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Adjuvantes. Francisco José de la Prada Alvarez. Servicio de Nefrología. Hospital Universitario Son Dureta. 2.2 Según la causa subyacente se reconocen tres tipos generales de dolor: 1) nociceptivo somático 2) nociceptivo visceral 3) neuropático.

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Adjuvantes

Adjuvantes

Francisco José de la Prada Alvarez.

Servicio de Nefrología.

Hospital Universitario Son Dureta





  • 2.2 Según la causa subyacente se reconocen tres tipos generales de dolor:

    1) nociceptivo somático 2) nociceptivo visceral 3) neuropático.

  • 2.2.1 El dolor nociceptivo somático proviene de la estimulación de nociceptores específicos en los tejidos cutáneo y conjuntivo profundo (músculos, tendones, huesos, etc.), y se suele asociar a lesión o enfermedad. El dolor somático se describe a menudo como “sordo” o “agudo” y como “algia”. El dolor somático suele ser constante y por lo general se controla al eliminar la causa o al tratar la patología subyacente.

Programa Informed


  • 2.2 Según la causa subyacente se reconocen tres tipos generales de dolor:

    • 1) nociceptivo somático 2) nociceptivo visceral 3) neuropático.

  • 2.2.2 El dolor nociceptivo visceral es un dolor que se origina por la lesión, distensión, obstrucción o inflamación de los órganos torácicos, abdominales o pélvicos. Por ejemplo, el dolor visceral puede provenir de la obstrucción de una víscera hueca (p. ej., el intestino), la distensión o la isquemia de los componentes del intestino o por el rápido estiramiento de la cápsula de un órgano sólido (hígado).

Programa Informed


  • 2.2 Según la causa subyacente se reconocen tres tipos generales de dolor:

    • 1) nociceptivo somático 2) nociceptivo visceral 3) neuropático.

  • 2.2.3 El dolor neuropático está causado por la lesión o la destrucción de los nervios localizados en la periferia o en el sistema nervioso central. Esto provoca una función anormal del nervio, que se manifiesta como un dolor que se califica de “quemazón”, “latigazo” u “hormigueo”. El dolor neuropático puede ser constante y sostenido, pudiendo existir un dolor intermitente, sobreimpuesto, similar a un choque, que se describe como eléctrico o en escopetazo. Además, pueden aparecer sensaciones anormales como alodinia, parestesia y disestesia.

Programa Informed


Programa Informed generales de dolor:


Programa Informed generales de dolor:


  • Los analgésicos adyuvantes tricíclicos son la amitriptilina, la doxepina, la imipramina, la desipramina y la nortriptilina. Son especialmente útiles en los síndromes de dolor neuropático.

  • Los analgésicos adyuvantes anticonvulsivantes son la carbamazepina, la difenilhidantoína, el ácido valproico, el divalproato sódico y gabapentina. Son especialmente útiles en el dolor neuropático lancinante.

  • La dexametasona y la prednisona son los corticoides utilizados con mayor frecuencia en el tratamiento del dolor. Una serie de alteraciones dolorosas responden a su empleo, entre ellas el dolor óseo metastásico, el aumento de la presión intracraneal, la compresión aguda de la médula espinal y el dolor neuropático debido a la infiltración o la compresión por el tumor.

  • La metotrimeprazina es un analgésico neuroléptico de probada utilidad en los pacientes con cáncer avanzado que tienen dolor con ansiedad, agitación o náuseas.

  • El clonazepam es una benzodiazepina ampliamente aceptada en el tratamiento del dolor neuropático.

Programa Informed


Anticonvulsivantes
Anticonvulsivantes amitriptilina, la doxepina, la imipramina, la desipramina y la nortriptilina. Son especialmente útiles en los síndromes de dolor neuropático.

  • Los anticonvulsivantes utilizados en el manejo del dolor incluyen la carbamazepina, la difenilhidantoína y los fármacos relacionados con el ácido valproico y gabapentina. Todos se han mostrado útiles en el tratamiento del dolor neuropático.

  • Los anticonvulsivantes se han utilizado para el tratamiento del dolor desde hace más de 50 años.

  • Fenitoina, Carbamacepina, ácido valproico, gabapentina, topiramate, vigabatrina, tiagabina, levetiracetam, zonisamida y oxcarbacepina.

Programa Informed


Anticonvulsivantes1
Anticonvulsivantes amitriptilina, la doxepina, la imipramina, la desipramina y la nortriptilina. Son especialmente útiles en los síndromes de dolor neuropático.

  • Limitaciones de uso.

    • Los más antiguos (fenitoina, carbamacepina y acido valproico) requieren monitorizacion sanguínea y de la función hepática.

    • Efectos secundarios en un alto porcentaje de pacientes.

Programa Informed


Programa Informed amitriptilina, la doxepina, la imipramina, la desipramina y la nortriptilina. Son especialmente útiles en los síndromes de dolor neuropático.


Programa Informed amitriptilina, la doxepina, la imipramina, la desipramina y la nortriptilina. Son especialmente útiles en los síndromes de dolor neuropático.


Anticonvulsivantes2
Anticonvulsivantes amitriptilina, la doxepina, la imipramina, la desipramina y la nortriptilina. Son especialmente útiles en los síndromes de dolor neuropático.

  • Gabapentina: el más efectivo; debe considerarse de primera elección en el tratamieto del dolor neuropático.

  • Neuralgia del trigémino: carbamacepina y luego lamotrignina, toppiromato, o gabapentina, solos o en combinación.

  • Neuropatía diabética: carbamazepine, gabapentina y oxcarbacepina.

  • Fenitoina: barato, disponible por vía oral y parenteral.

Programa Informed


N03AA-Barbitúricos amitriptilina, la doxepina, la imipramina, la desipramina y la nortriptilina. Son especialmente útiles en los síndromes de dolor neuropático.

Programa Informed


N03AB-Hidantoinas amitriptilina, la doxepina, la imipramina, la desipramina y la nortriptilina. Son especialmente útiles en los síndromes de dolor neuropático.

Programa Informed


N03AD-Carboxamidas amitriptilina, la doxepina, la imipramina, la desipramina y la nortriptilina. Son especialmente útiles en los síndromes de dolor neuropático.

Programa Informed


N03AG-Acidos grasos amitriptilina, la doxepina, la imipramina, la desipramina y la nortriptilina. Son especialmente útiles en los síndromes de dolor neuropático.

Programa Informed


Gabapentina
Gabapentina amitriptilina, la doxepina, la imipramina, la desipramina y la nortriptilina. Son especialmente útiles en los síndromes de dolor neuropático.

N03AX-Otros antiepilépticos

Programa Informed


Gabapentina1
Gabapentina amitriptilina, la doxepina, la imipramina, la desipramina y la nortriptilina. Son especialmente útiles en los síndromes de dolor neuropático.

  • Molécula estructuralmente relacionada con GABA.

  • No se une a los receptores GABA, ni influye en su síntesis ni recaptación.

  • Parece que se une a receptores de calcio voltaje dependientes, localizados presinapticamente, que modulan la liberación de neurotransmisores excitatorios relacionados con la nociocepcion y la genesis de epilepsia.

Programa Informed


Gabapentina2
Gabapentina amitriptilina, la doxepina, la imipramina, la desipramina y la nortriptilina. Son especialmente útiles en los síndromes de dolor neuropático.

  • DOSING: ADULTSAnticonvulsant: Oral:  Initial: 300 mg 3 times/day, if necessary the dose may be increased up to 1800 mg/day  Maintenance: 900-1800 mg/day administered in 3 divided doses; doses of up to 2400 mg/day have been tolerated in long-term clinical studies; up to 3600 mg/day has been tolerated in short-term studies  Note: If gabapentin is discontinued or if another anticonvulsant is added to therapy, it should be done slowly over a minimum of 1 week.

  • Chronic pain (unlabeled use): Oral: 300-1800 mg/day given in 3 divided doses has been the most common dosage range

  • Postoperative pain (unlabeled use): 300-1200 mg 1-2 hours before surgery

  • Postherpetic neuralgia: Day 1: 300 mg, Day 2: 300 mg twice daily, Day 3: 300 mg 3 times/day; dose may be titrated as needed for pain relief (range: 1800-3600 mg/day, daily doses >1800 mg do not generally show greater benefit)

Programa Informed


Gabapentina3
Gabapentina amitriptilina, la doxepina, la imipramina, la desipramina y la nortriptilina. Son especialmente útiles en los síndromes de dolor neuropático.

  • DOSING: PEDIATRIC

  • Anticonvulsant: Oral  Children 3-12 years: Initial: 10-15 mg/kg/day in 3 divided doses; titrate to effective dose over ~3 days; dosages of up to 50 mg/kg/day have been tolerated in clinical studies    Children 3-4 years: Effective dose: 40 mg/kg/day in 3 divided doses    Children 5-12 years: Effective dose: 25-35 mg/kg/day in 3 divided doses  Children >12 years: Refer to adult dosing.

  • Note: If gabapentin is discontinued or if another anticonvulsant is added to therapy, it should be done slowly over a minimum of 1 week

Programa Informed


Gabapentina4
Gabapentina amitriptilina, la doxepina, la imipramina, la desipramina y la nortriptilina. Son especialmente útiles en los síndromes de dolor neuropático.

  • DOSING: ELDERLY —

  • Studies in elderly patients have shown a decrease in clearance as age increases. This is most likely due to age-related decreases in renal function; dose reductions may be needed.

Programa Informed


Gabapentina5
Gabapentina amitriptilina, la doxepina, la imipramina, la desipramina y la nortriptilina. Son especialmente útiles en los síndromes de dolor neuropático.

  • DOSING: RENAL IMPAIRMENT —

  • Hemodialysis: Dialyzable

  • Gabapentin Dosage Adjustments in Renal Impairment

    • Clcr 60 mL/minute): 300-1200 mg 3 times/day

    • Clcr >30-59 mL/minute: 200-700 mg twice/day

    • Clcr >15-29 mL/minute: 200-700 mg/day

    • Clcr 15 mL/minute: 100-300 mg/day

    • Clcr <15 mL/minute: Reduce daily dose in proportion to creatinine clearance.

  • Hemodialysis single supplemental dose: 125-350 mg (given after each 4 hours of hemodialysis).

Programa Informed


Gabapentina6
Gabapentina amitriptilina, la doxepina, la imipramina, la desipramina y la nortriptilina. Son especialmente útiles en los síndromes de dolor neuropático.

  • ADVERSE REACTIONS SIGNIFICANT — As reported in patients >12 years of age, unless otherwise noted in children (3-12 years)

  • >10%:  Central nervous system: Somnolence (20%; children 8%), dizziness (17% to 28%; children 3%), ataxia (13%), fatigue (11%)  Miscellaneous: Viral infection (children 11%)

Programa Informed


Gabapentina7
Gabapentina amitriptilina, la doxepina, la imipramina, la desipramina y la nortriptilina. Son especialmente útiles en los síndromes de dolor neuropático.

  • ADVERSE REACTIONS SIGNIFICANT — As reported in patients >12 years of age, unless otherwise noted in children (3-12 years)

  • 1% to 10%:  Cardiovascular: Peripheral edema (2% to 8%), vasodilatation (1%)  Central nervous system: Fever (children 10%), hostility (children 8%), emotional lability (children 4%), fatigue (children 3%), headache (3%), ataxia (3%), abnormal thinking (2% to 3%; children 2%), amnesia (2%), depression (2%), dysarthria (2%), nervousness (2%), abnormal coordination (1% to 2%), twitching (1%), hyperesthesia (1%)  Dermatologic: Pruritus (1%), rash (1%)  Endocrine & metabolic: Hyperglycemia (1%)  Gastrointestinal: Diarrhea (6%), nausea/vomiting (3% to 4%; children 8%), abdominal pain (3%), weight gain (adults and children 2% to 3%), dyspepsia (2%), flatulence (2%), dry throat (2%), xerostomia (2% to 5%), constipation (2% to 4%), dental abnormalities (2%), appetite stimulation (1%)  Genitourinary: Impotence (2%)  Hematologic: Leukopenia (1%), decreased WBC (1%)  Neuromuscular & skeletal: Tremor (7%), weakness (6%), hyperkinesia (children 3%), abnormal gait (2%), back pain (2%), myalgia (2%), fracture (1%)  Ocular: Nystagmus (8%), diplopia (1% to 6%), blurred vision (3% to 4%), conjunctivitis (1%)  Otic: Otitis media (1%)  Respiratory: Rhinitis (4%), bronchitis (children 3%), respiratory infection (children 3%), pharyngitis (1% to 3%), cough (2%)  Miscellaneous: Infection (5%)

Programa Informed


Gabapentina8
Gabapentina amitriptilina, la doxepina, la imipramina, la desipramina y la nortriptilina. Son especialmente útiles en los síndromes de dolor neuropático.

  • CONTRAINDICATIONS — Hypersensitivity to gabapentin or any component of the formulation

  • DRUG INTERACTIONS — CNS depressants: Sedative effects may be additive with CNS depressants; includes ethanol, barbiturates, narcotic analgesics, and other sedative agents. Monitor for increased effect.

Programa Informed


Gabapentina9
Gabapentina amitriptilina, la doxepina, la imipramina, la desipramina y la nortriptilina. Son especialmente útiles en los síndromes de dolor neuropático.

  • EMABARAZO —

    • Efectos teratogénicos en animales de experimentación.

  • LACTANCIA —

    • Pasa a la leche materna. Los recien nacidos pueden estar expuestos a 1 mg/kg/dia de gabapentina

Programa Informed


Gabapentina10
Gabapentina amitriptilina, la doxepina, la imipramina, la desipramina y la nortriptilina. Son especialmente útiles en los síndromes de dolor neuropático.

  • TOXICOLOGY / OVERDOSE COMPREHENSIVE —

  • Acute oral overdoses up to 49 g have been reported; double vision, slurred speech, drowsiness, lethargy, and diarrhea were observed.

  • Tratamiento:

    • De soporte.

    • Lavado gastrico, carbón activado, catárticos.

    • Hemodialisis.

Programa Informed


Gabapentina11
Gabapentina amitriptilina, la doxepina, la imipramina, la desipramina y la nortriptilina. Son especialmente útiles en los síndromes de dolor neuropático.

  • PHARMACODYNAMICS / KINETICSAbsorption: 50% to 60% from proximal small bowel by L-amino transport system

  • Distribution: Vd: 0.6-0.8 L/kg

  • Protein binding: <3%

  • Bioavailability: Inversely proportional to dose due to saturable absorption:  900 mg/day: 60%  1200 mg/day: 47%  2400 mg/day: 34%  3600 mg/day: 33%  4800 mg/day: 27%

  • Half-life elimination: 5-7 hours; anuria 132 hours; during dialysis 3.8 hours

  • Excretion: Proportional to renal function; urine (as unchanged drug)

Programa Informed


Programa Informed amitriptilina, la doxepina, la imipramina, la desipramina y la nortriptilina. Son especialmente útiles en los síndromes de dolor neuropático.


Antidepresivos
Antidepresivos amitriptilina, la doxepina, la imipramina, la desipramina y la nortriptilina. Son especialmente útiles en los síndromes de dolor neuropático.

  • Los tricíclicos se han mostrado efectivos en el tratamiento del dolor neuropático, especialmente las disestesias continuas y el dolor lancinante.

  • También son útiles en el dolor con depresión e insomnio (Cherny, 1995, 254–255).

  • Sus mecanismos de acción analgésica consisten en un efecto bloqueador del dolor a la altura de la médula, una mejoría del humor y una potenciación o favorecimiento de la analgesia opioide.

  • Efectos adversos: sedación, síntomas colinérgicos y de la conducción cardíaca como la sequedad de boca, la visión borrosa, la retención urinaria y anomalías de la conducción cardíaca.

Programa Informed


Antidepresivos1
Antidepresivos amitriptilina, la doxepina, la imipramina, la desipramina y la nortriptilina. Son especialmente útiles en los síndromes de dolor neuropático.

  • Ninguno de los ADT tienen la indicación para el tratamiento del dolor.

  • La Amitriptilina es el más estudiado, pero también se han utilizado doxepin, imipramine, nortriptyline, y desipramine

  • Tienen efectos analgésicos independientes y capacidad para controlar los sintoma depresivos asociados con el dolor crónico.

  • Mecanismo analgésico desconocido.

    • Inhibición de la recaptación de seroronina y norpeinefrina.

    • Potenciación del sistema opioide endógeno.

  • En el dolor crónico se usan a dosis inferiores a las usdas en la depresión.

Programa Informed


Antidepresivos2
Antidepresivos amitriptilina, la doxepina, la imipramina, la desipramina y la nortriptilina. Son especialmente útiles en los síndromes de dolor neuropático.

  • El efecto analgésico puede ocurrir tras días de tratamiento, y a veces son necesarias semanas de tratamiento antes de obtener un efecto beneficioso.

  • A veces es necesario cambiar a otro ADT si no se obtiene tratamiento.

  • Estan contraindicados en pacientes con alteracion del ritmo cardíaco y alteraciones gastrointestinales.

Programa Informed


N06AA-Antidepresivos inhibidores no selectivos de monoaminas amitriptilina, la doxepina, la imipramina, la desipramina y la nortriptilina. Son especialmente útiles en los síndromes de dolor neuropático.

Programa Informed


N06AB-Antidepresivos inhibidores selectivos de la recaptación de serotonina

Nota 1: Otros antidepresivos Inhibidores Selectivos de la Recaptación de Serotonina (ISRS) como los fármacos:

Fluvoxamina (Dumirox) Paroxetina (Seroxat), Sertralina (Besitran) y Citalopram (Seropram) no están incluidos en la Guía. Cuando un paciente ingresa con un tratamiento de origen ambulatorio se considera adecuado seguir con el mismo tratamiento mientras el paciente permanezca ingresado. Consultar programa de intercambio terapéutico.

Nota 2: Escitalopram (Cipralex, Entact, Esertia) y programa de intercambio terapéutico. Se acuerda no incluir Escitalopram en la Guía Farmacoterapéutica (Reunión CFT 09-02-2005) Dentro del programa de intercambio terapéutico (PIT) del hospital, los pacientes que ingresen en tratamiento con escitalopram se pasarán a citalopram, siendo la equivalencia de dosis:Escitalopram 10 mg equivale a citalopram 20 mg. Escitalopram 20 mg equivale a citalopram 40 mg. El escitalopram es el S(+)-enantiómero del antidepresivo citalopram

Programa Informed


N06AF-Antidepresivos Inhibidores no selectivos de la MAO recaptación de serotonina

Programa Informed


N06AX-Otros antidepresivos recaptación de serotonina

Programa Informed


Amitriptilina
Amitriptilina recaptación de serotonina

  • Mecanismo de acción:

    • Aumenta la concentración sináptica de serotonina y/o norepinefrina en el SNC por inhibición de su recaptación por la membrana presinaptica de la neurona.

Programa Informed


N06AA-Antidepresivos inhibidores no selectivos de monoaminas recaptación de serotonina

Programa Informed


Amitriptilina1
Amitriptilina recaptación de serotonina

  • DOSING: ADULTSDepression: Oral: 50-150 mg/day single dose at bedtime or in divided doses; dose may be gradually increased up to 300 mg/day.

  • Chronic pain management (unlabeled use): Oral: Initial: 25 mg at bedtime; may increase as tolerated to 100 mg/day.

  • Migraine prophylaxis (unlabeled use): Oral: Initial: 10-25 mg at bedtime; usual dose: 150 mg; reported dosing ranges: 10-400 mg/day

Programa Informed


Amitriptilina2
Amitriptilina recaptación de serotonina

  • DOSING: PEDIATRIC

  • Chronic pain management (unlabeled use): Oral: Initial: 0.1 mg/kg at bedtime, may advance as tolerated over 2-3 weeks to 0.5-2 mg/kg at bedtime

  • Depressive disorders:  Children (unlabeled use): Oral: Initial doses of 1 mg/kg/day given in 3 divided doses with increases to 1.5 mg/kg/day have been reported in a small number of children (n=9) 9-12 years of age; clinically, doses up to 3 mg/kg/day (5 mg/kg/day if monitored closely) have been proposed  Adolescents: Initial: 25-50 mg/day; may administer in divided doses; increase gradually to 100 mg/day in divided doses.

  • Migraine prophylaxis (unlabeled use): Oral: Initial: 0.25 mg/kg/day, given at bedtime; increase dose by 0.25 mg/kg/day to maximum 1 mg/kg/day. Reported dosing ranges: 0.1-2 mg/kg/day; maximum suggested dose: 10 mg.

Programa Informed


Amitriptilina3
Amitriptilina recaptación de serotonina

  • DOSING: ELDERLY —

  • Depression: Oral: Initial: 10-25 mg at bedtime; dose should be increased in 10-25 mg increments every week if tolerated; dose range: 25-150 mg/day.

  • DOSING: RENAL IMPAIRMENT — Nondialyzable

  • DOSING: HEPATIC IMPAIRMENT — Use with caution and monitor plasma levels and patient response.

Programa Informed


Los efectos anticolinérgicos pueden provocar en pacientes en HD aumento de la sed y del peso (boca seca), hiperglucemia, y aumento de la osmolaridad extracelular.La hipoK, hipoCa y alcalosis transitoria intradiálisis (factores que alteran el intervalo QT) pueden aumenta la susceptibilidad a la aparición de arritmias cardíacas.

Programa Informed


Amitriptilina4
Amitriptilina en HD aumento de la sed y del peso (boca seca), hiperglucemia, y aumento de la osmolaridad extracelular.

  • USE — Relief of symptoms of depression

  • USE - UNLABELED / INVESTIGATIONAL —

    • Analgesic for certain chronic and neuropathic pain;

    • prophylaxis against migraine headaches;

    • treatment of depressive disorders in children

Programa Informed


Amitriptilina5
Amitriptilina en HD aumento de la sed y del peso (boca seca), hiperglucemia, y aumento de la osmolaridad extracelular.

  • ADVERSE REACTIONS SIGNIFICANT — Anticholinergic effects may be pronounced; moderate to marked sedation can occur (tolerance to these effects usually occurs).

  • Frequency not defined.

  • Cardiovascular: Orthostatic hypotension, tachycardia, ECG changes (nonspecific), AV conduction changes, cardiomyopathy (rare), MI, stroke, heart block, arrhythmia, syncope, hypertension, palpitation

  • Central nervous system: Restlessness, dizziness, insomnia, sedation, fatigue, anxiety, cognitive function impaired, seizure, extrapyramidal symptoms, coma, hallucinations, confusion, disorientation, coordination impaired, ataxia, headache, nightmares, hyperpyrexia

  • Dermatologic: Allergic rash, urticaria, photosensitivity, alopecia

  • Endocrine & metabolic: Syndrome of inappropriate ADH secretion

  • Gastrointestinal: Weight gain, xerostomia, constipation, paralytic ileus, nausea, vomiting, anorexia, stomatitis, peculiar taste, diarrhea, black tongue

  • Genitourinary: Urinary retention

  • Hematologic: Bone marrow depression, purpura, eosinophilia

  • Neuromuscular & skeletal: Numbness, paresthesia, peripheral neuropathy, tremor, weakness

  • Ocular: Blurred vision, mydriasis, ocular pressure increased

  • Otic: Tinnitus

  • Miscellaneous: Diaphoresis, withdrawal reactions (nausea, headache, malaise)

  • Postmarketing and/or case reports: Neuroleptic malignant syndrome (rare), serotonin syndrome (rare)

Programa Informed


Amitriptilina6
Amitriptilina en HD aumento de la sed y del peso (boca seca), hiperglucemia, y aumento de la osmolaridad extracelular.

  • DRUG INTERACTIONS — Substrate of CYP1A2 (minor), 2B6 (minor), 2C9 (minor), 2C19 (minor), 2D6 (major), 3A4 (minor); Inhibits CYP1A2 (weak), 2C9 (weak), 2C19 (weak), 2D6 (weak), 2E1 (weak)

  • Altretamine: Concurrent use may cause orthostatic hypertension.

  • Amphetamines: TCAs may enhance the effect of amphetamines; monitor for adverse CV effects.

  • Anticholinergics: Combined use with TCAs may produce additive anticholinergic effects.

  • Antihypertensives: Amitriptyline inhibits the antihypertensive response to bethanidine, clonidine, debrisoquin, guanadrel, guanethidine, guanabenz, guanfacine; monitor BP; consider alternate antihypertensive agent.

  • Beta-agonists: When combined with TCAs may predispose patients to cardiac arrhythmias.

  • Bupropion: May increase the levels of tricyclic antidepressants; based on limited information, monitor response.

  • Carbamazepine: Tricyclic antidepressants may increase carbamazepine levels; monitor.

  • Cholestyramine and colestipol: May bind TCAs and reduce their absorption; monitor for altered response.

  • Cisapride: May increase the risk of QTc prolongation and/or arrhythmia; concurrent use is contraindicated.

  • Clonidine: Abrupt discontinuation of clonidine may cause hypertensive crisis; amitriptyline may enhance the response (also see note on antihypertensives).

  • CNS depressants: Sedative effects may be additive with TCAs; monitor for increased effect; includes benzodiazepines, barbiturates, antipsychotics, ethanol, and other sedative medications.

Programa Informed


Amitriptilina7
Amitriptilina en HD aumento de la sed y del peso (boca seca), hiperglucemia, y aumento de la osmolaridad extracelular.

  • DRUG INTERACTIONS — Substrate of CYP1A2 (minor), 2B6 (minor), 2C9 (minor), 2C19 (minor), 2D6 (major), 3A4 (minor); Inhibits CYP1A2 (weak), 2C9 (weak), 2C19 (weak), 2D6 (weak), 2E1 (weak)

  • CYP2D6 inhibitors: May increase the levels/effects of amitriptyline; example inhibitors include chlorpromazine, delavirdine, fluoxetine, miconazole, paroxetine, pergolide, quinidine, quinine, ritonavir, and ropinirole.

  • Epinephrine (and other direct alpha-agonists): Pressor response to I.V. epinephrine, norepinephrine, and phenylephrine may be enhanced in patients receiving TCAs. (Note: Effect is unlikely with epinephrine or levonordefrin dosages typically administered as infiltration in combination with local anesthetics.)

  • Fenfluramine: May increase tricyclic antidepressant levels/effects.

  • Hypoglycemic agents (including insulin): TCAs may enhance the hypoglycemic effects of tolazamide, chlorpropamide, or insulin; monitor for changes in blood glucose levels; reported with chlorpropamide, tolazamide, and insulin.

  • Levodopa: Tricyclic antidepressants may decrease the absorption (bioavailability) of levodopa; rare hypertensive episodes have also been attributed to this combination.

  • Linezolid: Hyperpyrexia, hypertension, tachycardia, confusion, seizures, and deaths have been reported with agents which inhibit MAO (serotonin syndrome); this combination should be avoided.

  • Lithium: Concurrent use with a TCA may increase the risk for neurotoxicity.

  • MAO inhibitors: Hyperpyrexia, hypertension, tachycardia, confusion, seizures, and deaths have been reported (serotonin syndrome); this combination should be avoided.

Programa Informed


Amitriptilina8
Amitriptilina en HD aumento de la sed y del peso (boca seca), hiperglucemia, y aumento de la osmolaridad extracelular.

  • DRUG INTERACTIONS — Substrate of CYP1A2 (minor), 2B6 (minor), 2C9 (minor), 2C19 (minor), 2D6 (major), 3A4 (minor); Inhibits CYP1A2 (weak), 2C9 (weak), 2C19 (weak), 2D6 (weak), 2E1 (weak)

  • MAO inhibitors: Hyperpyrexia, hypertension, tachycardia, confusion, seizures, and deaths have been reported (serotonin syndrome); this combination should be avoided.

  • Methylphenidate: Metabolism of amitriptyline may be decreased.

  • Phenothiazines: Serum concentrations of some TCAs may be increased; in addition, TCAs may increase concentration of phenothiazines; monitor for altered clinical response.

  • QTc prolonging agents: Concurrent use of tricyclic agents with other drugs which may prolong QTc interval may increase the risk of potentially fatal arrhythmias; includes type Ia and type III antiarrhythmics agents, selected quinolones (sparfloxacin, gatifloxacin, moxifloxacin, grepafloxacin), cisapride, and other agents.

  • Ritonavir: Combined use of high-dose tricyclic antidepressants with ritonavir may cause serotonin syndrome in HIV-positive patients; monitor.

  • Sucralfate: Absorption of tricyclic antidepressants may be reduced with coadministration.

  • Sympathomimetics, indirect-acting: Tricyclic antidepressants may result in a decreased sensitivity to indirect-acting sympathomimetics; includes dopamine and ephedrine; also see interaction with epinephrine (and direct-acting sympathomimetics).

  • Tramadol: Tramadol's risk of seizures may be increased with TCAs.

  • Valproic acid: May increase serum concentrations/adverse effects of some tricyclic antidepressants.

  • Warfarin (and other oral anticoagulants): Amitriptyline may increase the anticoagulant effect in patients stabilized on warfarin; monitor INR.

Programa Informed


Amitriptilina9
Amitriptilina en HD aumento de la sed y del peso (boca seca), hiperglucemia, y aumento de la osmolaridad extracelular.

  • PREGNANCY RISK FACTOR — C

  • PREGNANCY IMPLICATIONS — Teratogenic effects have been observed in animal studies. Amitriptyline crosses the human placenta; CNS effects, limb deformities and developmental delay have been noted in case reports.

  • LACTATION — Enters breast milk/not recommended

Programa Informed


Amitriptilina10
Amitriptilina en HD aumento de la sed y del peso (boca seca), hiperglucemia, y aumento de la osmolaridad extracelular.

  • MONITORING PARAMETERS — Monitor blood pressure and pulse rate prior to and during initial therapy; evaluate mental status; monitor weight; ECG in older adults and patients with cardiac disease

  • REFERENCE RANGE — Therapeutic:

    • Amitriptyline and nortriptyline 100-250 ng/mL (SI: 360-900 nmol/L);

    • nortriptyline 50-150 ng/mL (SI: 190-570 nmol/L); Toxic: >0.5 mcg/mL;

    • plasma levels do not always correlate with clinical effectiveness

Programa Informed


Amitriptilina11
Amitriptilina en HD aumento de la sed y del peso (boca seca), hiperglucemia, y aumento de la osmolaridad extracelular.

  • TOXICOLOGY / OVERDOSE COMPREHENSIVE —

  • Symptoms include agitation, confusion, hallucinations, urinary retention, hypothermia, hypotension, ventricular tachycardia, and seizures.

  • Following initiation of essential overdose management, toxic symptoms should be treated.

  • Sodium bicarbonate is indicated when the QRS interval is >0.10 seconds or the QTc is >0.42 seconds.

  • Ventricular arrhythmias often respond to phenytoin 15-20 mg/kg (adults) with concurrent systemic alkalinization (sodium bicarbonate 0.5-2 mEq/kg I.V.).

  • Arrhythmias unresponsive to this therapy may respond to lidocaine 1 mg/kg I.V. followed by a titrated infusion.

  • Physostigmine (1-2 mg slow I.V. for adults or 0.5 mg slow I.V. for children) may be indicated in reversing cardiac arrhythmias that are due to vagal blockade, or for anticholinergic effects, but should only be used as a last measure in life-threatening situations.

  • Seizures usually respond to diazepam I.V. boluses (5-10 mg for adults up to 30 mg or 0.25-0.4 mg/kg/dose for children up to 10 mg/dose). If seizures are unresponsive or recur, phenytoin or phenobarbital may be required.

Programa Informed


Amitriptilina12
Amitriptilina en HD aumento de la sed y del peso (boca seca), hiperglucemia, y aumento de la osmolaridad extracelular.

  • PHARMACODYNAMICS / KINETICS

  • Onset of action: Migraine prophylaxis: 6 weeks, higher dosage may be required in heavy smokers because of increased metabolism; Depression: 4-6 weeks, reduce dosage to lowest effective level

  • Distribution: Crosses placenta; enters breast milk

  • Metabolism: Hepatic to nortriptyline (active), hydroxy and conjugated derivatives; may be impaired in the elderly

  • Half-life elimination: Adults: 9-27 hours (average: 15 hours)

  • Time to peak, serum: ~4 hours

  • Excretion: Urine (18% as unchanged drug); feces (small amounts)

  • PATIENT INFORMATION — Do not discontinue medication abruptly. Full effect may not occur for 3-6 weeks. Avoid alcohol. May cause urine to turn blue-green. May cause drowsiness. Dry mouth may be helped by sips of water, sugarless gum, or hard candy.

Programa Informed


Programa Informed en HD aumento de la sed y del peso (boca seca), hiperglucemia, y aumento de la osmolaridad extracelular.


Benzodiacepinas
Benzodiacepinas en HD aumento de la sed y del peso (boca seca), hiperglucemia, y aumento de la osmolaridad extracelular.

  • Las benzodiazepinas son un tipo de fármaco con propiedades sedantes, relajantes musculares y amnésicas. Tienen una serie de aplicaciones, incluyendo el manejo de la ansiedad, el control del insomnio, el manejo de la agitación y la premedicación anestésica (para producir sedación).

  • El clonazepam tiene propiedades anticonvulsivantes y es la única benzodiazepina con efectos analgésicos conocidos sobre el dolor neuropático, especialmente el lancinante.

Programa Informed


Benzodiacepinas1
Benzodiacepinas en HD aumento de la sed y del peso (boca seca), hiperglucemia, y aumento de la osmolaridad extracelular.

  • Benzodiazepines — Benzodiazepines may be utilized in patients who would benefit from anxiolysis. These are commonly employed in cancer patients and in non-malignant pain complicated by anxiety disorder.

  • The disadvantage of this class of drugs relates to their addictive potential, as well as their potentiation of sedative effects and respiratory depression in patients who use opioids concurrently.

  • Clonazepam is especially useful for neuropathic pain.

Programa Informed


Clonazepam
Clonazepam en HD aumento de la sed y del peso (boca seca), hiperglucemia, y aumento de la osmolaridad extracelular.

  • Clonazepam — Clonazepam is a benzodiazepine that has been used successfully in providing relief for both chronic malignant and non-malignant pain syndromes such as headaches, temporomandibular joint dysfunction, and phantom limb pain [22-24].

  • It acts by enhancing GABA receptor mediated chloride channels. Clonazepam is particularly effective when used in combination with other neuropathic analgesics and in patients with prominent anxiety disorder and insomnia.

  • The dose of clonazepam should initially be 0.5 mg at bedtime; the dose is slowly increased to 0.5 to 1 mg three times per day. Doses of up to 20 mg/day have been used in epilepsy; 1 to 6 mg per day is generally successful in treating headache and pain.

  • The most common side effects are drowsiness, dizziness, fatigue, and sedation. As with other benzodiazepines, clonazepam may produce physical and psychological dependence; abrupt discontinuation is prohibited.

Programa Informed


N03AE-Benzodiacepinas en HD aumento de la sed y del peso (boca seca), hiperglucemia, y aumento de la osmolaridad extracelular.

Nota 1: 1 gota=0,1 mg

Programa Informed


Clonazepam1
Clonazepam en HD aumento de la sed y del peso (boca seca), hiperglucemia, y aumento de la osmolaridad extracelular.

  • MECHANISM OF ACTION — The exact mechanism is unknown, but believed to be related to its ability to enhance the activity of GABA; suppresses the spike-and-wave discharge in absence seizures by depressing nerve transmission in the motor cortex

Programa Informed


Clonazepam2
Clonazepam en HD aumento de la sed y del peso (boca seca), hiperglucemia, y aumento de la osmolaridad extracelular.

  • DOSING: ADULTSSeizure disorders: Oral:  Initial daily dose not to exceed 1.5 mg given in 3 divided doses; may increase by 0.5-1 mg every third day until seizures are controlled or adverse effects seen (maximum: 20 mg/day)  Usual maintenance dose: 0.05-0.2 mg/kg; do not exceed 20 mg/day

  • Panic disorder: Oral: 0.25 mg twice daily; increase in increments of 0.125-0.25 mg twice daily every 3 days; target dose: 1 mg/day (maximum: 4 mg/day)

  • Discontinuation of treatment: To discontinue, treatment should be withdrawn gradually. Decrease dose by 0.125 mg twice daily every 3 days until medication is completely withdrawn.

Programa Informed


Clonazepam3
Clonazepam en HD aumento de la sed y del peso (boca seca), hiperglucemia, y aumento de la osmolaridad extracelular.

  • DOSING: PEDIATRIC

  • Seizure disorders (see Use): Oral:

  • Children <10 years or 30 kg:  Initial daily dose: 0.01-0.03 mg/kg/day (maximum: 0.05 mg/kg/day) given in 2-3 divided doses; increase by no more than 0.5 mg every third day until seizures are controlled or adverse effects seen.  Usual maintenance dose: 0.1-0.2 mg/kg/day divided 3 times/day; not to exceed 0.2 mg/kg/day.

  • Children >10 years or 30 kg: Refer to adult dosing.

Programa Informed


Clonazepam4
Clonazepam en HD aumento de la sed y del peso (boca seca), hiperglucemia, y aumento de la osmolaridad extracelular.

  • DOSING: ELDERLY — Refer to adult dosing. Initiate with low doses and observe closely.

  • DOSING: RENAL IMPAIRMENT — Hemodialysis: Supplemental dose is not necessary.

Programa Informed


Programa Informed en HD aumento de la sed y del peso (boca seca), hiperglucemia, y aumento de la osmolaridad extracelular.


Clonazepam5
Clonazepam en HD aumento de la sed y del peso (boca seca), hiperglucemia, y aumento de la osmolaridad extracelular.

  • USE — Alone or as an adjunct in the treatment of petit mal variant (Lennox-Gastaut), akinetic, and myoclonic seizures; petit mal (absence) seizures unresponsive to succimides; panic disorder with or without agoraphobia

  • USE - UNLABELED / INVESTIGATIONAL — Restless legs syndrome; neuralgia; multifocal tic disorder; parkinsonian dysarthria; bipolar disorder; adjunct therapy for schizophrenia

Programa Informed


Clonazepam6
Clonazepam en HD aumento de la sed y del peso (boca seca), hiperglucemia, y aumento de la osmolaridad extracelular.

  • ADVERSE REACTIONS SIGNIFICANT — Reactions reported in patients with seizure and/or panic disorder. Frequency not defined.

  • Cardiovascular: Edema (ankle or facial), palpitation

  • Central nervous system: Amnesia, ataxia (seizure disorder ~30%; panic disorder 5%), behavior problems (seizure disorder ~25%), coma, confusion, depression, dizziness, drowsiness (seizure disorder ~50%), emotional lability, fatigue, fever, hallucinations, headache, hypotonia, hysteria, insomnia, intellectual ability reduced, memory disturbance, nervousness; paradoxical reactions (including aggressive behavior, agitation, anxiety, excitability, hostility, irritability, nervousness, nightmares, sleep disturbance, vivid dreams); psychosis, slurred speech, somnolence (panic disorder 37%), suicidal attempt, vertigo

  • Dermatologic: Hair loss, hirsutism, skin rash

  • Endocrine & metabolic: Dysmenorrhea, libido increased/decreased

  • Gastrointestinal: Abdominal pain, anorexia, appetite increased/decreased, coated tongue, constipation, dehydration, diarrhea, gastritis, gum soreness, nausea, weight changes (loss/gain), xerostomia

  • Genitourinary: Colpitis, dysuria, ejaculation delayed, enuresis, impotence, micturition frequency, nocturia, urinary retention, urinary tract infection

  • Hematologic: Anemia, eosinophilia, leukopenia, thrombocytopenia

  • Hepatic: Alkaline phosphatase increased (transient), hepatomegaly, transaminases increased (transient)

  • Neuromuscular & skeletal: Choreiform movements, coordination abnormal, dysarthria, muscle pain, muscle weakness, myalgia, tremor

  • Ocular: Blurred vision, eye movements abnormal, diplopia, nystagmus

  • Respiratory: Chest congestion, cough, bronchitis, hypersecretions, pharyngitis, respiratory depression, respiratory tract infection, rhinitis, rhinorrhea, shortness of breath, sinusitis

  • Miscellaneous: Allergic reaction, aphonia, dysdiadochokinesis, encopresis, "glassy-eyed" appearance, hemiparesis, lymphadenopathy

Programa Informed


Clonazepam7
Clonazepam en HD aumento de la sed y del peso (boca seca), hiperglucemia, y aumento de la osmolaridad extracelular.

  • DRUG INTERACTIONS — Substrate of CYP3A4 (major)

  • (For additional information: Launch Lexi-Interact™ Drug Interactions Program )

  • 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.

  • CYP3A4 inducers: CYP3A4 inducers may decrease the levels/effects of clonazepam. Example inducers include aminoglutethimide, carbamazepine, nafcillin, nevirapine, phenobarbital, phenytoin, and rifamycins.

  • CYP3A4 inhibitors: May increase the levels/effects of clonazepam. Example inhibitors include azole antifungals, clarithromycin, diclofenac, doxycycline, erythromycin, imatinib, isoniazid, nefazodone, nicardipine, propofol, protease inhibitors, quinidine, telithromycin, and verapamil.

  • Disulfiram: Disulfiram may inhibit the metabolism of clonazepam; monitor for increased benzodiazepine effect.

  • 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.

  • Theophylline: May partially antagonize some of the effects of benzodiazepines; monitor for decreased response; may require higher doses for sedation.

  • Valproic acid: The combined use of clonazepam and valproic acid has been associated with absence seizures.

Programa Informed


Clonazepam8
Clonazepam en HD aumento de la sed y del peso (boca seca), hiperglucemia, y aumento de la osmolaridad extracelular.

  • PREGNANCY RISK FACTOR — D (show table)

  • PREGNANCY IMPLICATIONS — Clonazepam was shown to be teratogenic in some animal studies. Clonazepam crosses the placenta. Benzodiazepine use during pregnancy is associated with increased risk of congenital malformations. Nonteratogenic effects (including neonatal flaccidity, respiratory and feeding problems, and withdrawal symptoms) during the postnatal period have also been reported with benzodiazepine use. Epilepsy itself, number of medications, genetic factors, or a combination of these probably influence the teratogenicity of anticonvulsant therapy.

  • LACTATION — Enters breast milk/not recommended

  • BREAST-FEEDING CONSIDERATIONS — Clonazepam enters breast milk; clinical effects on the infant include CNS depression, respiratory depression reported (no recommendation from the AAP).

Programa Informed


Clonazepam9
Clonazepam en HD aumento de la sed y del peso (boca seca), hiperglucemia, y aumento de la osmolaridad extracelular.

  • PHARMACODYNAMICS / KINETICSOnset of action: 20-60 minutes

  • Duration: Infants and young children: 6-8 hours; Adults: 12 hours

  • Absorption: Well absorbed

  • Distribution: Adults: Vd: 1.5-4.4 L/kg

  • Protein binding: 85%

  • Metabolism: Extensively hepatic via glucuronide and sulfate conjugation

  • Half-life elimination: Children: 22-33 hours; Adults: 19-50 hours

  • Time to peak, serum: 1-3 hours; Steady-state: 5-7 days

  • Excretion: Urine (<2% as unchanged drug); metabolites excreted as glucuronide or sulfate conjugates

  • PATIENT INFORMATION — Drug may cause physical or psychological dependence; avoid abrupt discontinuation after prolonged use. Avoid alcohol and other CNS depressants. Avoid activities needing good psychomotor coordination until CNS effects are known.

Programa Informed


Benzodiazepines for chronic pain en HD aumento de la sed y del peso (boca seca), hiperglucemia, y aumento de la osmolaridad extracelular.

Programa Informed


Programa Informed en HD aumento de la sed y del peso (boca seca), hiperglucemia, y aumento de la osmolaridad extracelular.


Programa Informed en HD aumento de la sed y del peso (boca seca), hiperglucemia, y aumento de la osmolaridad extracelular.


N05C-Hipnóticos y sedantes en HD aumento de la sed y del peso (boca seca), hiperglucemia, y aumento de la osmolaridad extracelular.

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.

Programa Informed


N05B-Ansiolíticos en HD aumento de la sed y del peso (boca seca), hiperglucemia, y aumento de la osmolaridad extracelular.

Nota 1: Ketazolam (Sedotime) se considera equivalente terapéutico de Diazepam.

Programa Informed


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