Nsaid Gastropathy 2gx4

NSAID Gastropathy : Epidemiology and pathophysiolog Hirlan

The use of NSAIDs is common in the treatment of pain inflamation fever Low dose ASA is use routinely in primary and secondary Prophylaxis of CV event NSAID use increase among elderly

The use of NSAID from OTC is also increase

Prevalence of NSAID use Study in USA, NSAID use increase among elderly  

70% at least once weekly 34% at least daily

More than 111 million NSAID prescription per year Indonesia ?

Patofisiologi gastropati OAINS Arachidonic acid COX-1 (constitutive)

COX-2 (induced by inflammatory st COX-2 selective NSAIDs 



Non-selective NSAIDs

Prostaglandins

Prostaglandins

• Gastrointestinal cytoprotection

•



Platelet activity

Vane & Botting 1995

• Inflammation

• •

Pain Fever

COX 2 hypothesis 

COX 2 is the primary intended target for anti-inflamatory but no or little effect on inhibition to COX 1 by selectivly activity

Animal model : Indicated that both COX 1 and COX 2 must be inhibited for UGIE to occur

Upper GI events ( UGIE ) caused by NSAID o Dispeptic and sign of GERD with or without erosion o Peptic ulceration o Bleeding of peptic ulcer o Perforation o Stricture

Incidence of UGIE o 1 of every 20 NSAID o 1 of ev severery 7 NSAID

Annual incidence UGIE associated UGIE 2.0 – 4.5 % Risk of severe complication 0.2 – 1.9 %

GI safety of COXIB Cochrane systematic review : o COXIB produced significantly fewer UGI Ulcer ( RR 0,26. 95% CI 0.23-0.30 ) and ulcer complication ( RR 0.39. 95% CI 0.310.30. o Fewer withdrawals caused by GI symptoms, compared with conventional NSAID .

Risk factors of UGIE associated with NSA High risk - History of a previously complicated ulcer - Multiple risk factors >2 Moderate risk - Age 65 years or more - High dose NSAID therapy - A previous history of Uncomplicated ulcer - Concurrent use of aspirin or corticosteroid or anticoagulant Low risk - no risk factors

Cardiovascular events associated with NSAID Meta-analysis : o All COXIB were associated with an increase CV risk compared to placebo (rate ratio 1.42. 95% CI 1.13-1.78)

o Dose dependent increase in CV events was also abserved with celecoxib o No significant difference in CV risk between COXIB and NSAID conventional, Naproxen was the only posible exceptional

Treatment and Prevention of NSAID related Because the central mechanism of UGIE are prostaglandin depletion and topical injury by the acidic property of NSAID,

Treatment and prophylaxis : Replacement with prostaglandin synthesis or acid suppression

Prevention and treatment Selection of patients for therapy o Indication for NSAID used o The risk factors for having UGIE and CV events associated with NSAID used o What is the NSAID of choice : non selective or Coxib o The dose of NSAID

Early Dispepsia and symptom of acid regurgitation o poorly correlated with the result of endoscopic study. 50% patients with dispepsia had normal mucosal appearance on endoscopy 40% patient with erosive and ulcer were asymptomatic o Adaptation proses ? o H2RA induced masking effect to UGIE o NSAID can be continued

Active ulcer associated with NSAID NSAID should be discontinued, if possible. PPI are superior to H2RA and misoprostol in healing NSAID associated ulcers If NSAID should be continued, PPI are the first Choice.

Ulcer healing in those NSAID was discontinu 95

%

NSAID continued 63

NSAID discontinued

Gastric ulcer associated NSAID H2RA standart dose at 8 weeks

PPI are superior to standart dose of H2RA Omeprazole 20mg /day vs omeprazole 40mg/day vs Ranitidine 150mg bid %

80

79 63

Ulcer healing at 8 weeks NSAID was used continuesly

Ome 20 m/dayg Ome 40 mg/day Ran 150mg BFD

PPI are superior to Mesoprostol in healing NSAID associated ulcer %

89

89

77

Ulcer healing at 8 weeks NSAID was used continuosly

Ome 20 mg/day Ome 40 mg/day Meso 200mg Qid

Role of COXIB in Ulcer healing o Animal study : Cox 2 up regulated in gastric ulcer o istration of COX 2 inhibitors retards the healing of gastric ulcer

No data to recommendation of substitution of NSAID with COXIB in patients with active ulcer

Misoprostol for NSAID related UGIE preventi o Misoprostol 400 – 800 mg/day reduced

risk of NSAID induced ulcer

o Meta-analysis : Only misoprostol 800 mg/day reduced ulcer complication by 40% compared with placebo Side effect occurred in 30% responders o Lower dose fails to prevent ulcer complication

Prevention of NSAID related its complications GI Risk

Low

moderate

High

CV risk Low

HIGH

NSAID

NSAID+ PPI Alternatif therapy or misoprostolor COXIB +PPI /nisoprostol

Naproxen + Naproxen + Avoid NSAID and PPI/misoprostolPPI/misoprostolCOXIB

PPI are tha agent of choice for therapy and prophylaxis of NSAID associated UGIE

Thank you