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TREATMENT OF ARTHRITIS

CENTRAL NERVOUS SYSTEM AGENTS


Amelia Usmiah Musa
P1503216004
BIOMEDIK FARMAKOLOGI
rheumatoid arthritis including acute flares of
chronic disease, ankylosing spondylitis,
osteoarthritis, acute painful shoulder (bursitis
and/or tendinitis) & acute gouty arthritis
CENTRAL NERVOUS SYSTEM AGENTS OF
ARTHRITIS: ES: sakit kepala, pusing, rasa lelah,
ototoksisitas

Antireumatik
Analgesik AINS Obat Pirai Pemodifikasi
Asam mefenamat, diklofenak, derivat AINS (kolkisin, ketorolak),
Penyakit
Penghambat sitokin, metrotreksat,
asam propionat, oksikam, nabumeton,
nimesulide, COX-2 selektif uricostatic, uricosuric azatioprin, leflunomid, sulfasalazine,
Prinsip Analgesik AINS

AINS umumnya bersifat AI, analgesik, & antipiretik.


Sebagian efek antipiretik pada dosis besar-> toksik-> AI sendi: artritis & spondylitis ankilosa.
1. Respon individual terhadap AINS bisa sangat bervariasi->
gagal obat bisa dicoba dengan obat derivat kimiawi sejenis
2. Iritan mukosa lambung
3. Toksiksisitas ginjal
4. Inhibition of COX-1 is thought to be associated with gastrointestinal and renal toxicity while
inhibition of COX-2 provides anti-inflammatory activity
5. Avoid use of NSAIDs in pregnant women starting at 30 weeks of gestation (third trimester)
- Orally effective; Inhibit PG synthesis; analgesic, anti- inflammatory &
antipyretic; reversibly inhibit PA (Platelet Aggregation)
All NSAIDS have the following characteristics:
- Similar Adverse effects (e.g., GI irritation, Renal toxicity)
- Most useful for RA & some for dysmenorrhea
NSAID (ES: mual, gastritis,
eritema kulit dan sakit kepala)
SENDI:

COX-2 inhibitor COX


COX-2 selektif
preferential nonselektif
generasi 1: selekoksib, parekoksib, etorikoksib Asam mefenamat, derivat asam
Etodolak, diklofenak, meloksikam, Generasi 2: lumirakosib: propionat, indomethacin, piroksikam,
nabumeton, nimesulide Kurang efektif, secara umum tidak terbukti lebih aman ketorolac: saluran cerna

NSAIDs for osteoarthritis


The American College of Rheumatology published recommendations for NSAID use in osteoarthritis in 2012
The guidelines state that in general, NSAIDs should be avoided in patients with a history of GI complications
If NSAIDs are still deemed necessary, the following recommendations may help prevent future events:
For patients 75 years, topical NSAIDs are preferred over oral
upper GI ulcer, (-) GI bleed in the past year, use a COX-2 selective NSAID or a nonselective NSAID + PPI
GI bleed in the past year, use a COX-2 selective NSAID + PPI
Pemilihan obat untuk rematik
Variasi respons antar pasien terhadap AINS tidak begitu saja dapat dikaitkan berdasarkan klasifikasi
kimiawi, dosis, atau beratnya penyakit reumatik

Dokter minimal mengenal secara baik 4 AINS berbeda-> pemilihan sesuai dengan kondisi pasien
Dalam 4 obat AINS tersebut harus:
1 T panjang ->nabumeton, meloxicam (asam enolat)
1 T singkat ->etodolak (asam asetat), ibuprofen (asam propionate), diklofenak (asam asetat),
mefenamat
minimal 2 klaifikasi kimiawi lain
Analgesik AINS
Asam asetat
diklofenak
derivat indol-asam asetat
->indometasin

Asam fenamat (anthranilic


acid derivatives)
Asam mefenamat

derivat asam propionat


Analgesik AINS obat pirai
ibuprofen
ketoprofen
Flurbiprofen
naproxen
fenorofen
oksaprozin

derivat asam enolat->


oksikam
piroksikam
meloksikam
Derivat indol-asam asetat-
Kolkisin Asam asetat->ketorolak
>etodolak

Bukan asam:
nabumeton (keton)

COX-2 selektif
generasi 1: selekoksib,
parekoksib, etorikoksib
Generasi 2: lumirakosib
1. Analgesic- reduces prostaglandin levels
2. Anti-Inflammatory- decreased vasodilator prostaglandins
What are the 3 major actions of NSAIDS? 3. Anti-pyretic- decrease in mediator prostaglandin
a. Mediator PG elevates set-pt for temp. control in fever
b. Induces cooling via vasodilation & sweating
PGE2 generally acts as a vasodilator by? Stimulating the Gs- protein pathway
What is a potent vasodilator and inhibitor of platelet adhesion to the
Prostanoids (Therefore , it is anti-Thrombotic)
endothelium, and acts through the Gs-protein pathway?
What can also make the vascular endothelium more "leaky" thereby
Leukotrienes (and prostaglandins)
promoting EDEMA formation during inflammation?
Gastric and Intestinal Ulcers
What are the General Adverse Effects of NSAIDs? Nausea & Vomiting
Pregnancy- prolong labor
GI Injury, Nausea & Vomiting, Bleeding, Renal Injury, Delayed
Major Adverse Effects?
gestation and labor
PGI2 reg. renal homeostatic mech.
What 2 prostaglandins play a role in Renal Injury?
and PGE2- reg. Na+ / H20 retention
PGI2 inhibition- causing Acute renal failure and hyperkalemia
How do NSAIDS interfere with prostaglandins, causing Renal Injury?
PGE2 inhibition- causing Peripheral edema & increased BP
inhibit uterine contractility and prolong the length of gestation and the
duration of labor
What are Tocolytic agents (e.g., NSAIDs)?
o MOA: Cox inhibitors interfere with the pathway Arachodonic Acid >
PGF2- alpha
What has been shown to decrease the risk of developing colorectal cancer? o NSAIDS
Acetic Acid Derivatives (Indomethacin, Ketorolac, Diclofenac)
Propionic Acid Derivatives (Ibuprofen, Naproxen, Ketoprofen,)
What are the Non-Selective NSAIDS (Most widely used)? Fenamates (Mefenamic acid)
Oxicams (Piroxicam, Meloxicam)
Nabumetone

Clinical Uses of Acetic Acid Derivatives? Pain, Inflammation, Fever, and Anti-coagulant
Mechanism of Action of Acetic Acid Derivatives? REVERSIBLE COX Inhibitor
Adverse effects &Treatment (TX) of Acetic Acid - Fetal vascular problems (indomethacin), GI injury: Ulcers (ketorolac, diclofenac)
Derivatives? (PGE1), Severe headache (indomethacin), Hypersensitivity (indomethacin),
Clinical Uses of Propionic Acid Derivatives? Pain, Musculoskeletal disorders (Inflammation)
Mechanism of Action of Propionic Acid Derivatives? REVERSIBLE COX Inhibitor
Adverse effects of Propionic Acid Derivatives? - LOW (milder vs. other NSAIDS), GI irritation
Which NSAIDS cause Therapeutic disadvantages of upper GI disturbances? Acetic Acids: Indomethacin
What are the other Therapeutic disadvantages of Indomethacin? Very potent CNS distubances, Hypersensitivity: Rash, uticaria
What Acetic Acid Derivative is for short term mngt of pain, alt. to
Ketorolac
opiods, not used for more than 5 days?
RA Ostoarthritis
What is the clinical use of Diclofenac? Solar Keratoses
Acute Pain
Clinical Uses of Fenamates? Pain, Musculoskeletal disorders (e.g, RA, osteoarthritis)
Mechanism of Action of Fenamates? REVERSIBLE COX Inhibitor
Adverse effects of Fenamates? GI irritation:DIARRHEA (mefenamic acid), Long-term use (> 1 week

Pharmacokinetics of Oxicams? LONG half-life, dosing 1x day


Mechanism of Action of Oxicams? REVERSIBLE COX Inhibitor; Relatively selective COX-2 inhibitor (meloxicam)
Adverse effects of Oxicams? GI irritation, platelet aggregation, bleeding (piroxicam > meloxicam)
Clinical Uses of Nabumetone? Rheumatoid arthritis
Pharmacokinetics of Nabumetone? PRODRUG (CYP1A2), LONG half-life (27h), dosing 1x day
Mechanism of Action of Nabumetone? Reversible COX Inhibitor (2 >1)
Adverse effects of Nabumetone? GI irritation, ulceration, bleeding, SEVERE RENAL TOXICITY
What is the only Selective COX-2 NSAID approved by the FDA? Celecoxib
Rheumatoid arthritis, Osteoarthritis, Dysmenorrhea, Colon Cancer
Clinical Uses of Celecoxib:
(COX-2 is high in cancer cells & angiogenesis )
DOES NOT inhibit Platelet Aggregation and LESS GI injury (vs.
Advantages (vs. NON-Selective) of Celecoxib:
naproxen, ibuprofen, and diclofenac)
Relatively long half-life (11h), dosing 1-2x day; Metabolized by P450
Pharmacokinetics of Celecoxib
Enzymes (i.e., CYP2C9)
Mechanism of Action of Celecoxib REVERSIBLE COX Inhibitor
Adverse effects of Celecoxib HIGH RISK of cardiovascular effects (i.e., PRO-THROMBIC)
Drug Interactions of Celecoxib CYP2C9 Inhibitors (e.g., fluconozole) or Inducers (e.g., rifampin for TB)
Which class of NSAIDS has lower toxicity and better acceptance in some patients? Propionic Acids (Ibuprofen, Ketoprofen)
Which NSAIDS have the longest life? Oxicams: Piroxicam & Meloxicam (50 hrs)
Which NSAID is a prodrug via CYP1A2 to active metabolite? Nabumetone
Regarding pro-drug interactions, If you have a CYP1A2 inducer, what Higher levels, toxicity (because induction increases metabolism to
happens? active form)
If you have Pro-drug interaction with CYP1A2 inhibitor? Active metabolite goes down, Therapy is inhibited
(RS)-2-(4-(2-Methylpropyl)phenyl) propanoic acid
Synonyms isobutylphenylpropionic acid

Farmakodinamik: COX- inhibitor nonselektif. Target: Inhibition: Prostaglandin G/H synthase, Cystic fibrosis transmembrane
I: reduce fever (including postimmunisation fever), mild to severe pain (including pain relief after surgery), dysmenorrhea,
osteoarthritis, dental pain, headaches, pain from kidney stones, inflammatory diseases such as juvenile idiopathic arthritis,
RA, osteoarthritis, ankylosing spondylitis, gout, psoriatic arthritis, synovitis of osteoarthritis, sinusitis, bruise, acne (topical),
patent ductus arteriosus, Cystic Fibrosis (CF), migraines, severe orthostatic hypotension
O: 30 mnt, Time to reach peak plasma concentration = 47 minutes (suspension), 62 minutes (chewable tablets), 120 minutes
(conventional tablets)
D: 3-4 X 4-5 mg/kg., analgesik: 4X8mg/kg, Inflamasi: 4x 8,5 mg/kg; 2x 600-800 mg.
ES: saluran cerna, jarang: adalah eritema kulit, sakit kepala, trombosipenia, ambliopia toksik reversibel
KI relatif: wanita hamil dan menyusui
mutlak: G > 30 w, eksaserbasi ulkus peptic, insufisiensi ginjal, hemophilia, trauma otak, stroke hemoragik, asma
Interaksi: Avoid alcohol.Take with food to reduce gastric irritation, ibuprofen bersama aspirin mengantagonis efek aspirin
terhadap trombosit sehingga meniadakan sifat kardioprotektif & pencegahan stroke aspirin, allowing sufficient time between
doses of ibuprofen & immediate-release (IR) aspirin can avoid this problem.aspirin IR,>30 mnt, i buprofen; ibuprofen, >8h,
aspirin IR. Inhibitors: CYP2C9
Dangerous to take along with ibuprofen and other NSAIDs: These supplements include those that can prevent antiplatelet
aggregation, including ginkgo, garlic, ginger, bilberry, dong quai, feverfew, ginseng, turmeric, meadowsweet and willow, those
that contain coumarin, including chamomile, horse chestnut, fenugreek & red clover, and those that increase the risk of
bleeding, like tamarind

Farmakokinetik:
A: Bioavailability 80100% (oral), 87% (rectal), topical, IV, Food delays the time to reach peak plasma concentrations by 30-60 minutes
& reduces peak plasma concentrations by 30-50%. Extent of absorption is unaffected.
D: Protein binding 90-98%
M: Hepatic, CYP2C9
E: urin 95%T 1.3-3 h
(RS)-2-(3-benzoylphenyl)propanoic acid

Farmakodinamik: COX- inhibitor nonselektif. Target: Inhibition: Prostaglandin G/H synthase


I: alleviate pain, arthritis-related inflammatory pains or severe toothaches that result in the inflammation of
the gums, symptomatic treatment of acute and chronic rheumatoid arthritis, osteoarthritis, ankylosing
spondylitis, primary dysmenorrhea and mild to moderate pain associated with musculotendinous trauma
(sprains and strains), postoperative (including dental surgery) or postpartum pain, migraines, synovitis of
osteoarthritis, Topical patches are being used for treatment of musculoskeletal pain. Nerve pain such as
sciatica, postherpetic neuralgia and referred pain for radiculopathy in the form of a cream, ointment, liquid,
spray, or gel
D: 2X12,5-100 mg. 1X1mg/lb IV
KI relatif: > 6 d IV, wanita hamil
mutlak: G trimester III
Interaksi: Take with food to reduce gastric irritation. Avoid alcohol. should not be used in combination with
other NSAIDs or corticosteroids, as this increases the risk of gastrointestinal (GI) ulceration. It should also be
used with caution with other anticoagulants. It is commonly used with omeprazole, sucralfate, and cimetidine
to help protect the GI tract. Inhibitors: CYP2C8, CYP2C9

Farmakokinetik:
A: Oral, topical, rectal, intravenous, Rapidly and well-absorbed orally, with peak plasma levels occurring within 0.5 to 2 h. Food prolongs rate of
absorption and decreases peak plasma concentration. Extent of absorption is not affected, pure S dexketoprofen, its trometamol salt is said to be
particularly rapidly reabsorbed
D: 99% bound, primarily to albumin
M: Rapidly and extensively metabolized in the liver, primarily via conjugation to glucuronic acid, CYP2C9
E: In a 24 h, approximately 80% in the urine
4-(6-methoxy-2-naphthyl)-2-butanone

Farmakodinamik: COX-2 preferential


I: treat pain & inflammation, acute & chronic treatment of signs &
symptoms of osteoarthritis, synovitis of osteoarthritis, & rheumatoid
arthritis, Ankylosing Spondylitis, Soft Tissue Rheumatism
D: 1X500-1000 mg. Max: 2000 mg, renal insufficiency: 500-750 mg.
ES: saluran cerna (Nausea, Stomach Upset), Skin Rash, Acute
Toxicity
Interaksi
Take with food for faster absorption. Avoid alcohol
KI relatif: wanita hamil, gagal ginjal, gagal hati
KI mutlak: menyusui

Farmakokinetik:
A: Well absorbed from GIT. Coadministration of food increases the rate of absorption and subsequent appearance of 6MNA ((the active metabolite) in the
plasma but does not affect the extent of conversion of nabumetone into 6MNA ((methoxy-2-naphthylacetic acid)
D: 6MNA, > 99% bound to plasma proteins
M: rapid biotransformation to the principal active metabolite 6MNA. Approximately 35% of a 1000 mg oral dose of nabumetone is converted to 6MNA and
50% is converted into unidentified metabolites.
E: Urine, T (18,8-26,2 h). Increased in patients with renal insufficiency. Pada kelompok usia lanjut t 1/2 ini bertambah panjang dengan 3-7 jam.
Etodolac: (RS)-2-(1,8-Diethyl-4,9-dihydro-3H-pyrano[3,4-b]indol-1-yl)acetic acid

Farmakodinamik: AINS yang lebih selektif terhadap COX-2 dibanding AINS umumnya. Tidak jelas
perbedaan efektivitas dibanding AINS lainnya. Masa kerjanya pendek. Juga menghambat
bradikinin yang juga diketahui merupakan salah satu mediator perangsang nyeri. Antipyresis may
occur by central action on the hypothalamus, resulting in peripheral dilation, increased cutaneous
blood flow, and subsequent heat loss. Administered as a racemate. As with other NSAIDs, the S-
form has been shown to be active while the R-form is inactive. Also has uricosuric action
D: 3-4X200-400 mg, 2x500 mg, maksimum (<60 kg) 600, (60 kg)1000, (>60 kg) 1200 mg.
Interaksi
Take with food to reduce gastric irritation. Food increases the time to peak concentration of regular
release oral formulations by 1.4 to 3.8 hours with no effect on extent of absorption. Avoid alcohol.
KI relatif: menyusui, anak, anticoagulants, lithium, sertraline, fluoxetine, ciclosporin, elective
surgery
KI mutlak: allergy, G, peptic ulcer, poor kidney function
ES: Abdominal or stomach bloating, burning, cramping, or pain belching bloody or black, tarry
stools blurred vision body aches or pain cloudy urine congestion constipation cough or hoarseness
decrease in urine output or decrease in urine-concentrating ability diarrhea dizziness dryness or
soreness of throat feeling of indigestion fever or chills headache increased bleeding time itching
skin loss of appetite lower back or side pain nausea and vomiting nervousness pain in the chest
below the breastbone painful or difficult urination pale skin pounding in the ears rash runny nose
severe stomach pain slow or fast heartbeat swelling tender, swollen glands in neck trouble in
swallowing troubled breathing with exertion unusual bleeding or bruising unusual tiredness or
weakness voice changes vomiting of blood or material that looks like coffee grounds weight loss

Farmakokinetik:
A: >80%, bioavilability + 80%
D: protein binding 99-100%, terutama albumin
M: liver CYP2C9, UDP-glucuronosyltransferase
E: renal (72%), fecal 16% T (3,3-11,3 h).
(4-hydroxy-2-methyl-N-(5-methyl-2-thiazolyl)-2H-1,2-benzothiazine-3-carboxamide-1,1-dioxide

Farmakodinamik: preferential COX-2 inhibitor, tetapi penghambatan COX-1


pada dosis terapi tetap nyata. Target: Inhibition: Prostaglandin G/H synthaseI:
anti-inflammatory with analgesic & fever reducer effect, relieve the symptoms
(nyeri & radang) of arthritis, osteoarthritis, pada penyakit reumatik; osteoartritis
yang memburuk (jangka pendek),synovitis of osteoarthritis, ankilosing
spondilitis, rheumatoid arthritis, juvenile rheumatoid arthritis > 2 y, primary
dysmenorrhea, as an analgesic, especially where there is an inflammatory
components. O: 30-60 menit
D:1X7,5-15 mg P: 0,125 mg/kg D max: 7,5 mg.
KI relatif: severe heart failure, asma
mutlak: gagal ginjal tanpa dialisis, gagal hati berat, AINS hypersensitive
ES: < diclofenac, piroxicam, naproxen
Interaksi: Take without regard to meals. Inhibitor CYP2C8, CYP2C8

Farmakokinetik:
A: Oral 89%
D: 99.4%
M: Hepatic (CYP2C9 and 3A4-mediated)
E: Urine and faeces equally. T1/2 20-50 h
2-{2-[(2,6-dichlorophenyl)amino]phenyl}acetic acid

Farmakodinamik: inhibition of both leukocyte migration & the enzyme cylooxygenase (COX-1 and COX-2),
COX-2 inhibitor preferential, Blockage of voltage-dependent sodium channels (after activation of the channel,
diclofenac inhibits its reactivation also known as phase inhibition), Blockage of acid-sensing ion channels
(ASICs), Positive allosteric modulation of Potassium Chanel (diclofenac opens these channels, leading to
hyperpolarization of the cell membrane), Antipyretic effects may be due to action on the hypothalamus,
resulting in peripheral dilation, increased cutaneous blood flow, and subsequent heat dissipation. Target:
Inhibition: Prostaglandin G/H synthase, Sodium channel protein type 4 subunit alpha, Acid-sensing ion channel
1, Phospholipase A2 membrane associated Protein, Potassium voltage-gated channel (Potentiator):
Arachidonate 5-lipoxygenase
I: analgesic and antipyretic. arthritis, RA, polymyositis, dermatomyositis, osteoarthritis, dental pain,
temporomandibular joint (TMJ) pain, spondylarthritis, ankylosing spondylitis, gout attacks, kidney stones,
gallstones, acute migraines, postoperative or post-traumatic pain, in particular when inflammation is also
present, dysmenorrhea, endometriosis, ocular inflammation, actinic keratosis, juvenile Idiopathic Arthritis (JIA),
pericarditis, acute Musculoskeletal injury, synovitis of osteoarthritis
ES: 15 % pasien peningkatan transaminase umumnya reversibel
KI relatif: G trimester I,II , dengue, tukak lambung
mutlak: G trimester III, Allergiy to NSAID, Active duodenal ulceration or gastrointestinal bleeding,
Inflammatory bowel disease, NYHA III/IV, Pain management in the setting of coronary artery
bypass graft (CABG) surgery, Child-Pugh Class C, GFR <30 ml/min
D: 100-150 mg/d/2-3; geriatric: 2x25 mg.
Interaksi: Avoid alcohol. Take with food to reduce irritation. Inhibitors: Cytochrome P-450 CYP2C9, CYP2E1 ,
CYP1A2 (weak)

Farmakokinetik:
A: Completely absorbed from the gastrointestinal tract
D: Protein binding >99%
M: Hepatic,40-50% metabolism tingkat pertama, CYP1A2 , CYP2B6 , CYP2C19 , CYP2C8 , CYP2C9 , CYP3A4 , UGT2B7
E: urin (65%) & biliar (35%) T 1-3 h, terakumulasi di sinovial
Farmakodinamik: Mefenamic acid binds the prostaglandin synthetase receptors
COX-1 and COX-2, inhibiting the action of prostaglandin synthetase. Target:
inhibits Prostaglandin G/H synthase
I: mild to moderate pain, inflammation, and fever, menstrual pain ( mengurangi
kehilangan darah secara bermakna), prophylaxis perimenstrual migraine
headache (2 days prior to the onset of flow or 1 day prior to the expected onset
of the headache and continuing for the duration of menstruation), rheumatoid
arthritis, osteoarthritis
D: 2-4 kali 250-500 mg sehari. D max: 1500 mg
ES: dispepsia, diare sampai diare berdarah & gejala iritasi lain terhadap mukosa
lambung, lansia: diare hebat lebih sering dilaporkan, hipersensitivita: eritema
&bronkokonstriksi. Anemia hemolitik pernah dilaporkan
KI relatif: <14 y, G, pemberian tidak melebihi 7 hari
mutlak: diarrhe berdarah, hematemesis (vomiting blood), hematuria (blood in
urine), skin rash, itching and swelling, sore throat. It has been associated with
acute liver damage.
In 2008 the US label was updated with a warning concerning a risk of premature
closure of the ductus arteriosus in pregnancy
Interaksi: Avoid alcohol.Take with food.Inhibitors: P-450 CYP2C8, CYP2C9

Farmakokinetik:
A: rapidly absorbed after oral administration, bioavailabilitas 90%
D: Protein binding 90%
M: Hepatic, CYP2C8, CYP2C9 , also glucuronidated directly,
E: kidneys 66%, fecal 20-25% T 2 h
4-Hydroxy-2-methyl-N-(2-pyridinyl)-2H-1,2-benzothiazine-3-carboxamide 1,1-dioxide

Farmakodinamik: COX nonselektif


I: inflamasi sendi, reduce the pain, inflammation, and stiffnnonselektifI: hanya untuk
penyakit ess caused by rheumatoid arthritis, osteoarthritis, gout, spondilitis ankilosa
diberikan pada pasien yang tidak memberi respons cukup dengan AINS yang lebih
aman.
D: 1X10-20 mg.
ES : 11-46%, 4-12% harus stop. tersering: GIT, berat: tukak lambung. Lainnya:
pusing, tinitus, nyeri kepala dan eritema kulit. Juni 2007 karena ES serius di saluran
cerna lambung dan reaksi kulit yang hebat, oleh EMEA (European Medicines Agency)
(badan POM se Eropa) dan pabrik penemunya, piroksikam hanya dianjurkan
penggunaannya oleh spesialis rematologi, inipun sebagai terapi lini ke dua bila obat
lain tidak berhasil.
KI relatif: wanita hamil, pasien tukak lambung dan pasien yang sedang minum
antikoagulan
KI mutlak: G> 30 w
Interaksi: Take with food. Avoid alcohol

Farmakokinetik:
A: berlangsung cepat di lambung
D: terikat 99% pada protein plasma, menjalani siklus enterohepatik, Obat ini. Kadar taraf mantap dicapai
sekitar 7-10 hari dan kadar dalam plasma kira-kira sama dengan kadar di cairan sinovia.
M: Liver-mediated hydroxylation and glucuronidation
E: Urine, faeces .T > 45-50 h -> dapat diberikan hanya 1X/ d
(+)-(S)-2-(6-Methoxynaphthalen-2-yl)propanoic
acid

Farmakodinamik: COX- inhibitor nonselektif. Target: Inhibition: Prostaglandin G/H synthase


I: reduce mild to moderate pain, fever, inflammation, and stiffness caused by conditions such as acute
migraine, arthritis, osteoarthritis, kidney stones, rheumatoid arthritis, juvenile rheumatoid, Juvenile
Idiopathic Arthritis (JIA), other rheumatic or musculoskeletal disorders, psoriatic arthritis, gout, ankylosing
spondylitis, tendinitis, bursitis, primary dysmenorrhea, "bridge therapy" in medication-overuse headache
to transition patients off other medications, backache, headaches, toothache, synovitis of osteoarthritis,
used to differentiate between infectious fevers and neoplastic or connective tissue disease-related fevers
D:Inisial:1X750-825 mg d1, 1-2X5-10 mg/kg, 2x250-375, bila perlu 2x500 1XCR. D max: 1250 mg/d.
ES: dispepsia ringan sampai perdarahan lambung, sakit kepala, pusing, rasa lelah, ototoksisitas.
Gangguan terhadap hepar dan ginjal pernah dilaporkan
KI relatif: < 16 y, advance renal disease,
mutlak: Serious GI: bleeding, ulceration, perforation, late pregnancy
Interaksi: Avoid alcohol.Take with a full glass of water. Take with food. Naproxen should not be taken with
antidepressants, lithium, methotrexate, probenecid, a blood thinner, heart or blood pressure medications,
including diuretics or steroid medicine (such as prednisone)
NSAID painkillers such as naproxen may interfere with and reduce the efficacy of SSRI antidepressants

Farmakokinetik:
A: Oral, rectal, 95% (oral)
D: >99% albumin-bound
M: Hepatic, CYP2C9, CYP2C98, CYP1A2, UDP-glucuronosyltransferase, Sulfotransferase
E: renal. T1/2 12-24 h
4-[5-(4-Methylphenyl)-3-(trifluoromethyl)pyrazol-1-yl]benzenesulfonamide

Farmakodinamik: COX-2 selektif


I: NSAID urticaria, mild-moderate pain, osteoarthritis, rheumatoid arthritis, acute
pain, musculoskeletal pain, painful menstruation, ankylosing spondylitis,
juvenile rheumatoid arthritis who are older than two years of age and weigh
more than 10 kg (22 lb), postoperative pain, major depression, bipolar disorder,
and schizophrenia
D: 200 mg/d/:1-2, JRA < 25 kg: 2X50 mg, > 25 kg: 2X100 mg.
ES: meningkatkan terjadi risiko kardiovaskular seperti trombosis & serangan
jantung
KI relatif: hypersensitivitas NAID, periopertative pain of CABG, active GIT
bleeding
KI mutlak: G> 30 w
Interaksi: Take without regard to meals. Dengan makanan penyerapan
berkurang 20-30%

Farmakokinetik:
A: Well absorbed from GIT. Taking this product with a high-fat meal will delay the Cmax, but total absorption will be increased by 10 to
20%
D: 97% (mainly to serum albumin)
M: Hepatic (mainly CYP2C9)
E: Faeces (57%), urine (27%) . T 7.8 hours; 11 hours (mild hepatic impairment); 13 hours (moderate-severe hepatic impairment)
Obat pirai

Anti inflamasi
Penurun asam urat
akut
Kolkisin, indometasin

Uricostatic Uricosuric
Ekskresi UA>600 mg/d <600mg/d
Xantin oxidase inhibitor:
Probenecid, sulfinpirazon
allopurinol
N-[(7S)-1,2,3,10-Tetramethoxy-9-oxo-5,6,7,9-tetrahydrobenzo[a]heptalen-7-yl]acetamide
alkaloid
Colchicum autumnale sejenis bunga leli

Farmakodinamik: Berikatan dengan protein mikrotubular dan menyebabkan depolimerisasi dan


menghilangnya mikrotubul fibrilar granulosit dan sel bergerak lainnya->penghambatan migrasi granulosit ke
tempat radang sehingga penglepasan mediator inflamasi juga dihambat, mencegah penglepasan
glikoprotein dari leukosit yang pada pasien gout menyebabkan nyeri dan radang sendi
I: spesifik terhadap penyakit pirai dan beberapa artritis lainnya sedang sebagai antiradang umum kolkisin
tidak efektif. Kolkisin tidak memiliki efek analgesik
D: 0,5-0,6 mg tiap jam atau 1,2 sebagai dosis awal diikuti 0,5-0,6 mg tiap 2 jam sampai penyakit hilang atau
gejala saluran cerna timbul, IV: 1-2 mg dilanjutkan dengan 0,5 mg tiap 12-24 jam. Dosis jangan melebihi 4
mg dengan satu regimen pengobatan. Untuk mencegah iritasi akibat ekstravasasi sebaiknya larutan 2 ml
diencerkan menjadi 10 ml dengan larutan garam faal. Profilaksis: 0,5-1 mg/d.
ES: muntah, mual dan diare, dapat sangat mengganggu terutama dengan dosis maksimal, stop, IV dengan

https://encrypted- dosis terapi (-), bila ekstravasasi dapat menimbulkan peradangan, nekrosis kulit serta jaringan lemak.
Depresi sumsum tulang, purpura, neuritis perifer, miopati, anuria, alopesia, gangguan hati, reaksi alergi dan
kolitis hemoragik jarang, umumnya pada dosis berlebihan dan pada pembenan IV, gangguan ekskresi akibat
kerusakan ginjal dan kombinasi keadaan tersebut. DIC merupakan manifestasi keracunan berat timbul
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dalam 48 jam, sering fatal
KI relatif: hypersensitivitas NSAID, periopertative pain of CABG, active GIT bleeding
JUcr6vVSO-19jH9 KI mutlak: prophylactic regimens of oral in patients with advanced renal failure (including those on dialysis)
Interaksi: Avoid alcohol since it increases uric acid levels. Drink liberally. Take without regard to meals

Farmakokinetik:
A: rapidly absorbed after oral administration, probably from the jejunum and ileum. rate and extent of absorption are depending on
the tablet dissolution rate; variability in gastric emptying, intestinal motility, and pH at the absorption site; and the extent to which
colchicine is bound to microtubules in gastrointestinal mucosal cells.
D:Protein binding 35-44%
M: Faeces (65%), urin 10-20% T1/2 26.6-31.2 h
2-[1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl]acetic acid

Farmakodinamik: COX- inhibitor nonselektif, greater selectivity for COX-1, Seperti kolkisin, indometasin menghambat motilitas
leukosit pollmorfonuklear. Target: inhibits motility of polymorphonuclear leukocytes, similar to colchicine, uncouples oxidative
phosphorylation in cartilaginous (and hepatic) mitochondria, like salicylates decreased cerebral blood flow. Inhibition: Prostaglandin
G/H synthase, Phospholipase A2 membrane associated, Prostaglandin reductase 2
I: reduce pain, stiffness, and swelling from inflammation.moderate to severe pain, acute pain, rheumatoid arthritis including acute
flares of chronic disease, ankylosing spondylitis, osteoarthritis, acute painful shoulder (bursitis and/or tendinitis), acute gouty
arthritis, Patent Ductus Arteriosus (PDA), synovitis of osteoarthritis, dysmenorrhea, fever and pain associated with malignant
diseases (especially tumor fever associated with liver involvement, lymphogranulomatosis), headaches caused by the Valsalva
maneuver, juvenile arthritis, migraine, pericarditis, pseudogout, psoriatic arthritis, reactive arthritis, renal colic (pain due to kidney
stones), trigeminal autonomic cephalgias, delay premature labor, reduce amniotic fluid in polyhydramnios, Walaupun obat ini efektif
tetapi karena toksis maka penggunaan obat ini dibatasi.
D: 2-4 X 25 mg,Untuk mengurangi gejala reumatik di malam hari, indometasin diberikan 50-100 mg sebelum tidur.
ES: tergantung dosis, insidensnya cukup tinggi. Pada dosis terapi, 1/3 menghentikan pengobatan karena ES. Nyeri abdomen,
diare, perdarahan lambung, pankreatitis. Sakit kepala hebat kira-kira 20-25% pasien dan sering disertai pusing, depresi dan rasa
bingung. Halusinasi dan psikosis pernah dilaporkan. Juga dilaporkan menyebabkan agranulositosis, anemia aplastik dan
trombositopenia. Vasokonstriksi pembuluh koroner pernah dilaporkan. Hiperkalemia dapat terjadi akibat hambatan yang kuat
terhadap biosintesis PG di ginjal. Alergi dapat pula timbul dengan manifestasi urtikaria, gatal dan serangan asma
KI relatif: minor ache/pain, < 14 y, (kecuali PDA), hamil, pasien psikiatri, epilepsy, Parkinson, penyakit lambung, pre-existing bone
marrow damage (frequent blood cell counts are indicated), dengue, bleeding tendencies of unknown origin
mutlak: concurrent peptic ulcer, or history of ulcer disease, allergy to NSAIDs, children <2 years of age (with the exception of
neonates with patent ductus arteriosus), severe pre-existing renal and liver damage, concurrent with potassium sparing diuretics,
patients who have a PDA dependent heart defect (such as transposition of the great vessels), significant hypertension (high blood
pressure), G trimester I, III
Interaksi: Avoid alcohol. Take with food or antacids to reduce irritation mengurangi efek natriuretik dari diuretik tiazid dan furosemid
serta memperlemah efek hipotensif obat -bloker, Inhibitor :CYP2C19, P-glycoprotein/ABCB1, UGT1A1

Farmakokinetik:
A: Bioavailability: 92~100% (oral), 8090% (rectal)
D: Protein binding 92-99%
M: Hepatic, CYP2C19 , CYP2C9, P-glycoprotein/ABCB1
E: renal 60% biliary->fecal 33% . T 2.6-4 h
Allopurinol:1H-pyrazolo[3,4-d]pyrimidin-4(2H)-one

Farmakodinamik: menghambat xantin oksidase, enzirn yang mengubah hipoxantin menjadi xantin dan
selanjutnya rnenjadi asam urat. Melalui mekanisme umpan balik menghambat sintesis purin yang
merupakan prekursor xantin. It also acts as an antimetabolite on some simpler organisms
I: Pengobatan jangka panjang mengurangi frekuensi serangan, menghambat pembentukan tofi,
memobilisasi asam urat dan mengurangi besamya tofi. Mobilisasi asam urat ini dapat ditingkatkan
dengan memberikan urikosurik.pirai sekunder akibat polisitemia vera, metaplasia mieloid, leukemia,
limfoma, psoriasis, hiperurisemia akibat obat, dan radiasi. Koterapi IBD, epilepsy (adenosine agonist,
which inhibits glutamine release from excitatory neurons, but does not change the plasma concentration
of other epilepsy drugs)
D: pirai ringan 200-400 mg/d, pirai berat: 400-600 mg/d, gangguan fungsi ginjal dosis: 100-200 mg/d
hiperurisemia sekunder: 100-200 mg/d. 6-10 y: 300 mg/d.<6 y: 150 mg/d.
ES: sering: kulit kemerahan (stop). Gangguan saluran cerna kadang-kadang,dapat meningkatkan
frekuensi serangan sehingga sebaiknya pada awal terapi diberikan juga kolkisin. Serangan biasanya
menghilang setelah beberapa bulan pengobatan alergi berupa demam, menggigil, leukopenia atau
leukositosis, eosinofilia, artralgia dan pruritus pernah dilaporkan.
KI relatif: (-), penyesuaian dosis
KI mutlak: alergi allopurinol
Iinteraksi: Take with a full glass of water. Take with food. Avoid alcohol. menghambat oksidasi
merkaptopurin, dosis merkaptopurin harus dikurangi sarnpai 25-35% bila diberikan bersamaan

Farmakokinetik:
A: Approximately 80-90% absorbed from the gastrointestinal tract.
D:Protein binding -
M: Allopurinol and oxypurinol are not bound to plasma proteins Hepatic by Aldehyde oxidase-> oxipurinol 80%; 10% allopurinol
ribosides
E: 20% of the ingested allopurinol is excreted in the feces . T1/2 1-3 h (oxipurinol 18-30 h)
4-(dipropylsulfamoyl)benzoic acid
Farmakodinamik: Prototypical uricosuric agent. It inhibits the renal excretion of organic anions
and reduces tubular reabsorption of urate. Also been used to treat patients with renal
impairment, and, because it reduces the renal tubular excretion of other drugs, has been used
as an adjunct to antibacterial therapy. During World War II, probenecid was used to extend
limited supplies of penicillin
I: mencegah dan mengurangi kerusakan sendi serta pembentukan tofi pada penyakit pirai,
hiperurisemia sekunder
D: 2X250 mg/d for 1 w, diikuti 2X 500 mg/d. Increase liquid intake, avoid alcohol.
ES: sering: angguan saluran cerna, nyeri kepala & reaksi alergi
KI relatif: riwayat gangguan diskrasia darah, nefrolitiasis
KI mutlak: pirai serangan akut, < 2 y, GFR<30, porfiria, hypersensitivity to probenecid.
Interaksi: Take with food to reduce irritation. Salisilat mengurangi efek probenesid.
Probenesid menghambat ekskresi renal dari sulfinpirazon, indometasin, penisilin, PAS,
sulfonamid dan juga berbagai asam organik, sehingga dosis obat tersebut harus disesuaikan
bila diberikan bersamaan

Farmakokinetik:
A: Human Intestinal 0.9972.
D:Protein binding tidak linier, tergantung konsentrasi plasma, max: 74%, menembus plasenta
M: hepar
E: renal (77-88%) alkalinization increases excretion. .T1/2 2-12 h
Sulfinpyrazon: 1,2-diphenyl-4-[2-(phenylsulfinyl)ethyl]pyrazolidine-3,5-dione

Farmakodinamik: A uricosuric drug that is used to reduce the serum urate levels in gout
therapy. lacks anti-inflammatory, analgesic, and diuretic properties, berdasarkan
hambatan reabsorpsi tubular asam urat. Kurang efektif menurunkan kadar asam urat
dibandingkan dengan allopurinol
I: Mencegah dan mengurangi kelainan sendi dan tofi pada penyakit pirai kronik,
profilaksis gout, hiperurisemia, gouty arthritis, Platelet Aggregation
D: 2X100-200 mg/d, ditingkatkan sampai 400-800 mg kemudian dikurangi sampai dosis
efektif minimal.
ES: 10-15 % pasien yang mendapat sulfinpirazon mengalami gangguan saluran cerna,
kadang-kadang perlu dihentikan pengobatannya, dapat menigkatan efek obat
hipoglikemik
KI relatif: riwayat gangguan diskrasia darah, nefrolitiasis
KI mutlak: renal impairment or a history of uric acid kidney stones, hipersensitivitas
AINS, penyakit jantung, gangguan fungsi ginjal
Interaksi: Take with food to reduce irritation

Farmakokinetik:
A: oral baik
D:Protein binding 98-99%
M: hepar by CYP2C9, CYP3A4
E: renal
()-5-benzoyl-2,3-dihydro-1H-pyrrolizine-1-carboxylic acid

Farmakodinamik: COX nonselektif analgesik poten dengan efek anti-inflamasi sedang, with
analgesic and antipyretic properties. The biological activity of ketorolac tromethamine is associated
with the S-form. Ketorolac tromethamine is a racemic mixture of [-]S- and [+]R-enantiomeric
I: short-term management of moderate to severe pain, pain associated with
inflammation,osteoarthritis and control acute pain, burns, isolated extremity fracture or dislocation
with severe painanalgesia perioperative, analgesik pascabedah memperlihatkan efektivitas
sebanding morfin/meperidin dosis umum; masa kerjanya lebih panjang dan efek sampingnya lebih
ringan.Onset: approx 30 minutes
Peak effects: 45-60 minutes
D: IM 30-60 mg, IV 15-30 mg (14-65 y) > 65 15 mg; oral 5-30 mg
ES: nyeri di tempat suntikan, gangguan saluran cerna, kantuk, pusing & sakit kepala yang dilaporkan
terjadi kira-kira 2x placebo, dapat menigkatan efek obat hipoglikemik
KI relatif: kehamilan, gagal hati
KI mutlak: Known hypersensitivity to the drug or it's components. 2) Allergies to Aspirin or other
NSAID's
Interaksi: Take with food to reduce GI irritation. IM administration has been found to reduce the
diuretic effects of Lasix

Farmakokinetik:
A: oral & IM berlangsung cepat mencapai puncak dalam 30-50 mnt. Bioavailabilitas oral 80%. 100% injeksi
D: hampir seluruhnya terikat protein plasma.
M: hepar
E: Kidney: 91.4% (mean) Biliary: 6.1% (mean)T1/2 3.5 h to 9.2 h, young adults; 4.7 h to 8.6 h, elderly (mean age 72)
Methotrexat: (2S)-2-[(4-{[(2,4-Diaminopteridin-6-yl)methyl](methyl)amino}benzoyl)amino]pentanedioic acid

Farmakodinamik: APP drugs of choice, menghambat terjadinya lesi erosi, antimetabolite with immunosuppressant
properties. Inhibitor of tetrahydrofolate dehydrogenase and prevents the formation of tetrahydrofolate, necessary for
synthesis of thymidylate, an essential component of DNA. a chemotherapy agent and immune system suppressant
I: artritis juvenil kronik, artritis psoriasis, cancer, autoimmune diseases, ectopic pregnancy, and for medical abortions.
Types of cancers it is used for include breast cancer, leukemia, lung cancer, lymphoma, and osteosarcoma. Types of
autoimmune diseases it is used for include psoriasis, adults with severe, active rheumatoid arthritis (ACR criteria), or
children with active polyarticular-course juvenile rheumatoid arthritis and Crohn's disease, lupus eritematosus sistemik,
dan gangguan lain
D:Oral: Awal 7,5 mg/w, 15-25 mg/w ,ditingkatkan sampai 30-35 mg/w bila perlu, (WBC DC, PLT, Cr, fungsi hati)
ES: umumnya mual & ulkus mukosa saluran cema. Hepatotoksisitas terkait dosis berupa peningkatan aminase serum
terjadi tetapi jarang sampai rnenyebabkan sirosis. Biopsi hati dianjurkan dilakukan setiap 5 tahun. Suatu reaksi paru
dengan sesak napas akut dan reaksi pseudolimfomatosa dilaporkan terjadi
Interaksi: Milk appears to reduce its absorption. Take without regard to meals. Limit caffeine intake.

Farmakokinetik:
A: generally well absorbed with a mean bioavailability of 60% at lower doses, 3550% at higher doses
D: protein binding: 3550% (parent drug),9193% (7-hydroxymethotrexate)
M: hepar by CYP3A4
E: Urine (80100%), faeces (small amounts) T1/2 310 hours (lower doses), 815 hours (higher doses)
2-hydroxy-5-[(E)-2-{4-[(pyridin-2-yl)sulfamoyl]phenyl}diazen-1-yl]benzoic acid

Farmakodinamik: derivat sulfonamide, Inhibition of cytokine expression and neutrophil migration


I: APP, and other types of inflammatory arthritis (e.g. psoriatic arthritis), artritis juvenil kronik, spondilitis ankilosa
dan uveitis yang menyertainya, Polyarticular Juvenile Rheumatoid Arthritis (when NSAIDs are ineffective),
inflammatory bowel diseases including ulcerative colitis(maintenance therapy in remission) and Crohn's disease
(treatment of mild and moderate forms), Proctitis

Leflunamid: 5-methyl-N-[4-(trifluoromethyl) phenyl]-isoxazole-4-


carboxamide
Kontrol WBC DC, PLT, fungsi hati/bulan u/ 3 bulan pertama
Absolute contraindications: porphyria, aplastic anemia, granulocytopenia, renal and hepatic impairment,
obstruction of the urinary tract, pediatric patients up to 6 years (for the treatment of juvenile rheumatoid
arthritis), pediatric patients up to 10 years (in the presence of chronic inflammatory bowel disease), lactation,
hypersensitivity to the drug, as well as to salicylates or sulfonamides.
Relative contraindications (sulfasalazine prescribed with caution under medical supervision): atopic dermatitis,
bronchial asthma, systemic forms of juvenile rheumatoid arthritis (high risk of serum sickness), severe allergic
reactions (high risk of cross-reactions to thiazide diuretics, furosemide, carbonic anhydrase inhibitors,
sulfonylureas), pregnancy.
Interaksi: Take with a full glass of water No iron, zinc or fluoride within 2 hours of taking this medication. Take
with food

Farmakokinetik:
A: < 30%, usus halus menghasilkan bioavailabilitas 10- <15%
D: protein binding 50-70%
M: hepar by asetilasi, hidroxilasi, glukoronidasi
E: urin, feses
Leflunamid: 5-methyl-N-[4-(trifluoromethyl) phenyl]-isoxazole-4-carboxamide

Farmakodinamik: menghambat enzim dihidroorotat dehidrogenase untuk sintesis pyramidin yang


menghambat proliferasi sel T yang butuh kadar besar dari pyramidin, O: 4-6 w
I: active moderate-to-severe rheumatoid arthritis & psoriatic arthritis
D: loading dose 3 hari dengan 100 mg dianjutkan dengan 20 mg per hari sampai remisi.

ES: The mostLeflunamid:
common(>1%),5-methyl-N-[4-(trifluoromethyl) phenyl]-isoxazole-4-
in approximately descending order of frequency:diarrhea, respiratory
tract infections, hair loss, high blood pressure, carboxamide
rash, nausea, bronchitis, headache, abdominal pain,
abnormal liver function tests, back pain, indigestion, urinary tract infection, dizziness, infection, joint
disorder, itchiness, weight loss, loss of appetite, cough, gastroenteritis, pharyngitis, stomatitis,
tenosynovitis, vomiting, weakness, allergic reaction, chest pain, dry skin, eczema, paraesthesia,
pneumonia, rhinitis, synovitis, cholelithiasis & shortness of breath. uncommon (0.1-1%): constipation,
oral thrush, stomatitis, taste disturbance, thrombocytopenia and hives.
Rarely (in 0.1%):anaphylaxis, angiooedema, anaemia, agranulocytosis, eosinophilia, leucopenia,
pancytopenia, vasculitis, toxic epidermal necrolysis, Stevens-Johnson syndrome, cutaneous lupus
erythematosus, severe infection, interstitial lung disease, cirrhosis & liver failure
KI relatif: mild to moderate renal insufficiency
KI mutlak: severe renal insufficiency, pregnancy, women of childbearing potential (unless
contraception used), menyusui
Interaksi: Take without regard to meals

Farmakokinetik:
A: Well absorbed, peak plasma concentrations appear 6-12 hours after dosing
D: protein binding >99.3%.
M: hepar by CYP1A2
E: renal excretion as well as by direct biliary excretion. In a 28 day study of drug elimination (n=3) using a single dose of radiolabeled compound,
approximately 43% of the total radioactivity was eliminated in the urine and 48% was eliminated in the feces.. T : 2 w
6-[(1-Methyl-4-nitro-1H-imidazol-5-yl)sulfanyl]-7H-purine

Farmakodinamik: Prodrug of mercaptopurine. mercaptopurine are incorporated into replicating


DNA, halting replication, as well as blocking the pathway for purine synthesis. It thus most
strongly affects proliferating cells, such as the T cells and B cells of the immune system.
Zat aktifnya 6-tioguanin menghambat sintesis asam inosinat, fungsi sel dan sel T, produksi
imunoglobulin dan sekresi interteukin-2
I:immunosuppressive medication: RA yang tidak respon dengan obat laiin, Crohn's disease,
ulcerative colitis, kidney transplants rejection, hepatitis aktif kronik, nephritls lupus eritematosus
sismetik, dermatomisitis, pemfigus vulgaris, poliateritis nodosa, anemia hemolitik yang didapat,
purpura trombositopenia idiopatik, pioderma gangrenosum, Multiple Sclerosis (MS), Pericarditis,
Psoriasis, uveitis
D: RA: 1,5-2,5 mg/kgBB/d/:1-2, (turunkan dosis dalam keadaan tertentu) penggunaan bersama
allopurinol dosis diturunkan < 2 mg/kg BB
ES: serupa imunosupresif lainnya yaitu supresi sumsum tulang, saluran cerna & penurunan daya
tahan tubuh terhadap infeksi: herpes zoster
KI relatif: Infeksi aktif serius, G
KI mutlak:, riwayat reaksi hipersensitivitas
Interaksi: Take with food to reduce irritation

Farmakokinetik:
A: well absorbed from the gut to about 88%.
D: protein binding 2030%
M: Activated non-enzymatically, deactivated mainly by xanthine oxidase, proses metilasi di eritrosit & hepar
E: renal 98% as metabolites T1/2 2680 minutes (azathioprine) 35 hours (drug plus metabolites)
Penghambat sitokin
RA: ketidakseimbangan antara sitokin yang pro dan anti-inflamasi.

Anti-sitokin

Ada obat antibodi monoklonal atau reseptor yang mentarget sitokin ini.
ES: peningkatan kemungkinan infeksi, hematologi: pansitopenia, anemia aplastik & disfungsi neurologis.

Anti-TNF IL-1 inhibitor


etan
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inflixi
mab,
adali
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anakinra
ab
TNF is a naturally occurring cytokine that is involved in normal inflammatory and immune responses. Elevated levels
of TNF are found in the synovial fluid of rheumatoid arthritis patients and play an important role in both the pathologic
inflammation and the joint destruction that are hallmarks of rheumatoid arthritis.
recombinant human IgG1 monoclonal antibody specific for human tumor necrosis factor (TNF)
alpha, produced by recombinant DNA technology using a mammalian cell expression system. It
consists of 1330 amino acids and has a molecular weight of approximately 148 kilodaltons
T max 3d2h-7d19h T1/2 10-20 d, metabolisme: opsonisasi di RE, boavailibility 64%

Farmakodinamik

Farmakodinamik: binds specifically to TNF-alpha and blocks its interaction with the p55 and p75 cell surface TNF receptors so blocks its general cytokine effects, thereby reducing TNF-induced inflammation
(including changes in the levels of adhesion molecules responsible for leukocyte migration) and halting tissue destruction. After treatment, a rapid decrease in levels of acute phase reactants of inflammation (C-
reactive protein (CRP) and erythrocyte sedimentation rate (ESR)) and serum cytokines (IL-6) was observed compared to baseline in patients with rheumatoid arthritis. Serum levels of matrix metalloproteinases
(MMP-1 and MMP-3) that produce tissue remodeling respon-ible for cartilage destruction were also decreased after administration.
I: treatment of immune system mediated diseases: RA (in adults for reducing signs and symptoms and inhibiting the progression of structural damagewith moderately to severely active rheumatoid arthritis who have
had an inadequate response to one or more DMARDs), psoriatic arthritis (aggravated), chronic plaque psoriasis (moderate-severe in adults ), severe ankylosing spondylitis in adults , Uveitis penyerta Crohn's Disease
(CD), Ulcerative Colitis (moderate-severe in adults), Pyoderma Gangrenosum, hidroadenitis suppurativa (moderate-severe), moderate to severe polyarticular juvenile idiopathic arthritis (JIA) in children 4 and older,
use alone, or with methotrexate or similar medicines, Moderate-Severe Hidradenitis Suppurativa
D: adults: 40 mg subcutaneously/w. P: 10 kg (22 pounds)-< 15 kg (33 pounds):10 mg subcutaneously/w, 15 kg (33 pounds)-< 30 kg (66 pounds): 20 mg subcutaneously/w, > 30 kg (66 pounds): 40 mg
KI mutlak: hypersensitivity to adalibmumab or any of its components
SE: The most common: injection site reactions. increases the risk of rare serious infections. There is a two-fold risk of serious infections. It should not be used during periods of active infection. Its most notable
infectious complication is the reactivation of tuberculosis. Deep fungal and other serious and atypical infection. It has been associated infrequently with skin rashes. malignancy
Rare: worsening or initiation of CHF, a lupus-like syndrome, a promotion of lymphoma, medically significant cytopenias, and worsening or initiation of a multiple sclerosis/neurological disease.
There has been reported pancytopenia and elevated transamines.
combination of two naturally occurring soluble human 75-kilodalton TNF receptors linked to an Fc portion of an
IgG1. The effect is an artificially engineered dimeric fusion protein
Etanercept is produced by recombinant DNA technology in a Chinese hamster ovary (CHO) mammalian cell
expression system.
T 1/2 in RA: 3-5 d; 2d 2o h in healthy

Farmakodinamik: biopharmaceutical that treats autoimmune diseases by interfering with tumor


necrosis factor (TNF; a soluble inflammatory cytokine) by acting as a TNF inhibitor
Dimeric fusion protein consisting of the extracellular ligand-binding portion of the human 75 kilodalton
(p75) tumor necrosis factor receptor (TNFR) linked to the Fc portion of human IgG1. The Fc
component of etanercept contains the CH2 domain, the CH3 domain and hinge region, but not the
CH1 domain of IgG1. It consists of 934 amino acids
I: moderately to severely active RA in adults and chronic moderate to severe plaque psoriasis in
adults, manage signs and symptoms of polyarticular idiopathic arthritis in those aged 4 to 17 after
insufficient response to one or more disease-modifying anti-rheumatic drugs, juvenile rheumatoid
arthritis, improve psoriatic arthritis and ankylosing spondylitis, Graft Versus Host Disease (GVHD),
Hidradenitis Suppurativa (HS), Pyoderma Gangrenosum and ankylosing spondylitis
D: MODERATE TO SEVERE Rheumatoid Arthritis For adult patients, 50 mg weekly x 24
Interaksi:
Absolute contraindications: porphyria, aplastic anemia, granulocytopenia, renal and hepatic
impairment, obstruction of the urinary tract, pediatric patients up to 6 years (for the treatment of
juvenile rheumatoid arthritis), pediatric patients up to 10 years (in the presence of chronic
inflammatory bowel disease), lactation, hypersensitivity to the drug, as well as to salicylates or
sulfonamides.
Relative contraindications (sulfasalazine prescribed with caution under medical supervision): atopic
dermatitis, bronchial asthma, systemic forms of juvenile rheumatoid arthritis (high risk of serum
sickness), severe allergic reactions (high risk of cross-reactions to thiazide diuretics, furosemide,
carbonic anhydrase inhibitors, sulfonylureas), pregnancy.
ES: Common: injection site reaction (3-5 d), lower the immune:sinusitis, headache, Serius: TB, Infeksi
virus, fungi, bakteri seluruh tubuh, unusual cancer yang memulai di <18 y
combination with methotrexate
Tumor necrosis factor (TNF-alpha) binding antibody (chimeric IgG1), composed of human constant and
murine variable regions, produced by a recombinant cell line cultured by continuous perfusion.
artificial antibody. It was originally developed in mice as a mouse antibody. Because humans have immune
reactions to mouse proteins, the mouse common domains were replaced with similar human antibody
domains. They are monoclonal antibodies and have identical structures and affinities to the target. Because
they are a combination of mouse and human antibody amino acid sequences, they are called a "chimeric
monoclonal antibody
7-12 d in Crohn's disease, plaque psoriasis and RA

Farmakodinamik: Ichimeric human-murine anti-human tumor necrosis factor (TNF) monoclonal antibody. It binds to tumor necrosis factor alpha (TNFa) and inhibits
binding of TNFa with its receptors. This reduces production of pro-inflammatory cytokines such as interleukins (IL) 1 and 6. This also limits leukocyte migration and
expression of adhesion molecules by endothelial cells and leukocytes. Infliximab also limits the activation of neutrophil and eosinophil functional activity, reduces
production of tissue degrading enzymes produced by synoviocytes and/or chondrocytes. decreases synovitis and joint erosions in collagen-induced arthritis and
allows eroded joints to heal.
I: to manage signs and symptoms of rheumatoid arthritis (in conjunction with methotrexate), ankylosing spondylitis, psoriatic arthritis, and juvenile arthritis, also to
manage the signs and symptoms, as well as to induce and maintain clinical remission in adults with moderate to severe active Crohn's disease or ulcerative colitis.
the most frequently used biological agent in treating relapsing polychondritis
D: 0,3 mg/kg at 0, 2 and 6 weeks followed by a maintenance regimen of 3 mg/kg every 8 w. incomplete response: consideration > 10 mg/kg or treating as often as
every 4 weeks bearing in mind that risk of serious infections is increased at higher doses
Interaksi:
Absolute contraindications: Active infection, malignancy, diagnosed within the past 5 years, with a potential for progression, class III or IV (NYHA), Demyelinating
disease
Relative contraindications: Situations associated with a high risk of infection: latent untreated tuberculosis, chronic infections, uncontrolled diabetes. Cancer diagnosed
more than 5 years ago, treated, and considered cured, Premalignant lesions, e.g., polyps in the colon or urinary bladder, cervical dysplasia, myelodysplasia. Pregnant
or breastfeeding woman
ES: can lower the ability of your immune system to fight infections, Some patients, especially those 65 years and older, have had serious infections caused by viruses,
fungi or bacteria that have spread throughout the body, including tuberculosis (TB) and histoplasmosis. Some of these infections have been fatal. Risk of Cancer
Anakinra is a recombinant, nonglycosylated human interleukin-1 receptor antagonist (IL-1Ra).
The difference between anakinra and the native human IL-1Ra is that anakinra has an extra methionine residue
at the amino terminus.
It is manufactured by using the E. coli expression system. Anakinra is composed of 153 amino acid residues
absolute bioavailability of 95% for healthy adults after a 70 mg subcutaneous bolus injection. Peak plasma
concentrations of anakinra generally occurred 3-7 h of clinically relevant doses for patients with RA. T 1/2 4 t-6 h

Farmakodinamik: biopharmaceutical that treats autoimmune diseases by interfering with tumor necrosis factor (TNF; a soluble
inflammatory cytokine) by acting as a TNF inhibitor. Dimeric fusion protein consisting of the extracellular ligand-binding portion of the
human 75 kilodalton (p75) tumor necrosis factor receptor (TNFR) linked to the Fc portion of human IgG1. The Fc component of etanercept
contains the CH2 domain, the CH3 domain and hinge region, but not the CH1 domain of IgG1. It consists of 934 amino acids
I: Reduce the signs and symptoms, and slow the damage of moderate to severe active rheumatoid arthritis (RA) in people age 18 years
and older when 1 or more other drugs for RA have not worked, Treat people with a form of Cryopyrin-Associated Periodic Syndromes
(CAPS) called Neonatal-Onset Multisystem Inflammatory Disease (NOMIDRecurrent Pericarditis
D: 1 to 2 mg/kg
Interaksi:
Absolute contraindications: allergic to: proteins made from bacteria called E. coli, anakinra or any of the ingredients, Preexisting
malignant diseases, neutropenia , GFR<30
Relative contraindications: Preexisting active tuberculosis, Concomitant application of live-virus vaccines (see Interactions). Lactation
SE: can lower the ability of your immune system to fight infections. Serious infections may give you a higher chance for getting an
infection or make any infection worse. Neutropenia.
Serious side effects that are rare include: Malignancies. Lymphoma, Allergic reactions.
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