OTC analgesics & antipyretics
OTC drugs available:
salicylates (aspirin, choline salicylate, Mg salicylate and Na salicylate)
Paracetamol (acetaminophen)
ibuprofen
Naproxen Na
Ketprofen
All are similar but Naproxen has slightly a longer duration of action
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),
Salicylates
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
Aspirin
Pharmacokinetics:
- ASA is absorbed by passive diffusion of the nonionised from from the stomach/small intestine
- Factors affecting absorption (=5, what are they?)
- 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)
Therapeutic Considerations:
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
The prostaglandin thromboxane A2 (TxA2) causes platelets to aggregate
Aspirin inhibits synthesis of TxA2 by irreversible acetylation of COX enzyme.
Other salicylates & NSAIDs also inhibit COX but have a shorter duration of inhibitory action because they cannot acetylate COX; that is, their action is reversible.
. 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)
3. GI irritation & bleeding
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
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
5. Pregnancy/ Lactation
- Avoid ASA in both
Avoid ASA especially during the 3rd trimester/pregnancy
Why? > Effect on 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
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 13-26 (patient selection criteria not established)
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
Aspirin toxicity
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
150-300 mg/kg moderate
>300 mg/kg severe
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
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
التعليقات
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
Hydrolysed by cutaneous esterases to salicylic acid that has anti-inflammatory effect
However, The British National Formulary (2007) states that choline salicylate is of doubtful value when used topically
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
- could be used by ASA allergic patients
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
An effective analgesic and antipyretic (works centrally), weak anti-inflammatory (not used clinically for this purpose)
Used for mild to moderate pain of non-visceral origin
Paediatric dose= 10-15 mg/kg q 4-6 hrs
Adult dose: 325-650 mg q 4-6 hrs or 1000 mg 3-4 times daily (do not exceed 4g/day)
Rectal bioavailability=50-60% (compare with ASA)
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.
Paracetamol- Overdose
Hepatotoxicity after ingestion of a single dose of 10-15 g (150-250 mg/kg)
20-25 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
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?)
Therapeutic Consideration
Acetaminophen is safe in pregnancy and breast-feeding
The only Ad. E in nursing infants is a rarely occurring maculopapular rash
~ is hepatotoxic if > 4 g/day especially for people at risk
Avoid alcohol and fasting while using paracetamol
No significant D#D interactions with paracetamol
Recent research: effect of warfarin may be enhanced (??)
Indications: mild to moderate pain of non-visceral origin & dysmenorrhoea. Antipyretic and anti-inflammatory
ibuprofen >> aspirin or other salicylates or acetaminophen for the relief of dysmenorrhoea
Dose: for those > 12 years old, 200-400 mg q 4-6 hrs not to exceed 1,200 mg per day
Overdose: asymptomatic (43%) or minimal symptoms (abd pain, N&V, lethargy, dizziness..)
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
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%).
C/I: in 3rd trimester of pregnancy (similar effect to ASA)
compatible with breast-feeding
Very similar to Naproxen and ibuprofen except that label advise to avoid in nursing mothers.
Not teratogenic/toxic during pregnancy but it should not be used (similar effect to ASA)
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.
Comparative efficacy:
ASA and paracetamol >> same effectiveness
ibuprofen at least as effective as ASA in analgesia
as effective as but not superior to ASA in managing RA
Ibuprofen superior to paracetamol in analgesia and anti-inflammatory effects. But as effective as paracetamol as an antipyretic.
Naproxen and ibuprofen v similar
Combination Products:
active ingredients (e.g. ASA, ibuprofen or paracetamol) are sometimes mixed with caffeine or antihistamines in OTC products to enhance the analgesia
Combinations of such active ingredients with decongestants (e.g. phenylphrine) are useful in treatment of sinus headaches.