Transcript Analgesia en pacientes con ERC

Analgesia en pacientes con
ERC
Francisco José de la Prada Alvarez
Servicio de Nefrología
Hospital Son Dureta
2
3
M01-ANTIINFLAMATORIOS Y ANTIRREUMÁTICOS NO
ESTEROIDEOS
Ver en el grupo N02B otros analgésicos y antiinflamatorios no
esteroideos disponibles en el hospital
NOMBRE
GENÉRICO
PRESENTACIÓN
VIA
NOMBRE COMERCIAL
Diclofenac
Amp 75 mg/3 ml
Comp 50 mg
Sup 100 mg
IM, IV
OR
REC
Voltaren
Ibuprofeno
Jbe 100 mg/5ml
Comp 400 mg
Comp 600 mg
Sobres 200 mg
OR
OR
OR
OR
Dalsy jarabe
Neobrufen
Indometacina
Caps 25 mg
Sup 100 mg
OR
REC
Inacid, Artrinovo
Isonixina
Sup inf 200 mg
REC
Nyxin
Piroxicam
Caps 20 mg
Comp 20 mg
OR
OR
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.
4
N02B-Analgésicos no narcóticos y antipiréticos
Ver en grupo M01 otros analgésicos no narcóticos y antipiréticos
NOMBRE GENÉRICO
PRESENTACIÓN
Com
NOMBRE COMERCIAL
Acetilsalicilato
de lisina (1)(4)
Sobres 1,8 g
Vial 900 mg/5 ml
OR
IM,IV
Inyesprin oral forte
Inyesprin iny(4)
Acido Acetilsalicílico
Comp 500 mg
Comp 300 mg
Comp 125 mg
OR
OR
OR
Ácido Acetilsalicilíco, Adiro, Aspirina
Aspirina infantil
Ketorolaco
Comp 10 mg
Amp 30 mg/1 ml
OR
IV. IM
Droal, Toradol
Metamizol (Dipirona)
(Noramidopirina)
Amp 2000 mg/5 ml
Caps 575 mg
Sup 1 g
Sup 500 mg
IV, IM, OR
OR
REC
REC
Nolotil, Lasain
Paracetamol
Comp 500 mg
Gts 100 mg/ml (2)
Sup 150 mg
Sup 250 mg
Vial 1g/100ml
OR
OR
REC
REC
IV
Termalgin, Dolgesic, Gelocatil (650 mg)
Apiretal
Febrectal Lactante
Melabon Infantil
Perfalgan
Paracetamol +Codeína
Comp 300mg +15mg
Comp 650 mg + 30 mg
OR
OR
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.
5
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.
6
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.
7
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.
8
Semivida corta
Semivida larga
Para dolor moderado-severo
Agonistas puros
Morfina
Metanol
Petidina
Levorfanol
Heroina
Fentanilo
Sulfentanilo
Tramadol
Oxicodona
Oximorfona
Para dolor ligero-moderado
Codeina
Tramadol
Dihidrocodeina
Oxicodona
Dextropropoxifeno
9
Semivida corta
Semivida larga
Pentazosina
Butorfanol
Nalbufina
Dezocina
AgonistasAntagonistas
Meperidina
Agonistas parciales
Buprenorfina
10
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.
11
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.
12
DOSIS EQUIANALGESICAS ENTRE LOS DISTINTOS OPIOIDES
ADMINSTRADOS POR VIA ORAL
Morfina
30-60 mg
Meperidina
300 mg
Metadona
15-20 mg
Tramadol
300-600 mg
Codeina
400 mg
Dihidrocodeina
240 mg
Hidromorfona
7,5 mg
Levorfanol
4 mg
Oxicodona
30 mg
13
Equivalent opioid doses
Drug
Time to onset
(minutes)
Oral dose
(mg)
Morphine sulfate parenteral
Morphine sulfate oral (MSIR, Roxanol)
Parenteral
dose (mg)
10 q4 hr
15 to 60
Morphine sulfate controlled release
(MS contin, Oramorph)
30 q4 hr
90 q12 hr
not available
Codeine
10 to 30
200 q4 hr
100 to 120 q4
hr
Oxycodone (Percocet, Percodan, Tylox)
15 to 30
15 to 20
q4 hr
not available
Oxycodone controlled release
(Oxycontin)
15 to 30
45 to 60
q12 hr
not available
Hydromorphone (Dilaudid)
15 to 30
8 q4 hr
1.5-3.0 q4 hr
Levorphanol (Levodromoran)
30 to 90
4 q6 to q8
hr
2 q6 to q8 hr
Meperidine (Demerol)
10 to 45
300 q2 to
q3 hr
100 q2 to q3
hr
Methadone (Dolophine)
30 to 60
20* q6 to
q12 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.
14
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
– Initial Oral Dose
– Children: n/a
– Adults: n/a
Levorphanol:
Equianalgesic Dose
– Oral: Acute: 4 mg; Chronic: 1
mg
– Parenteral: Acute: 2 mg;
Chronic: 1 mg
– Initial Oral Dose
– Children: 0.04 mg/kg
– Adults: 2-4 mg/kg
Meperidine:
Equianalgesic Dose
– Oral: 300 mg
– Parenteral: 75 mg
– Initial Oral Dose
– Children: Not recommended
– Adults: Not recommended
15
Opioid Analgesics - Initial Oral Dosing Commonly Used for
Severe Pain
Hydromorphone:
Equianalgesic Dose
– Oral: 7.5 mg
– Parenteral: 1.5 mg
– Initial Oral Dose
– Children: 0.06 mg/kg
– Adults: 4-8 mg
Methadone:
Equianalgesic Dose
– Oral: 10 mg
– Parenteral: 5 mg
– Initial Oral Dose
– Children: 0.2 mg/kg
– Adults: 5-10 mg
Morphine:
Equianalgesic Dose
– Oral: 30 mg
– Parenteral: 10 mg
– Initial Oral Dose
– Children: 0.3 mg/kg
– Adults: 15-30 mg
Nalbuphine:
Equianalgesic Dose
– Oral: n/a
– Parenteral: 10 mg
– Initial Oral Dose
– Children: n/a
– Adults: n/a
16
Opioid Analgesics - Initial Oral Dosing Commonly Used for
Severe Pain
Pentazocine:
Equianalgesic Dose
– Oral: 50 mg
– Parenteral: 30 mg
– Initial Oral Dose
– Children: n/a
– Adults: n/a
Oxycodone:
Equianalgesic Dose
– Oral: 20 mg
– Parenteral: n/a
– Initial Oral Dose
– Children: 0.3 mg/kg
– Adults: 10-20 mg
Oxymorphone:
Equianalgesic Dose
– Oral: 1 mg
– Parenteral: n/a
– Initial Oral Dose
– 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.
17
18
N02A-Analgésicos narcóticos (Opioides)
NOMBRE GENÉRICO
PRESENTACIÓN
VIA
NOMBRE COMERCIAL
Buprenorfina
Comp 0,2 mg
Amp 0,3 mg/1 ml
SL
IM, IV
Buprex CE
Codeína
Comp 28 mg
OR
Codeisan
Dihidrocodeína (Hidrocodona)
Comp 60 mg
OR
Contugesic
Fentanilo (2)
Parche 2,5 mg (3)
Parche 5 mg (3)
Parche 10 mg (3)
TOP
TOP
TOP
Durogesic 25
Durogesic 50
Durogesic 100
Metadona
Amp 10 mg/1 ml
Comp 5 mg
Comp 40 mg
SC, IM
OR
OR
Metasedin CE
Morfina cloruro
Amp 10 mg/1 ml
(sin conservantes)
Vial 400 mg/20 ml
(vial multidosis, sin conservantes)
Amp 10 ml.
SC, IV, IM
SC
IV, IM
IV, IM
Cloruro Mórfico Braun 1 % CE
Morfina Braun 2 % s/c CE
Morfina Braun 4 % s/c CE
Morfina clorhidrato
Jbe 10 mg/ml
OR
Brompton FM CE
Morfina sulfato
Comp 10 mg
Comp 20 mg
OR
OR
Sevredol CE (1)
Morfina sulfato retard
Comp 10 mg
Comp 30 mg
Comp 60 mg
Comp 100 mg
OR
OR
OR
OR
MST Continus CE
Petidina (Meperidina)
Amp 100 mg/2 ml
SC, IM, IV
Dolantina CE
Tramadol
Caps 50 mg
Comp retard 200 mg
Comp retard 300 mg
Amp 100 mg/2 m
OR
OR
OR
SC, IM, IV
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.
19
N02B-Analgésicos no narcóticos y antipiréticos
Ver en grupo M01 otros analgésicos no narcóticos y antipiréticos
NOMBRE GENÉRICO
PRESENTACIÓN
Com
NOMBRE COMERCIAL
Acetilsalicilato
de lisina (1)(4)
Sobres 1,8 g
Vial 900 mg/5 ml
OR
IM,IV
Inyesprin oral forte
Inyesprin iny(4)
Acido Acetilsalicílico
Comp 500 mg
Comp 300 mg
Comp 125 mg
OR
OR
OR
Ácido Acetilsalicilíco, Adiro, Aspirina
Aspirina infantil
Ketorolaco
Comp 10 mg
Amp 30 mg/1 ml
OR
IV. IM
Droal, Toradol
Metamizol (Dipirona)
(Noramidopirina)
Amp 2000 mg/5 ml
Caps 575 mg
Sup 1 g
Sup 500 mg
IV, IM, OR
OR
REC
REC
Nolotil, Lasain
Paracetamol
Comp 500 mg
Gts 100 mg/ml (2)
Sup 150 mg
Sup 250 mg
Vial 1g/100ml
OR
OR
REC
REC
IV
Termalgin, Dolgesic, Gelocatil (650 mg)
Apiretal
Febrectal Lactante
Melabon Infantil
Perfalgan
Paracetamol +Codeína
Comp 300mg +15mg
Comp 650 mg + 30 mg
OR
OR
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.
20
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
21
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.
22
Properties of opioid receptors
Mu
Mu1
Supraspinal analgesia
Bradycardia
Sedation
Mu2
Respiratory depression
Euphoria
Physical dependence
Delta
Spinal analgesia
Respiratory depression
Kappa
Spinal Analgesia
Respiratory depression
Sedation
Sigma
Dysphoria, delirium
Hallucinations
Tachycardia, hypertension
23
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
24
25
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
26
Codeina
DOSING: HEPATIC IMPAIRMENT —
Dosing adjustment is probably necessary
in hepatic insufficiency.
27
Dosis
de
carga
Codeina
Dosis de
manteni
miento
FG > 50
ml/min
FG 10-50
ml/min
FG < 10
ml/min
Dosis
suplemta
ria tras
HD
DPCA
TSCR
100 %
75%
50%
Descono
-cida
Desonocida
75%
Vida media de eliminación prolongada en pacientes en diálisis.
28
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
29
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
30
Codeina
Embarazo y Lactancia.
– Contraindicado.
31
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.
32
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)
33
N02A-Analgésicos narcóticos (Opioides)
NOMBRE GENÉRICO
PRESENTACIÓN
VIA
NOMBRE COMERCIAL
Buprenorfina
Comp 0,2 mg
Amp 0,3 mg/1 ml
SL
IM, IV
Buprex CE
Codeína
Comp 28 mg
OR
Codeisan
Dihidrocodeína
(Hidrocodona)
Comp 60 mg
OR
Contugesic
Fentanilo (2)
Parche 2,5 mg (3)
Parche 5 mg (3)
Parche 10 mg (3)
TOP
TOP
TOP
Durogesic 25
Durogesic 50
Durogesic 100
Metadona
Amp 10 mg/1 ml
Comp 5 mg
Comp 40 mg
SC, IM
OR
OR
Metasedin CE
Morfina cloruro
Amp 10 mg/1 ml
(sin conservantes)
Vial 400 mg/20 ml
(vial multidosis, sin conservantes)
Amp 10 ml.
SC, IV, IM
SC
IV, IM
IV, IM
Cloruro Mórfico Braun 1 % CE
Morfina Braun 2 % s/c CE
Morfina Braun 4 % s/c CE
Morfina clorhidrato
Jbe 10 mg/ml
OR
Brompton FM CE
Morfina sulfato
Comp 10 mg
Comp 20 mg
OR
OR
Sevredol CE (1)
Morfina sulfato retard
Comp 10 mg
Comp 30 mg
Comp 60 mg
Comp 100 mg
OR
OR
OR
OR
MST Continus CE
Petidina (Meperidina)
Amp 100 mg/2 ml
SC, IM, IV
Dolantina CE
Tramadol
Caps 50 mg
Comp retard 200 mg
Comp retard 300 mg
Amp 100 mg/2 m
OR
OR
OR
SC, IM, IV
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.
34
35
Tramadol
Análogo sintético de
codeina.
Analgésico no
narcótico de acción
periférico y central.
36
Tramadol
Mecanismo de acción:
– Inhibición de la recaptación de NA y
serotonina por las celulas nerviosas.
– Actúa sobre los receptores opioides Mu.
37
N02A-Analgésicos narcóticos (Opioides)
NOMBRE
GENÉRICO
PRESENTACIÓN
VIA
NOMBRE
COMERCIAL
Tramadol
Caps 50 mg
Comp retard 200 mg
Comp retard 300 mg
Amp 100 mg/2 ml
OR
OR
OR
SC,
IM,
IV
Adolonta, Tralgiol
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
10-20 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.
39
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)
40
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.
41
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 (ChildPugh Class C) hepatic dysfunction.
42
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
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
TSCR
Tramadol
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
6-9 tablets: 20-30 mg every 12 hours
10-12 tablets: 30-40 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
ADVERSE REACTIONS SIGNIFICANT
>10%:
Central nervous system: Fatigue, drowsiness, dizziness,
somnolence
Dermatologic: Pruritus
Gastrointestinal: Nausea, vomiting, constipation
Neuromuscular & skeletal: Weakness
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
PHARMACODYNAMICS / KINETICS
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
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
TSCR
Oxicodona
64
65
N02A-Analgésicos narcóticos (Opioides)
NOMBRE
GENÉRICO
PRESENTACIÓN VIA
NOMBRE
COMERCIAL
Fentanilo (2)
Parche 2,5 mg (3)
Parche 5 mg (3)
Parche 10 mg (3)
Durogesic 25
Durogesic 50
Durogesic 100
TOP
TOP
TOP
Actiq®: 200 mcg, 400 mcg, 600 mcg, 800 mcg, 1200 mcg, 1600 mcg
CE: Control de estupefacientes.
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.
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®
135-224 mg morphine oral/day = 50 mcg/hour Duragesic®
225-314 mg morphine oral/day = 75 mcg/hour Duragesic®
315-404 mg morphine oral/day = 100 mcg/hour Duragesic®
405-494 mg morphine oral/day = 125 mcg/hour Duragesic®
495-584 mg morphine oral/day = 150 mcg/hour Duragesic®
585-674 mg morphine oral/day = 175 mcg/hour Duragesic®
675-764 mg morphine oral/day = 200 mcg/hour Duragesic®
765-854 mg morphine oral/day = 225 mcg/hour Duragesic®
855-944 mg morphine oral/day = 250 mcg/hour Duragesic®
945-1034 mg morphine oral/day = 275 mcg/hour Duragesic®
1035-1124 mg morphine oral/day = 300 mcg/hour Duragesic®
69
Dosing Conversion Guidelines1,2
Morphine (I.M./I.V.):
10-22 mg/day: recommended fentanyl transdermal dose: 25 mcg/hour
23-37 mg/day: recommended fentanyl transdermal dose: 50 mcg/hour
38-52 mg/day: recommended fentanyl transdermal dose: 75 mcg/hour
53-67 mg/day: recommended fentanyl transdermal dose: 100 mcg/hour
Oxycodone (oral):
30-67 mg/day: recommended fentanyl transdermal dose: 25 mcg/hour
67.5-112 mg/day: recommended fentanyl transdermal dose: 50 mcg/hour
112.5-157 mg/day: recommended fentanyl transdermal dose: 75 mcg/hour
157.5-202 mg/day: recommended fentanyl transdermal dose: 100
mcg/hour
Oxycodone (I.M./I.V.):
15-33 mg/day: recommended fentanyl transdermal dose: 25 mcg/hour
33.1-56 mg/day: recommended fentanyl transdermal dose: 50 mcg/hour
56.1-78 mg/day: recommended fentanyl transdermal dose: 75 mcg/hour
78.1-101 mg/day: recommended fentanyl transdermal dose: 100 mcg/hour
Codeine (oral):
150-447 mg/day: recommended fentanyl transdermal dose: 25 mcg/hour
448-747 mg/day: recommended fentanyl transdermal dose: 50 mcg/hour
748-1047 mg/day: recommended fentanyl transdermal dose: 75 mcg/hour
1048-1347 mg/day: recommended fentanyl transdermal dose: 100
mcg/hour
70
Dosing Conversion Guidelines1,2
Hydromorphone (oral):
8-17 mg/day: recommended fentanyl transdermal dose: 25 mcg/hour
17.1-28 mg/day: recommended fentanyl transdermal dose: 50 mcg/hour
28.1-39 mg/day: recommended fentanyl transdermal dose: 75 mcg/hour
39.1-51 mg/day: recommended fentanyl transdermal dose: 100 mcg/hour
Hydromorphone (I.M./I.V.):
1.5-3.4 mg/day: recommended fentanyl transdermal dose: 25 mcg/hour
3.5-5.6 mg/day: recommended fentanyl transdermal dose: 50 mcg/hour
5.7-7.9 mg/day: recommended fentanyl transdermal dose: 75 mcg/hour
8-10 mg/day: recommended fentanyl transdermal dose: 100 mcg/hour
Meperidine (I.M.):
75-165 mg/day: recommended fentanyl transdermal dose: 25 mcg/hour
166-278 mg/day: recommended fentanyl transdermal dose: 50 mcg/hour
279-390 mg/day: recommended fentanyl transdermal dose: 75 mcg/hour
391-503 mg/day: recommended fentanyl transdermal dose: 100 mcg/hour
71
Dosing Conversion Guidelines1,2
Methadone (oral):
20-44 mg/day: recommended fentanyl transdermal dose: 25 mcg/hour
45-74 mg/day: recommended fentanyl transdermal dose: 50 mcg/hour
75-104 mg/day: recommended fentanyl transdermal dose: 75 mcg/hour
105-134 mg/day: recommended fentanyl transdermal dose: 100 mcg/hour
Methadone (I.M.):
10-22 mg/day: recommended fentanyl transdermal dose: 25 mcg/hour
23-37 mg/day: recommended fentanyl transdermal dose: 50 mcg/hour
38-52 mg/day: recommended fentanyl transdermal dose: 75 mcg/hour
53-67 mg/day: recommended fentanyl transdermal dose: 100 mcg/hour
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
ADVERSE REACTIONS SIGNIFICANT
>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
ADVERSE REACTIONS SIGNIFICANT
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
one-third 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
Dosis
de
carga
Fentanilo
Dosis
de
manteni
miento
FG > 50
ml/min
FG 10-50
ml/min
FG < 10
ml/min
Dosis
suplemta
ria tras
HD
DPCA
TSCR
100%
75%
50%
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
N02A-Analgésicos narcóticos (Opioides)
NOMBRE GENÉRICO
PRESENTACIÓN
VIA
NOMBRE COMERCIAL
Morfina cloruro
Amp 10 mg/1 ml
(sin conservantes)
Vial 400 mg/20 ml
(vial multidosis, sin
conservantes)
Amp 10 ml.
SC, IV,
IM
SC
IV, IM
IV, IM
Cloruro Mórfico Braun 1 %
CE
Morfina Braun 2 % s/c CE
Morfina Braun 4 % s/c CE
Morfina clorhidrato
Jbe 10 mg/ml
OR
Brompton FM CE
Morfina sulfato
Comp 10 mg
Comp 20 mg
OR
OR
Sevredol CE (1)
Morfina sulfato retard
Comp 10 mg
Comp 30 mg
Comp 60 mg
Comp 100 mg
OR
OR
OR
OR
MST Continus CE
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.
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
DOSING: PEDIATRIC —
– 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.
DOSING: RENAL IMPAIRMENT
– 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)
Local: Pain at injection site
Neuromuscular & skeletal: Weakness
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
PHARMACODYNAMICS / KINETICS
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
PHARMACODYNAMICS / KINETICS
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
PHARMACODYNAMICS / KINETICS
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
Dosis
de
carga
Morfina
Dosis
de
manteni
miento
FG > 50
ml/min
FG 10-50
ml/min
FG < 10
ml/min
Dosis
suplemta
ria tras
HD
DPCA
TSCR
100%
75%
50%
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
N02A-Analgésicos narcóticos (Opioides)
NOMBRE GENÉRICO
PRESENTACIÓN
VIA
NOMBRE
COMERCIAL
Buprenorfina
Comp 0,2 mg
Amp 0,3 mg/1 ml
SL
IM, IV
Buprex CE
Metadona
Amp 10 mg/1 ml
Comp 5 mg
Comp 40 mg
SC, IM
OR
OR
Metasedin CE
Petidina (Meperidina)
Amp 100 mg/2 ml
SC, IM, IV
Dolantina CE
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.
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: 0.150.6 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 46 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
DRUG INTERACTIONS — 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
PHARMACODYNAMICS / KINETICS
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
N02A-Analgésicos narcóticos (Opioides)
NOMBRE GENÉRICO
PRESENTACIÓN
VIA
NOMBRE
COMERCIAL
Buprenorfina
Comp 0,2 mg
Amp 0,3 mg/1 ml
SL
IM, IV
Buprex CE
Metadona
Amp 10 mg/1 ml
Comp 5 mg
Comp 40 mg
SC, IM
OR
OR
Metasedin CE
Petidina (Meperidina)
Amp 100 mg/2 ml
SC, IM, IV Dolantina CE
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.
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 50-100 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
DOSING: PEDIATRIC —
– 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
DOSING: RENAL IMPAIRMENT
– 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
Local: Pain at injection site
Neuromuscular & skeletal: Weakness
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
DRUG INTERACTIONS
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
PHARMACODYNAMICS / KINETICS
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
Dosis
de
carga
Meperidina
Dosis
de
manteni
miento
FG > 50
ml/min
FG 10-50
ml/min
FG < 10
ml/min
75%
50%
Dosis
suplemta
ria tras
HD
DPCA
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.