expo aines final

7/27/2019 Expo Aines Final

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CENTRAL UNIVERSITY OF ECUADOR

FACULTY OF MEDICAL SCIENCES

MEDICAL CAREER

FARMACOLOGY

NSAIDs


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Dysmenorrhea


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Patient is a 21 years old

female who complains of

a dull cramping with her

menses each month. Her

symptoms have occurred

since she began her

period at age 13;however, they have been

progressively getting

worse since age 16.


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Her menses typically lasts

five days and comes

regularly at 28 day

intervals. She has pelvic

pain throughout her

menses. Every three to

four months, she will missa day of work due to the

severe cramping pain.


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She notes that several days prior to her

period, she has a feeling of fullness in her

lower abdomen and is achy uncomfortable.


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Past Medical History:Obesity

Past Surgical History:Right knee arthroscopy , extraction of wisdomteeth,

Social History:Pt admits to smoking marijuana from the ageof 16-18, denies illicit drug use since. Pt deniestobacco use and rare alcohol use. Pt does not

exercise. Pt describes her physical activity aslimited to a rare leisurely walk with her friendsafter work


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Family History: Mother deceased age 54,

ovarian cancer; Father, 65, diabetes, obesity,

venous stasis; paternal grandparentsunknown; maternal grandparents, living,

Grandmother breast cancer survivor,

otherwise in good health; Grandfather,glaucoma, hypertension


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Physical Exam:Vital signs: Ht: 1.60 m Wt. 78 kg, BMI 30.4, HR 70, BP 135/85, RR 18

General:21 years old Caucasian female. Good hygiene, cooperative, andpleasant demeanor. Body habitus is overweight

Head - Normal cephalic, atraumatic.No lacerations, bruises, orother discoloration;

Eyes - red reflex intact, 2 cotton wool spots noted on the rightretina in the right upper quadrant, no papilledema,

Ears - , tympanic membranes intact without erythema or fluid;

Nose/Throat - has mild septal deviation to the left, mucosa is moistand pink, good oral hygiene, no erythema, post nasal drip, or sorespresent in the throat


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Cardio/Pulm: heart rate and rhythm regular

without murmurs, gallops, clicks,

Abd: abdomen obese, non-tender, although

pain near the iliac fossa, no masses palpated,

bowel sounds present X 4 quadrants, no

masses or polyps palpated on rectal exam,

Hemoccult negative


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Definition

Abdominal or pelvic pain during

menstruation.

Can start up to 48 hours before it

Usually persists for 48-72 hours.

1 2 3 4 5282726

Flujo menstrual

Dolor


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Types of dysmenorrhea

Primary.

No identifiable anatomical cause.

Spasmodic.

Secondary.

Associated with an identifiable pathology.Failure.


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Primary Dysmenorrhea Secondary Dysmenorrhea

Acute pain or spasmodic Continuing pain and heavy

Appear 24 to 48 hours beforemenstruation and continued until two

days after

It usually occurs a week before mensesand persists throughout the cycle

Frequent in women aged 17 to 25 years Women over age 30 years

Consult a doctor Symptom of underlying disease
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Pimary dysmenorrhea.

90% of all cases.

Starts 6-24 monthsafter menarche.

More common inchildren under 20years.

Up to 50% ofadolescents have hadit.


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Pathophysiology

Increase in endometrial prostaglandin

production.

Mainly PGF2 y PGE2.

Thromboxanes increased.

Leukotrienes increase.

Increased circulating vasopressin.


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Prostaglandins Effects

Uterine motility changes.

Local vascular changes

Neurosensory changes.


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Uterine motility changes

Increased frequency ofuterine contractions.

Uterine peristalsisarrhythmia.

Increased uterine tone at rest(> 10 mmHg).

Increasing the strength ofuterine contraction (> 120mmHg).


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Altered uterine vasculature.

Vasoconstriction.

Decreased myometrial pressure flow.

Increased local consumption.

Uterine ischemia (angina uterine).

Altered sensitivity.

Hypersensitivity nociceptive fibers, productsof cell death.


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LH


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LH

induction COX2

Increases PGs


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progesterona

LH

LH

supression COX2

Dicreases PGs

Increases PGDH


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COX2

aumento PGs

Decreases PGDH

= apoptosis

= increases K+ y H+ libre


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PGs

TBXs

ADH


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contraction

PGs

TBXs

contraction

contraction

ADH


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PGs

TBXs

isquemia

ADH


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PGs

TBXs

painpain

pain

isquemia

ADH


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PGs

TBXs

isquemiaPGs

LTs

K+

H+

ADH


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PGs

TBXs

isquemiaPGs

LTs

painpain

pain

ADH


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Classic clinically

Colicky pain, pelvic or lower abdominal.

Sign few hours before or at the onset of

menstruation.

Radiating to the back and external genitalia.

General symptoms.Asthenia and adynamia.

Headache.


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Diagnosis

The primary objectives are:

Identify dysmenorrhea.

Differentiate between primary and secondary.

The clinical history is critical in the diagnosis of

dysmenorrhea.

Usually both diagnostic purposes can be

achieved with the clinical history.


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INFLAMMATORY

REACTION

ENZYMEACTIVATION

RELEASE OFCHEMICALMEDIATORS

EXTRAVASATION OFFLUID

MIGRATIONDAMAGE CELL

TISSUE REPAIR

THE INFLAMMATIONIS THE RESPONSE OF

LIVING TISSUES TOINJURY


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It is a group of anti-inflammatory non-

steroidal that share therapeutic actions and

adverse effects. Its effects are similar to

those produced by the steroids but withoutits adverse effects.

Their main effects are:

Anti-inflammatory.

Analgesic.

Antipyretic.

What is NSAIDS?


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The search issubstances that willrelieve the pain and

lower fever is as old asthe man. The history of

the Ecuadorianmedicine tells us that

was in Malacatos,province of Loja the

site where it hasspread the use ofcinchona bark as

"febrifuge"

Still the pain, fever,inflammation

conditions present in a

number ofpathological tables is

not surprising thatNSAIDS are the

medications mostprescription and

consumption, andmost were sold freelyin pharmacies and

other stores.


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COX-1: constitutive,protector of thegastric mucosa,regulating renal

function, amongothers. Its inhibitionis associated withdamage to the

gastric mucosa dueto the lack of the"barrier of thegastric mucosa".

COX-2: Inducible,associated withinflammatoryprocesses. It occurs in

macrophages,monocytes, endothelialcells that generate PGsand mediate painperception and the

inflammation. Their inhibition has an

anti-inflammatoryeffect. It is alsoconstitutive in some

territories, such as the

CYCLE-OXIGENASAS

MECHANISM OF ACTION OF NSAIDS


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MECHANISM OF ACTION OF NSAIDS

ACT BY INHIBITING THE SYNTHESIS OF PROSTAGLANDINS


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PHYSIOLOGICAL NSAIDS

Stimulate inflammatory

response

Inhibit inflammatory

response

Stimulates terminations

painfulInhibit terminations

painful

Stimulates the increase of

the temperature

Reduces body

temperature increased

ANTI-INFLAMMATORY EFFECT

ANALGESIC EFFECT

ANTIPYRETIC EFFECT


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1.- Salicylates: Acetylsalicylic Acid

2.- Pyrazolone and analogues: Phenylbutazone

3.- Derived Indolaceticos: indomethacin

4.- Derived Arilaceticos: Diclofenac

5.- Aryl Derivatives: Ibuprofen Ketoprofen

6.- Oxicams: Piroxicam

7.- Fenamatos: mefenamic acid

8.- Aminonicotinicos: Flunixin Meglumine.

CLASSIFICATION

According to chemical structure:


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1.- Non-selective COX-1/ COX-2: Ibuprofen

2 .- Selective COX-1: indomethacin

3.- Selective COX-2: Meloxicam

According to inhibition of the

cycle-oxigenasas


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ANALGESIC

ACTIONRefers to the inhibition of

prostaglandin synthesis to central

and peripheral level. At the

peripheral level prevents the

awareness of nociceptors by

reducing the perception of pain and

at the central level, stimulating the

secretion is endogenousneurotransmitters that inhibit the

pain. Also would the reduction of

inflammation.

EFFECTS


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ANTIPYRETIC

ACTIONCorresponds to a

consequence of inhibition

of prostaglandin synthesis

at the central level.

Reduces the release of

PGE2 to level hypothalamic

and reduces body

temperature when it isincreased .

EFFECTS


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ANTI-

INFLAMMATORY

ACTIONIts action is based not only onthe inhibition of prostaglandins

(important mediators in the

inflammatory process ) but who

are also responsible for

interfering with the signals that

trigger the inflammatory cells.

EFFECTS


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ACTION

ANTIDYSMENORRHEA

By inhibiting prostaglandins, reducepain and other symptoms of

dysmenorrhea. Decreases the uterine

contractility and pressure by inhibiting

both the ischemic pain and spasmodic.

Also acts to reduce headaches,

nausea and vomiting.

EFFECTS


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Is frequently

nausea,

vomiting,

abdominalpain ,

heartburn,

constipationamong others.

Gastrointestinal Disorders


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It decreases the

renal blood flow

and glomerular

filtration , occurs

retention of Na+,K+ and H2O.

Increased blood

pressure

Skin reactions:Urticaria, rash

Kidney Failure


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Do not use in patients with hypersensitivity

to the drug.

Patients with gastrointestinal disorders

Patients with concomitant chronicdiseases, such as liver, kidney, heart .

CONTRAINDICATION


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TREATMENTtherapeutic objective is reduction of

pain


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NSAIDs

Simple analgesics are best used asself-treatment of adolescents:

Paracetamol

Aspirin

IbuprofenNaproxen


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A systematic review of 73randomized controlled trialsconcluded that NSAIDs weresuperior to placebo for the

treatment of primarydysmenorrhea pain and

reduced the number of daysabsent from school and

work.

Many NSAIDs have beenstudied for this purpose but

there is no literature toindicate the efficacy of

either agent to one another.

The choice NSAID is bestguided by cost and

availability.

Included studies


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Included studies

Included comparisons eligible for the review

were as follows:

NSAID versus placebo: 41 trials

NSAID versus NSAID: 14 trials

Two NSAIDs versus placebo: 15 trials NSAID versus paracetamol: one trial NSAID versus paracetamol and placebo: two

trials

Nineteen different types of

COX-1NSAIDs

Aspirin

Naproxen

Piroxicam

Diclofenac

Fenoprofe

n Ibuprofen

Indometh

acin

Ketoprofe

n

Naproxen

Nimesulid

e Piroxicam.

Only two types of COX-2

NSAIDS were evaluated

Etoricoxib Meloxicam

D f NSAID


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Aceclofenac (100 mg daily)

Aspirin (650 mg; 4 hrly)

Dexketoprofen (12.5 to 25 mg; six

hourly)

Diclofenac (up to 200 mg daily

Etodolac (200 to 300 mg twice daily)

Fenoprofen(100 to 200 mg; 4 hourly) Fentiazac (100 mg; twice daily)

Flufenamic acid (200 mg; eight hourly)

Flurbiprofen (100 mg; twice daily)

Ibuprofen (400 mg; three, four or six

times daily)

Indomethacin (25 mg tablets or 100mg

suppositories; three times daily)

Etoricoxib (120 mg), Meloxicam (7.5 to15mg),

both daily

Ketoprofen (25- 50 mg; six hourly, with or

without a loading dose of 25-70 mg)

Lysine clonixinate (125 mg; six hourly)

Meclofenamate sodium (100 mg; 8 hourly)

Mefenamic acid (250 mg; 8 hrly)

Naproxen/ naproxen sodium (250-275 mg; four

to eight hourly, sometimes with a loading dose

of 500-550 mg) Niflumic acid (250 mg; three times daily)

Nimesulide (50 to100 mg twice daily)

Piroxicam (20-40 mg daily, by tablet or

suppository)

Tolfenamic acid (200 mg; eight hourly).

Doses of COX-2 inhibitors used :

COX-1NSAIDs

Doses of NSAIDs

EFFECTS OF


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INTERVENTIONSPAIN RELIEF

1) NSAIDS VERSUS PLACEBO.

There were 41

trials

The studies analysed a totalof 2121 women, 1631 incrossover trials and 490women in parallel trials.

NSAIDs were significantlymore effective than placebo

at producing moderate orexcellent pain relief (OR4.50, 95% CI: 3.85-5.27;

I2=53%).

The most precise findingwas for naproxen (OR 3.67,

95% CI: 2.94 to 4.58; 16studies, I2=52%).


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Compared withplacebo diclofenac

reduced pain by65% (MD 65.96,95% CI: 55.70-

76.22, two studies)

Meloxicam by 34%(MD 34, 95% CI:15.88-52.12, one

study.

The other 8 studiescompared 7

different NSAIDsversus placebo,using 5 different

pain scales.

In all cases NSAIDswere significantly

more effective thanplacebo inproducing

moderate/excellentpain relief and/or inreducing pain scores

with the exceptionof aspirin (for whichthere was only one

relevant study)

1) NSAIDS VERSUS PLACEBO.


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They compared the following NSAIDs versus placebo:

aspirin, diclofenac, fenoprofen, ibuprofen,indomethacin, naproxen, nimesulide, piroxicam.

All NSAIDs were significantly more effective thanplacebo

Aspirin which was not found to be not significantlydifferent to placebo

EFFECTS OF


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2) NSAIDS VERSUS NSAIDsINTERVENTIONS

Aspirin vs fenoprofen

Diclofenac vs - Meloxicam

- Ibuprofen

-Nimesulide

Ibuprofen vs - Piroxicam

- Lysine

clonixinate

Mefenamic acid vs -

Meloxicam

-

Tolfenamic acid

Naproxen vs - Diclofenac

- Ketoprofen

- Etoricoxib

- Flurbiprofen

- Ibuprofen

- Piroxicam

There were fifteen, none of which compared

the same two NSAIDs.They made the following comparisons:

2) NSAIDS VERSUS NSAIDS


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Diclofenacreduced pain on aVAS 100 point scale

significantly more thanmeloxicam

Fenoprofen reduced painintensity significantly more

than aspirin

Naproxen reduced painscores significantly morethan Ibuprofen and was

significantly more likely toachieve effective pain

relief than ketoprofen

Other head-to-headcomparisons between

NSAIDs showed nostatistically significant

difference between them.

One found indomethacinsignificantly more effectivethan aspirin and one foundno statistically significant

difference betweennaproxen and diflusinal

2) NSAIDS VERSUS NSAIDS

3) NSAIDS VERSUS PARACETAMOL


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3) NSAIDS VERSUS PARACETAMOL

Resulted in a statistically significant difference in theproportion of women reporting good, excellent or

complete pain relief, favouring NSAIDs overparacetamol (OR 1.89, 95% CI: 1.05-3.43).

Naproxen vsparacetamol

(1 studio )

Ibuprofen vsparacetamol(2 studies )


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DISCUSSION

Overwhelming evidence of the efficacy of NSAIDs in relieving thepain of dysmenorrhea

The review was unable to determine what is most effective NSAIDsfor dysmenorrhea or whether individual NSAIDs have a similarlyeficacioa.

Also it was found that the pain relief efficacy of NSAIDs is superior toparacetamol.


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Tolerability and Safety of NSAIDs

More adverseeffects thanplacebo:

Headache

Dizziness

Dryness

Sleepiness

Gastrointestinal Effects

Indomethacin


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Indomethacin

Neurological sideeffects

Dexketoprofen

Gastrointestinal

side effects

Naproxen

More likely tocause the two

Etoricoxib

No different fromthe effectivenessof naproxen

Meloxicam

Less effective in

relieving painthan diclofenac


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Among NSAIDs no significantdifference was found

between adverse

NSAIDs are a very effectivetreatment for dysmenorrhea,

but q women using themneed to be aware of the side

effects they entail.

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