1. OTC analgesics & antipyretics

2. OTC analgesics/antipyretics
OTC drugs available in the USA:
salicylates (aspirin, choline salicylate, Mg salicylate and Na salicylate)
acetaminophen
ibuprofen
Naproxen Na
Ketprofen
All are similar but Naproxen has slightly a longer duration of action

3. OTC analgesics/antipyretics
The strength of these products available OTC is less than same products available on prescription
Onset of all of these drugs is ½-1 hr, maximum effect between 2-3 hrs and duration of action is 4-6 hrs.
All will reduce temp by (1.1°- 1.7°C),

4. Dosage of common OTC drugs
Agent
Dosage (maximum)
Analgesic
Anti-inflammatory
Acetaminophen
mg q4h (4000 mg) -
Aspirin
10-15 mg/kg/dose q 4-6 h
(4 g/day)
mg /kg/day q 6-8 hrs
Ibuprofen
mg q 4-6 hr (1,200 mg/day)
mg 3-4 td (3,200 mg in 2 wks)
Naproxen Na
220 mg q 8-12 hr
(660 mg/day)
mg 2 t d
(1,650 mg/day for 2 wks)
Ketoprofen
mg q 6-8 hr
(75 mg/day)
50-75 mg, 3-4 t d
(300 mg/day)

8. Salicylates Aspirin Active moiety: salicylic acid (irritating)
Choline salicylate: stable in oral solution
Mg salicylate + Na salicylate: can be used for patients allergic to aspirin
Inhibit COX in periphery and CNS
Aspirin
Indication: (1) mild to moderate pain of musculoskeletal NOT visceral origin. (2) Fever
DOC in RA

9. Aspirin
Overdose:
with chronic therapy (100 mg/kg per day for at least 2 days)> mild intoxication- HA, dizziness, N & V, hyperventilation, mental confusion, lassitude….
Acute intoxication- dose-dependent:
<150 mg/kg mild
mg/kg moderate
>300 mg/kg severe

10. Aspirin
Symptoms: lethargy, tinnitus, tachypnea, pulmonary edema, convulsions, coma, haemorrhage and dehydration.
First respiratory alkalosis followed by metabolic acidosis (why?)
Hypoglycemia (why?) and fever may be severe in children.
Bleeding from GIT or mucosal surface > petechiae at autopsy

11. Petechiae

12. Aspirin
OD Management: ipecac syrup, gastric lavage, activated charcoal
Administration of ipecac syrup or any oral solution to a pt who’s convulsing is absolutely C/I aspiration
in children < 1yr old > vomiting should be induced only under medical supervision

13. Aspirin Pharmacokinetics:
- ASA is absorbed by passive diffusion of the nonionised from from the stomach/small intestine
- Rectal absorption is slow and unreliable (60-75%)
Enteric-coated ~:
1. Eliminates local gastric irritation
2. Delayed absorption by food (why?)
3. Not suitable for acute pain relief. Preferred for RA (why?)
Buffered ~:
1. no difference in gastric damage from plain ASA
2. Absorbed more rapidly than non buffered ASA
Effervescent ~: rapidly absorbed, but no evidence if rapid analgesia. Avoid in patients with restricted Na+ intake (CHF, RF, HTN)

14. Aspirin Therapeutic Considerations: acetyl group (good and bad?!!)
1. Impaired platelet aggregation
acetyl group (good and bad?!!)
ASA should be D/C 48 hrs before surgery and shouldn’t be used as analgesic in dental extraction, or surgery etc
C/I: haemophilia, hypoprthrombinemia, vit K deficiency, Hx of bleeding or PUD

15. Aspirin
If peripheral anti-inflammatory effect is not needed > acetaminophen is best alternative
If peripheral anti-inflammatory effect is needed but C/I > the Rx drugs salsalate or choline Mg trisalicylate are best alternatives (do not affect platelets) or other NSAIDS
Chronic ASA use >> chronic blood loss from GIT >> iron deficiency anaemia

16. Aspirin 2. Effect on uric acid elimination (dose-dependent)
Avoid all salicylates in all patients with Hx of gout or hyperuricemia (why?)
1-2 g/day plasma level of uric acid
2-3 g/day little/ no effect
> 5 g/day plasma level of uric acid
(Toxicity)

17. Aspirin 3. GI irritation & bleeding 4. Aspirin Allergy
two mechanisms of gastric damage (what are they?)
Avoid in: elderly, PUD or bleeding, alcoholic liver disease
Ingesting alcohol + ASA= incidence of GI bleeding
4. Aspirin Allergy
- If you experience gastritis or heart burn after aspirin use
NOT
hypersensitivity
Common S.E
NOT C/I
for future use

18. Aspirin Aspirin allergy is uncommon, < 1% of patients
within 3 hours of ASA ingestion: urticaria, oedema, difficulty in breathing, rhinitis, bronchospasm or shock
Most common in patients with asthma, urticaria or nasal polyps
15% cross-reaction with Tartrazine (colour)
Cross reaction with other NSAIDS (rate for acetaminophen 6% and for ibuprofen 97%)
patients allergic to ASA > avoid all NSAIDs > use acetaminophen or nonacetylated salicylates (eg, Na salicylate) instead

19. Aspirin 5. Pregnancy/ Lactation - Avoid ASA in both
Avoid ASA especially during the 3rd trimester/pregnancy
Why? > Effect of mother (=3), effect on fetus (haemorrhage, growth retardation, congenital intoxication, premature closure of ductus arteriosus > still birth)
Paracetamol is the analgesic of choice in these periods
However,…..

20. Updates: NSAIDS and Pregnancy
September 6, 2011 — Use of nonaspirin nonsteroidal anti-inflammatory drugs (NSAIDs) in early pregnancy is linked to twice the risk for miscarriage, according to the results of a nested case-control study reported online September 6 in the Canadian Medical Association Journal.
Of the 4705 patients with spontaneous abortion, 352 (7.5%) had NSAID exposure, as did 1213 (2.6%) of 47,050 control participants. The use of nonaspirin NSAIDs during pregnancy was significantly associated with the risk for spontaneous abortion, after adjustment for potential confounders. There was no apparent dose-response effect.

21. Aspirin Unlabelled/Investigational Use:
Low doses have been used in the prevention of pre-eclampsia, recurrent spontaneous abortions, pematurity, fetal growth retardation (including complications associated with autoimmune disorders such as lupus)
60-80 mg/day during gestational weeks (patient selection criteria not established)

22. Aspirin 6. Reye’s Syndrome
Acute potentially fatal illness (50%) occurs almost exclusively in children < 15 years of age
Produces fatty liver + encephalopathy
Occurs usually within 1-7 days of viral infections with influenza or chickenpox.
Ch.Ch: persistent vomiting, CNS damage, signs of hepatic injury & stupor > convulsions > coma
Nonacetylated NSAIDs > not associated with Reye’s

23. International Aspirin/Reye’s Syndrome Warning statements
UK: March 2002, the CSM recommended a revised warning statement:“Do not give aspirin to children under 12 years unless medically indicated, and avoid in children aged up to and including 15 years if feverish”.
USA: “Children and teenagers who have or are recovering from chicken pox, flu symptoms or flu should NOT use this product. If nausea, vomiting, or fever occur, consult a doctor because these symptoms could be an early sign of Reye’s Syndrome, a rare but serious illness.”  final rule issued on 17 April 2003, on all oral and rectal OTC drug products containing aspirin, and on OTC drug products containing non-aspirin salicylates

24. Australia, April 2004

25. NSAIDs- D#D interactions
Analgesic
Drug
Potential Interaction
Management/
Prevention measures
Aspirin
Valproic acid
valproic acid level
> toxicity
Avoid concurrent use, use Naproxen
Salicylates
sulfonylureas
hypoglycemic effect
Avoid concurrect use, monitor glucose level whn changing salicylate level
NSAIDs (several)
Anti-hypertensive agents
anti-HTN effect, hyperkalemia with K-sparing D or ACE-I
Monitor BP, K level and cardiac function

26. NSAIDs- D#D interactions
Analgesic
Drug
Potential Interaction
Management/
Prevention measures
Salicylates
Uricosoric agents
uricosoric effect,
uric acid
Avoid concurrent use, avoid all NSAID in patients with gout, hyperurecemia
NSAIDs
Alcohol
GI bleeding risk
Minimise alcohol intake while using NSAIDs
Warfarin
risk of bleeding
Avoid concurrent use

27. NSAIDs- D#D interactions
Analgesic
Drug
Potential Interaction
Management/
Prevention measures
NSAIDs (several)
Methotrexate (MTX)
MTX clearance
> MTX toxicity> pancytopenia
Avoid NSAIDs with high dose MTX therapy, monitor with concurrent use.
Ibuprofen, high dose of salicylates
Phynetoin
Displacement from plasma proteins >
phynetoin toxicity
Monitor unbound phynetoin level, adjust dose
Digoxin
renal clearance
Monitor digoxin level, adjust doses
Aminoglycosides
Monitor antibiotics level, adjust doses

28. Non-acetylated salicylates
choline salicylate:
an oral liquid preparation
Fishy odour> mask by fruit juice, carbonated beverages, water but NOT alkaline solution (eg. Antacids; why?)
Not as effective antipyretic as ASA or acetaminophen in children

29. Non-acetylated salicylates
Mg salicylate:
- avoid in case of compromised renal function
- could be used by ASA allergic patients
Na salicylate:
- avoid in patients with Na restriction intake

30. Comparison of aspirin and non-acytelated salicylates
Less effect on platelet aggregation
Less GI erosions and bleeding
Fewer renal complications
cross-reactivity in aspirin intolerant patients
Less anti-inflammatory effect

31. Acetaminophen
An effective analgesic and antipyretic (works centrally), no anti-inflammatory (not used clinically for this purpose)
Used for mild to moderate pain of non-visceral origin
Paediatric dose= mg/kg q 4-6 hrs
Adult dose: mg q 4-6 hrs or 1000 mg 3-4 times daily (do not exceed 4g/day)
Rectal bioavailability=50-60% (compare with ASA)

33. Children tips! 
capsule content > emptied into a teaspoon containing a small amount of drink or soft food and NOT into a glass of liquid (why?)
Mixing with a hot beverage can result in bitter taste.
Recalculation of paediatric dose according to body weight is important every time as under-dose may occur sometimes (why?)

34. Acetaminophen- Overdose
Hepatotoxicity after ingestion of a single dose of g ( mg/kg)
 g  fatal
first 2 days: abdominal pain, N & V, drowsiness, confusion
2-4 days: clinical manifestaions of hepatotoxicty: ALT & AST, bilirubin in plasma, prothrombin time

35. Acetaminophen- Overdose
The most serious Ad.E of acetaminophen OD is Hepatic Necrosis (dose dependent)
Renal tubular necrosis and hypoglycemic coma may also occur
Management: immediate vomiting induction by ipecac syrup and activated charcoal
If activated charcoal was used at home > should be made known to emergency medical personnel (why?)

36. Acetaminophen- Therapeutic Consideration
Acetaminophen is safe in pregnancy and breast-feeding
The only Ad. E in nursing infants is a rarely occurring maculopapular rash

37. Acetaminophen- Therapeutic Consideration
~ is hepatotoxic if > 4 g/day especially for people at risk
Avoid alcohol and fasting while using acetaminophen
No significant D#D interactions with acetaminophen

38. The appropriate dosing for acetaminophen is 10 to 15 mg/kg per dose given every 4 to 6 hours orally, which produces an antipyretic effect within 30 to 60 minutes in approximately 80% of children. The appropriate dosing for ibuprofen is 10 mg/kg per dose.

39. Ibuprofen- Therapeutic Considerations
ibuprofen >> aspirin or other salicylates or acetaminophen for the relief of dysmenorrhoea
Ibuprofen Dose: for those > 12 years old, mg q 4-6 hrs not to exceed 1,200 mg per day
Can be given as young as 6 months old
Overdose: asymptomatic (43%) or minimal symptoms (abd pain, N&V, lethargy, dizziness..)

40. Ibuprofen- Therapeutic Considerations
Less gastric bleeding and ulceration than ASA (S.E: dyspepsia, heartburn, Nausea, anorexia, epigastric pain)
Ibuprofen effect on platelet aggregation, unlike that of ASA, is reversible within 24 hours.
Caution: avoid using alcohol or warfarin+ ibuprofen  prolongation of prothrombin time

41. Ibuprofen- Therapeutic Considerations
Patients with Hx of impaired renal function, CHF or diseases that compromise the renal haemodynamics should not self-medicate with ibuprofen (why?)  because ibuprofen reduces the renal blood flow and GFR by inhibiting the synthesis of renal prostaglandins BUN and serum creatinine
C/I: in aspirin intolerant patients (cross reaction 97%).
No data about passage in milk, thus better to avoid.
D#D: Table 7, similar to other NSAIDs- Note: Phynetoin and Li+

42. Naproxen-Na Analgesic, anti-inflammatory and antipyretic
For minor pain
Not recommended for those < 12 yr old (only under medical supervision)
Dose: mg q 8-12 hrs (if years old)
Very similar to ibuprofen in OD and D#D
compatible with breast-feeding

43. Ketoprofen
Very similar to Naproxen and ibuprofen except that label advise to avoid in nursing mothers.
Not recommended for patients < 16 year old
Dose: > 16 years 12.5 mg q 4-6 hours (maximum 75 mg/day), may take a second dose after 1 hour if needed.
1 tablet of ketoprofen (12.5mg) is equivalent to 1 tablet (200 mg) of ibuprofen.

44. March 3, 2011 — Treatment of febrile children should focus on improving the child's comfort rather than bringing the temperature down to normal levels or preventing the onset of fever, according to a new clinical report issued by the American Academy of Pediatrics (AAP).
According to the study authors, there is "no evidence that reducing fever reduces morbidity or mortality from a febrile illness" or that it decreases the recurrence of febrile seizures.
The article outlines strategies to counsel caregivers about treating febrile illness, stating that acetaminophen and ibuprofen, "when used in appropriate doses, are generally regarded as safe and effective agents in most clinical situations."