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Analgesia en pacientes con ERC

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Analgesia en pacientes con ERC Powered By Docstoc
					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                           PRESENTACIÓN                                 VIA              NOMBRE COMERCIAL
GENÉRICO
Diclofenac                       Amp 75 mg/3 ml                               IM, IV           Voltaren
                                 Comp 50 mg                                   OR
                                 Sup 100 mg                                   REC
Ibuprofeno                       Jbe 100 mg/5ml                               OR               Dalsy jarabe
                                 Comp 400 mg                                  OR               Neobrufen
                                 Comp 600 mg                                  OR
                                 Sobres 200 mg                                OR
Indometacina                     Caps 25 mg                                   OR               Inacid, Artrinovo
                                 Sup 100 mg                                   REC
Isonixina                        Sup inf 200 mg                               REC              Nyxin
Piroxicam                        Caps 20 mg                                   OR               Sasulen, Feldene 20,
                                 Comp 20 mg                                   OR               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                  Sobres 1,8 g                      OR            Inyesprin oral forte
de lisina (1)(4)                  Vial 900 mg/5 ml                  IM,IV         Inyesprin iny(4)
Acido Acetilsalicílico            Comp 500 mg                       OR            Ácido Acetilsalicilíco, Adiro, Aspirina
                                  Comp 300 mg                       OR            Aspirina infantil
                                  Comp 125 mg                       OR
Ketorolaco                        Comp 10 mg                        OR            Droal, Toradol
                                  Amp 30 mg/1 ml                    IV. IM
Metamizol (Dipirona)              Amp 2000 mg/5 ml                  IV, IM, OR    Nolotil, Lasain
(Noramidopirina)                  Caps 575 mg                       OR
                                  Sup 1 g                           REC
                                  Sup 500 mg                        REC
Paracetamol                       Comp 500 mg                       OR            Termalgin, Dolgesic, Gelocatil (650 mg)
                                  Gts 100 mg/ml (2)                 OR            Apiretal
                                  Sup 150 mg                        REC           Febrectal Lactante
                                  Sup 250 mg                        REC           Melabon Infantil
                                  Vial 1g/100ml                     IV            Perfalgan
Paracetamol +Codeína              Comp 300mg +15mg                  OR            Termalgin Codeína;
                                  Comp 650 mg + 30 mg               OR            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 agonistas-
antagonistas, 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

Agonistas-
Antagonistas
                      Pentazosina      Butorfanol
                      Nalbufina        Dezocina
                      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

                                         Time to onset   Oral dose    Parenteral
 Drug                                    (minutes)       (mg)         dose (mg)
 Morphine sulfate parenteral                                          10 q4 hr
 Morphine sulfate oral (MSIR, Roxanol)   15 to 60        30 q4 hr
 Morphine sulfate controlled release                     90 q12 hr    not available
 (MS contin, Oramorph)
 Codeine                                 10 to 30        200 q4 hr    100 to 120 q4
                                                                      hr
 Oxycodone (Percocet, Percodan, Tylox)   15 to 30        15 to 20     not available
                                                         q4 hr
 Oxycodone controlled release            15 to 30        45 to 60     not available
 (Oxycontin)                                             q12 hr
 Hydromorphone (Dilaudid)                15 to 30        8 q4 hr      1.5-3.0 q4 hr
 Levorphanol (Levodromoran)              30 to 90        4 q6 to q8   2 q6 to q8 hr
                                                         hr
 Meperidine (Demerol)                    10 to 45        300 q2 to    100 q2 to q3
                                                         q3 hr        hr
 Methadone (Dolophine)                   30 to 60        20* q6 to    10 q6 hr
                                                         q12 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:                Levorphanol:
   Equianalgesic Dose            Equianalgesic Dose
   – Oral: n/a                   – Oral: Acute: 4 mg; Chronic: 1
   – Parenteral: 0.4 mg            mg
   – Initial Oral Dose           – Parenteral: Acute: 2 mg;
   – Children: n/a                 Chronic: 1 mg
   – Adults: n/a                 – Initial Oral Dose
                                 – Children: 0.04 mg/kg
  Butorphanol:                   – Adults: 2-4 mg/kg
   Equianalgesic Dose
   – Oral: n/a                  Meperidine:
   – Parenteral: 2 mg            Equianalgesic Dose
   – Initial Oral Dose           – Oral: 300 mg
   – Children: n/a               – Parenteral: 75 mg
   – Adults: n/a                 – Initial Oral Dose
                                 – Children: Not recommended
                                 – Adults: Not recommended
                                                               15
Opioid Analgesics - Initial Oral Dosing Commonly Used for
                        Severe Pain

 Hydromorphone:                 Morphine:
  Equianalgesic Dose             Equianalgesic Dose
                                 – Oral: 30 mg
  – Oral: 7.5 mg                 – Parenteral: 10 mg
  – Parenteral: 1.5 mg           – Initial Oral Dose
  – Initial Oral Dose            – Children: 0.3 mg/kg
  – Children: 0.06 mg/kg         – Adults: 15-30 mg
  – Adults: 4-8 mg
                                Nalbuphine:
                                 Equianalgesic Dose
 Methadone:                      – Oral: n/a
  Equianalgesic Dose             – Parenteral: 10 mg
  – Oral: 10 mg                  – Initial Oral Dose
  – Parenteral: 5 mg             – Children: n/a
                                 – Adults: n/a
  – Initial Oral Dose
  – Children: 0.2 mg/kg
  – Adults: 5-10 mg
                                                         16
Opioid Analgesics - Initial Oral Dosing Commonly Used for
                        Severe Pain

 Pentazocine:                   Oxymorphone:
  Equianalgesic Dose             Equianalgesic Dose
                                 – Oral: 1 mg
  – Oral: 50 mg                  – Parenteral: n/a
  – Parenteral: 30 mg            – Initial Oral Dose
  – Initial Oral Dose            – Children: n/a
  – Children: n/a                – Adults: n/a
  – Adults: n/a
                                From "Principles of Analgesic Use
                                in the Treatment of Acute Pain
 Oxycodone:                     and Cancer Pain,"Am Pain Soc,
  Equianalgesic Dose            Fifth Ed.
  – Oral: 20 mg
  – Parenteral: n/a
  – Initial Oral Dose
  – Children: 0.3 mg/kg
  – Adults: 10-20 mg
                                                                17
18
                N02A-Analgésicos narcóticos (Opioides)



NOMBRE GENÉRICO                                  PRESENTACIÓN                          VIA           NOMBRE COMERCIAL

Buprenorfina                                     Comp 0,2 mg                           SL            Buprex CE
                                                 Amp 0,3 mg/1 ml                       IM, IV


Codeína                                          Comp 28 mg                            OR            Codeisan
Dihidrocodeína (Hidrocodona)                     Comp 60 mg                            OR            Contugesic

Fentanilo (2)                                    Parche 2,5 mg (3)                     TOP           Durogesic 25
                                                 Parche 5 mg (3)                       TOP           Durogesic 50
                                                 Parche 10 mg (3)                      TOP           Durogesic 100

Metadona                                         Amp 10 mg/1 ml                        SC, IM        Metasedin CE
                                                 Comp 5 mg                             OR
                                                 Comp 40 mg                            OR

Morfina cloruro                                  Amp 10 mg/1 ml                        SC, IV, IM    Cloruro Mórfico Braun 1 % CE
                                                  (sin conservantes)                   SC            Morfina Braun 2 % s/c CE
                                                 Vial 400 mg/20 ml                     IV, IM        Morfina Braun 4 % s/c CE
                                                 (vial multidosis, sin conservantes)    IV, IM
                                                 Amp 10 ml.


Morfina clorhidrato                              Jbe 10 mg/ml                          OR            Brompton FM CE

Morfina sulfato                                  Comp 10 mg                            OR            Sevredol CE (1)
                                                 Comp 20 mg                            OR

Morfina sulfato retard                           Comp 10 mg                            OR            MST Continus CE
                                                 Comp 30 mg                            OR
                                                 Comp 60 mg                            OR
                                                 Comp 100 mg                           OR

Petidina (Meperidina)                            Amp 100 mg/2 ml                       SC, IM, IV    Dolantina CE

Tramadol                                         Caps 50 mg                            OR            Adolonta, Tralgiol
                                                 Comp retard 200 mg                    OR            Zytram
                                                 Comp retard 300 mg                    OR
                                                 Amp 100 mg/2 m                        SC, IM, IV

                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                  Sobres 1,8 g                      OR            Inyesprin oral forte
de lisina (1)(4)                  Vial 900 mg/5 ml                  IM,IV         Inyesprin iny(4)
Acido Acetilsalicílico            Comp 500 mg                       OR            Ácido Acetilsalicilíco, Adiro, Aspirina
                                  Comp 300 mg                       OR            Aspirina infantil
                                  Comp 125 mg                       OR
Ketorolaco                        Comp 10 mg                        OR            Droal, Toradol
                                  Amp 30 mg/1 ml                    IV. IM
Metamizol (Dipirona)              Amp 2000 mg/5 ml                  IV, IM, OR    Nolotil, Lasain
(Noramidopirina)                  Caps 575 mg                       OR
                                  Sup 1 g                           REC
                                  Sup 500 mg                        REC
Paracetamol                       Comp 500 mg                       OR            Termalgin, Dolgesic, Gelocatil (650 mg)
                                  Gts 100 mg/ml (2)                 OR            Apiretal
                                  Sup 150 mg                        REC           Febrectal Lactante
                                  Sup 250 mg                        REC           Melabon Infantil
                                  Vial 1g/100ml                     IV            Perfalgan

Paracetamol +Codeína              Comp 300mg +15mg                  OR            Termalgin Codeína;
                                  Comp 650 mg + 30 mg               OR            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   Dosis de   FG > 50   FG 10-50   FG < 10   Dosis      DPCA      TSCR
           de      manteni    ml/min    ml/min     ml/min    suplemta
           carga   miento                                    ria tras
                                                             HD

Codeina                       100 %     75%        50%       Descono    Desono-   75%
                                                             -cida      cida




          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                           SL            Buprex CE
                                                 Amp 0,3 mg/1 ml                       IM, IV

Codeína                                          Comp 28 mg                            OR            Codeisan


Dihidrocodeína                                   Comp 60 mg                            OR            Contugesic
(Hidrocodona)
Fentanilo (2)                                    Parche 2,5 mg (3)                     TOP           Durogesic 25
                                                 Parche 5 mg (3)                       TOP           Durogesic 50
                                                 Parche 10 mg (3)                      TOP           Durogesic 100

Metadona                                         Amp 10 mg/1 ml                        SC, IM        Metasedin CE
                                                 Comp 5 mg                             OR
                                                 Comp 40 mg                            OR

Morfina cloruro                                  Amp 10 mg/1 ml                        SC, IV, IM    Cloruro Mórfico Braun 1 % CE
                                                  (sin conservantes)                   SC            Morfina Braun 2 % s/c CE
                                                 Vial 400 mg/20 ml                     IV, IM        Morfina Braun 4 % s/c CE
                                                 (vial multidosis, sin conservantes)    IV, IM
                                                 Amp 10 ml.


Morfina clorhidrato                              Jbe 10 mg/ml                          OR            Brompton FM CE

Morfina sulfato                                  Comp 10 mg                            OR            Sevredol CE (1)
                                                 Comp 20 mg                            OR

Morfina sulfato retard                           Comp 10 mg                            OR            MST Continus CE
                                                 Comp 30 mg                            OR
                                                 Comp 60 mg                            OR
                                                 Comp 100 mg                           OR

Petidina (Meperidina)                            Amp 100 mg/2 ml                       SC, IM, IV    Dolantina CE

Tramadol                                         Caps 50 mg                            OR            Adolonta, Tralgiol
                                                 Comp retard 200 mg                    OR            Zytram
                                                 Comp retard 300 mg                    OR
                                                 Amp 100 mg/2 m                        SC, IM, IV


                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          PRESENTACIÓN         VIA     NOMBRE
GENÉRICO                                     COMERCIAL
Tramadol        Caps 50 mg           OR      Adolonta, Tralgiol
                Comp retard 200 mg   OR      Zytram
                Comp retard 300 mg   OR
                Amp 100 mg/2 ml      SC,
                                     IM,
                                     IV




                                                                  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 (Child-
  Pugh 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   Dosis de   FG > 50   FG 10-50   FG < 10   Dosis      DPCA   TSCR
           de      manteni    ml/min    ml/min     ml/min    suplemta
           carga   miento                                    ria tras
                                                             HD

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   Dosis     FG > 50   FG 10-50   FG < 10   Dosis      DPCA   TSCR
            de      de        ml/min    ml/min     ml/min    suplemta
            carga   manteni                                  ria tras
                    miento                                   HD

Oxicodona




                                                                                 64
65
 N02A-Analgésicos narcóticos (Opioides)




NOMBRE              PRESENTACIÓN VIA                 NOMBRE
GENÉRICO                                             COMERCIAL
Fentanilo (2)       Parche 2,5 mg (3)       TOP      Durogesic 25
                    Parche 5 mg (3)         TOP      Durogesic 50
                    Parche 10 mg (3)        TOP      Durogesic 100


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 (opioid-
  tolerant 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   Dosis     FG > 50   FG 10-50   FG < 10   Dosis       DPCA        TSCR
            de      de        ml/min    ml/min     ml/min    suplemta
            carga   manteni                                  ria tras
                    miento                                   HD

Fentanilo                     100%      75%        50%       No          No          No
                                                             aplicable   aplicable   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           SC, IV,     Cloruro Mórfico Braun 1 %
                                 (sin conservantes)      IM          CE
                                Vial 400 mg/20 ml        SC          Morfina Braun 2 % s/c CE
                                (vial multidosis, sin    IV, IM      Morfina Braun 4 % s/c CE
                                conservantes)             IV, IM
                                Amp 10 ml.
Morfina clorhidrato             Jbe 10 mg/ml             OR          Brompton FM CE
Morfina sulfato                 Comp 10 mg               OR          Sevredol CE (1)
                                Comp 20 mg               OR
Morfina sulfato retard          Comp 10 mg               OR          MST Continus CE
                                Comp 30 mg               OR
                                Comp 60 mg               OR
                                Comp 100 mg              OR



 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:
                                                                                              92
 –   El preparado sin conservante también se puede administrar via epidural e intratecal.
                            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-6-
glucuronide might cause toxicity with renal insufficiency.
All of the metabolites (ie, morphine-3-glucuronide, morphine-6-
glucuronide, and normorphine) have been suggested as possible
causes of neurotoxicity (eg, myoclonus).




                                                                103
          Dosis   Dosis     FG > 50   FG 10-50   FG < 10   Dosis      DPCA       TSCR
          de      de        ml/min    ml/min     ml/min    suplemta
          carga   manteni                                  ria tras
                  miento                                   HD

Morfina                     100%      75%        50%       Ninguna    Descono-   Dosis FG
                                                                      cida       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              SL            Buprex CE
                            Amp 0,3 mg/1 ml          IM, IV
Metadona                    Amp 10 mg/1 ml           SC, IM        Metasedin CE
                            Comp 5 mg                OR
                            Comp 40 mg               OR
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: 0.15-
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
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 agonistas-
antagonistas, 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              SL            Buprex CE
                            Amp 0,3 mg/1 ml          IM, IV
Metadona                    Amp 10 mg/1 ml           SC, IM        Metasedin CE
                            Comp 5 mg                OR
                            Comp 40 mg               OR
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 meperidine-
induced 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   Dosis     FG > 50   FG 10-50   FG < 10   Dosis      DPCA   TSCR
             de      de        ml/min    ml/min     ml/min    suplemta
             carga   manteni                                  ria tras
                     miento                                   HD

Meperidina                               75%        50%




  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.