The document describes a randomized clinical trial that evaluated the effectiveness of oral contraceptives for treating dysmenorrhea in adolescent girls. The trial found that oral contraceptives provided significant relief from dysmenorrhea pain compared to placebo and were well-tolerated. Overall, the study demonstrated oral contraceptives to be an effective treatment option for dysmenorrhea in adolescent girls.

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:6
I 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 for
children, pregnant and with breastfeeding.
But
there 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 pain
especially when associated with inflammation or
trauma.
NSAID Child Age
Ibuprofen [OTC ] > 2 years
Naproxen [OTC] > 12 years
Ketoprofen [OTC] > 16 years
Aspirin  is greatly restricted due to its association
with Reye’s 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 analgesics
Are 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 in
Pregnant 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. Aspirin
Pregnancy 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 neonates
Breast- avoid—possible risk of Reye’s syndrome; regular
feeding 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 effects
N.B:
Ibuprofen is not excreted in breast milk; so compatible
with breastfeeding.
Naproxen is also compatible with breastfeeding.

16. Conclusion
Children 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:7
Voltaren and Cataflam both contain
diclofenac, but I heard that only Cataflam can
be used by hypertensive patients, what do you
think?

18. Answer:7
Voltaren ( contains diclofenac sodium) POM
Slower onset of
action
Cataflam (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 pressure
Blood Blood
Volume pressure
Cardiac
0utput

21. Non-pharmacologic therapy of
hypertension
• 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 fewer
drinks per day)
(6) smoking cessation.
• Lifestyle modification alone is appropriate therapy for patients with
prehypertension. Patients diagnosed with stage 1 or 2 hypertension
should
be placed on lifestyle modifications and drug therapy concurrently.

22. Conclusion:

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

24. Answer:8
Oral 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. Don’t take an NSAID with alcohol.
2. Don’t 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 Suppository
From local rectal irritation
to rectal bleeding. (hemorrhoids?)
Some NSAID eye drops(irritant)

29. Some Parenteral NSAIDs(painful)

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

31. Answer:9 various stimuli “ triggers” can
Once 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:10
A young woman is suffering severe
abdominal pain diagnosed as primary
dysmenorrhea. How should this
menstrual pain be treated?

36. Answer:10
Primary dysmenorrhoea:
classically presents as a cramping lower
abdominal pain that often begins during
the day before bleeding starts.
The pain gradually eases after the start
of menstruation and is often gone by the
end 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. Medication
The Cause of the pain of dysmenorrhoea:
is thought to be due to prostaglandin (PG-2 ) activity.
the use of analgesics that
inhibit the synthesis of prostaglandins is logical.
BUT
The pharmacist has to make sure that the patient is not
already taking an NSAID.

38. Caution
When to refer to the doctor
1. Presence of abnormal vaginal
discharge
2. Abnormal bleeding
3. Symptoms suggest secondary dysmenorrhea
4. Severe intermenstrual pain and bleeding
5. Failure of medication
6. Pain with a late period (possibility of an ectopic
pregnancy)
7. Presence of fever

39. Management
1. Simple explanation
2. sympathy
3. reassurance.
4. Treatment with simple analgesics
is often very effective in dysmenorrhoea.

40. Treatments
Ibuprofen 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 200–400 mg three times daily with maximum
daily dose of 1200 mg.
A variety of proprietary brands of ibuprofen is available;
Brufen Ibufen Marcofen

42. Caution
1) 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 Advantages
1. 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 is
the treatment of suffering with nausea and vomiting
dysmenorrhoea. 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
Trial
Oral Contraceptives for Dysmenorrhea in Adolescent Girls
A Randomized Trial
Anne Rachel Davis, MD, Carolyn Westhoff, MD, Katharine O’Connell, 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) Lippincott's Illustrated Reviews: Pharmacology, 4th Edition.
7) Pharmacotherapy Handbook, 7th Edition.
8) Novartis Cataflam insert.
9) FDA drug risk categorization during pregnancy. http://www.fda.gov
10) www.ConsumerReportsHealth.org/BestBuyDrugs
11) Oral Contraceptives for Dysmenorrhea in Adolescent Girls, A
Randomized Trial; Anne Rachel Davis, MD, Carolyn Westhoff, MD,
Katharine O’Connell, MD, and Nancy Gallagher, RN. July, 2005.

49. E-mail: ahm.alsawy@yahoo.com
Or
ahm.alsawy@facebook.com