Some Spotlights about Pain management

1. By:Ahmed F. El-Sawy,Fourth Year Student, Faculty of Pharmacy, Alexandria University, Egypt, May 2012.THIS PRESENTATION:I was awarded The Best Presenter of The Academic Year 2011-2012 for this presentation by the Department of Pharmaceutics.

2. Ahmed El-Sawy, 44078

3. Question:6I heard that all analgesics are not safe for children, pregnant and with breastfeeding, is that true?

4. Answer:6 No, not all analgesics are not safe forchildren, pregnant and with breastfeeding. Butthere are some analgesics considered as safe.

5. Pregnant &Children breastfeeding Non-opioid Aspirin analgesics Paracetamol Paracetamol NSAIDs NSAIDs Aspirin

6. Children Paracetamol safe. NSAIDs useful. Ibuprofen 2 years. Naproxen 12 years. Ketoprofen 16 years. Aspirin restricted. Opioids severe pain.Pregnant Paracetamol safe. Aspirin restricted. {Exception?} Opioids restricted. NSAIDs contraindicated during 3rd trimester.Breastfeeding Paracetamol safe. Aspirin restricted. Ibuprofen compatible. Naproxen compatible.

7. Choice of analgesics in Children: Non-opioid analgesics are used in infants and children either alone for minor pain or as an adjunct to opioid analgesics in severe pain (they can reduce opioid requirements perhaps by up to 40% => "opioid dose-sparing" effect.). Paracetamol is frequently used but it lacks any anti-inflammatory effect.

8. NSAIDs such as ibuprofen are useful for minor painespecially when associated with inflammation ortrauma. NSAID Child Age Ibuprofen [OTC ] > 2 years Naproxen [OTC] > 12 years Ketoprofen [OTC] > 16 yearsAspirin is greatly restricted due to its associationwith Reyes syndrome. (children under 16 years)

9. Children severe pain: Opioids ((POM))1. Opioid agonists: (weak opioids & strong opioids)Weak codeine(1st choice weak opioid) & hydrocodone.Strong morphine, hydromorphine & fentanyl.N.B: codeine is demethylated by LMEs to the active morphine, so LME-inhibitors (e.g. quinidine & fluoxetine) can abolish its metabolic activation and activity.2. Opioid partial agonists: pentazocine & buprenorphine.N.B: tramadol (strong centrally acting analgesic with antidepressant activity) used as antidepressant & NOT in acute pain due to high risk of nausea & vomiting.3. Opioid antagonists: naloxone; for opioid intoxication.N.B: Dependence, N, V, C, resp. depression, sedation & tolerance are opioids adverse effects.

10. Adjuvant analgesicsAre drugs with weak or no analgesic action alone, but enhance the action of analgesics when co- administered with them. Antidepressants (TCA: amitriptyline & desipramine). Anticovulsants (Gabapentin, pregabalin & carbamazepine). Topical: lidocaine & capsaicin-OTC. Sk. M. relaxants: Dantroline sod. is the only peripheral acting directly on muscles (less side effects).

11. Choice of analgesics inPregnant and Breastfeeding: Aspirin is classified as FDA pregnancy category C ( adverse effects on animals & no controlled human studies ) risk during Trimesters 1 and 2 and category D ( positive evidence of human fetal risk ) during Trimester 3. Salicylates are excreted in breast milk.Aspirin should be avoided during pregnancy {Exceptions??} and while breast-feeding.

12. AspirinPregnancy 1. impaired platelet function (haemorrhage). 2. delayed onset and increased duration of labour (increased blood loss). 3. with high doses, closure of fetal ductus arteriosus in utero and possibly persistent pulmonary hypertension of newborn. 4. kernicterus in jaundiced neonatesBreast- avoidpossible risk of Reyes syndrome; regularfeeding use of high doses could impair platelet function and produce hypoprothrombinaemia in infant if neonatal vitamin K stores low.

13. =APS=APLS=APLA=Hughes Syndrome=Sticky Blood autoimmune disorder in which the body recognizes certain normal components of blood and/or cell membranes as foreign substances and produces antibodies against them. Patients with these antibodies may experience blood clots, including heart attacks and strokes, and miscarriages. There is no cure for APS, but there is treatment. The treatment of choice for patients with APS who have had a blood clot is anticoagulant therapy; Aspirin and heparin .

14. Paracetamol ( Acetaminophen ) is generally recognized as the treatment of choice of mild-to-moderate pain.It crosses the placenta, but considered as safe during pregnancy.It appears in the breast milk, but considered compatible with breastfeeding.

15. NSAIDs , no evidence that they are teratogenic either in humans or in animals. BUT contraindicated during 3rd trimester of pregnancy; As they Cause: delayed parturition prolonged labor increased postpartum bleeding adverse fetal cardiovascular effectsN.B:Ibuprofen is not excreted in breast milk; so compatible with breastfeeding.Naproxen is also compatible with breastfeeding.

16. ConclusionChildren Paracetamol safe. NSAIDs useful. Ibuprofen 2 years. Naproxen 12 years. Ketoprofen 16 years. Aspirin restricted. Opioids severe pain.Pregnant Paracetamol safe. Aspirin restricted. Opioids restricted. NSAIDs contraindicated during 3rd trimester.Breastfeeding Paracetamol safe. Aspirin restricted. Ibuprofen compatible. Naproxen compatible.

17. Question:7Voltaren and Cataflam both containdiclofenac, but I heard that only Cataflam canbe used by hypertensive patients, what do youthink?

18. Answer:7Voltaren ( contains diclofenac sodium) POM Slower onset of actionCataflam (contains diclofenac potassium) POM Immediate-release tablets with rapid onset of action

19. Diclofenac According to NOVARTIS: 1. NSAIDs, including Cataflam , should be used with caution in patients with hypertension.2. NSAIDs can lead to onset of new hypertension or worsening of preexisting hypertension, either of which may contribute to the increased incidence of CV events. Patients taking thiazides or loop diuretics may have impaired response to these therapies when taking NSAIDs.3. Blood pressure (BP) should be monitored closely during the initiation of NSAID treatment and throughout the course of therapy.

20. Effect of dietary sodium Na & H2O intake on blood retention pressureBlood BloodVolume pressure Cardiac 0utput

21. Non-pharmacologic therapy ofhypertension All patients with prehypertension and hypertension should be prescribed lifestyle modifications, including(1) weight reduction if overweight(2) adoption of the Dietary Approaches to Stop Hypertension eating plan(3) dietary sodium restriction ideally to 1.5 g/day (3.8 g/day sodium chloride)(4) Regular aerobic physical activity(5) moderate alcohol consumption (two or fewerdrinks per day)(6) smoking cessation. Lifestyle modification alone is appropriate therapy for patients withprehypertension. Patients diagnosed with stage 1 or 2 hypertension shouldbe placed on lifestyle modifications and drug therapy concurrently.

22. Conclusion:

23. Question:8Although NSAIDs are used to relieve pain, the administration of some of their dosage forms might be irritant and painful. Comment.

24. Answer:8Oral dosage forms (tablets, capsules & oral suspension):GI side effects associated with NSAID use can be both local and systemic.Local effects occur due to local irritation. Resolved by lowering the dose, changing to another NSAID, taking an enteric form of an NSAID and by taking each NSAID dose with food or a large glass of water.

25. Systemic effects can be extremely serious. Regardless of the route of administration, NSAIDs (with the exception of the selective or COX-2 inhibiting drugs) interfere with prostaglandin synthesis throughout the entire body. the patient is at risk of adverse events such as perforation and hemorrhage of the esophagus, stomach, and the small or large intestine.

26. Patient counseling to GI irritation:1. Dont take an NSAID with alcohol.2. Dont take more than one type of NSAID, with the exception of a small daily dose of aspirin for heart attack prevention.3. Take NSAIDs with a full glass of water or milk, with meals, or with a prescribed antacid.4. Remain upright 30 minutes after administration to reduce gastric irritation or ulcer formation.5. NSAIDs should be used at the lowest effective dose for the shortest time they are needed.6. Avoid fasting because fasting can increase toxicity

27. Topical dosage forms (gels and creams):The use of topical NSAIDs gels or creams to treat pain has been reported to cause a photocontact dermatitis. Most commonly this has occurred with ketoprofen gel with an incidence of 0.013-0.028/1000. Often the reaction appears after stopping the application when the skin is next exposed to sunlight

28. Diclofenac-rectal SuppositoryFrom local rectal irritationto rectal bleeding. (hemorrhoids?)Some NSAID eye drops(irritant)

29. Some Parenteral NSAIDs(painful)

30. Question:9A patient with history of asthma is suffering from low back pain, would a NSAID be safe to use?

31. Answer:9 various stimuli triggers canOnce asthma develops, precipitate asthma. Aspirin and NSAIDs are of the asthma triggers. Handbook of Nonprescription Drugs 16th Ed

32. But!!Not all asthmatic patients have the same triggers, and even for the same patient, his response to a certain particular trigger changes over time.The mechanism of asthma precipitation includes degranulation of mast cells and the release of histamine and leukotrienes that cause severe bronchoconstriction.Asthmatic patients should be cautious about the use of NSAIDs !!!!

33. Why should asthmatic patient be cautious about the use of NSAIDs?Because of increased risk of aspirin sensitivity; 4% of asthmatic patients have this problem( Severe life- threatening symptoms from rashes, nasal congestion, cough, worsening asthma to anaphylaxis ).And there is a significant potential for cross- sensitivity to other NSAIDs such as ibuprofen and naproxen.

34. Role of the pharmacist & patient counseling: The pharmacist can check if a person with asthma has used aspirin or ibuprofen before. If they have done so without problems, they can continue. For sensitive patients, they should be cautioned to:1. Check the labels of headache and pain relief medications to see if they contain any NSAIDs.2. Avoid any other agents that contain salicylates such as oil of wintergreen.

35. Question:10A young woman is suffering severe abdominal pain diagnosed as primary dysmenorrhea. How should this menstrual pain be treated?

36. Answer:10Primary dysmenorrhoea:classically presents as a cramping lowerabdominal pain that often begins during the day before bleeding starts.The pain gradually eases after the startof menstruation and is often gone by theend of the first day of bleeding.N.B: Secondary dysmenorrhea occurs one week before menstruation. pain may get worse once bleeding starts or during sexual intercourse.

37. MedicationThe Cause of the pain of dysmenorrhoea:is thought to be due to prostaglandin (PG-2 ) activity. the use of analgesics thatinhibit the synthesis of prostaglandins is logical. BUTThe pharmacist has to make sure that the patient is not already taking an NSAID.

38. CautionWhen to refer to the doctor1. Presence of abnormal vaginal discharge2. Abnormal bleeding3. Symptoms suggest secondary dysmenorrhea4. Severe intermenstrual pain and bleeding5. Failure of medication6. Pain with a late period (possibility of an ectopic pregnancy)7. Presence of fever

39. Management1. Simple explanation2. sympathy3. reassurance.4. Treatment with simple analgesics is often very effective in dysmenorrhoea.

40. TreatmentsIbuprofen Hyoscine Caffeine (DOC) Aspirin Paracetamol

41. 1.Ibuprofen: (drug of choice ):But !!!(take care in case of previous use of aspirin, and history of GI problems and asthma .)It inhibits the synthesis of prostaglandin.Dose of 200400 mg three times daily with maximum daily dose of 1200 mg.A variety of proprietary brands of ibuprofen is available; Brufen Ibufen Marcofen

42. Caution1) Ibuprofen is contraindicated in case of peptic ulcer.2) Should be taken with or after food to minimize GI problems.3) Should not be taken by anyone who is sensitive to aspirin.4) Should be used with caution in anyone who is asthmatic, because such patients are more likely to be sensitive to ibuprofen.The pharmacist can check if a person with asthma has used ibuprofen before. If they have done so without problems, they can continue.

43. 2. Aspirin: (less effective than Ibuprofen)1. Inhibits the synthesis of prostaglandins.2. Cause GI upsets and is more irritant to the stomach.3. In presence of symptoms of nausea and vomiting with dysmenorrhoea, aspirin is probably best avoided.4. To be taken with or after meals.

44. 3. Paracetamol: (less effective !!! than Ibuprofen and Aspirin ) : Disadvantages Advantages1. Has little or no 1. Useful treatment when the effect on the patient cannot take ibuprofen or aspirin because of stomach levels of problems or potential prostaglandins. sensitivity.2. Less effective for 2. Useful when the patient isthe treatment of suffering with nausea and vomitingdysmenorrhoea. as well as pain, since it does not irritate the stomach.

45. 4. Hyoscine:Smooth muscle relaxant, with antispasmodic action that reduces cramping.Contraindicated in women with glaucoma.Contraindicated with tricyclic antidepressants due to additive anticholinergic effects (dry mouth, constipation, blurred vision).

46. 5. Caffeine: There is some evidence (from a trial comparing combined ibuprofen and caffeine with ibuprofen alone and caffeine alone) that caffeine may enhance analgesic effect. Drinking tea, coffee or cola.

47. Clinical11/2003 8/2001 to TrialOral Contraceptives for Dysmenorrhea in Adolescent GirlsA Randomized Trial Anne Rachel Davis, MD, Carolyn Westhoff, MD, Katharine OConnell, MD, and Nancy Gallagher, RN. This trial demonstrated that a low-dose oral contraceptive was more effective than placebo for moderate or severe primary dysmenorrhea in adolescents. The improvement in dysmenorrhea during OC use was consistent across measures.

48. References(Questions 6 to 10)1) Handbook of Nonprescription Drugs, APhA, 16th Edition.2) Symptoms in the Pharmacy: A Guide to the Management of Common Illness, A. Blenkinsopp, J. Blenkinsopp and P. Paxton, 5th Edition.3) British National Formulary BNF-61.4) Australian Pharmaceutical Formulary and Handbook, 21st Edition.5) Egyptian Drug Guide, 3rd Edition.6) Lippincotts Illustrated Reviews: Pharmacology, 4th Edition.7) Pharmacotherapy Handbook, 7th Edition.8) Novartis Cataflam insert.9) FDA drug risk categorization during pregnancy. http://www.fda.gov10) www.ConsumerReportsHealth.org/BestBuyDrugs11) Oral Contraceptives for Dysmenorrhea in Adolescent Girls, A Randomized Trial; Anne Rachel Davis, MD, Carolyn Westhoff, MD, Katharine OConnell, MD, and Nancy Gallagher, RN. July, 2005.

49. E-mail: [email protected] Or [email protected]

Some Spotlights about Pain management

Health & Medicine

opioids severe pain

pregnant paracetamol safe

breastfeeding paracetamol safe

carolyn westhoff

katharine oconnell

nancy gallagher

high doses

ketoprofen 16 years