Transcript OTC analgesicsx

OTC analgesics & antipyretics
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
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),
Dosage of common OTC drugs
Agent
Dosage (maximum)
Analgesic
Acetaminophen 650-1.000 mg q4h (4000
mg)
Anti-inflammatory
-
Aspirin
10-15 mg/kg/dose q 4-6 h 80-100 mg /kg/day q 6-8
hrs
(4 g/day)
Ibuprofen
200-400 mg q 4-6 hr
(1,200 mg/day)
400-800 mg 3-4 td (3,200
mg in 2 wks)
Naproxen Na
220 mg q 8-12 hr
(660 mg/day)
275-550 mg 2 t d
(1,650 mg/day for 2 wks)
Ketoprofen
12.5-25 mg q 6-8 hr
(75 mg/day)
50-75 mg, 3-4 t d
(300 mg/day)
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
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
150-300 mg/kg
>300 mg/kg
mild
moderate
severe
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
Petechiae
Aspirin
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
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
2-3 g/day
> 5 g/day
plasma level of uric acid
little/ no effect
plasma level of uric acid
(Toxicity)
Aspirin
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
NOT C/I
for future use
Common S.E
NOT
hypersensitivity
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
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,…..
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 dose20
response effect.
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
13-26 (patient selection criteria not
established)
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
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
Australia,
April 2004
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)
Antihypertensive
agents
anti-HTN effect,
hyperkalemia with Ksparing D or ACE-I
Monitor BP, K level and
cardiac function
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
NSAIDs
Warfarin
risk of bleeding
Avoid concurrent use
NSAIDs- D#D interactions
Analgesic
Drug
Potential
Interaction
NSAIDs
(several)
Methotrexate MTX clearance
(MTX)
> MTX toxicity>
pancytopenia
Avoid NSAIDs with high
dose MTX therapy, monitor
with concurrent use.
Ibuprofen,
high dose
of
salicylates
Phynetoin
Monitor unbound phynetoin
level, adjust dose
NSAIDs
(several)
Digoxin
renal clearance
Monitor digoxin level,
adjust doses
NSAIDs
(several)
Aminoglycosi
des
renal clearance
Monitor antibiotics level,
adjust doses
Displacement from
plasma proteins >
phynetoin toxicity
Management/
Prevention measures
Comparison of aspirin and nonacytelated salicylates
Less effect on platelet aggregation
Less GI erosions and bleeding
Fewer renal complications
cross-reactivity in aspirin intolerant
patients
Less anti-inflammatory effect
Acetaminophen
An effective analgesic and antipyretic (works
centrally), no anti-inflammatory (not used clinically for
this purpose)
Used for mild to moderate pain of nonvisceral 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)
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Acetaminophen- 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
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
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.
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IbuprofenTherapeutic Considerations
ibuprofen >> aspirin or other salicylates or
acetaminophen for the relief of dysmenorrhoea
Ibuprofen Dose: for those > 12 years old, 200-400
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..)
IbuprofenTherapeutic 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
IbuprofenTherapeutic 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+
Naproxen-Na
Analgesic, anti-inflammatory and antipyretic
For minor pain
Not recommended for those < 12 yr old
(only under medical supervision)
Dose: 220-440 mg q 8-12 hrs (if 12-65 years old)
Very similar to ibuprofen in OD and D#D
compatible with breast-feeding
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.
 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."
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