Documentos de Académico
Documentos de Profesional
Documentos de Cultura
PROCESO INFLAMATORIO
DOLOROSO
Reaccin inflamatoria
La inflamacin es normal,
protectivo, de defensa ante trauma
fsico, qumico o x
microrganismos.
Fenmeno complejo con actividad
de varios tipos de clulas y
mediadores.
El proceso AGENTE AGRESOR
inflamatori
chuch.. Ayayayyy!!!
o
(mediadores de la inflam)
Calor
Dolor Rubor Edema
Bradicinina Dilatacin Ardor Escape de plasma
Histamina pqos vasos Activ nociceptores por vasodilatacin
Il-1 x autacoides: H,bradic
Serot,Pg, Sust P.
PROCESO INFLAMATORIO
Mediadores qumicos
x Tx A2
PgE2: sec Ac gastrico y sec moco PgE2: inflamacin y piretgeno
PgI2: vasodil y fibrinolisis
-PgE2. tejidos inflamados (quemad solar, edema, AR). vasodilatador eritema y edema; dolor. Agente piretgeno.
-Otros en t. inflamado x COX-2:
PgF2a (uteroconst y broncocont, en dismenorrea),
PgI2 (vasodilat y fibrinolisis).
PgD2 (vasodil, *agreg plaquet, uterorelaj, GI-relajante. TX A2 (vasocontrac y agreg plaq)
FUNCIONES de la COX-1 y COX-2
COX-1 COX-2
1. Produce Inflamacin, dolor y fiebre
1. Mantiene la homeostasis de la en sitio de la lesin (inducible), pero
mucosa gstrica (PgE2). too constitutiva en rion, endotelio y
2. Mantiene la homeostasis renal. cerebro (PgE2).
2. Mantiene la funcin y respuesta
3. Participa en la funcin de renal.
plaquetas. 3. Mantiene la funcion del aparato
4. Induce la produccion de reproductor (ovulacin, labor de
parto, etc).
Tromboxano A2 (agregante plaq y 4. Promueve la sntesis de
vasoconstrictor) (ASA inhibe su prostaciclina (PgI2) necesaria para
produc = corazn). mantener el normal funcionamiento
vascular y evitar la trombosis y
efectos isqumicos.
A.I.N.E.S
ANTI-INFLAMATORIOS NO ESTEROIDALES
AINES. CLASIFICACION QUIMICA
1.
Pirazolonas oxicamos
Celecoxib, Rofecoxib
Etoricoxib
Metamizol
(Retirado x hepatotoxicidad) Lumiracoxib
Fenilbutazona
AINES CLASIFICACION SEGN
VIDA MEDIA
inducible y constitutiva en
rion, cerebro y
endotelio (PgI).
Pg=vasodilatac
Asma Tromboxano A2
Rinitis
x * leucotrienes Agregacin plaquetaria y
vasoconstrictor Prostaciclina
(PGI2). Inh
agregac plaquet y
Aspirina a dosis baja inh COX-1 y x ende inh a Tromboxano A2= inh agregacion
vasodilatador
plaquetaria, pero a dosis terapeutica se hace mas selectiva a COX-2 o
los COX-2 selectivos no inh a Tx-A2
-Desarrollo folicular y ruptura, *x meloxicam (CO?)
AINES tradicionales o
no selectivos
INHIBEN la COX-1 y COX-2
del cido araquidnico.
PRINCIPALES EFECTOS
FARMACOLOGICOS
Anti-inflamatorios
Antipireticos
Analgesicos
bloquear too R NMDA
OTROS
- la agregacin plaquetaria
- la contraccin uterina (tocoliticos y dismenorrea)
-Cierre del conducto arterioso en infantes
-Px de Ca de colon y poliposis intestinal (ASA)
GENERALIDADES
Absorben pcipalmente en 2da porcin del
duodeno.
Niveles plasmticos detectables en 15-30 min.
- Analgesia: diclofenaco, nimesulida y naproxeno en 15 min.
(Valore R/B) Ibuprofeno en 30 min.
1. Enfermedades musculo-esqueleticas
2. Enfermedades respiratorias agudas
3. Enfermedades de la cavidad bucal
4. Enfermedades ginecolgicas
AINES
EFECTOS
INDESEABLES
Many adverse reactions are associated with the use of the
NSAIDs. However, many patients take these drugs and
experience few, if any, side effects.
Some of the adverse reactions associated with the use of these
drugs are listed here:.
ADVERSE REACTIONS
Gastrointestinal tract: nausea, vomiting, diarrhea, constipation, epigastric pain, indigestion, abdominal
distress or discomfort, intestinal ulceration, stomatitis, jaundice, bloating, anorexia, and dry mouth
Renalhematuria, cystitis, elevated blood urea nitrogen, polyuria, dysuria, oliguria, and acute renal
failure in those with impaired renal function
Special senses: visual disturbances, blurred or diminished vision, diplopia, swollen or irritated
eyes, photophobia, reversible loss of color vision, tinnitus, taste change, and rhinitis
Skin: rash, erythema, irritation, skin eruptions, exfoliative dermatitis, Stevens-Johnson syndrome,
ecchymosis, and purpura
In general, the NSAIDs are contraindicated during the 3rd trimester of pregnancy and during
lactation. Most NSAIDs are classified as Pregnancy Category B. In general, the NSAIDs are used
with extreme caution during pregnancy, especially in large doses or during the 3rd trimester.
The NSAIDs are used cautiously in patients with bleeding disorders, renal disease, cardiovascular
disease, or hepatic impairment and in the elderly.
The NSAIDs prolong bleeding time and increase the effects of anticoagulants, lithium, cyclosporine,
and the hydantoins. These drugs may decrease the effects of diuretics or antihypertensive drugs.
Long-term use of the NSAIDs with acetaminophen may increase the risk of renal impairment.
AINES
CONTRAINDICACIONES
Hipersensibilidad:
1. Analgesia:
5. Efectos Metablicos
+ sobredosificacin: hiperglicemia y glucosuria.
Balance nitrogenado negativo y reduccin de la
lipognesis. Acidosis metabolica.
Acciones y efectos del ASA y del AS
6. Efectos locales.
Aplicado tpicamente tienen efecto queratolitico
(callicida y verrugas).
Reyes syndrome
Children or teenagers with influenza or chickenpox
(virus) should NOT take the salicylates,
particularly aspirin, because their use appears to
be associated with Reyes syndrome (a
lifethreatening condition characterized by
vomiting and lethargy, progressing to coma).
This rare but lifethreatening disorder is
characterized by vomiting and lethargy,
progressing to coma. Therefore, use of salicylates
in children with chickenpox, fever, or flu-like
symptoms is not recommended.
Acetaminophen is recommended for the
management of symptoms associated with these
disorders.
2. DERIVADOS DEL
ACIDO ACETICO
Usado como:
antirreumtico, tocoltico, actualmente usado
para plipos intestinales.
Diclofenaco, aceclofenaco y
ketorolaco.
a. DICLOFENACO
SDICO y POTSICO
1. La velocidad de absorcin
est influenciada por los alimentos.
-En desuso x
diarrea y potencial hemoltico
-No ventaja sobre otros AINES
6. OXICAMOS
Piroxicam, tenoxicam y meloxicam
PIROXICAM
(artronil, feldene)
Es sulfonanilida.
Inhibicin preferencial de la sntesis de Pg va
inhibicin de COX-2.
Hepatotxico!
inhibidores selectivos-COX-2
1996 Meloxicam
1997 Nimesulida
Celecoxib (Celebrex)
1999
Rofecoxib (Vioxx-MSD, retirado)
Valdecoxib (retirado, Bextra-Pfizer)
2001 Parecoxib ( inyectable)
2002 Etoricoxib (arcoxia 60,90 y 120 mg)
Luminacoxib (prexige 400 mg)
5.
inhibidores selectivos-CoX-2
1996 Meloxicam
1997 Nimesulida
Celecoxib
1999
Rofecoxib
Valdecoxib
2001
2002 Parecoxib
Etoricoxib
En nuestro pas Ecuador se comercializa
el lumiracoxib 400mg (prexige) retirado
en otros paises en el 2007 por reacciones
hepticas, as como el etoricoxib 60mg,
90 mg y 120 mg (arcoxia)
Fosfolipasa A2
Glucocorticoides
Glucocorticoides
inducible y constitutiva en
rion, cerebro y
endotelio (PgI).
Troboxano A2
Agregacin plaquetaria y
vasoconstrictor Prostaciclina
(PGI2). Inh
Aspirina a dosis baja inh COX-1 y x ende inh a Tromboxano A2= inh agregacion agregac plaquet y
plaquetariapero a dosis terapeutica se hace mas selectiva a COX-2 o vasodilatador
los COX-2 selectivos ya no inh a Tx-A2
-Desarrollo folicular y ruptura, *x meloxicam CO?)
VENTAJAS y DESVENTAJAS de los COX-2
DESVENTAJAS BENEFICIOS
1. NO > eficacia q` otros AINES (falsa impresion).
2. Infarto de y Trombosis. +pctes con hist de: 1. riesgo de ulceracion- sangrado GI
infarto , angina, HTA, hiperlipidemia, tabaco, en 50-60% en comparacion con
diabetes, obesidad, viejos (--18 meses). otros AINES.
3. El riesgo de dao renal es = a los AINES
convencionales (viejos, post-cirugia, dao 2. Rp en pctes con riesgo de lesiones
renal) (Funcion renal es mantenida x Pg via GI: historia de ulceras, tomando
de COX-2). corticoides, tomando
4. No son modificadores de la enfermedad (ejm. anticoagulantes, post-cirugia.
Metrotexate) en AR.
5. Caros (USD) 3. la recurrencia de polipos
6. Usar con precaucion en pctes con falla renal y colonicos.
cardiaca e HTA (monitoreo).
7. Interacciones medicamentosas (too otros
AINES): AnticoagO, prednisona, diureticos, B-
bloq, inh ACE I otros anti-HTA.
8. NO a pctes con historia o riesgo de
coronariopatias, HTA, etc
FDA-Bextra
Bextra (valdecoxib tablets): FDA has concluded that the overall risk versus
benefit profile is unfavorable at this time and has requested the manufacturer
of Bextra, Pfizer, Inc., to voluntarily withdraw Bextra from the market. This
request is based on:
the lack of adequate data on the cardiovascular safety of long-term use of
Bextra, along with the increased risk of adverse CV events in short-term
coronary artery bypass surgery (CABG) trials that FDA believes may be relevant
to chronic use,
reports of serious and potentially life-threatening skin reactions, including
deaths, in patients using Bextra. The risk of these serious skin reactions in
individual patients is unpredictable, occurring in patients with and without a
prior history of sulfa allergy, and after both short- and long-term use, and
the lack of any demonstrated advantages for Bextra compared with other
NSAIDs.
Pfizer has agreed to suspend sales and marketing of Bextra in the U.S. pending
further discussions with the agency.
FDA-Celecoxib
Celebrex (celecoxib tablets): We have concluded that the benefits of Celebrex outweigh
the potential risks in properly selected and informed patients. FDA has decided to allow
Celebrex to remain and has asked Pfizer to take the actions listed below:
Revise the Celebrex label to include a boxed warning containing the class NSAID
warnings and contraindication about CV and GI risk, plus specific information on the
controlled clinical trial data that demonstrate an increased risk of adverse CV events for
celecoxib.
Encourage practitioners to use the lowest effective dose for the shortest duration
consistent with individual patient treatment goals.
Include a Medication Guide as part of the labeling. It will be required to be given at the
time the drug is dispensed to inform patients of the potential for CV and GI risk
associated with NSAIDS, in general, and Celebrex specifically. The Medication Guide will
inform patients of the need to discuss with their doctor the risks and benefits of using
NSAIDs and the importance of using the lowest effective dose for the shortest duration
possible.
Commit to conduct a long-term study of the safety of Celebrex compared to naproxen and
other appropriate drugs.