1. DR MOHAMMED MALIK AFROZ ANALGESICS

2. SPECIFIC LEARNING OBJECTIVE TO KNOW THE WORKING CLASSIFICATION OF ANALGESICS TO KNOW THE DIFFERENT ANALGESICS AND ITS ACTION TO KNOW THE ADVERSE EFFECT OF THESE ANALGESICS

3. FORMAT DEFINITION AND CLASSIFICATION OF ANALGESICS WORKING MECHANISM OF DIFFERENT ANALGESICS ADVERSE EFFECTS OF THESE ANALGESICS

4. INTRODUCTION ALGESIA ( PAIN): IT IS AN ILLDEFINED, UNPLEASANT SENSATION, USUALLY EVOKED BY AN EXTERNAL OR INTERNAL NOXIOUS STIMULUS. ANALGESIC: A DRUG THAT DIRECTIVELY RELIVEVES PAIN BY ACTING IN THE CNS OR ON PERIPHERAL PAIN MECHANISMS WITHOUT SIGNIFICANTLY ALTERING CONSCIOUNESS.

5. TYPES OF ANALGESICS A. OPIOID NARCOTIC/MORPHINE LIKE ANALGESICS B. NON-OPIOID/NON-NARCOTIC/ASPRIN- LIKE/ ANTI-PYRETIC OR ANTI- INFLAMMATORY ANALGESICS

6. CLASSIFICATION OF NSAID – NON STEROIDAL ANTI INFLAMMATORY DRUGS A. Analgesic and anti – Inflammatory 1.Salicylates : Aspirin, Salicylamide, Benorylate, Diflunisal. 2.Pyrazolone derivatives: Phenylbutazone, Oxyphenbutazone. 3.Indole derivatives : Indomethacin, Sulindac. 4.Propionic acid derivatives: Ibuprofen, Naproxen, Ketoprofen, Fenoprofen, Flurbiprofen. 5.Anthranilic acid derivative: Mephenamic acid.

7. 6.Aryl-acetic acid derivatives : Diclofenac, Tolmetin 7.Oxicam derivatives : Piroxicam, Tenoxicam,Meloxicam. 8.pyrrole derivative : Ketorolac. 9.Sulfonailide derivative : Nimesulide 10.Alkanones : Nabumetone

8. WORKING PRINCIPLE of NSAIDS  Most NSAIDS block cyclo – oxygenase enzymes involved in prostaglandin synthesis which exists in two forms:  COX-1 and COX-2  During inflammation, pain,fever, arachidonic acid is liberated from phospholipids fraction of the cell membrane, arachidonic acid is then enzymatically (CYCLO – OXYGENASE ENZYME) converted to prostaglandin(PGI 2 ) and thromboxane A2 in presence of enzyme cyclooxygenase

9. B.Analgesic poor but good anti – Inflammatory 1.Para – aminophenol derivative : Paracetamole (Acetaminophen) 2.Pyrazolone derivatives: Metamizol (Dipyrone), Propiphenazone. 3.Benzoxazocine Derivative : Nefopam

10. SALICYLATES  Salicylates are esters or salts of salicylic acid  Pharmacological actions of salicylates:  1)C.N.S. produce relief of pain without hypnosis or impairment of mental activity. Used for relief of dull aching, throbbing pain of low intensity coming from integument structures such as muscle and joints, also relieves tooth ache. (Action by acting at thalamic and hypothalamic sites) C.N.S.

11.  Antipyretic action : In fever the thermostatic mechanism is set at a higher level and salicylates act centrally to reset this mechanism at the normal level. (It acts by inhibition of brain prostaglandin synthesis).  GIT produces epigastric distress, nausea, vomiting due to stimulation of C.T.Z. and irritation of gastric mucous membrane. Can cause dyspepsia, erosive gastritis, frank peptic ulceration and gastrointestinal haemorrhage leading to hematemesis or melena. Hence administer after food.  C.V.S: in therapeutic does no adverse effect & in higher doses paralysis of vasomotor center.

12.  Adverse reactions : 1) Allergic reaction: skin rash, urticaria, pruritus angioneuurotic edema, bronchial asthma, anaphylactic shock and thrombo cytopenic purpura. 2) G.I.T : dyspepsia, nausea, vomiting, heart burn. 3) Haemopoietic system : in large doses reduces plasma prothrombin level 4) Liver and kidney : may cause fatty infiltration and acute renal failure 5) Pregnancy lactation :delays onset of labour,and may cause greater blood loss at delivery. pulmonary hypertension in new born.

13. 6) Salicylism : prolonged administration of salicylates may cause a condition of mild salicylate intoxication, head ache dizziness, vertigo, tinnitus, difficulty in hearing dimness of vision, drowsiness, lethargy mental confusions, vomiting,diahorrea. Reye's syndrome :  In children under 12years when treated with aspirin for chicken pox or influenza suffered from Reye's syndrome.

14. Preparation and dosage :  1.Aspirin tablets - 300 mg or 350mg tabs.  2.Injectable preparation (lysine acetylsalicylate 450mg + glycine 50mg/vial for dissolving in 5ml water and i.v injection)

15.  Precautions and contraindications: Allergic Peptic ulcer Bleeding tendencies Chronic liver diseases Children suffering from chicken pox or influenza Pregnant women-low birth weight babies.

16.  Therapeutic uses : 1.Local action – keratolytic, Fungistatic. 2.Analgesic 3.Antipyretic. 4.Anti inflammatory. 5.Acute rheumatic fever 6.Rheumatoid arthritis 7.Osteoarthritis 8.Postmyocardial infarction and post stroke patients

17. PHENYLACTIC ACID DERIVATIVES DICLOFENAC SODIUM: Analgesic,antiinflammatory and antipyretic drug Inhibits PG synthesis and short lasting antiplatelet action Its concentration in synovial fluid is three times more than in plasma. PREPATATION:-  Dosage:60mgbid/tid.i.m-75mg 1-2 times/day. Diclofen,dicloran,diclomol,inac,oxalgin,

18.  Indications: Osteoarthritis, rheumatoid arthritis, ankylosing spondylitis,bursitis Dysmenorrhoea, Post traumatic and postoperative inflammatory conditions  Adverse effects: Epigastric pain,nausea, dizziness, headache, rashes Aplastic anemia

19. PROPIONIC ACID DERIVATIVES IBUPROFEN, NAPROXEN, FENOPROFEN, FLURBIPRCFEN, KETOPROFEN:-  Have analgesic,anti pyretic and anti inflammatory properties similar to aspirin but are better tolerated orally although they may produce gastric irritation and ulceration.

20. They are highly bound to plasma protein 90-99% As they inhibit platelet function should be avoided with anticoagulants Better tolerated then aspirin Not to be prescribed in pregnant women and peptic ulcer patient  Uses:- patients with Rheumatoid arthritis, ankylosing spondylitis who cannot tolerate aspirin. Soft tissue injuries fractures,vasectomy, tooth extraction, post partum and post operatively It is available as an `Over The Counter Drug’

21. Adverse effects:- 1. Gastric discomfort, nausea, vomting-common. 2. Gastric erosion, occult blood loss- rare. 3. CNS:- headache, dizziness, blurring of vision, tinnitus & depression. 4. Rashes, itching& other hypersensitivity reactions.  Contraindications:- Avoided to pregnant women, peptic ulcer patients.  DOSAGE:1.2-1.8 g/day. BRUFEN,IBUGESIC,IBUGIN. IBUBROFEN(400mg)+PARACETMOL(325 mg) ANAFLAM,BRUCET,CALPOL,FLEXON,COBIFLAM, MAGADOL.

22. ANTHRALIC ACID DERIVATIVES  MEFENAMIC ACID : It is an anthralic acid derivative Useful in chronic dull aching pain. It is a weaker analgesic than aspirin. Toxic reaction include gastric upset, diarrhoea, dizziness, head ache, skin rashes, haemolytic anemia and blood dyscrasias. It exerts peripheral as well as central analgesic action Indicated primarily as analgesic in muscle joint and soft tissue pain 250-500mg TID

23. PYROLO PYRROLE DERIVATIVE  KETOROLAC. Highly potent member of a new class of analgesic compound. Both anti – Inflammatory and analgesic but more systemic analgesic than anti inflammatory, potent than indo – methacin, naproxen, phenyl – butazone..  Dosage:30-60mg IM. Oral- 20mg initially then 10mg 4-6 hrs. ketonov, ketorol dt.

24.  Adverse effects:- nausea, abdominal pain, dyspepsia, ulceration, loose stools, drowsiness, headache, dizziness, nervousness, pruritis, rise in serum transaminase.  Contraindications:- Should not be given to patients on anticoagulants.  Uses:-  1)post operative pain, acute musculoskeletal pain-15 -30 mg i.m. or i.v. for every 4 to 6 hours. 2) renal colic, migraine, pain due to metastasis.

25. SULFONANILIDE DERIVATIVE Nimesulide:  Newer NSAID is a relatively weak inhibitor of PG synthesis (selective for COX-2 )  Used primarily for short lasting painful inflammatory conditions like sports injuries, sinusitis and other ear,nose,throat disorders, dental surgeries, bursitis, low backache,dysmenorrhoea, postoperative pain and osteoarthritis.  It can be given in asthmatics.  CONTRAINDICATIONS:gi bleed, peptic ulcer, hepatic dysfunction, pregnancy, lactation.

26.  ADVERSE EFFECTS : epigastralgia, heart burn, nausea, loose motions.  Dermotological:-rash, pruritis.  CNS:- somnolence, dizziness.  Renal:-hematuria,  Liver:- hepatic failure.  Dosage : 100 mg BD, Completely absorbed orally,metabolized and excreted in urine.

27. VALDECOXIB Indications :  Signs and symptoms of osteoarthritis and adult rheumatoid arthritis  Pain associated with dysmenorrhoea  Post surgical analgesia Mechanism of action:  Selective COX-2 inhibitor

28.  Dosage and administration : In osteoarthritis and rheumatoid arthritis (10mg once daily) Pain associated with primary dysmenorrhoea 20mg twice daily as needed Peak plasma concentration: 161.1  Adverse effects: Increase incidence of nausea in some trials  Dos age and ad min istr atio n :

29. ROFECOXIB Indications:  For relief of signs and symptoms of osteoarthritis  For management of acute pain in adults  For treatment of primary dysmenorrhoea  for relief of postorthopedic surger y pains

30. Pharmacokinetic profile : Rofecoxib is moderately 87% bound to plasma proteins The half life is approximately 17 hours,allowing for once daily dosing Available as 50mg, 25mg, 12.5mg and bottle of 60ml suspension Administered orally Eliminated by hepatic metabolism, with less than 1% recovered unchanged in urine

31.  Mechanism of action: Inhibition of prostaglandin synthesis, primarily via inhibition of cyclooxygenase-2 (COX-2) isoenzyme, Rofecoxib is 800 times more selective for COX-2 relative to COX-1  Adverse effects: Diarrhoea Headache Insomnia Edema Nausea Upper respiratory tract infections

32.  Osteoarthritis : The recommended starting dose of rofecoxib is 12.5 mg once daily. The maximum daily dose is 25mg Management of acute pain and treatment of dysmenorrhea The recommended oral dose is 50mg once daily for a maximum of 5 days

33.  USE IN CHILDREN Safety and effectiveness in pediatric patients below the age of 18yrs have not been evaluated  USE IN PREGNANT WOMEN Rofecoxib should only be used in pregnant women only when the benefit clearly outweighs the potential risk In late pregnancy it should be avoided because it may cause premature closure of the ductus arteriosus It should be avoided in nursing women

34. COMBINATION NSAID-OPIATE ANALGESIC MEDICATIONS TYLENOL(acetaeminophen 300mg + codeine 30mg) INDICATIONS: moderate to severe pain CONTRAINDICATIONS: allergy, renal or liver impairment SIDE EFFECTS: nausea, abdominal pain, head ache, dizziness, rash, constipation, fluid retention, peripheral edema. EMPIRIN(aspirin 325mg + codeine 30mg) – moderate to severe pain COMBUNOX(ibuprofen 400mg + oxycodone 5mg) – moderate to severe pain. VICODIN, LORCET, LORTAB(hydrocodone 5mg + acetoaminop hen 500mg)

35. USE OF ANALGESIA IN PREGNANCY AND LACTATION:  NSAIDS may predispose to ineffective contractions during labour, increased bleeding during delivery or premature closure of the ductus arteriosus of the heart. NSAIDS are therefore contraindicated in the third trimester.

36. USE OF ANALGESIC FOR ELDERLY PATIENTS:  Acetaminophen is the analgesic of choice in the elderly  NSAIDS are a major concern due to the potential for GIT bleeding,which become more likely with increasing age,if there is history of gastric bleeding and if high doses of NSAIDS or multiple NSAIDS are used.

37. Thank you