NSAIDs include-
Propionic acid- Fenoprofen, Flurbiprofen, Ibuprofen, Ketoprofen, Naproxen, Naproxen Sodium, Oxaprozin
Acetic acids-  Diclofenac sodium, Etodolac, Indomethicin, Ketorolac, Nabumetone, Sulindac, Tolmetin
Fenamates (anthralic acids) - Meclofenamate, Mefenamic acxid
Oxicams- Piroxicam
Refer- Ibuprofen

Interacting drugs - summary

NSAIDs +

+ Anticoagulants 
Coadmnistration  prolong prothrombin time (PT).
Consider effects of NSAIDs, on platelet function and gastric mucosa.
Monitor PT and  patients closely,

+ ACE inhibitors 
Antihypertensives effects of captopril  blunted or completely abolished
by indomethacin

+ Beta blockers
Antihypertensive effects of beta-blockers impaired.
Sulindac and naproxen did not affect atenolol.

+ Cyclosporine
Naphrotoxicity of both agents increased

+ Digoxin
Ibuprofen and indomethicin increase digoxin levels

+ Dypridamole
Indomethicin and dipyridamole coadministration may agument
water retension.                 

+ Hydantoins
Serum phenytoin levels increased, resulting in increase in
pharmacologic and toxic effects of phenytoin

+ Lithium
Serum lithium levels increased, however sulindac has no effect or
 may decrease lithium levels   

+ Loop diuretics 
Effects of loop diuretics  decreased

+ Methotrexate
Risks of methotrexate toxicity (eg Stomatitis,bone marrow suppression,
  nephrotoxicity)  increased

+ Penicillamine
  Indomethacin increase bioavailabilty of penicillinamine

+ Sympathomimetics
   Indomethacin and phenylpropanolamine coadministration result in
     increased blood pressure

+ Thiazide diuretics
   Decreased antihypertensive and diuretic action of thiazides occur with
    concurrent indomethacin. Naproxen has also been implicated.
    Sulindac may  enhance effects of  thiazides

+ NSAIDs

Cimetidine+
 NSAIDs plasma concentrations  increased or decreased by cimetidine,
  Also, indomethacin and sulindac  increased  ranitidine and cimetidine
   bioavailability

Probenecid +
Probenecid increase  concentrations and possibly  toxicity of the
  NSAIDs

Salicylates +
Plasma concentrations of NSAIDs decreased by salicylates.
Avoid  concomittant use, since it offers no therapeutic advantage
and  significantly increase incidence of GI effects.

Dimethyl sulfoxide + DMSO + Sulindac
 DMSO  ( Dimethyl sulfoxide ) decrease the formation of active metabolite 
 of sulindac,  resulting in a decreased therapeutc effect.  with
                                          

 
GI-

Nausea (with or without vomiting)  ( 9%  diclofenanc, etodolac,  fenoprofen, fluribiprofen,
indomethicin, nabumetone , naproxen, oxaproxen sulindac,  Ketoprofen > 3%,

Ketorolac 12%, meclofenamate 11%, tometin 11%

Vomiting - diclofenac < 1%, etodolac  3 %, fenoprofen 8%, flurbiprofen 1 to 3%
 ketoprofen > 1%, ketorilac < 3%, nabumetone  3%, naproxen < 1%,
oxaproxen < 3%, piroxicam < 1%, tolmetrin  9% 

 Diarrhea -  diclofenac 8%, etodolac 7%, flurbiprofen7%,
 indomethicin < 3%, ketoprofen  > 3%, ketorolac 7%, meclofenamate  30%,
 mefenamic acid 5%, nabumetone  14%, naproxen < 3%, oxaproxen 8%,
  piroxicam  3%, sulindac  9%, tolmetrin  9%

 Constipation- diclofenac  9%,  etodolac  3%,  fenoprofen  9%, flurbiprofen  3%
 ibuprofen < 3%,  indomethicin < 3%, ketoprofen  > 3%,ketorolac <3% ,
.meclofenamate  3%, nabumetone   9%, naproxen  9 %, oxaproxen  9%,
  piroxicam  3%,  sulindac 9%, tolmetrin  <3 %

  Abdominal distress/cramps, pain -  diclofenac  9%, etodolac  9%,fenoprofen < 3%,
   flurbiprofen < 3%,  indomethicin < 3%, ketoprofen  > 3%, ketorolac 13 %,
   meclofenamate  9%,  nabumetone  12%, naproxen   9 %, oxaproxen <3 %,
   piroxicam  3%, sulindac 10%, tolmetrin  9%

  Dyspepsia-  diclofenac  9%, etodolac 10%, fenoprofen  9 %, flurbiprofen  9%,
  ibuprofen  9 %, indomethicin  9%,  ketoprofen  11%, ketorolac 12 %,
  nabumetone  13%, naproxen   9 %, oxaproxen  9%, piroxicam  9%,
   sulindac  9%, tolmetrin  9%

  Flatulence-  diclofenac 3%, etodolac  9%, fenoprofen <3 %, flurbiprofen  3%
  indomethicin < 1%, ketoprofen  > 3%, ketorolac <3 %, meclofenamate 9%, 
  nabumetone   9%, oxaproxen < 3 %, piroxicam  3%, sulindac  3%,
  tolmetrin  9%
                  
  Anorexia  -   etodolac  < 1%,  fenoprofen <3 %, indomethicin < 1%,  ketoprofen  > 1%
                       meclofenamate 1 to 3%, nabumetone  < 1%, oxaproxen < 3 %, piroxicam < 3%,
                       sulindac 1 to 3%, tolmetrin 1 to 3%

  Stomatisis - diclofenac < 1%, etodolac < 1%, flurbiprofen  <1%, indomethicin < 1%,
                       ketoprofen  > 1%, ketorolac <3 %, meclofenamate 1 to 3%, nabumetone 1 to 3%
                       naproxen  < 3 %, oxaproxen < 1 %, piroxicam 1 to 3%, sulindac  <1%, tolmetrin  <1%

CNS-             dizziness( 3 to 9% -flurbiprufen and diclofenac 1% to 3%)
                      headaches, (ketorolac 17%, fenoprofen 15%, indomethicin 11%, diclofenac , flurbiprufen,
                       meclofenamate , nabumetone, naproxen and tolmetin 3 to 9%, ketoprofen > 3%)
                       somnolence/drowsiness, (fenoprofen 15%, naproxen 3 to 9% , oxaprozin < 3% )

                      lightheadedness, verigo, nervousness, excitation, paresthesia, peripheral neuropathy,
                      tremor, convusions, aggravation of epilepsy and parkinsonism, myalgia, muscle weakness,
                       asthenia, somnolence, malaise, fatigue, insomnia, confusion, inability to concentrate,
                      depression, emotional lability.

Cardiovascular- congestive heart failure, exacerbation of angitis, hypotension, hypertension, palpitations,
                       arrhythmias, tachycardia, vasodilation, peripheral edema anf fliud retention, chest pain,
                       sinus bradycardia, peripheral vasculitis

Renal-           hematuria, cystitis, urinary tract infection, azotemia, nocturia, proteinuria, elevated BUN,
                       increased serum creatinine, decreased creatinine clearance, polyuria, dysuria, urinary
                       frequency, pyuria, oliguria, anuria, renal insufficiency, including renal failure, acute renal
                       failure in patients with impaired renal function, renal papilary necrosis,nephrosis,
                      nephrotic syndrome,glomerular and intestinal nephritis, urinary casts. 

Hematologic- neutropenia, eosinophillia, leukopenia, pancytopenia, thrombocytopenia, agranulocytosis,
                      garnulocytopenia, aplastic anemi, hemolytic anemia, decreases in hemoglobin and
                       hematrocrit, anemia secondary to obvious or ocult bleding, hypocaogulability, epistaxis,
                       menomerorrhagia, menorrhagia,hemorrhage, bruising, bone marrow depression, mild
                      hepatic toxicity.  

Special senses- visual disrurbances,blurred vision, photophobia, amblyopia, scotoma, swollen ordry
                        irritated eyes, corneal deposits, retinal degeneration, retinal haemorrhage and
                       pigmentaion change, conjuntivitis,iritis, reversible loss of color vision, hearing dusturbances
                       or loss, deafness, ear pain, chanage in taste (metallic or bitter ) diplopia, optic neuritis,
                       catracts, tinnitus, parosmia

Hypersentivity- asthma, amaphylaxis, acute respiratory distress, rapid fall in blood pressure resembling
                    shock-like state angioedema, dyspnea, angitis

Dermatologic- rash, erythema, urticaria, desquamation, vesilobullous eruptions, cutaneous vasculitis,
                     toxic epidermal necrolysis, exfoliative dermatitis, erythema mutiforme, Stevens-Johnson
                     syndrome, erythema nodosum, angioneurotic edema, ecchymosis, petechiae, purpura
                      alopecia, pruritus, eczema, skindiscoloration, hyperpigmentation,oncychosis,
                      photosentivity, skin irritation, peeling, rash/dermatitis including maculopapular type. 

Metabolic- decreased or increased appetite, weight decrease or increase, glycosuria, hyperglycemia,
                   hyperkalemia, hyponatremia, flushing or sweating, menstrual disorders impotence, vaginal
                    bleeding, diabetes mellitus.

Miscellaneous- thirst, pyrexia, (fever and chills) sweating, breast changes, gynaecomastia, muscle
                   cramps, facial edema, serum sickness, pain, aseptic menignitis.

Active petic ulcer,Hypersens,recent GI bleeding disorders, neonates.

Warnings-

GI effects- serious GI  toxicity  such as bleeding, ulceration and perforation can occur at any time,  with or without warning symptoms, in patients treated chronically with NSAIS therapy
 Although minor upper GI  problems (eg dyspepsia)  are common, usually developing early in therapy   remain alert for uncertion and bleeding in patients treated chronically with NSAID  even in absence of  previous GI  tract symptoms

Do not give indomethicin or sulindac to patients with active GI lesions or a history of recurrent GI lesions, unless the very high risk is warranted risk and patients can be monitored very closely

If diarrhea occurs with mefanamic acid or meclofenamate reduce dosage or temporarily discontinue use.

CNS  effects- indomethicin may aggravate depression or other psychiatric disturbances, epilepsy,  and parkinsonism, use with considerable caution.

  Some of these agents may cause headache ( highest incidence with fenoprofen, indomethicin,   and ketorolac ). If headache pesists despite dosage reduction, discontinue use           

Renal effects- acute renal insufficiency , intestinal nephritis, hyperkalemia, hyponatremia, and  renal papillary necrosis may occur

Acute renal insufficiency - patients with preexisting renal disease or compromised  renal pefusion  are at greatest risk. 

Renal function impairment- NSAID  metabolites are eliminated  primarily by kidneys, use with caution. Assess renal function before and during therapy. Monitor serum and creatinine  clearance. Reduce dosage to avoid excessive accumulation

Hypersensitivity- A potentially fatal apparent hypersensitivity syndrome has occured with sulindac this syndrome may include constitutional symptoms, cutaneous findings, involvement of major organs or other less specific findings

Anaphylactoid reactions - these reactions have occurred in patients with aspirin hypersensitivity and  in patients who continued with tolmetrin, then restarted it. These reactions appear to occur more often with tolmetrin than other NSAIDs not structurally related.

Elderly- age appears to increase the possibility of adverse reactions to NSAIDs. The risk of serious  ulcer disease is increased in elderly patienrs (. 65 yerars of age) taking NSAIDs. This risk appears to  increase with dose.

Pregnancy- avoid during pregnancy especially in the third trimester.

Lactation- do not use use in nursing mothers because of the effect on infants cardiovascular system.

Children-  Safety and efficacy of NSAIDs in children are not established

 Special precautions:
Asthma, renal or hepatic disorders, bleeding disorders, cardiovascular disease. Patients
receiving coumarin anticoagulants. Aspirin, NSAID induced allergy. Pregnancy.

Monitoring- serious GI tract ulceration and bleeding can occur without warning . Follow chronicaly  treated  patients for signs and symptoms of ulceration and bleeding , inform them of the importance of this follow-up.

Steroid dosage-  if reduced or eliminated during therapy, reduce slowly and observe patient slowly for evidence of adverse effects.

Platelet aggregation- NSAID can inhibit paltelet aggregation,the effect is quantitatively less and shorter duration than seen with aspirin.Use with caution in persons with intrinsic coagulation defects and in those on anticoagulant therapy.

Hematologic effects- frequently determine hemoglobin values in patients with initial values < 10g/dl who are to receive long term threapy.

Cardiovascular effects- may cause fluid retention and peripheral edema. Use caution in compromised cardiac function hypertension or other conditions predisposing to fluid retention.
 
Ophthalmic effects- perform ophthalmic studies in patients who develop eye complaints during therapy.Effects include blurred or diminished vision, changes incolorvision, corneal deposits and retinal disturbances.

Infection- NSAIDs may mask the usual signs of infection. Use with extra care in the presence of existing controlled infection.

Hepatic effects- if symptoms or signs suggesting liver dysfunction or an abnormal test occurs, evaluate  for more severe hepatic reactions. Discontinue treatment if abnormal test persist or worsen or if clinical signs and symptoms consistent wiith liver disease develop or if systemic manifestations occur  (eg. eosinophillia)

Pancreatitis- has occured in patients receiving sulindac. If pancreatis is suspected discontinue drug,  start supportive therapy and monitor closely.

Auditory effects- perform periodic auditory function tests during chronic fenoprofen therapy in patients  with impaired hearing.

Dermatologic effects- promptly discontinue mefanamic acid if rash appears.

Concomittant therapy- do not use naproxen sodium and naproxen concomittantly, both drugs circulate as naproxen anion.

Photosentivity- may occur. Take protective measures.

    
1. Side effects of NSAIDs  can cause discomfort and rarely, more serious side effects such as  GI bleeding which may result in hospitalisation and even fatalites. NSAIDs  are often  essential    in manangement of arthiritis and have a major role  in treating pain but they also may  be commonly employed for less serious conditions. Appraise potential patients of potential risks. 

2. Avoid aspirin and alcoholic beverages while taking medication.

3. If GI upset occurs, take with food, milk or antacids. For GI upset with tolmetin, use antacids other  than sodium bicabonate, bioavailbility is affected by food and milk.
 If GI symptoms persist, consult physician

4. May cause cause drowsiness, dizziness, or blurred vision, patients should observe   caution while driving or peforming other tasks  requiring alertness 

5. Notify physician if skin rash, itching, visual disturbances, weight gain, edema, black stools, or persistent headache occurs.

6. Mefanamic acid and meclofenamate - if rash , diarrhea or other digestive problems occur,  discontinue use and consult a physician

7. Ibuprofen ( otc use ) - do not take for > 3 days for fever or 10 days for pain, If these symptoms  persist, worsen or if new symptoms develop, contact a physician  

8. Allergies-  Tell your doctor if you have ever had any unusual or allergic reaction to NSAID
    or any other  medicines e.g.   Aspirin or other salicylates
   

9. Diet- Make sure your doctor knows if you are on any special diet, such as low-sodium
   or low sugar. Some of these medicines contain certain sodium or sugar.

10. Pregnancy- If you are pregnant do not take any of these medicines including
   non-prescription OTC drugs- ibuprofen or naproxen without dscussing its use with your   doctor.

11. Breast feeding-    Indomethicin- passes into breast milk and has been reported to cause unwanted effects in nursing  babies. Meclofenamate- use not recommended.     

12. Children-
      Ibuprofen- ibuprofen has been tested in children 6 months of age and older

     Not shown  to cause any different side effects than they do in adults  Indomethicin and  

    Tolmetin- indomethicin and tolmetin and have cause any different  effects than they do in  adults
      Naproxen- studies in children have shown that skin rash may be more likely  to occur.
      Oxaprozin- oxaprozin has been used in children with arthiritis.
       Phenylbutazone- use of phenylbutazone in children up to 15 years of age not  recommened.
      Other anti-inflammatory drugs- no specific information on use in children available.

13. Elderly- Certain side effects such as confusion, swelling of the face, feet or lower legs
      or sudden  decrease in the amount of urine may occur in elderly patients.
      With phenylbutazone ,blood problems  may also occur in the elderly.

13. Other medicines-  Let your doctor know if you are taking any other medicines .e,g.  Anticoagulants or
       Cefamandole or  Cefoperazone, Heparin - change of bleeding may be increased        
                                  
14. Other medical problems- Make sure you tell your doctor, if you have any other medical
       problems-  Alcohol abuse or Bleeding problems or Colitis ,Crohns disease, diverticulitis
      ,stomach ulcer, or other stomach or intestinal problems - chance of side effects may
       be increased
                              
 15 Missed dose-  If you are taking the medicine regularly and you miss a dose, take it as
      soon as possible.  However ifis time for the next dose, skip the missed dose and go    back  to your regular  dosing schedule.  Do not double doses.

 17. Storage- Keep the medicines our of reach of children
          Store the medicines away heat and direct light. Do not store tablets  or capsules
          in the bath room, in damp places near the kitchen sink .
          Heat and moisture will cause the medicines to break down             
          Do not store out dated medicines  or medicines no longer needed.
          Make sure that  all discarded medicines are kept out of reach of children      
     

Delays absorption but not very significant

Pregnancy-

Category B- Ketoprofen, naproxen, flubiprofen, diclofenac. Category C- Etodolac, ketorolac, mefanamic acid, nabumetone, oxaprozin, tolmetin

Safety for use during pregnancy not established. Use is not recommended.

Lactation- Most NSAIDs are excreted in the breast milk.