.6 mg/kg within an 8-hour period if
needed
Status epilepticus:
I.V.:
Infants >30 days and Children <5 years: 0.05-0.3 mg/kg/dose given over 3-5 minutes, every 15-30 minutes to a
maximum total dose of 5 mg or 0.2-0.5 mg/dose every 2-5 minutes to a maximum total dose of 5 mg; repeat in 2-4
hours as needed
Children 5 years: 0.05-0.3 mg/kg/dose given over 3-5 minutes, every 15-30 minutes to a maximum total dose of
10 mg or 1 mg/dose every 2-5 minutes to a maximum of 10 mg; repeat in 2-4 hours as needed
Rectal: 0.5 mg/kg/dose then 0.25 mg/kg/dose in 10 minutes if needed (prepare dose using parenteral
formulation)
Anticonvulsant (acute treatment): Rectal gel:
Children <2 years: Safety and efficacy have not been studied
Children 2-5 years: 0.5 mg/kg
Children 6-11 years: 0.3 mg/kg
Children 12 years: Refer to adult dosing.
Note: Dosage should be rounded upward to the next available dose, 2.5, 5, 7.5, 10, 12.5, 15, 17.5, and 20
mg/dose; dose may be repeated in 4-12 hours if needed; do not use for more than 5 episodes per month or more
than one episode every 5 days.
Muscle spasm associated with tetanus: I.V., I.M.:
Infants >30 days: 1-2 mg/dose every 3-4 hours as needed
Children 5 years: 5-10 mg/dose every 3-4 hours as needed
Diazepam
DOSING: ELDERLY
– Oral absorption is more reliable than I.M..
Oral:
– Initial:
– Anxiety: 1-2 mg 1-2 times/day; increase gradually
as needed, rarely need to use >10 mg/day.
– Skeletal muscle relaxant: 2-5 mg 2-4 times/day
Rectal gel: Due to the increased half-life in
elderly and debilitated patients, consider
reducing dose.
Diazepam
PHARMACODYNAMICS / KINETICS
I.V.: Status epilepticus:
Onset of action: Almost immediate
Duration: 20-30 minutes
Absorption: Oral: 85% to 100%, more reliable than I.M.
Food: Diazepam serum levels may be increased if taken with food.
Diazepam effect/toxicity may be increased by grapefruit juice; avoid
concurrent use.
Protein binding: 98%.
Metabolism: Hepatic.
Half-life elimination:
– Parent drug: Adults: 20-50 hours;
– increased half-life in neonates, elderly, and those with severe hepatic
disorders;
– Active major metabolite (desmethyldiazepam): 50-100 hours; may be
prolonged in neonates
Diazepam
Rango terapéutico:
– Diazepam: 0.2-1.5 mcg/mL
(SI: 0.7-5.3 µmol/L);
– N-desmethyldiazepam (nordiazepam): 0.1-0.5
mcg/mL
(SI: 0.35-1.8 µmol/L)
Diazepam
Sobredosis:
– Sintomas: somnolencia, confusion, coma,
reflejos hipotónicos, disnea, hipotension,
alteración de la coordinación.
– Tratamiento de soporte. Rara vez se requiere
ventilación mecánica.
– Flumazenil (Anexate): bloquea
selectivamenten la unión de la
benzodiacepinas a los receptores del SNC,
revirtiendo la depresión del SNC, pero no la
depresión respiratoria.
Diazepam
Embarazo:
– Teratogenico.
– Atraviesa la placenta.
– Se han descrito hipotonía, hipotermia,
sintomas de abstinencia dificultad respiratoria
y para la alimentación en neonatos cuyas
madres toman BZDP.
Contraindicados en la lactancia.
Benzodiacepinas
Dosis
de
carga
Dosis
de
manteni
miento
FG > 50
ml/min
FG 1050
ml/min
FG < 10
ml/min
Dosis
suplemt
aria tras
HD
DPCA
TSCR
Diazepam
5-20
mg IV
bolus
5-20
mg/2-4
horas IV
100%
100%
100%
Ninguna
Descon
ocida
100%
Lorazepam
1-4 mg
IV
bolus
0,5-10
mg/hora
IV
100%
100%
100%
Ninguna
Descono
cida
Dosis
FG 1050
ml/min
Midazolam
2-8 mg
IV
bolus
2-5
mg/hora
IV
100%
100%
50%
No
aplicable
No
aplicable
No
aplicable
Diazepam
INYECCION IV: SI
– Administrar en venas de gran calibre o bien a través del equipo de
suero. En general la ampolla debe administrarse directamente, sin
diluir y muy lentamente (*). Se recomienda no sobrepasar la
velocidad de 5 mg por minuto en adultos; en niños debe administrarse
en al menos 3 minutos. La administración demasiado rápida puede
causar hipotensión y depresión respiratoria severa.
– (*) En caso de diluir la ampolla debe realizarse en una proporción de 1
ml de Valium y 1 ml de agua p.i. o SF. (Si diluimos en proporciones
más altas, ejemplo la ampolla de 2 ml de Valium en 10 ml-50 ml de SF,
se produce precipitación: La jeringa tiene un aspecto turbio y lechoso y
no es recomendable administrarla).
INFUSION INTERMITENTE: SI
– Una ampolla de 2 ml debe diluirse en al menos 50-100 ml de SF ó
SG5% y administrar en 15-30 minutos.
INFUSION CONTINUA: NO RECOMENDADO
– Disponemos de pocos datos sobre esta vía de administración, aunque
puede estar indicada cuando se pautan dosis altas y continuas de
Diazepam (Ej.: Tétanos).
Diazepam
INYECCION IM: SI
– Inyección intramuscular profunda. La absorción es
lenta y algo errática, por lo que se recomienda pasar
a la vía oral siempre que sea posible.
SUEROS COMPATIBLES: SF, SG5%.
OBSERVACIONES:
– Evitar extravasación o administración intraarterial.
– Diazepam se une a algunos componentes de los
plásticos del material usado en su administración y
no es recomendable guardarlo preparado en jeringas.
N03AE-Benzodiacepinas
NOMBRE
GENÉRICO
PRESENTACIÓN
VÍA
NOMBRE
COMERCIAL
Clobazam
Comp 10 mg
Comp 20 mg
OR
OR
Noiafren
Clonazepam
Amp 1 mg/2 ml
Comp 0,5 mg
Comp 2 mg
Gts 2,5 mg/ml (1)
IM, IV
OR
OR
OR
Rivotril
Diazepam
Amp 10 mg/2 ml
Comp 5 mg
Comp 10 mg
Microenema 5 mg
IM, IV
Valium, Diazepam
REC
Stesolid
Nota 1: 1 gota=0,1 mg
N05C-Hipnóticos y sedantes
NOMBRE
GENÉRICO
PRESENTACIÓN
VÍA
NOMBRE
COMERCIAL
Clometiazol (1)
Caps 192 mg
OR
Distraneurine
Flurazepam (2)
Caps 30 mg
OR
Dormodor
Hidrato de cloral
Jbe 50 mg/ml
Enema 100 mg/ml
OR
REC
Hidrato de Cloral FM
Lorazepam (3)
Comp 1 mg
OR
Orfidal
Lormetazepam
Comp 2 mg
OR
Loramet , Noctamid
Midazolam
Amp 15 mg/3 ml
IM,IV Dormicum
Zolpidem (4)
Comp 10 mg
OR
Stilnox
Nota 2: Flunitrazepam (Rohipnol ) se considera equivalente terapéutico de Flurazepam.
Nota 3: Bromazepam (Lexatin) se considera equivalente terapéutico de Lorazepam.
Nota 4: Zopiclona (Limovan) y Midazolam comp (Dormicum comp ) se consideran
equivalentes terapéuticos del Zolpidem. Consultar programa de equivalencias.
Midazolam
DOSING: ADULTS
La dosis debe ser individualizada segun la edad del paciente, las patologías
subyacentes y las medicaciones concurrentes. Debe reducirse la dosis un
30% si se administran ´narcóticos u otros depresores del SNC. Debe haber
disponible equipo de resucitación respiratoria.
Conscious sedation: I.V.: Initial: 0.5-2 mg slow I.V. over at least 2 minutes;
slowly titrate to effect by repeating doses every 2-3 minutes if needed; usual
total dose: 2.5-5 mg; use decreased doses in elderly.
Initial: Some patients respond to doses as low as 1 mg; no more than 2.5
mg should be administered over a period of 2 minutes. Additional doses of
midazolam may be administered after a 2-minute waiting period and
evaluation of sedation after each dose increment. A total dose >5 mg is
generally not needed. If narcotics or other CNS depressants are
administered concomitantly, the midazolam dose should be reduced by
30%.
Maintenance: 25% of dose used to reach sedative effect
Midazolam
DOSIS: ADULTOS
Preoperative sedation:
I.M.: 0.07-0.08 mg/kg 30-60 minutes prior to surgery/procedure; usual dose: 5 mg;
Note: Reduce dose in patients with COPD, high-risk patients, patients 60 years of
age, and patients receiving other narcotics or CNS depressants
I.V.: 0.02-0.04 mg/kg; repeat every 5 minutes as needed to desired effect or up to
0.1-0.2 mg/kg
Intranasal (not an approved route): 0.2 mg/kg (up to 0.4 mg/kg in some studies);
administer 30-45 minutes prior to surgery/procedure
Anesthesia: I.V.:
Induction:
Unpremedicated patients: 0.3-0.35 mg/kg (up to 0.6 mg/kg in resistant cases)
Premedicated patients: 0.15-0.35 mg/kg
Maintenance: 0.05-0.3 mg/kg as needed, or continuous infusion 0.25-1.5
mcg/kg/minute
Sedation in mechanically-ventilated patients: I.V. continuous infusion: 100 mg in 250
mL D5W or NS (if patient is fluid-restricted, may concentrate up to a maximum of 0.5
mg/mL); initial dose: 0.02-0.08 mg/kg (~1 mg to 5 mg in 70 kg adult) initially and
either repeated at 5-15 minute intervals until adequate sedation is achieved or
continuous infusion rates of 0.04-0.2 mg/kg/hour and titrate to reach desired level of
sedation
Midazolam
ANCIANOS.
– La dosis debe ser individualizada segun la edad del paciente,
las patologías subyacentes y las medicaciones concurrentes.
– Debe reducirse la dosis un 30% si se administran narcóticos u
otros depresores del SNC.
– Debe haber disponible equipo de resucitación respiratoria.
I.V.: Conscious sedation:
– Initial: 0.5 mg slow I.V.; give no more than 1.5 mg in a 2-minute
period.
– If additional titration is needed, give no more than 1 mg over 2
minutes, waiting another 2 or more minutes to evaluate sedative
effect.
– A total dose >3.5 mg is rarely necessary.
Midazolam
DOSING: PEDIATRIC
Notes: The dose of midazolam needs to be individualized based on the patient's age, underlying diseases, and
concurrent medications. Decrease dose (by ~30%) if narcotics or other CNS depressants are administered
concomitantly. Personnel and equipment needed for standard respiratory resuscitation should be immediately
available during midazolam administration. Children <6 years may require higher doses and closer monitoring than
older children; calculate dose on ideal body weight
Conscious sedation for procedures or preoperative sedation:
Oral: 0.25-0.5 mg/kg as a single dose preprocedure, up to a maximum of 20 mg; administer 30-40 minutes prior
to procedure. Children <6 years, or less cooperative patients may require as much as 1 mg/kg as a single dose;
0.25 mg/kg may suffice for children 6-16 years of age.
Intranasal (not an approved route): 0.2 mg/kg (up to 0.4 mg/kg in some studies), administered 30-45 minutes
prior to procedure
I.M.: 0.1-0.15 mg/kg 30-60 minutes before surgery or procedure; range 0.05-0.15 mg/kg; doses up to 0.5 mg/kg
have been used in more anxious patients; maximum total dose: 10 mg
I.V.:
Infants <6 months: Limited information is available in nonintubated infants; dosing recommendations not clear;
infants <6 months are at higher risk for airway obstruction and hypoventilation; titrate dose in small increments to
desired effect; monitor carefully
Infants 6 months to Children 5 years: Initial: 0.05-0.1 mg/kg; titrate dose carefully; total dose of 0.6 mg/kg may
be required; usual maximum total dose: 6 mg
Children 6-12 years: Initial: 0.025-0.05 mg/kg; titrate dose carefully; total doses of 0.4 mg/kg may be required;
usual maximum total dose: 10 mg
Children 12-16 years: Dose as adults; usual maximum total dose: 10 mg
Conscious sedation during mechanical ventilation: I.V.: Children: Loading dose: 0.05-0.2 mg/kg, followed by initial
continuous infusion: 1-2 mcg/kg/minute; titrate to the desired effect; usual range: 0.4-6 mcg/kg/minute
Status epilepticus refractory to standard therapy (unlabeled use): I.V.: Infants >2 months and Children: Loading
dose: 0.15 mg/kg followed by a continuous infusion of 1 mcg/kg/minute; titrate dose upward every 5 minutes until
clinical seizure activity is controlled; mean infusion rate required in 24 children was 2.3 mcg/kg/minute with a range
of 1-18 mcg/kg/minute.
Midazolam
ADVERSE REACTIONS SIGNIFICANT —
>10%: Respiratory: Decreased tidal volume and/or respiratory rate
decrease, apnea (3% children)
1% to 10%:
Cardiovascular: Hypotension (3% children)
Central nervous system: Drowsiness (1%), oversedation,
headache (1%), seizure-like activity (1% children)
Gastrointestinal: Nausea (3%), vomiting (3%)
Local: Pain and local reactions at injection site (4% I.M., 5% I.V.;
severity less than diazepam)
Ocular: Nystagmus (1% children)
Respiratory: Cough (1%)
Miscellaneous: Physical and psychological dependence with
prolonged use, hiccups (4%, 1% children), paradoxical reaction (2%
children)
<1% (Limited to important or life-threatening): Agitation, amnesia,
bigeminy, bronchospasm, emergence delirium, euphoria,
hallucinations, laryngospasm, rash
Midazolam
CONTRAINDICATIONS.
Hypersensitivity to midazolam or any component
of the formulation, including benzyl alcohol
(cross-sensitivity with other benzodiazepines
may exist);
parenteral form is not for intrathecal or epidural
injection;
narrow-angle glaucoma;
concurrent use of potent inhibitors of CYP3A4
(amprenavir, atazanavir, or ritonavir);
pregnancy
Midazolam
DRUG INTERACTIONS — Substrate of CYP2B6 (minor), 3A4 (major); Inhibits
CYP2C8 (weak), 2C9 (weak), 3A4 (weak)
CNS depressants: Sedative effects and/or respiratory depression may be additive
with CNS depressants; includes ethanol, barbiturates, narcotic analgesics, and other
sedative agents; monitor for increased effect. If narcotics or other CNS depressants
are administered concomitantly, the midazolam dose should be reduced by 30% if
<65 years of age, or by at least 50% if >65 years of age.
CYP3A4 inducers: CYP3A4 inducers may decrease the levels/effects of midazolam.
Example inducers include aminoglutethimide, carbamazepine, nafcillin, nevirapine,
phenobarbital, phenytoin, and rifamycins.
CYP3A4 inhibitors: May increase the levels/effects of midazolam. Example inhibitors
include azole antifungals, clarithromycin, diclofenac, doxycycline, erythromycin,
imatinib, isoniazid, nefazodone, nicardipine, propofol, protease inhibitors, quinidine,
telithromycin, and verapamil.
Levodopa: Therapeutic effects may be diminished in some patients following the
addition of a benzodiazepine; limited/inconsistent data
Oral contraceptives: May decrease the clearance of some benzodiazepines (those
which undergo oxidative metabolism); monitor for increased benzodiazepine effect
Saquinavir: A 56% reduction in clearance and a doubling of midazolam's half-life were
seen with concurrent administration with saquinavir.
Theophylline: May partially antagonize some of the effects of benzodiazepines;
monitor for decreased response; may require higher doses for sedation
Midazolam
EMBARAZO.
– Contraindicado.
LACTANCIA.
– Contraindicado
Midazolam
Sobredosis:
– Sintomas: depresion respiratoria, hipotension,
coma, estupor, confusion y apnea
– Tratamiento de soporte. Rara vez se requiere
ventilación mecánica.
– Flumazenil (Anexate): bloquea
selectivamenten la unión de la
benzodiacepinas a los receptores del SNC;
puede no revertirse la reaccion respiratoria a
la hipoxia.
Midazolam
PHARMACODYNAMICS / KINETICS
Onset of action: I.M.: Sedation: ~15 minutes; I.V.: 1-5 minutes
Peak effect: I.M.: 0.5-1 hour
Duration: I.M.: Up to 6 hours; Mean: 2 hours
Distribution: Vd: 0.8-2.5 L/kg; increased with congestive heart failure
(CHF) and chronic renal failure
Protein binding: 95%
Metabolism: Extensively hepatic via CYP3A4
Bioavailability: Mean: 45%
Half-life elimination: 1-4 hours; prolonged with cirrhosis, congestive
heart failure, obesity, and elderly
Excretion: Urine (as glucuronide conjugated metabolites); feces
(~2% to 10%)
Midazolam
Proteger de la luz. Conservar entre 15 y 30 ºC
INYECCION IV DIRECTA: SI
– Administrar en forma de inyección IV lenta. Esta vía de administración
se utiliza en la sedación anterior al inicio de la intervención diagnostica
o quirúrgica administrando 5-10 minutos antes una dosis de 0,05
mg/kg. La dosis de mantenimiento es un 25% de la dosis inicial. En la
inducción a la anestesia, también se inyecta por vía IV lenta en 20-30
segundos y la dosis habitual es de 0,3 mg/kg de peso.
INFUSION INTERMITENTE: NO RECOMENDABLE
– No se recomienda el uso de esta vía para las indicaciones terapéuticas
del Midazolam.
INFUSION CONTINUA: NO RECOMENDABLE
– No se recomienda el uso de esta vía para las indicaciones terapéuticas
del Midazolam.
Midazolam
INYECCION IM: SI
– Administrar en forma de inyección IM profunda en una zona de gran
masa muscular. Esta vía de administración se utiliza en la sedación
preoperatoria. La dosis suele ser de 0,07-0,1 mg/kg administrada 30-60
minutos antes de la intervención.
SUEROS COMPATIBLES: SF, SG5%
Las soluciones de 1 ampolla en 500 ml son estables a temperatura
ambiente 24 horas.
OBSERVACIONES:
– La solución de la ampolla de midazolam es estable hasta un máximo de
1 hora a temperatura ambiente cuando se mezcla en la misma jeringa
con: Atropina sulfato, Escopolamina bromhidrato, Morfina sulfato o
Meperidina.
– Injection: Sodium content of 1 mL: 0.14 mEq
Benzodiacepinas
Dosis
de
carga
Dosis
de
manteni
miento
FG > 50
ml/min
FG 1050
ml/min
FG < 10
ml/min
Dosis
suplemt
aria tras
HD
DPCA
TSCR
Diazepam
5-20
mg IV
bolus
5-20
mg/2-4
horas
100%
100%
100%
Ninguna
Descono
cida
100%
Lorazepam
1-4 mg
IV
bolus
0,5-10
mg/hora
100%
100%
100%
Ninguna
Descono
cida
Dosis
FG 1050
ml/min
Midazolam
2-8 mg
IV
bolus
2-5
mg/hora
100%
100%
50%
Descon
ocida
Descon
ocida
Descon
ocida
N05C-Hipnóticos y sedantes
NOMBRE
GENÉRICO
PRESENTACIÓN
VÍA
NOMBRE
COMERCIAL
Clometiazol (1)
Caps 192 mg
OR
Distraneurine
Flurazepam (2)
Caps 30 mg
OR
Dormodor
Hidrato de cloral
Jbe 50 mg/ml
Enema 100 mg/ml
OR
REC
Hidrato de Cloral FM
Lorazepam (3)
Comp 1 mg
OR
Orfidal
Lormetazepam
Comp 2 mg
OR
Loramet , Noctamid
Midazolam
Amp 15 mg/3 ml
IM,IV
Dormicum
Zolpidem (4)
Comp 10 mg
OR
Stilnox
Nota 2: Flunitrazepam (Rohipnol ) se considera equivalente terapéutico de Flurazepam.
Nota 3: Bromazepam (Lexatin) se considera equivalente terapéutico de Lorazepam.
Nota 4: Zopiclona (Limovan) y Midazolam comp (Dormicum comp ) se consideran
equivalentes terapéuticos del Zolpidem. Consultar programa de equivalencias.
Opioides
Todos tienen similares propiedades analgésicas
y sedantes en dosis equipotentes.
Carecen de efectos amnésicos.
Su principal problema es la tolerancia.
Pueden usarse:
– Sulfato de morfina.
– Fentanilo.
– Hidromorphona.
Alfentanilo y sulfentanilo no aportan ventajas
(salvo su vida media ultracorta) y son más
caros.
Neurolepticos
Su principal indicación es el Delirio.
Haloperidol:
– Potente acción neuroleptica.
– Mínima actividad anticolinérgica.
Mecanismo de acción:
– Butirofenona. Antipsicótica.
– Bloquea los receptores dopaminérgicos D1 y D2 mesolímbicos
en el cerebro.
– Disminuye la libreación de hormonas hipotalámicas e
hipofisiarias
– Parece que deprime el sistema reticular activador ascendente
afectando al metabolismo basal, la temperatura corporal el tono
vasomotor y la emesis.
N05AD-Butirofenonas
NOMBRE
GENÉRICO
PRESENTACIÓN
VÍA
NOMBRE
COMERCIAL
Haloperidol
Amp 5 mg/1 ml
Gts 2 mg/ml (2)
Comp 10 mg
IM
OR
OR
Haloperidol
(2): 1 gota=0,1 mg.
Haloperidol
DOSING: ADULTS
Psychosis:
Oral: 0.5-5 mg 2-3 times/day; usual maximum: 30 mg/day
I.M. (as lactate): 2-5 mg every 4-8 hours as needed
I.M. (as decanoate): Initial: 10-20 times the daily oral dose administered at
4-week intervals. Maintenance dose: 10-15 times initial oral dose; used to
stabilize psychiatric symptoms.
Delirium in the intensive care unit (unlabeled use, unlabeled route):
I.V.: 2-10 mg; may repeat bolus doses every 20-30 minutes until calm
achieved then administer 25% of the maximum dose every 6 hours;
monitor ECG and QTc interval
Intermittent I.V.: 0.03-0.15 mg/kg every 30 minutes to 6 hours
Oral: Agitation: 5-10 mg
Continuous I.V. infusion (100 mg/100 mL D5W): Rates of 3-25 mg/hour
have been used.
Rapid tranquilization of severely-agitated patient (unlabeled use;
administer every 30-60 minutes):
Oral: 5-10 mg
I.M.: 5 mg
Average total dose (oral or I.M.) for tranquilization: 10-20 mg
Haloperidol
DOSING: PEDIATRIC
Sedation/psychotic disorders: Oral:
Children: 3-12 years (15-40 kg): Initial: 0.05 mg/kg/day or 0.25-0.5
mg/day given in 2-3 divided doses; increase by 0.25-0.5 mg every 57 days; maximum: 0.15 mg/kg/day
Usual maintenance:
Agitation or hyperkinesia: 0.01-0.03 mg/kg/day once daily
Nonpsychotic disorders: 0.05-0.075 mg/kg/day in 2-3 divided
doses
Psychotic disorders: 0.05-0.15 mg/kg/day in 2-3 divided doses
Children 6-12 years: Sedation/psychotic disorders: I.M. (as lactate):
1-3 mg/dose every 4-8 hours to a maximum of 0.15 mg/kg/day;
change over to oral therapy as soon as able.
Haloperidol
DOSING: ELDERLY —
– Nonpsychotic patients, dementia behavior: Initial:
Oral: 0.25-0.5 mg 1-2 times/day; increase dose at 4to 7-day intervals by 0.25-0.5 mg/day. Increase
dosing intervals (twice daily, 3 times/day, etc) as
necessary to control response or side effects.
Haloperidol
NIVELES DE REFERENCIA
Therapeutic: 5-20 ng/mL (SI: 10-40
nmol/L) (psychotic disorders - less for
Tourette's and mania)
Toxic: >42 ng/mL (SI: >84 nmol/L)
Haloperidol
SOBREDOSIS.
– Síntomas: sueño profundo, distonía,
agitación, arritmias y sintomas
extrapiramidales.
– Tratamiento: medidas de soporte.
– Arritmias cardíacas criticas: Lidocaina.
– Sintomas extrapiramidales: Agentes
anticolinérgicos. Benztropine mesylate I.V. 1-2
mg (adult). Efectivo en 2-5 minutes.
Neurolepticos
PHARMACODYNAMICS / KINETICS
– Onset of action: Sedation: I.V.: ~1 hour
– Time to peak, serum: 20 minutes
– Duration: Decanoate: ~3 weeks
– Protein binding: 90%
– Metabolism: Hepatic to inactive compounds
– Bioavailability: Oral: 60%
– Half-life elimination: 20 hours
– Excretion: Urine (33% to 40% as metabolites) within
5 days; feces (15%)
Haloperidol
EMBARAZO:
– No recomendado.
LACTANCIA
– No recomendado.
Neurolepticos
Efectos secundarios:
– Taquicardia ventricular.
Asociado a dosis inicial elevada.
Evitar en pacientes con riesgo de arritmias: QTc largo,
disfunción hepática, alteraciones electrolíticas y
miocardiopatia dilatada.
– Reacciones distónicas, parkinsonismo (más
frecuentes por via oral), diskinesia tardia, akatisia,
sindrome neuropleptico maligno.
– Hipotension arterial si hipovolemia.
– No depresión respiratoria.
Haloperidol
ADMINISTRACION:
INYECCION IV DIRECTA: SI
Administrar la dosis prescrita en forma de inyección IV lenta, en al
menos 1 minuto por cada dosis de 5 mg. Se puede administrar sin
diluir o diluido en 10-50 ml de SF o SG5%,
INFUSION INTERMITENTE: SI
Diluir la dosis en 50-100 ml de SG5% y administrar en 30 minutos.
INFUSION CONTINUA: SI
Diluir la dosis en 500 ml de SG5%.
INYECCION IM: SI
Se recomienda no administrar más de 3 ml por inyección.
Haloperidol
SUEROS COMPATIBLES: SG5%. A concentraciones altas (1mg/ml)
es incompatible con SF.
OBSERVACIONES:
Si la agitación es aguda se recomienda administrar de 1 a 2 ampollas.
Proteger de la luz. Conservar entre 15 y 30 refrigerar.
Neurolepticos
Haloperidol
Dosis
de
carga
Dosis de
manteni
miento
FG > 50
ml/min
FG 10-50
ml/min
FG < 10
ml/min
Dosis
supleme
ntaria
tras HD
DPCA
TSCR
2 -10
mg IV
en
bolus,
duplican
-dose
cada 20
- 30
minutos
50-100%
dosis
total de
caga en
dosis
divididas
en 24
horas
100%
100%
100%
Ninguna
Ninguna
Dosis de
FG 1050%
0.5-2 mg si agitación leve.
2-5 mg si agitación moderada.
10-20 mg si agitación severa.
Infusión contínua a 10 mg/h con incrementos de 5 mg/hora cada 30 minutos.
Neurolepticos
Olanzapine.
– Antipsicótico oral de 2ª generación.
– No se ha detectado arritmias ni prolongación
del QT.
N05AX-Antipsicóticos atípicos
NOMBRE
GENÉRICO
PRESENTACIÓN
VÍA
NOMBRE
COMERCIAL
Clotiapina
Comp 40 mg
OR
Etumina
Clozapina
Comp 100 mg
OR
Leponex
Olanzapina
Comp 5 mg
Comp 10 mg
Vial 10 mg/ 2ml
OR
OR
IM
Zyprexa
Risperidona
Comp 1 mg
Comp 3 mg
Comp 6 mg
Sol 1 mg/ml 30 ml
OR
OR
OR
OR
Risperdal
Nota 1: 1 gota=1 mg.
Nota 2: 1 gota=0,1 mg.
Nota 3: 1 gota=1 mg.
Nota 4: 1 gota= 1 mg.
Propofol
Anestésico.
Hipnótico y sedante.
Metabolismo hepático
(Glucoroconjugación).
Eliminacion renal de metabolitos inactivos.
Acúmulo en tejidos grasos (posibilidad de
sedación prolongada).T1/2 31 horas.
Propofol
DOSING: ADULTS — Dosage must be individualized based on total body weight and titrated to the desired
clinical effect. Wait at least 3-5 minutes between dosage adjustments to clinically assess drug effects. Smaller
doses are required when used with narcotics. The following are general dosing guidelines (see "Symbols and
Abbreviations Used in This Handbook" in front section of this book for explanation of ASA classes):
Induction:
General anesthesia:
ASA I or II, <55 years: I.V.: 2-2.5 mg/kg (~40 mg every 10 seconds until onset of induction)
Debilitated, ASA III or IV, hypovolemic: Refer to elderly dosing.
Cardiac anesthesia: I.V.: 0.5-1.5 mg/kg (~20 mg every 10 seconds until onset of induction)
Neurosurgical patients: I.V.: 1-2 mg/kg (~20 mg every 10 seconds until onset of induction)
Maintenance:
ASA I or II, <55 years:
I.V. infusion: Initial: 150-200 mcg/kg/minute for 10-15 minutes; decrease by 30% to 50% during first 30 minutes
of maintenance; usual infusion rate: 100-200 mcg/kg/minute (6-12 mg/kg/hour)
I.V. intermittent bolus: 20-50 mg increments as needed
Debilitated, ASA III or IV, hypovolemic: I.V. Infusion: Refer to elderly dosing.
Cardiac anesthesia: I.V. infusion:
Low-dose propofol with primary opioid: 50-100 mcg/kg/minute (see manufacturer's labeling)
Primary propofol with secondary opioid: 100-150 mcg/kg/minute
Neurosurgical patients: I.V. infusion: 100-200 mcg/kg/minute (6-12 mg/kg/hour)
Monitored anesthesia care sedation:
Initiation:
ASA I or II, <55 years: Slow I.V. infusion: 100-150 mcg/kg/minute for 3-5 minutes or slow injection: 0.5 mg/kg
over 3-5 minutes
Debilitated, neurosurgical, or ASA III or IV patients: Use similar doses to healthy adults; avoid rapid I.V. boluses
Maintenance:
ASA I or II, <55 years: I.V. infusion using variable rates (preferred over intermittent boluses): 25-75
mcg/kg/minute or incremental bolus doses: 10 mg or 20 mg
Debilitated, neurosurgical, or ASA III or IV patients: Use 80% of healthy adult dose; do not use rapid bolus
doses (single or repeated)
Propofol
DOSING: ADULTS — Dosage must be individualized based on total
body weight and titrated to the desired clinical effect. Wait at least 35 minutes between dosage adjustments to clinically assess drug
effects. Smaller doses are required when used with narcotics.
ICU sedation in intubated mechanically-ventilated patients: Avoid
rapid bolus injection; individualize dose and titrate to response
Continuous infusion: Initial: 0.3 mg/kg/hour (5 mcg/kg/min);
increase by 0.3-0.6 mg/kg/hour (5-10 mcg/kg/min) every 5-10
minutes until desired sedation level is achieved; usual maintenance:
0.3-4.8 mg/kg/hour (5-80 mcg/kg/min) or higher. Elderly, debilitated,
or ASA III or IV patients: Refer to elderly dosing. Some clinicians
recommend daily interruption of infusion to perform clinical
evaluation.
Propofol
DOSING: PEDIATRIC — Dosage must be individualized based on
total body weight and titrated to the desired clinical effect; wait at
least 3-5 minutes between dosage adjustments to clinically assess
drug effects; smaller doses are required when used with narcotics;
the following are general dosing guidelines (see "Symbols and
Abbreviations Used in This Handbook" in front section of this book
for explanation of ASA classes):
General anesthesia:
Induction: I.V.: Children 3-16 years, ASA I or II: 2.5-3.5 mg/kg over
20-30 seconds; use a lower dose for children ASA III or IV
Maintenance: I.V. infusion: Children 2 months to 16 years, ASA I or
II: Initial: 200-300 mcg/kg/minute; decrease dose after 30 minutes if
clinical signs of light anesthesia are absent; usual infusion rate: 125150 mcg/kg/minute (range: 125-300 mcg/kg/minute; 7.5-18
mg/kg/hour); children 5 years may require larger infusion rates
compared to older children.
Propofol
DOSING: ELDERLY
General anesthesia:
Induction: Elderly, debilitated, ASA III or IV, hypovolemic: I.V.: 1-1.5 mg/kg
(~20 mg every 10 seconds until onset of induction)
Maintenance: Elderly, debilitated, ASA III or IV, hypovolemic: I.V. infusion:
50-100 mcg/kg/minute (3-6 mg/kg/hour)
Monitored anesthesia care sedation:
Initiation: Elderly, debilitated, ASA III or IV, neurosurgical: I.V.: Use doses
similar to healthy adults; avoid rapid I.V. boluses
Maintenance: Elderly, debilitated, ASA III or IV, neurosurgical: I.V.: Use
80% of healthy adult dose; do not use rapid bolus doses (single or
repeated)
ICU sedation in intubated mechanically-ventilated patients: Avoid rapid
bolus injection; individualize dose and titrate to response: Continuous
infusion: Elderly, debilitated, ASA III or IV: Reduce dose by 80%; reduce
dose after adequate sedation established and adjust to response (ie,
evaluate frequently to use minimum dose for sedation).
Propofol
Principal efecto secundario: HipoTA
Otros: bradicardia, arritmias, efectos neurológicos
(procovulsivante, mioclonías, movimiento
coreoatetósicos, meningismo), acidosis respiratoria
(aumento de producción de CO2), pancreatitis,
hipertrigliceridemia, anafilaxis y coloración verdosa de la
orina.
Acidosis láctica, insuficiencia renal aguda y
rabdomiolisis.
La administración contínua más de 24-48 horas se
relaciona con serias complicaciones.
La solución contiene 1,1 kcal/ml, principalmente en
forma de lípidos.
Frecuente contaminación bacteriana.
Propofol
DRUG INTERACTIONS — Substrate of CYP1A2 (minor), 2A6
(minor), 2B6 (major), 2C9 (major), 2C19 (minor), 2D6 (minor), 2E1
(minor), 3A4 (minor); Inhibits CYP1A2 (moderate), 2C9 (weak),
2C19 (moderate), 2D6 (weak), 2E1 (weak), 3A4 (strong)
CNS depressants: Additive CNS depression and respiratory
depression may necessitate dosage reduction when used with
anesthetics, benzodiazepines, opiates, ethanol, phenothiazines.
CYP1A2 substrates: Propofol may increase the levels/effects of
CYP1A2 substrates. Example substrates include aminophylline,
fluvoxamine, mexiletine, mirtazapine, ropinirole, theophylline, and
trifluoperazine.
CYP2B6 inhibitors: May increase the levels/effects of propofol.
Example inhibitors include desipramine, paroxetine, and sertraline.
CYP2C9 Inhibitors may increase the levels/effects of propofol.
Example inhibitors include delavirdine, fluconazole, gemfibrozil,
ketoconazole, nicardipine, NSAIDs, sulfonamides and tolbutamide.
Propofol
DRUG INTERACTIONS — Substrate of CYP1A2 (minor), 2A6 (minor), 2B6
(major), 2C9 (major), 2C19 (minor), 2D6 (minor), 2E1 (minor), 3A4 (minor);
Inhibits CYP1A2 (moderate), 2C9 (weak), 2C19 (moderate), 2D6 (weak),
2E1 (weak), 3A4 (strong)
CYP2C19 substrates: Propofol may increase the levels/effects of CYP2C19
substrates. Example substrates include citalopram, diazepam,
methsuximide, phenytoin, propranolol, and sertraline.
CYP3A4 substrates: Propofol may increase the levels/effects of CYP3A4
substrates. Example substrates include benzodiazepines, calcium channel
blockers, mirtazapine, nateglinide, nefazodone, tacrolimus, and venlafaxine.
Selected benzodiazepines (midazolam and triazolam), cisapride, ergot
alkaloids, selected HMG-CoA reductase inhibitors (lovastatin and
simvastatin), and pimozide are generally contraindicated with strong
CYP3A4 inhibitors.
Narcotics: Concomitant use may lead to increased sedative or anesthetic
effects of propofol, more pronounced decreases in systolic, diastolic, and
mean arterial pressures and cardiac output. Lower doses of propofol may
be needed. In addition, fentanyl may cause serious bradycardia when used
with propofol in pediatric patients.
Vecuronium: Propofol may potentiate the neuromuscular blockade of
vecuronium.
Propofol
EMBARAZO.
– No recomendado. Cruza la barrera
placentaria causando depresión neonatal.
LACTANCIA
– No recomendado.
Propofol
PHARMACODYNAMICS / KINETICS
– Onset of action: Anesthetic: Bolus infusion (dose dependent): 9-51
seconds (average 30 seconds)
– Duration (dose and rate dependent): 3-10 minutes
– Distribution: Vd: 2-10 L/kg; highly lipophilic
– Protein binding: 97% to 99%
– Metabolism: Hepatic to water-soluble sulfate and glucuronide
conjugates
– Half-life elimination: Biphasic: Initial: 40 minutes; Terminal: 4-7 hours (up
to 1-3 days)
– Excretion: Urine (~88% as metabolites, 40% as glucuronide metabolite);
feces (<2%)
Clearance: 20-30 mL/kg/minute; total body clearance exceeds liver
blood flow.
– Food: EDTA, an ingredient of propofol emulsion, may lead to
decreased zinc levels in patients on prolonged therapy (>5 days)
or those predisposed to deficiency (burns, diarrhea, and/or major
sepsis).
Propofol
ADMINISTRACION:
INYECCION IV DIRECTA: SI
Inyección en bolus repetidos, se pueden administrar incrementos de 25 mg (2,5 ml) a 50 mg (5
ml) de acuerdo con las necesidades clínicas. La velocidad de administración es de 2-4 ml cada
10 segundos.
INFUSION INTERMITENTE: SI
Diluir la dosis prescrita con SG5% sin exceder de la concentración de 2 mg/ml (como mínimo
deben utilizarse 4 ml de SG5% para diluir 1 ml de Propofol). Usualmente la velocidad de infusión
es de 4 a 12 mg/kg/h. En sedación UCI 1-4 mg/Kg/h.
También puede ser utilizada sin diluir, en infusión controlada por bombas u otros sistemas.
INFUSION CONTINUA: SI
Diluir la dosis prescrita con SG5% sin exceder de la concentración de 2 mg/ml (como mínimo
deben utilizarse 4 ml de SG5% para diluir 1 ml de Propofol). Usualmente la velocidad de infusión
es de 0,1-0,2 mg/kg/minuto.
También puede ser utilizada sin diluir, en infusión controlada por bombas u otros sistemas.
Velocidad de administración de propofol en infusión IV (ml/h o microgotas/min) cuando se
emplea la solución del 1 % ( 10 mg/ml sin diluir).
INYECCION IM: NO
Propofol
SUEROS COMPATIBLES: Unicamente SG5%. Una vez diluido en
SG5%, las soluciones son estables 6 horas a temperatura
ambiente.
OBSERVACIONES:
– Conservar por debajo de 25° C.
– Se trata de una emulsión de color blanco. Es importante no
guardar en nevera y evitar su congelación.
– Agitar los envases antes de usar. Si la ampolla presenta
partículas o decoloración debe desecharse.
Propofol
Dosis de
carga
Propofol 0,5
mg/kg/h.
Aumentar
0,3-0,6
mg/kg/h
cada 5-10
min.
Propofol
Dosis
de
manteni
miento
FG >
50
ml/min
FG 1050
ml/min
FG <
10
ml/min
Dosis
supleme
ntaria
tras HD
DPCA
TSCR
0,5-3
mg/g/h
100%
100%
100%
Descono
-cido
Desconocido
Dosis
de FG
10-50%
Amp 200 mg/20 ml
IV
Lipuro 1% Braun
Diprivan