Analgésicos y coadyuvantes en la enfermedad

Analgesia en pacientes con

ERC

Francisco José de la Prada Alvarez

Servicio de Nefrología

Hospital Son Dureta

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M01ANTIINFLAMATORIOS Y ANTIRREUMÁTICOS NO

ESTEROIDEOS

Ver en el grupo N02B otros analgésicos y antiinflamatorios no esteroideos disponibles en el hospital

NOMBRE

GENÉRICO

Diclofenac

Ibuprofeno

Indometacina

Isonixina

Piroxicam

PRESENTACIÓN

Amp 75 mg/3 ml

Comp 50 mg

Sup 100 mg

Jbe 100 mg/5ml

Comp 400 mg

Comp 600 mg

Sobres 200 mg

Caps 25 mg

Sup 100 mg

Sup inf 200 mg

Caps 20 mg

Comp 20 mg

VIA

IM, IV

OR

REC

OR

OR

OR

OR

OR

REC

REC

OR

OR

NOMBRE COMERCIAL

Voltaren

Dalsy jarabe

Neobrufen

Inacid, Artrinovo

Nyxin

Sasulen, Feldene 20,

Vitaxicam,

Feldene flas

Nota 1: Otros medicamentos del grupo de los AINEs como por ejemplo: Ketoprofeno ( Arcental, Fastum, Orudis ), Naproxeno

(Naprosyn), Aceclofenaco ( Airtal, Falcol, Gerbin ), Fenbufeno ( Cincopal), Flurbiprofeno ( Froben), Namebutona ( Dolsinal,, Relif ),

Tenoxicam ( Reutenox, Tilcotil ), Meloxicam (Movalis) y Tolmetin ( Artrocaptin) son medicamentos no incluidos en la Guía y se consideran equivalentes terapéuticos de los AINEs incluidos. Consultar programa de intercambio.

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N02BAnalgésicos no narcóticos y antipiréticos

Ver en grupo M01 otros analgésicos no narcóticos y antipiréticos

NOMBRE GENÉRICO

Acetilsalicilato de lisina (1)(4)

Acido Acetilsalicílico

Ketorolaco

Metamizol (Dipirona)

(Noramidopirina)

Paracetamol

Paracetamol +Codeína

PRESENTACIÓN

Sobres 1,8 g

Vial 900 mg/5 ml

Comp 500 mg

Comp 300 mg

Comp 125 mg

Comp 10 mg

Amp 30 mg/1 ml

Amp 2000 mg/5 ml

Caps 575 mg

Sup 1 g

Sup 500 mg

Comp 500 mg

Gts 100 mg/ml (2)

Sup 150 mg

Sup 250 mg

Vial 1g/100ml

Comp 300mg +15mg

Comp 650 mg + 30 mg

Com

OR

IM,IV

OR

OR

OR

OR

OR

REC

REC

IV

OR

OR

OR

IV. IM

IV, IM, OR

OR

REC

REC


Inyesprin oral forte

Inyesprin iny(4)

Ácido Acetilsalicilíco, Adiro, Aspirina

Aspirina infantil

Droal, Toradol

Nolotil, Lasain

Termalgin, Dolgesic, Gelocatil (650 mg)

Apiretal

Febrectal Lactante

Melabon Infantil

Perfalgan

Termalgin Codeína;

Gelocatil Codeina

Nota 1: 1,8 g de Acetilsalicilato de lisina=1g de Acido Acetil Salicílico.

Nota 2: gota=4 mg

Nota 3: Propacetamol es un precursor del Paracetamol. Propacetamol 1 g libera

Paracetamol 500 mg.

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Opioides

Los opiodes agonistas son aquellos que al fijarse al receptor mu dan lugar a una respuesta farmacológica, que en este caso es la eliminación del dolor.

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Opioides

Los opiodes antagonistas son aquellos que también se unen al receptor mu, pero ello no va seguido de una respuesta farmacológica, es decir, en este caso no se produciría analgesia.

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Opioides

Existe otro tipo de opioides denominados agonistasantagonistas , que son capaces de actuar como agonistas sobre un tipo de receptores y como antagonistas sobre otro tipo, por lo que producen respuestas imprevisibles.

En pacientes que reciben agonistas puros, los agonistas-antagonistas pueden precipitar reacciones de abstinencia.

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Agonistas puros

Semivida corta Semivida larga

Morfina

Petidina

Para dolor moderado-severo

Metanol

Levorfanol

Heroina

Fentanilo

Sulfentanilo

Tramadol

Oxicodona

Oximorfona

Para dolor ligero-moderado

Codeina

Dihidrocodeina

Dextropropoxifeno

Tramadol

Oxicodona

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Semivida corta

Agonistas-

Antagonistas

Agonistas parciales

Pentazosina

Nalbufina

Meperidina

Buprenorfina

Semivida larga

Butorfanol

Dezocina

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Tratamientos de rescate potenciales para el dolor intercurrente o irruptivo en pacientes con cancer

Opioides utilizados para el dolor crónico de base:

Agonistas puros preferentemente en formas de liberación retardada

– Morfina de liberación lenta

– Fentanilo via transdermica

Tratamiento de rescate: Agonistas puros en forma de liberación rápida o vias de absorción rápida:

– Morfina por via parenteral.

– Fentanilo por via transmucosa oral.

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Tratamientos de rescate potenciales para el dolor intercurrente o irruptivo en pacientes con cancer

Opioides utilizados para el dolor crónico de base:

Agonistas parciales:

– Buprenorfina de liberación transdermica.

Tratamiento de rescate:

– Agonistas parciales : buprenorfina sublingual .

– Agonistas puros :

Morfina por via parenteral.

Fentanilo por via transmucosa oral.

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DOSIS EQUIANALGESICAS ENTRE LOS DISTINTOS OPIOIDES

ADMINSTRADOS POR VIA ORAL

Morfina

Meperidina

30-60 mg

300 mg

Metadona

Tramadol

Codeina

15-20 mg

300-600 mg

400 mg

Dihidrocodeina

Hidromorfona

Levorfanol

Oxicodona

240 mg

7,5 mg

4 mg

30 mg

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Equivalent opioid doses

Drug

Morphine sulfate parenteral

Time to onset

(minutes)

Morphine sulfate oral (MSIR, Roxanol) 15 to 60

Morphine sulfate controlled release

(MS contin, Oramorph)

Codeine 10 to 30

Oxycodone (Percocet, Percodan, Tylox) 15 to 30

15 to 30 Oxycodone controlled release

(Oxycontin)

Hydromorphone (Dilaudid)

Levorphanol (Levodromoran)

15 to 30

30 to 90

Meperidine (Demerol)

Methadone (Dolophine)

10 to 45

30 to 60

Oral dose

(mg)

Parenteral dose (mg)

10 q4 hr

30 q4 hr

90 q12 hr not available

200 q4 hr

15 to 20 q4 hr

45 to 60 q12 hr

8 q4 hr

4 q6 to q8 hr

300 q2 to q3 hr

20* q6 to q12 hr

100 to 120 q4 hr not available not available

1.5-3.0 q4 hr

2 q6 to q8 hr

100 q2 to q3 hr

10 q6 hr

* A dose ratio of 1:4 (1 mg of oral methadone = 4 mg of oral morphine) is used for patients receiving less than 90 mg of morphine. Patients receiving 90 to 300 mg/day receive methadone at a ratio of 1:8. Finally, a ratio of 1:12 is used for patients receiving morphine doses greater than 300 mg/day.

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Opioid Analgesics - Initial Oral Dosing Commonly Used for

Severe Pain

Buprenorphine:

Equianalgesic Dose

– Oral: n/a

– Parenteral: 0.4 mg

– Initial Oral Dose

– Children: n/a

– Adults: n/a

Butorphanol:

Equianalgesic Dose

– Oral: n/a

– Parenteral: 2 mg


– Children: n/a

– Adults: n/a

Levorphanol:

Equianalgesic Dose

– Oral: Acute: 4 mg; Chronic: 1 mg

– Parenteral: Acute: 2 mg;

Chronic: 1 mg


– Children: 0.04 mg/kg

– Adults: 2-4 mg/kg

Meperidine:

Equianalgesic Dose

– Oral: 300 mg


–

Initial Oral Dose

– Children: Not recommended

– Adults: Not recommended

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Severe Pain

Hydromorphone:

Equianalgesic Dose

– Oral: 7.5 mg

– Parenteral: 1.5 mg



– Adults: 4-8 mg

Methadone:

Equianalgesic Dose

– Oral: 10 mg




– Adults: 5-10 mg

Morphine:

Equianalgesic Dose

– Oral: 30 mg




– Adults: 15-30 mg

Nalbuphine:

Equianalgesic Dose

– Oral: n/a



– Children: n/a

– Adults: n/a

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Severe Pain

Pentazocine:

Equianalgesic Dose

– Oral: 50 mg



– Children: n/a

– Adults: n/a

Oxymorphone:

Equianalgesic Dose

– Oral: 1 mg

– Parenteral: n/a


– Children: n/a

– Adults: n/a

From "Principles of Analgesic Use in the Treatment of Acute Pain and

Cancer Pain,"Am Pain Soc, Fifth

Ed.

Oxycodone:

Equianalgesic Dose

– Oral: 20 mg

– Parenteral: n/a



– Adults: 10-20 mg

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N02AAnalgésicos narcóticos (Opioides)


Buprenorfina

Codeína

Dihidrocodeína (Hidrocodona)

Fentanilo (2)

Metadona

Morfina cloruro

PRESENTACIÓN

Comp 0,2 mg

Amp 0,3 mg/1 ml

VIA

SL

IM, IV


Buprex CE

Comp 28 mg OR Codeisan

Comp 60 mg

Parche 2,5 mg (3)

Parche 5 mg (3)

Parche 10 mg (3)

Amp 10 mg/1 ml

Comp 5 mg

Comp 40 mg

Amp 10 mg/1 ml

(sin conservantes)

Vial 400 mg/20 ml

(vial multidosis, sin conservantes)

Amp 10 ml.

OR

TOP

TOP

TOP

SC, IM

OR

OR

SC, IV, IM

SC

IV, IM

IV, IM

Contugesic

Durogesic 25

Durogesic 50

Durogesic 100

Metasedin CE

Cloruro Mórfico Braun 1 % CE

Morfina Braun 2 % s/c CE


Morfina clorhidrato

Morfina sulfato

Morfina sulfato retard

Petidina (Meperidina)

Tramadol

Jbe 10 mg/ml

Comp 10 mg

Comp 20 mg

Comp 10 mg

Comp 30 mg

Comp 60 mg

Comp 100 mg

Amp 100 mg/2 ml

Caps 50 mg

Comp retard 200 mg

Comp retard 300 mg

Amp 100 mg/2 m

OR

OR

OR

OR

OR

OR

OR

SC, IM, IV

OR

OR

OR

SC, IM, IV

Brompton FM CE

Sevredol CE (1)

MST Continus CE

Dolantina CE

Adolonta, Tralgiol

Zytram

CE: Control de estupefacientes.

Nota 1: Comprimidos ranurados.

Nota 2: Uso restringido para tratamiento del dolor crónico.

Nota 3: Los parches de 2,5, 5 y 10 mg liberan respectivamente 25, 50 y 100 mcg/h durante 72 h.

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N02BAnalgésicos no narcóticos y antipiréticos

Ver en grupo M01 otros analgésicos no narcóticos y antipiréticos


Acetilsalicilato de lisina (1)(4)

Acido Acetilsalicílico

Ketorolaco

Metamizol (Dipirona)

(Noramidopirina)

PRESENTACIÓN

Sobres 1,8 g

Vial 900 mg/5 ml

Comp 500 mg

Comp 300 mg

Comp 125 mg

Comp 10 mg

Amp 30 mg/1 ml

Amp 2000 mg/5 ml

Caps 575 mg

Sup 1 g

Sup 500 mg

Paracetamol Comp 500 mg

Gts 100 mg/ml (2)

Sup 150 mg

Sup 250 mg

Vial 1g/100ml

Paracetamol +Codeína

Comp 300mg +15mg

Comp 650 mg + 30 mg

Com

OR

IM,IV

OR

OR

OR

OR

IV. IM

IV, IM, OR

OR

REC

REC

OR

OR

REC

REC

IV

OR

OR


Inyesprin oral forte

Inyesprin iny(4)

Ácido Acetilsalicilíco, Adiro, Aspirina

Aspirina infantil

Droal, Toradol

Nolotil, Lasain

Termalgin, Dolgesic, Gelocatil (650 mg)

Apiretal

Febrectal Lactante

Melabon Infantil

Perfalgan

Termalgin Codeína;

Gelocatil Codeina

Nota 1: 1,8 g de Acetilsalicilato de lisina=1g de Acido Acetil Salicílico.

Nota 2: gota=4 mg

Nota 3: Propacetamol es un precursor del Paracetamol. Propacetamol 1 g libera

Paracetamol 500 mg.

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Codeina

Opioide estructuralmente relacionada con la morfina.

Es un alcaloide presente en la

Papaver somniferum.

Estructuralmente es la metilmorfina y existen estudios que sugieren que sus efectos son, al menos en parte, consecuencia de la desmetilación en el organismo a morfina que sería el principio activo.

Sus propiedades analgésicas son similares a las de la morfina pero su potencia es sólo un 12%.

La codeína se comporta como un agonista opioide puro de los receptores Mu y, por esta razón, su mecanismo de acción y los efectos derivados de este son, en principio, similares a los de la morfina

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Codeina

Los opioides que actúan sobre el receptor mu aminoran la transmisión en la médula espinal, mediante una inhibición relacionada con la dosis, de la actividad del tracto neural.

En los ganglios basales del cerebro, los opioides activan el sistema inhibidor descendente, que limita la transmisión del dolor a la altura de la médula espinal.

Los opioides también producen cambios en el cerebro, lo que provoca una alteración de las respuestas emocionales y aminoran en gran medida la percepción del dolor.

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Properties of opioid receptors

Mu

Mu1

Supraspinal analgesia

Bradycardia

Sedation

Mu2

Respiratory depression

Euphoria

Physical dependence

Delta

Kappa

Spinal analgesia

Respiratory depression

Spinal Analgesia

Respiratory depression

Sedation

Sigma

Dysphoria, delirium

Hallucinations

Tachycardia, hypertension

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Codeina

DOSING: ADULTS or ELDERLY

Doses >1.5 mg/kg body weight are not recommended.

Pain management (analgesic):

Oral, regular release: 30 mg every 4-6 hours as needed ; patients with prior opiate exposure may require higher initial doses. Usual range: 15-120 mg every 4-6 hours as needed

Oral, controlled release formulation (Codeine Contin®, not available in

U.S.): 50-300 mg every 12 hours.

I.M., SubQ: 30 mg every 4-6 hours as needed; patients with prior opiate exposure may require higher initial doses. Usual range: 15-120 mg every 4-6 hours as needed; more frequent dosing may be needed

Cough (antitussive): Oral (for nonproductive cough): 10-20 mg/dose every 4-6 hours as needed; maximum: 120 mg/day

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Codeina

DOSING: PEDIATRIC —

Analgesic: Oral, I.M., SubQ:

– Children: 0.5-1 mg/kg/dose every 4-6 hours as needed; maximum: 60 mg/dose

Antitussive: Oral (for nonproductive cough):

– Children: 1-1.5 mg/kg/day in divided doses every 4-6 hours as needed:

– Alternative dose according to age:

2-6 years: 2.5-5 mg every 4-6 hours as needed; maximum: 30 mg/day

6-12 years: 5-10 mg every 4-6 hours as needed; maximum: 60 mg/day

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Codeina

DOSING: HEPATIC IMPAIRMENT —

Dosing adjustment is probably necessary in hepatic insufficiency.

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Codeina

Dosis de carga

Dosis de manteni miento

FG > 50 ml/min

FG 10-50 ml/min

FG < 10 ml/min

Dosis suplemta ria tras

HD

DPCA

100 % 75% 50%

TSCR

Descono

-cida

Desonocida

75%

Vida media de eliminación prolongada en pacientes en diálisis.

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Codeina

ADVERSE REACTIONS SIGNIFICANT

Frequency not defined: AST/ALT increased

>10%:

Central nervous system: Somnolencia

Gastrointestinal: Estreñimiento

1% to 10%:

Cardiovascular: Tachycardia or bradycardia, hypotension

Central nervous system: Dizziness, lightheadedness, false feeling of well being, malaise, headache, restlessness, paradoxical CNS stimulation, confusion

Dermatologic: Rash, urticaria

Gastrointestinal: Dry mouth, anorexia, nausea, vomiting

Genitourinary: Urination decreased, ureteral spasm

Hepatic: LFTs increased

Local: Burning at injection site

Neuromuscular & skeletal: Weakness

Ocular: Blurred vision

Respiratory: Dyspnea

Miscellaneous: Histamine release

<1% (Limited to important or life-threatening): Convulsions, hallucinations, insomnia, mental depression, nightmares

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Codeina

DRUG INTERACTIONS — Substrate of CYP2D6

(major), 3A4 (minor); Inhibits CYP2D6 (weak)

CYP2D6 inhibitors: May decrease the effects of codeine.

Example inhibitors include chlorpromazine, delavirdine, fluoxetine, miconazole, paroxetine, pergolide, quinidine, quinine, ritonavir, and ropinirole.

Decreased effect with cigarette smoking

Increased toxicity: CNS depressants, phenothiazines,

TCAs, other narcotic analgesics, guanabenz, MAO inhibitors, neuromuscular blockers

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Codeina

Embarazo y Lactancia.

– Contraindicado.

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Codeina

REFERENCE RANGE —

– Therapeutic: Not established;

– Toxic: >1.1 mcg/mL

Sobredosis:

– Symptoms include CNS and respiratory depression, gastrointestinal cramping, and constipation.

– Treatment includes naloxone 2 mg I.V

. (0.01 mg/kg for children), with repeat administration as necessary, up to a total of 10 mg.

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Codeina

PHARMACODYNAMICS / KINETICS

Onset of action: Oral: 0.5-1 hour ; I.M.: 10-30 minutes

Peak effect: Oral: 1-1.5 hours ; I.M.: 0.5-1 hour

Duration: 4-6 hours

Absorption: Oral: Adequate

Las propiedades farmacocinéticas de la codeína le confieren una aceptable biodisponibilidad oral (50%), lo que permite su administración (casi exclusiva) por esta vía.

Distribution: Crosses placenta; enters breast milk

Protein binding: 7%

Metabolism: Hepatic to morphine (active) 10% de codeina se metaboliza a morfina .

Half-life elimination: 2.5-3.5 hours .

Su baja semivida de eliminación obliga a la administración cada 4-6 h, lo que ha llevado a la comercialización de algunos derivados, como la dihidrocodeína

, en forma de preparados de liberación sostenida , especialmente indicadas en situaciones de dolor crónico

Excretion: Urine (3% to 16% as unchanged drug, norcodeine, and free and conjugated morphine)

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Buprenorfina

Codeína

Dihidrocodeína

(Hidrocodona)

Fentanilo (2)

PRESENTACIÓN

Comp 0,2 mg

Amp 0,3 mg/1 ml

Comp 28 mg

VIA

SL

IM, IV

OR


Buprex CE

Codeisan

Comp 60 mg OR Contugesic

Metadona

Morfina cloruro

Morfina clorhidrato

Morfina sulfato



Tramadol

Parche 2,5 mg (3)

Parche 5 mg (3)

Parche 10 mg (3)

Amp 10 mg/1 ml

Comp 5 mg

Comp 40 mg

Amp 10 mg/1 ml

(sin conservantes)

Vial 400 mg/20 ml


Amp 10 ml.

Jbe 10 mg/ml

Comp 10 mg

Comp 20 mg

Comp 10 mg

Comp 30 mg

Comp 60 mg

Comp 100 mg

Amp 100 mg/2 ml

Caps 50 mg

Comp retard 200 mg

Comp retard 300 mg

Amp 100 mg/2 m

TOP

TOP

TOP

SC, IM

OR

OR

SC, IV, IM

SC

IV, IM

IV, IM

OR

OR

OR

OR

OR

OR

OR

SC, IM, IV

OR

OR

OR

SC, IM, IV

Durogesic 25

Durogesic 50

Durogesic 100

Metasedin CE

Cloruro Mórfico Braun 1 % CE



Brompton FM CE

Sevredol CE (1)

MST Continus CE

Dolantina CE


Zytram





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Tramadol

Análogo sintético de codeina.

Analgésico no narcótico de acción periférico y central.

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Tramadol

Mecanismo de acción:

– Inhibición de la recaptación de NA y serotonina por las celulas nerviosas.

– Actúa sobre los receptores opioides Mu.

37


NOMBRE

GENÉRICO

Tramadol

PRESENTACIÓN VIA NOMBRE

COMERCIAL

Caps 50 mg

Comp retard 200 mg

Comp retard 300 mg

Amp 100 mg/2 ml

OR

OR

OR

SC,

IM,

IV


Zytram

38

Tramadol

PRESENTACIONES:

– Adolonta amp de 100 mg en 2 ml

– Tralgiol amp de 100 mg en 2 ml

ADMINISTRACION:

– INYECCION IV DIRECTA : SI

– Administrar lentamente.

– INFUSION INTERMITENTE : SI

Diluir la dosis prescrita en 50-100 ml de SF o SG5%. Administrar en 30-60 minutos.

– INFUSION CONTINUA : SI

Diluir la dosis prescrita, ejemplo 2 amp en 500 ml de SF o SG5%. El ritmo de infusión adecuado es de

1020 gotas/min ó 30-60 ml/h que equivalen a 12-44 mg/h de Tramadol.

– INYECCION IM : SI

– INYECCION SUBCUTANEA : SI

SUEROS COMPATIBLES : SF, SG5%.

OBSERVACIONES:

– La dosificacion máxima diaria en adultos por cualquier vía es de 400 mg/día.

– También se dispone de estudios de administración vía epidural.

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Tramadol

DOSING: ADULTS — Moderate-to-severe chronic pain: Oral:

– Caps 50 mg

50-100 mg every 4-6 hours (not to exceed 400 mg/day)

For patients not requiring rapid onset of effect, tolerability may be improved by starting dose at 25 mg/day and titrating dose by 25 mg every 3 days, until reaching 25 mg 4 times/day. Dose may then be increased by 50 mg every 3 days as tolerated, to reach dose of 50 mg 4 times/day.

– Comp retard 200 mg. Comp retard 300 mg

100 mg once daily; titrate every 5 days (maximum: 300 mg/day)

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Tramadol

DOSING: ELDERLY — Oral: >75 years:

– Caps 50 mg

50 mg every 6 hours (not to exceed 300 mg/day

– Comp retard 200 mg. Comp retard 300 mg

100 mg once daily; titrate every 5 days (maximum:

300 mg/day). Use with great caution.

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Tramadol

DOSING: RENAL IMPAIRMENT

– Clcr <30 mL/minute: 50 -100 mg dose every 12 hours

(maximum: 200 mg/day).

– Should not be used in patients with Clcr < 30 mL/minute.

DOSING: HEPATIC IMPAIRMENT

– Cirrhosis: Recommended dose: 50 mg every 12 hours.

– Should not be used in patients with severe (Child-

Pugh Class C) hepatic dysfunction.

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43

Tramadol

Efectos secundarios:

>10%:

Cardiovascular: Flushing (8% to 16%)

Central nervous system: mareos (16% to

33%), headache (8% to 32%), insomnia (7% to

11%), somnolence (7% to 25%)

Dermatologic: Pruritus (6% to 12%)

Gastrointestinal: Constipation (12% to 46%), nausea (15% to 40%)

Neuromuscular & skeletal: Weakness (4% to

12%)

44

Tramadol

Efectos secundarios:

1% to 10%:

Cardiovascular: Chest pain (1% to <5%), postural hypotension (2% to 5%), vasodilation (1% to <5%)

Central nervous system: Agitation, anxiety (1% to <5%), confusion (1% to <5%), coordination impaired (1% to <5%), depression (1% to <5%), emotional lability, euphoria, hallucinations, hypoesthesia, lethargy, malaise, nervousness (1% to <5%), pain, pyrexia, restlessness

Dermatologic: Dermatitis, rash

Endocrine & metabolic: Hot flashes (2% to 9%), menopausal symptoms (1% to

<5%)

Gastrointestinal: Abdominal pain, anorexia (<6%), diarrhea (5% to 10%), dry mouth

(5% to 10%), dyspepsia, flatulence, vomiting (5% to 9%), weight loss

Genitourinary: Urinary frequency (1% to <5%), urinary retention (1% to <5%), urinary tract infection (1% to <5%)

Neuromuscular & skeletal: Arthralgia (1% to <5%), hypertonia (1% to <5%), rigors

(<4%), paresthesia (1% to <5%), spasticity (1% to <5%), tremor (1% to <5%), creatinine phosphokinase increased

Ocular: Blurred vision (1% to <5%), miosis (1% to <5%)

Respiratory: Bronchitis (1% to <5%), cough (1% to <5%), dyspnea (1% to <5%), pharyngitis (1% to <5%), rhinorrhea (1% to <5%), sinusitis (1% to <5%)

Miscellaneous: Diaphoresis (2% to 6%), flu-like syndrome (<2%)

45

Tramadol

El tramadol presenta una baja o nula capacidad para causar cuadros de farmacodependencia.

Epileptógeno en situaciones con disminución del umbral de epilepsia

(uremia , tumores cerebrales)

46

Tramadol

DRUG INTERACTIONS — Substrate of CYP2B6 (minor), 2D6 (major), 3A4 (minor)

Carbamazepine: Tramadol metabolism is increased by carbamazepine. Avoid concurrent use; increases risk of seizures.

Cyclobenzaprine: May enhance the neuroexcitatory and/or seizure-potentiating effect of tramadol.

CYP2D6 inhibitors: May decrease the effects of tramadol. Example inhibitors include chlorpromazine, delavirdine, fluoxetine, miconazole, paroxetine, pergolide, quinidine, quinine, ritonavir, and ropinirole.

Ethanol: Tramadol may enhance the CNS depressant effect of ethanol.

MAO inhibitors: May increase the neuroexcitatory effects or risk of seizures .

Examples of inhibitors include isocarboxazid, linezolid, phenelzine, selegiline, and tranylcypromine.

Naloxone: May increase the risk of seizures (if administered in tramadol overdose).

Quinidine: May increase the tramadol serum concentrations and decrease serum concentrations of M1

SSRIs: May increase the neuroexcitatory effects or risk of seizures with tramadol. Examples of SSRIs include citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline.

Serotonin modulators: May enhance the adverse/toxic effects of tramadol. The development of serotonin syndrome may occur.

Sibutramine: May enhance the serotonergic effects of tramadol. Avoid concurrent use.

Tricyclic antidepressants: May increase the risk of seizures.

47

Tramadol

Embarazo y lactancia.

– Contraindicado.

– Atraviesa la placenta.

– Aparece en la leche materna.

48

Tramadol

Rango terapéutico:

– 100-300 ng/mL

49

Tramadol

Sobredosis:

– Clínica: Depresión del SNC, depresion respiratoria, letargia, coma, miosis, convulsiones, fallo cardíaco y muerte.

– Tratamiento sintomático.

– La administración de naloxona no revierte completamente los efectos del tramadol, y puede aumentar el riesgo de convulsiones.

– No se elimina mediante Hemodiálisis.

50

Tramadol

Farmacocinética:

– Inicio de acción en 1 horas.

– Duración de acción 9 horas.

– Absorción oral rápida y completa.

– VD 2,5-3 l/kg.

– Unión aproteinas plasmáticas: 20%.

– Metabolismo: Hepatico (demethylation, glucuronidation, and sulfation)

Metabolito activo (O-desmethyl tramadol)

Vida media de eliminación: Prolongada en ancianos, daño hepático y renal (en esta última X2).

– Tramadol: 6-8 horas.(obliga a su administración varias veces al día).

– O-desmethyl tramadol: 7-9 horas.

Excreccion: Urinaria (30% como fármaco; 60% como metabolito)

51

Tramadol

Dosis de carga


FG > 50 ml/min

FG 10-50 ml/min

FG < 10 ml/min


HD

DPCA TSCR

Clcr <30 mL/minute:

50

-100 mg dose every 12 hours (maximum: 200 mg/day).

Should not be used in patients with Clcr < 30 mL/minute.

52

53

Oxicodona

Agonista puro .

Se comercializa como medicamento de liberación controlada ( OxyContin

) o de liberación rápida (

OxyIR,

OxyNorm ).

– El OxyContin se presenta en comprimidos de 10, 20, 40 y 80 mg, y debido a su mecanismo de liberación lenta, es efectivo durante unas doce horas.

– Oxynorm caps. 5, 10 y 20 mg

– OXYNORM Concentrado 10 mg/ml solución oral

– OXYNORM Líquido 1 mg/ 1 ml sol.oral

54

Oxicodona

DOSING: ADULTS — Management of pain: Oral:

Regular or immediate release formulations: 2.5-5 mg every 6 hours

Controlled release:

Opioid naive (not currently on opioid): 10 mg every 12 hours

Currently on opioid/ASA or acetaminophen or NSAID combination:

1-5 tablets: 10-20 mg every 12 hours



May continue the nonopioid as a separate drug.

Currently on opioids: Use standard conversion chart to convert daily dose to oxycodone equivalent. Divide daily dose in 2 (for every

12-hour dosing) and round down to nearest dosage form.

Note: 80 mg or 160 mg tablets are for use only in opioid-tolerant patients. Special safety considerations must be addressed when converting to OxyContin® doses 160 mg every 12 hours. Dietary caution must be taken when patients are initially titrated to 160 mg tablets.

55

Oxicodona

DOSING: PEDIATRIC — Oral: Regular or immediate release formulations:

– 6-12 years: 1.25 mg every 6 hours as needed

– >12 years: 2.5 mg every 6 hours as needed

56

Oxicodona

DOSING: HEPATIC IMPAIRMENT —

Reduce dosage in patients with severe liver disease.

DOSING: RENAL IMPAIRMENT –

Se prolonga la vida media de eliminación.

Relacionado con casos de GNF fibrilar

57

Oxicodona


>10%:

Central nervous system: Fatigue, drowsiness, dizziness, somnolence

Dermatologic: Pruritus

Gastrointestinal: Nausea, vomiting, constipation


1% to 10%:

Cardiovascular: Postural hypotension

Central nervous system: Nervousness, headache, restlessness, malaise, confusion, anxiety, abnormal dreams, euphoria, thought abnormalities

Dermatologic: Rash

Gastrointestinal: Anorexia, stomach cramps, xerostomia, biliary spasm, abdominal pain, dyspepsia, gastritis

Genitourinary: Ureteral spasms, decreased urination

Local: Pain at injection site

Respiratory: Dyspnea, hiccups

Miscellaneous: Diaphoresis

<1% (Limited to important or life-threatening): Anaphylaxis, anaphylactoid reaction, dysphagia, exfoliative dermatitis, hallucinations, histamine release, hyponatremia, ileus, intracranial pressure increased, mental depression, paradoxical CNS stimulation, paralytic ileus, physical and psychological dependence, SIADH, syncope, urinary retention, urticaria, vasodilation, withdrawal syndrome (may include seizure)

Note: Deaths due to overdose have been reported due to misuse/abuse after crushing the sustained release tablets.

58

Oxicodona

CONTRAINDICATIONS —

Hypersensitivity to oxycodone or any component of the formulation;

Significant respiratory depression; hypercarbia; acute or severe bronchial asthma;

OxyContin® is also contraindicated in paralytic ileus (known or suspected); pregnancy

(prolonged use or high doses at term)

59

Oxicodona

Use with caution in the elderly, debilitated, severe hepatic or renal function.

Hemodynamic effects (hypotension, orthostasis) may be exaggerated in patients with hypovolemia, concurrent vasodilating drugs, or in patients with head injury .

Respiratory depressant effects and capacity to elevate CSF pressure may be exaggerated in presence of head injury, other intracranial lesion, or pre-existing intracranial pressure. Some preparations contain sulfites which may cause allergic reactions.

60

Oxicodona

DRUG INTERACTIONS — Substrate of

CYP2D6 (major)

CNS depressants, MAO inhibitors, general anesthetics, and tricyclic antidepressants: May potentiate the effects of opiate agonists; dextroamphetamine may enhance the analgesic effect of opiate agonists

CYP2D6 inhibitors: May decrease the effects of oxycodone. Example inhibitors include chlorpromazine, delavirdine, fluoxetine, miconazole, paroxetine, pergolide, quinidine, quinine, ritonavir, and ropinirole.

61

Oxicodona

Embarazo:

– Contraindicado.

Lactancia:

– Pasa a la leche materna. Usar con precaución.

62

Oxicodona


Onset of action: 10-15 minutes.

Peak effect: 0.5-1 hour

Duration: 3-6 hours;

– Controlled release: 12 hours

Metabolism: Hepatic (noroxycodona y oxymorfona)

Half-life elimination: 2-3 hours

Excretion: Urine (10% como fármaco)

63

Oxicodona

Dosis de carga


FG > 50 ml/min

FG 10-50 ml/min

FG < 10 ml/min


HD

DPCA TSCR

64

65


NOMBRE

GENÉRICO

PRESENTACIÓN VIA NOMBRE

COMERCIAL

Fentanilo (2) Parche 2,5 mg (3)

Parche 5 mg (3)

Parche 10 mg (3)

TOP

TOP

TOP

Durogesic 25

Durogesic 50

Durogesic 100

Actiq®: 200 mcg, 400 mcg, 600 mcg, 800 mcg, 1200 mcg, 1600 mcg




66

Fentanilo

Mecanismo de acción: Agonistas de los tres receptores opioides.

Se caracteriza por su elevada potencia farmacológica , muy por encima de la morfina, su elevada liposolubilidad , y su escasa biodisponibilidad tras la administración oral .

Inidicaciones:

– Parche transdérmico (Duragesic®): Tratamiento del dolor crónico moderado o severo.

– Transmucosal (Actiq®): Tratamiento del dolor irruptivo. (evita el primer paso hepático)

67

Fentanilo

Chronic pain management:

– Dosis inicial 25 mcg/h si el paciente no toma morfina o toma menos de 90 mg/dia.

68

Fentanilo

Dose conversion guidelines for transdermal fentanyl 1.

Recommended Initial Duragesic® Dose Based Upon Daily Oral

Morphine Dose1

– 60-134 mg morphine oral/day = 25 mcg/hour Duragesic®












69

Dosing Conversion Guidelines1,2

Morphine (I.M./I.V.):

10-22 mg/day: recommended fentanyl transdermal dose: 25 mcg/hour




Oxycodone (oral):


67.5-112 mg/day: recommended fentanyl transdermal dose: 50 mcg/hour



Oxycodone (I.M./I.V.):





Codeine (oral):





70


Hydromorphone (oral):





Hydromorphone (I.M./I.V.):

1.5-3.4 mg/day: recommended fentanyl transdermal dose: 25 mcg/hour




Meperidine (I.M.):





71


Methadone (oral):





Methadone (I.M.):





1The table should NOT be used to convert from transdermal fentanyl (eg,

Duragesic®) to other opioid analgesics. Rather, following removal of the patch, titrate the dose of the new opioid until adequate analgesia is achieved.

72

Fentanilo

Breakthrough cancer pain: Transmucosal:

Actiq® dosing should be individually titrated to provide adequate analgesia with minimal side effects. For patients who are tolerant to and currently receiving opioid therapy for persistent cancer pain. Initial starting dose: 200 mcg ; the second dose may be started 15 minutes after completion of the first dose. Consumption should be limited to 4 units/day or less . Patients needing more than 4 units/day should have the dose of their long-term opioid re-evaluated.

73

Fentanilo

DOSING: PEDIATRIC

– Breakthrough cancer pain: Children 16 years:

Transmucosal: Refer to adult dosing.

– Chronic pain management: Children 2 years (opioidtolerant patients): Transdermal patch: Refer to adult dosing.

74

Fentanilo

DOSING: ELDERLY —

– Elderly have been found to be twice as sensitive as younger patients to the effects of fentanyl .

– A wide range of doses may be used. When choosing a dose, take into consideration the following patient factors: age, weight, physical status, underlying disease states, other drugs used, type of anesthesia used, and the surgical procedure to be performed.

– Transmucosal: Dose should be reduced to 2.5-5 mcg/kg . Suck on lozenge vigorously approximately

20-40 minutes before the start of procedure.

75

Fentanilo

Transdermal patch (eg, Duragesic®):

– Apply to nonirritated and nonirradiated skin , such as chest, back, flank, or upper arm.

– Do not shave skin; hair at application site should be clipped .

– Prior to application, clean site with clear water and allow to dry completely.

– Do not use damaged or cut patches ; a rapid release of fentanyl and increased systemic absorption may occur. Firmly press in place and hold for 30 seconds.

– Change patch every 72 hours.

– Do not use soap, alcohol, or other solvents to remove transdermal gel if it accidentally touches skin; use copious amounts of water.

– Avoid exposing application site to external heat sources (eg, heating pad, electric blanket, heat lamp, hot tub).

76

Fentanilo

Transmucosal:

Foil overwrap should be removed just prior to administration.

Place the unit in mouth and allow it to dissolve. Do not chew . Actiq® units may be moved from one side of the mouth to the other.

The unit should be consumed over a period of 15 minutes . Unit should be removed after it is consumed or if patient has achieved an adequate response and/or shows signs of respiratory depression.

For patients who have received transmucosal product within 6-12 hours, it is recommended that if other narcotics are required, they should be used at starting doses 1/4 to 1/3 those usually recommended.

77

Fentanilo


>10%:

Cardiovascular: Hypotension, bradycardia

Central nervous system: CNS depression, confusion, drowsiness, sedation

Gastrointestinal: Nausea, vomiting, constipation, xerostomia

Local: Application-site reaction (iontophoretic system

14%)

Neuromuscular & skeletal: Chest wall rigidity (high dose

I.V.), weakness

Ocular: Miosis

Respiratory: Respiratory depression

Miscellaneous: Diaphoresis

78

Fentanilo


1% to 10%:

Cardiovascular: Cardiac arrhythmia, edema, orthostatic hypotension, hypertension, syncope, tachycardia

Central nervous system: Abnormal dreams, abnormal thinking, agitation, amnesia, anxiety, dizziness, euphoria, fatigue, fever, hallucinations, headache, insomnia, nervousness, paranoid reaction

Dermatologic: Erythema, papules, pruritus (iontophoretic system 6%), rash

Gastrointestinal: Abdominal pain, anorexia, biliary tract spasm, diarrhea, dyspepsia, flatulence, ileus

Genitourinary: Urinary retention (iontophoretic transdermal system 3%)

Hematologic: Anemia

Neuromuscular & skeletal: Abnormal coordination, abnormal gait, back pain, paresthesia, rigors, tremor

Respiratory: Apnea, bronchitis, dyspnea, hemoptysis, hypoxia, pharyngitis, rhinitis, sinusitis, upper respiratory infection

Miscellaneous: Hiccups, flu-like syndrome, speech disorder

<1% (Limited to important or life-threatening): Amblyopia, anorgasmia, aphasia, bradycardia, bronchospasm, circulatory depression, CNS excitation or delirium, convulsions, dental caries

(Actiq®), depersonalization, dysesthesia, ejaculatory difficulty, exfoliative dermatitis, gum line erosion (Actiq®), hyper-/hypotonia, laryngospasm, paradoxical dizziness, physical and psychological dependence with prolonged use, stertorous breathing, stupor, tachycardia, tooth loss (Actiq®), urinary tract spasm, urticaria, vertigo

79

Fentanilo

CONTRAINDICATIONS — Hypersensitivity to fentanyl or any component of the formulation; increased intracranial pressure; severe respiratory disease or depression including acute asthma

(unless patient is mechanically ventilated); paralytic ileus; severe liver or renal insufficiency ; pregnancy (prolonged use or high doses near term)

Transmucosal lozenges (Actiq®) or transdermal patches (eg,

Duragesic®) must not be used in patients who are not opioid tolerant. Patients are considered opioid-tolerant if they are taking at least 60 mg morphine/day, 30 mg oral oxycodone/day, 8 mg oral hydromorphone/day, 25 mcg transdermal fentanyl/hour, or an equivalent dose of another opioid for 1 week.

Transdermal patches are not for use in acute pain, mild pain, intermittent pain, or postoperative pain management.

80

Fentanilo

Transdermal patches (eg, Duragesic®):

Serious or life-threatening hypoventilation may occur , even in opioid-tolerant patients.

Serum fentanyl concentrations may increase approximately onethird for patients with a body temperature of 40ºC secondary to a temperature-dependent increase in fentanyl release from the patch and increased skin permeability .

Avoid exposure of application site to direct external heat sources.

Patients who experience adverse reactions should be monitored for at least 24 hours after removal of the patch. Transdermal patch does not contain any metal-based compounds; the printed ink used to indicate strength on the outer surface of the patch does contain titanium dioxide but the amount is minimal; adverse events have not been reported while wearing during an MRI.

Safety and efficacy of transdermal patch have been limited to children 2 years of age who are opioid tolerant.

81

Fentanilo

Actiq®:

For patients who have received transmucosal product within 6-12 hours, it is recommended that if other narcotics are required, they should be used at starting doses 1/4 to 1/3 those usually recommended.

Actiq® preparations contain an amount of medication that can be fatal to children . Keep all units out of the reach of children and discard any open units properly. Patients and caregivers should be counseled on the dangers to children including the risk of exposure to partially-consumed units. Safety and efficacy have not been established in children <16 years of age.

82

Fentanilo

DRUG INTERACTIONS

— Substrate of CYP3A4 (major); Inhibits CYP3A4 (weak)

Antipsychotic agents (phenothiazines): May enhance the hypotensive effect of analgesics (narcotic).

CNS depressants : Increased sedation with CNS depressants.;

CYP3A4 inhibitors: May increase the levels/effects of fentanyl. Potentially fatal respiratory depression may occur when a potent inhibitor is used in a patient receiving chronic fentanyl (eg, transdermal patch). Example inhibitors include azole antifungals, clarithromycin, diclofenac, doxycycline, erythromycin, imatinib, isoniazid, nefazodone, nicardipine, propofol, protease inhibitors, quinidine, telithromycin, and verapamil.

MAO inhibitors: Not recommended to use Actiq® within 14 days . Severe and unpredictable potentiation by MAO inhibitors has been reported with opioid analgesics.

Pegvisomant: Analgesics (narcotic) may diminish the therapeutic effect of pegvisomant.

Protease inhibitors: May decrease the metabolism, via CYP isoenzymes, of fentanyl.

Selective serotonin reuptake inhibitors (SSRIs): Analgesics (narcotic) may enhance the serotonergic effect of SSRIs. This may cause serotonin syndrome.

Sibutramine: Fentanyl may enhance the serotonergic effect of sibutramine.

83

Fentanilo

Embarazo:

– Su uso de forma crónica puede producir dependencia en el recien nacido.

– De forma aguda cruza la placenta pero se ha utilizado de forma segura durante el trabajo del parto.

Lactancia: Pasa a la leche materna. No recomendado.

84

Fentanilo

MONITORING PARAMETERS — Control de la función respiratoria y cardiovascular,

Tensión arterial y frecuencia cardíaca.

Transdermal patch: Monitorizar a las 24 horas de la aplicación del parche.

85

Fentanilo

Sobredosis:

Síntomas: depresión del SNC, depresión respiratoria, miosis.

Tratamiento:

– De soporte.

– Naloxone, 2 mg I.V

. with repeat administration as necessary up to a total of 10 mg, can also be used to reverse toxic effects of the opiate.

Los pacientes que presentan reacciones adversas durante el uso del parche transdérmico deben ser monitorizados durante

24 horas tras la retirada del parche .

86

Fentanilo

Farmacocinética:

Onset of action:

– Transmucosal: 5-15 minutes

– Peak effect: Transmucosal: Analgesic: 20-30 minutes

– Time to peak: Transdermal patch: 24-72 hours

Absorption:

Transmucosal: Rapid, ~25% from the buccal mucosa; 75% swallowed with saliva and slowly absorbed from GI tract

Actiq® contains 2 g sugar per unit.

Distribution: Highly lipophilic, redistributes into muscle and fat

Metabolism: Hepatic, primarily via CYP3A4

Bioavailability: Transmucosal: ~50% (range: 36% to 71%)

Half-life elimination: 2-4 hours

Transdermal patch: 17 hours (half-life is influenced by absorption rate)

Transmucosal: 6.6 hours (range: 5-15 hours)

Excretion: Urine (primarily as metabolites, 10% as unchanged drug)

87

Fentanilo

Dosis de carga


FG > 50 ml/min

FG 10-50 ml/min

FG < 10 ml/min


HD

DPCA

100% 75% 50%

TSCR

No aplicable

No aplicable

No aplicable

Su aclaramiento se reduce en pacientes con ERC avanzada, pudiendo aparecer sedación prologada y depresion respiratoria en pacientes con ERC avanzada.

(sobre todo en administración parenteral).

88

89

Morfina

Alcaloide de la Papaver somniferum.

Sigue constituyendo el analgésico más potente del que se dispone para tratar todo tipo de dolores agudos y muchos de los crónicos.

Modelo de agonista puro de los receptores opioides. Actúa activando los tres receptores opioides.

90



Morfina cloruro

Morfina clorhidrato

Morfina sulfato


PRESENTACIÓN

VIA

Amp 10 mg/1 ml

(sin conservantes)

Vial 400 mg/20 ml


Amp 10 ml.

SC, IV,

IM

SC

IV, IM

IV, IM

Jbe 10 mg/ml

Comp 10 mg

Comp 20 mg

Comp 10 mg

Comp 30 mg

Comp 60 mg

Comp 100 mg

OR

OR

OR

OR

OR

OR

OR


Cloruro Mórfico Braun 1 %

CE



Brompton FM CE

Sevredol CE (1)

MST Continus CE





91

Morfina

ADMINISTRACION:

INYECCION IV DIRECTA : SI

– Administrar la dosis precrita muy lentamente . Diluir la dosis en 4-5 ml de agua p.i. antes de administrar. La administración rápida aumenta el riesgo de aparición de efectos secundarios (depresión respiratoria, apnea, hipotensión).

INFUSION INTERMITENTE : SI

– Diluir la dosis prescrita en 50-100 ml de SF ó SG5%.

INFUSION CONTINUA : SI

– Diluir la dosis prescrita en 500-1000 ml de SF ó SG5%.

INYECCION IM : SI

– Esta vía es preferible sobre la vía subcutánea cuando deben administrarse dosis repetidas. Aunque la absorción es más irregular y la duración de acción menor que si se usa la vía sc.

INYECCION SUBCUTANEA : SI

– La absorción es más lenta que por vía IM, pero la analgesia suele ser más constante y duradera .

SUEROS COMPATIBLES : SF, SG5%

OBSERVACIONES :

– El preparado sin conservante también se puede administrar via epidural e intratecal.

92

Morfina

DOSING: ADULTS —

Acute pain (moderate-to-severe):

Oral: Prompt release formulations: Opiate-naive: Initial: 10 mg every 3 to

4 hours as needed; patients with prior opiate exposure may require higher initial doses: usual dosage range: 10-30 mg every 3-4 hours as needed

I.M., SubQ:.

Initial: Opiate-naive: 5-10 mg every 3-4 hours as needed ; patients with prior opiate exposure may require higher initial doses; usual dosage range:

5-20 mg every 3-4 hours as needed

Rectal: 10-20 mg every 3-4 hours

I.V.: Initial: Opiate-naive: 2.5-5 mg every 3 to 4 hours ; patients with prior opiate exposure may require higher initial doses. Note: Repeated doses

(up to every 5 minutes if needed) in small increments (eg, 1-4 mg) may be preferred to larger and less frequent doses.

93

94

Morfina


– Acute pain (moderate-to-severe): Children >6 months and <50 kg:

Oral (prompt release): 0.15-0.3 mg/kg every 3-4 hours as needed

I.M.: 0.1 mg/kg every 3-4 hours as needed

I.V.: 0.05-0.1 mg/kg every 3-4 hours as needed

I.V. infusion: Range: 10-30 mcg/kg/hour

– Sedation/analgesia for procedures: Adolescents >12 years: I.V.: 3-4 mg and repeat in 5 minutes if necessary

95

Morfina

DOSING: ELDERLY — Refer to adult dosing. Use with caution; may require reduced dosage in the elderly and debilitated patients .


– Clcr 10-50 mL/minute: Administer 75% of normal dose.

– Clcr <10 mL/minute: Administer 50% of normal dose.

DOSING: HEPATIC IMPAIRMENT — Unchanged in mild liver disease; substantial extrahepatic metabolism may occur. Excessive sedation may occur in cirrhosis.

96

Morfina

ADVERSE REACTIONS SIGNIFICANT —

>10%:

Cardiovascular: Palpitations, hypotension, bradycardia

Central nervous system: Somnolencia (48%, tolerance usually develops to drowsiness with regular dosing for 1-2 weeks); mareos (20%), confusion , headache (following epidural or intrathecal use)

Dermatologic: Pruritus (may be secondary to histamine release)

Note: Pruritus may be dose-related, but not confined to the site of administration.

Gastrointestinal: Nausea (28%, tolerance usually develops to nausea and vomiting with chronic use); constipation (40%, tolerance develops very slowly if at all); xerostomia (78%)

Genitourinary: Urinary retention (16%; may be prolonged, up to 20 hours, following epidural or intrathecal use)



Miscellaneous: Histamine release

97

Morfina

DRUG INTERACTIONS — Substrate of CYP2D6 (minor)

Antipsychotic agents: May increase hypotensive effects of morphine; monitor.

CNS depressants : May increase the effects/toxicity of morphine; monitor.

MAO inhibitors : May increase the effects/toxicity of morphine; some manufacturers recommend avoiding use within 14 days of MAO inhibitors

Pegvisomant: Therapeutic efficacy may be decreased by concomitant opiates, possibly requiring dosage adjustment of pegvisomant.

Rifamycin derivatives: May decrease levels/effects of morphine; monitor.

Selective serotonin reuptake inhibitors (SSRIs) and meperidine:

Serotonergic effects may be additive, leading to serotonin syndrome.

98

Morfina

PREGNANCY IMPLICATIONS — Morphine crosses the placenta.

The frequency of congenital malformations has not been reported to be greater than expected in children from mothers treated with morphine during pregnancy. Reduced growth and behavioral abnormalities in offspring have been observed in animal studies. Neonates born to mothers receiving chronic opioids during pregnancy should be monitored for neonatal withdrawal syndrome.

LACTATION — Enters breast milk

99

Morfina

REFERENCE RANGE —

– Therapeutic: Surgical anesthesia: 65-80 ng/mL (SI: 227-280 nmol/L);

– Toxic: 200-5000 ng/mL (SI: 700-17,500 nmol/L)

TOXICOLOGY / OVERDOSE COMPREHENSIVE —

Symptoms include respiratory depression, miosis, hypotension, bradycardia, apnea, and pulmonary edema.

Treatment includes

– airway support,

– establishment of an I.V. line, and

– administration of naloxone 2 mg I.V

. (0.01 mg/kg for children), with repeat administration as necessary, up to a total of 10 mg.

– Primary attention should be directed to ensuring adequate respiratory exchange.

100

Morfina


Onset of action:

– Oral (immediate release): ~30 minutes;

– I.V.: 5-10 minutes

Duration: Pain relief:

Immediate release formulations: 4 hours

Extended release epidural injection (DepoDur™): >48 hours

Absorption: Variable

Distribution: Vd: 3-4 L/kg; binds to opioid receptors in the CNS and periphery (eg, GI tract)

Protein binding: 30% to 35%

101

Morfina


Metabolism: Hepatic via conjugation with glucuronic acid to morphine-3-glucuronide (inactive), morphine-6-glucuronide

(active), and in lesser amounts, morphine-3-6-diglucuronide; other minor metabolites include normorphine (active) and the 3-ethereal sulfate

Bioavailability: Oral: 17% to 33% (first-pass effect limits oral bioavailability oral; parenteral effectiveness reportedly varies from

1:6 in opioid naive patients to 1:3 with chronic use)

Half-life elimination: Adults: 2-4 hours (immediate release forms)

Time to peak, plasma: Kadian®: ~10 hours

102

Morfina


Excretion: Urine (primarily as morphine-3-glucuronide, ~2% to 12% excreted unchanged); feces (~7% to 10%).

It has been suggested that accumulation of morphine-6glucuronide might cause toxicity with renal insufficiency.

All of the metabolites (ie, morphine-3-glucuronide, morphine-6glucuronide, and normorphine) have been suggested as possible causes of neurotoxicity (eg, myoclonus).

103

Morfina

Dosis de carga


FG > 50 ml/min

FG 10-50 ml/min

FG < 10 ml/min


HD

DPCA

100% 75% 50%

TSCR

Ninguna Desconocida

Dosis FG

10-50%

104

Buprenorfina

Agonista parcial . Ello significa que la activación del receptor opioide mu por la buprenorfina a dosis máximas no consigue alcanzar los efectos máximos de la morfina.

Presenta una intensa unión al receptor opioide , lo que tiene repercusiones en el tratamiento de la intoxicación aguda

Efecto máximo inferior al de morfina o fentanilo, pero difícil de revertir con antagonistas puros.

105

Buprenorfina

Cuando se administra buprenorfina a pacientes que están recibiendo agonistas puros, puede producirse un cierto grado de antagonismo funcional que, incluso, puede producir un cierto síndrome de abstinencia.

106


NOMBRE GENÉRICO PRESENTACIÓN

Buprenorfina

Metadona


Comp 0,2 mg

Amp 0,3 mg/1 ml

Amp 10 mg/1 ml

Comp 5 mg

Comp 40 mg

Amp 100 mg/2 ml

VIA NOMBRE

COMERCIAL

Buprex CE SL

IM, IV

SC, IM

OR

OR

Metasedin CE

SC, IM, IV Dolantina CE





107

Buprenorfina

DOSING: ADULTS —

Long-term use is not recommended

Acute pain (moderate to severe):

I.M.: Initial: Opiate-naive: 0.3 mg every 6-8 hours as needed; initial dose (up to 0.3 mg) may be repeated once in 30-60 minutes after the initial dose if needed; usual dosage range: 0.15-

0.6 mg every 4-8 hours as needed

Slow I.V.: Initial: Opiate-naive: 0.3 mg every 6-8 hours as needed; initial dose (up to 0.3 mg) may be repeated once in 30-60 minutes after the initial dose if needed

108

Buprenorfina

Heroin or opiate withdrawal (unlabeled use): I.M., slow I.V.: Variable;

0.1-0.4 mg every 6 hours

Opioid dependence : Sublingual:

Induction: Range: 12-16 mg/day (doses during an induction study used 8 mg on day 1, followed by 16 mg on day 2; induction continued over 3-4 days). Treatment should begin at least 4 hours after last use of heroin or short-acting opioid, preferably when first signs of withdrawal appear. Titrating dose to clinical effectiveness should be done as rapidly as possible to prevent undue withdrawal symptoms and patient drop-out during the induction period.

Maintenance: Target dose: 16 mg/day; range: 4-24 mg/day; patients should be switched to the buprenorphine/naloxone combination product for maintenance and unsupervised therapy

109

Buprenorfina

DOSING: PEDIATRIC

Acute pain (moderate to severe):

Children 2-12 years: I.M., slow I.V.: 2-6 mcg/kg every 4-

6 hours

Children 13 years: Refer to adult dosing.

DOSING: ELDERLY — Moderate to severe pain: I.M., slow I.V.: 0.15 mg every 6 hours; elderly patients are more likely to suffer from confusion and drowsiness compared to younger patients. Long-term use is not recommended.

110

Buprenorfina


— Substrate of CYP3A4 (major); Inhibits CYP1A2 (weak),

2A6 (weak), 2C19 (weak), 2D6 (weak)

Cimetidine : May increase sedation from narcotic analgesics; however, histamine blockers may attenuate the cardiovascular response from histamine release associated with narcotic analgesics.

CNS depressants : May produce additive respiratory and CNS depression; includes benzodiazepines, barbiturates, ethanol, and other sedatives. Respiratory and CV collapse was reported in a patient who received diazepam and buprenorphine.

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

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

Naltrexone: May antagonize the effect of narcotic analgesics; concurrent use or use within 7-10 days of injection for pain relief is contraindicated.

111

Buprenorfina

PREGNANCY IMPLICATIONS —

Withdrawal has been reported in infants of women receiving buprenorphine during pregnancy. Onset of symptoms ranged from day 1 to day 8 of life, most occurring on day 1.

LACTATION — Enters breast milk. Not recommended

112

Buprenorfina

TOXICOLOGY / OVERDOSE

COMPREHENSIVE —

Symptoms include CNS depression, pinpoint pupils, hypotension, and bradycardia.

Treatment is supportive.

– Naloxone may have limited effects in reversing respiratory depression ;

– Doxapram has also been used to stimulate respirations

113

Buprenorfina


Onset of action: Analgesic: 10-30 minutes

Duration: 6-8 hours

Absorption: I.M., SubQ: 30% to 40%

Distribution: Vd: 97-187 L/kg

Protein binding: High

Metabolism: Primarily hepatic ; extensive first-pass effect

Half-life elimination: 2.2-3 hours

Excretion: Feces (70%); urine (20% as unchanged drug)

114

Meperidina

Existe otro tipo de opioides denominados agonistasantagonistas , que son capaces de actuar como agonistas sobre un tipo de receptores y como antagonistas sobre otro tipo, por lo que producen respuestas imprevisibles.

En pacientes que reciben agonistas puros, los agonistas-antagonistas pueden precipitar reacciones de abstinencia.

115

Meperidina

Agonistas-antagonista.

Estos fármacos tienen afinidad, variable de unos a otros, por los diferentes subtipos de receptores. En general se comportan como agonistas totales de kappa, pero como agonistas parciales, e incluso antagonistas, de receptores mu.

Las consecuencias, dependen de si se ha administrado previamente un agonista total o no. En ausencia de éstos, el resultado es un efecto analgésico, resultado de la activación de receptores mu (parcial) y kappa (total). Ahora bien, si los pacientes están recibiendo un agonista total (morfina, fentanilo), el resultado será un desplazamiento del receptor y una activación parcial de éste por los agonistas-antagonistas .

En consecuencia, los pacientes sentirán un grado menor de analgesia , lo que se interpreta como un antagonismo, cuando con frecuencia realmente no lo es desde un punto farmacológico estricto.

116


NOMBRE GENÉRICO PRESENTACIÓN

Buprenorfina

Metadona

Comp 0,2 mg

Amp 0,3 mg/1 ml

Amp 10 mg/1 ml

Comp 5 mg

Comp 40 mg

Petidina (Meperidina) Amp 100 mg/2 ml

VIA NOMBRE

COMERCIAL

Buprex CE SL

IM, IV

SC, IM

OR

OR

Metasedin CE

SC, IM, IV Dolantina CE





117

Meperidina

INYECCION IV DIRECTA : SI

Administrar la dosis prescrita en forma de inyección IV lenta, para ello disolver con

SF de forma que la concentración final sea 5 o 10 mg/ml. Ejemplo tomar 1 o 2 ml de la ampolla con una jeringa y completar el volumen hasta 10 ml. Administrar en 1 a 2 minutos.

INFUSION INTERMITENTE : SI

Diluir la dosis prescrita en 50100 ml de SF ó SG5%. Administrar según pauta médica.( Ejemplo 0,3 mg/Kg/hora).

INFUSION CONTINUA : SI

En ocasiones, para mantener a un paciente sedado se utiliza el llamado "coctel lítico", éste está compuesto por: Meperidina (Dolantina), Clorpromazina (Largactil) y

Prometacina (Frinova). se administra en forma de infusión continua, en SF ó SG5%.

INYECCION IM : SI

Administrar la dosis prescrita en forma de inyección IM profunda. Es de elección especialmente en dosis múltiples se prefiere a la vía SC

INYECCION SUBCUTANEA : SI

Cuando deban administrarse dosis repetidas, es preferible la vía IM, ya que la vía SC es irritante de los tejidos.

SUEROS COMPATIBLES : SF, SG5% 118

Meperidina

DOSING: ADULTS —

– Not recommended for chronic pain.

– In patients with normal renal function, doses of 600 mg/24 hours and use for 48 hours are recommended

(American Pain Society, 1999).

Pain (analgesic):

I.M., SubQ: Initial: Opiate-naive: 50-75 mg every 3-4 hours as needed ; patients with prior opiate exposure may require higher initial doses.

119

Meperidina


– Oral, I.M., I.V., SubQ: Children: 1-1.5 mg/kg/dose every 3-4 hours as needed; 1-2 mg/kg as a single dose preoperative medication may be used; maximum 100 mg/dose. (Oral route is not recommended for acute pain.)

DOSING: ELDERLY —

– Oral: 50 mg every 4 hours

– I.M.: 25 mg every 4 hours

120

Meperidina


– Clcr 10-50 mL/minute: Administer 75% of normal dose.

– Clcr <10 mL/minute: Administer 50% of normal dose.

– Repeated use in renal impairment should be avoided due to potential accumulation of neuroexcitatory metabolite .

DOSING: HEPATIC IMPAIRMENT — Increased narcotic effect in cirrhosis; reduction in dose is more important for oral than I.V. route.

121

Meperidina

ADVERSE REACTIONS SIGNIFICANT —

Cardiovascular: Hypotension

Central nervous system: Fatigue, drowsiness, dizziness, nervousness, headache, restlessness, malaise, confusion, mental depression, hallucinations, paradoxical CNS stimulation, increased intracranial pressure, seizure (associated with metabolite accumulation), serotonin syndrome

Dermatologic: Rash, urticaria

Gastrointestinal: Nausea, vomiting, constipation, anorexia, stomach cramps, xerostomia, biliary spasm, paralytic ileus, sphincter of Oddi spasm

Genitourinary: Ureteral spasms, decreased urination



Respiratory: Dyspnea

Miscellaneous: Histamine release, physical and psychological dependence

122

Meperidina

PRECAUTIONS —

Meperidine is not recommended for the management of chronic pain.

When used for acute pain (in patients without renal or CNS disease), treatment should be limited to 48 hours and doses should not exceed 600 mg/24 hours.

Normeperidine (an active metabolite and CNS stimulant) may accumulate and precipitate anxiety, tremors, or seizures; risk increases with renal dysfunction and cumulative dose.

123

Meperidina


Substrate (minor) of CYP2B6, 2C19, 3A4

Acyclovir: May increase meperidine metabolite concentrations. Use caution.

Barbiturates: May decrease analgesic efficacy and increase sedative and/or respiratory depressive effects of meperidine.

Cimetidine: May increase meperidine metabolite concentrations; use caution.

CNS depressants (including benzodiazepines): May potentiate the sedative and/or respiratory depressive effects of meperidine.

MAO inhibitors: May enhance the serotonergic effect of meperidine, which may cause serotonin syndrome. Concurrent use with or within 14 days of an MAO inhibitor is contraindicated.

Phenothiazines: May potentiate the sedative and/or respiratory depressive effects of meperidine; may increase the incidence of hypotension.

Phenytoin: May decrease the analgesic effects of meperidine

Ritonavir: May increase meperidine metabolite concentrations; use caution.

Serotonin agonists: Serotonin agonists and meperidine may enhance serotonin levels in the brain.

Serotonin syndrome may occur.

Serotonin reuptake inhibitors: May potentiate the effects of meperidine, increasing serotonin levels in the brain. Serotonin syndrome may occur.

Sibutramine: May enhance the serotonergic effect of meperidine. Serotonin syndrome may occur.

Tricyclic antidepressants: May potentiate the sedative and/or respiratory depressive effects of meperidine. In addition, potentially may increase the risk of serotonin syndrome.

124

Meperidina

PREGNANCY IMPLICATIONS —

– Meperidine is known to cross the placenta , which may result in respiratory or CNS depression in the newborn.

LACTATION —

– Enters breast milk. contraindicated

125

Meperidina

REFERENCE RANGE — Therapeutic: 70-500 ng/mL

(SI: 283-2020 nmol/L); Toxic: >1000 ng/mL (SI: >4043 nmol/L)

TOXICOLOGY / OVERDOSE COMPREHENSIVE —

Symptoms include CNS depression, respiratory depression, mydriasis, bradycardia, pulmonary edema, chronic tremors, CNS excitability, and seizures.

Treatment of overdose includes airway support, establishment of an I.V. line, and administration of naloxone 2 mg I.V. (0.01 mg/kg for children), with repeat administration as necessary, up to a total of 10 mg.

Naloxone should not be used to treat meperidineinduced seizures. Naloxone does not reverse the adverse effects of normeperidine.

126

Meperidina


Onset of action: Analgesic: Oral, SubQ: 10-15 minutes; I.V.: ~5 minutes

Peak effect: SubQ.: ~1 hour; Oral: 2 hours

Duration: Oral, SubQ.: 2-4 hours

Absorption: I.M.: Erratic and highly variable

Distribution: Crosses placenta; enters breast milk

Protein binding: 65% to 75%

Metabolism: Hepatic; hydrolyzed to meperidinic acid (inactive) or undergoes

N-demethylation to normeperidine (active; has 1/2 the analgesic effect and

2-3 times the CNS effects of meperidine)

Bioavailability: ~50% to 60%; increased with liver disease

Half-life elimination:

Parent drug: Terminal phase: Adults: 2.5-4 hours, Liver disease: 7-11 hours

Normeperidine (active metabolite): 15-30 hours; can accumulate with high doses or with decreased renal function

Excretion: Urine (as metabolites)

127

Meperidina

Dosis de carga


FG > 50 ml/min

FG 10-50 ml/min

FG < 10 ml/min


HD

DPCA

75% 50%

TSCR

Clcr 10-50 mL/minute: Administer 75% of normal dose.

Clcr <10 mL/minute: Administer 50% of normal dose.

Repeated use in renal impairment should be avoided due to potential accumulation of neuroexcitatory metabolite .

128

Gracias.

Analgésicos y coadyuvantes en la enfermedad

Analgesia en pacientes con

ERC

Francisco José de la Prada Alvarez

Servicio de Nefrología

Hospital Son Dureta

DOSING: HEPATIC IMPAIRMENT —

Dosing adjustment is probably necessary in hepatic insufficiency.

Embarazo y Lactancia.

DOSING: ELDERLY — Oral: >75 years:

El tramadol presenta una baja o nula capacidad para causar cuadros de farmacodependencia.

Epileptógeno en situaciones con disminución del umbral de epilepsia

(uremia , tumores cerebrales)

Embarazo y lactancia.

Rango terapéutico:

Sobredosis:

50

DOSING: PEDIATRIC — Oral: Regular or immediate release formulations:

DOSING: HEPATIC IMPAIRMENT —

Reduce dosage in patients with severe liver disease.

DOSING: RENAL IMPAIRMENT –

Embarazo:

Lactancia:

Chronic pain management:

Embarazo:

Lactancia: Pasa a la leche materna. No recomendado.

MONITORING PARAMETERS — Control de la función respiratoria y cardiovascular,

Tensión arterial y frecuencia cardíaca.

Transdermal patch: Monitorizar a las 24 horas de la aplicación del parche.

Alcaloide de la Papaver somniferum.

Sigue constituyendo el analgésico más potente del que se dispone para tratar todo tipo de dolores agudos y muchos de los crónicos.

Modelo de agonista puro de los receptores opioides. Actúa activando los tres receptores opioides.

PREGNANCY IMPLICATIONS —

Withdrawal has been reported in infants of women receiving buprenorphine during pregnancy. Onset of symptoms ranged from day 1 to day 8 of life, most occurring on day 1.

LACTATION — Enters breast milk. Not recommended

PREGNANCY IMPLICATIONS —

LACTATION —

Gracias.

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