INSTITUTO POLITECNICO NACIONAL

Centro de Esudios Cientificos y Tecnologicos

# 4 “Lázaro Cárdenas”

FINAL ENGLISH WORK

TOPIC: ASPIRINA

MATTER: ENGLISH

GROUP: 6IV9

MEMBERS:

Andrade Sánchez Mariana Michel Neria Aguilar Luis Antonio Martinez Silvestre Roberto

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INDEX

SUMMARY................................................. .................................................. ................................. 2

INTRODUCTION AND BACKGROUND ............................................... ..................................... 3

OBJECTIVES ................................................. .................................................. ............................ 10

MATERIAL AND METHODS............................................... .................................................. .......

RESULTS AND DISCUSSION............................................... .................................................. 12

CONCLUSION................................................. .................................................. ........................ 19

BIBLIOGRAPHY................................................. .................................................. ...................... 21

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SUMMARY

Acetylsalicylic acid (ASA) is a crystalline powder derived from salicylic acid. TheThe first references for the use of salicylic acid date from 1953 BC.AAS belongs to the group of non-steroidal anti-inflammatories. It has propertiesanti-inflammatory, analgesic, antipyretic and uricosuric. Also, it is used asplatelet antiaggregant.There are other compounds derived from acetylsalicylic acid.The mechanism of action of ASA derives from an inhibition of the COX1 and COX-2 cyclooxygenases.ASA interacts with many drugs, so you have to avoid intakeconcomitant of ASA with these drugs.Biopharmaceutical aspects: Bioavailability depends on the pharmaceutical form,which can be: tablets, effervescent tablets, hard capsules of releaseprolonged, soft capsules, gastro-resistant tablets and granules.The first commercialized AAS were Aspirin (500 mg) and Adiro (100 and 300 mg)from Bayer®, and generics are also currently available

PHARMACOKINETIC ASPECTS:

- Oral absorption: ASA is absorbed mostly in the duodenum. This absorption

depends on the method of administration, the gastric pH and the speed of

gastric emptying

- Distribution: AAS suffers from intestinal and hepatic first-pass effects. Once in

general circulation binds to plasma proteins and the free fraction can suffer

hydrolysis to salicylic acid and distribution to all tissues.

- Metabolism: Salicylic acid is metabolized mainly by three

processes: conjugation with glycine, conjugation with glucuronic acid and oxidation to

gentisic acid.

- Excretion: The non-metabolized minority fraction is excreted in urine suffering

glomerular filtration processes, secretion and tubular reabsorption.

This work has a teaching purpose. The Faculty of Pharmacy is not responsible for the information contained therein.

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INTRODUCTION AND BACKGROUND

Historical facts

The first willow reference as a drug (containing salicylic acid) is found

in the papyrus of Ebbers, which is a medical-Egyptian text of the year 1543 a.C. In the he

They expose the anti-inflammatory, analgesic and antipyretic properties.

In the fourth century BC, Hippocrates observed as the willow bark powder (salix alba)

that contained salicyllins and had analgesic and antipyretic properties, was administered

to the sick of that time.

Galen used plant extracts that contained salicyllins for the treatment of

some diseases.

In the 18th century, willow bark extract was used to relieve fever, pain

and inflammation.

In 1834, the pharmacist Johann Pagenstecher discovered the salicylic acid obtained

from the Spinae ulmaria, which served to reduce pain.

In 1884, the chemist Felix Hoffman while researching for the Bayer laboratory

he wanted to create a compound with salicylic and acetic acids, and he got the acid

acetylsalicylic. In 1899 it was named aspirin and was marketed in

many countries, but with the arrival of ibuprofen and paracetamol their

production.

The word `` aspirin '' is formed by the `` a'' of acetil, `` spir'' to indicate the

presence of salicylic acid and the suffix `` in'' to create a word to be spelled

Same in German than in English.

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GENERAL FEATURES

Acetylsalicylic acid (ASA) is an ester of acetic acid with a pKa of 3.5

(although salicylic acid is a simple organic acid with pKa of 3.0).

Its chemical formula is C9H8O4. It has a molecular weight of 180.2.

It is a white crystalline powder or in the form of colorless crystals. It's fairly soluble in water

and very soluble in alcohol. It melts at approximately 143 ° C. Its density is 1.4

g / cm3

.

PHARMACODYNAMIC CHARACTERISTICS AND THERAPEUTIC APPLICATIONS

Acetylsalicylic acid is the prototype drug of the salicylates that belongs to the group

of antipyretic analgesics and non-steroidal anti-inflammatory drugs.

It has analgesic, anti-inflammatory and antipyretic action as the rest of its drugs

group but the relative efficacy may be different compared to the different

derivatives. They can be used in headaches, arthralgia, myalgia and moderate pain.

It also acts as an antiplatelet agent.

Another effect of acetylsalicylic acid is known, which is the uricosuric effect, which is

used in gout with a dose of 5 g / day to increase the elimination of uric acid,

but this effect is currently in disuse. It is only used for the latter

indication, when other drugs fail.

Currently in the Spanish pharmaceutical market, acetylsalicylic acid has

multiple uses that depend on the dose that is administered:

At a dose between 75 mg and 300 mg, it will be used as a platelet antiaggregant

(antithrombotic) that reduces the chances of clots

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blood In cerebrovascular diseases and prevention of thromboembolism.

The dose is 100-300 mg / day.

The mechanism is based on the inhibition of cyclooxygenase in platelets

by acetylation. Then the synthesis of thromboxane A2 is inhibited whose process

it is irreversible and the synthesis of the enzyme would be impeded.

At a higher dose (generally 500 mg), it will have an analgesic effect,

antipyretic and anti-inflammatory.

The antipyretic effect is used to reduce fever in children and adults.

The analgesic effect is the most used to relieve mild and moderate pain.

It is used in headache, migraine, lumbago, osteoarthritis, rheumatoid arthritis and fever

rheumatic The usual dose is 0.3-0.6 g and to reduce pain the dose will be

2g / day. For rheumatic fever, doses of 1 g are used every 4 hours.

The anti-inflammatory effect was used earlier in the treatment of rheumatic fever and

chronic polyarthritis, but currently corticosteroids have displaced salicylates

in this use. The daily dose is 500 mg every 4-6 hours, not exceeding 4 g per day.

The mechanism is based on the inhibition of cyclooxygenase and subsequent inhibition of

prostaglandin E2, prostaglandin I2 and thromboxane A2.

In children, doses of 10 mg / kg are used every 4-6 hours.

Compounds similar to acetylsalicylic

Salicylic acid (orthohydroxybenzoic acid) is very irritating and can only be used

in external application (topical use). For this reason, they have been synthesized for their use

generalized some of its derivatives: esters of salicylic acid, obtained from

substitutions within the carboxyl group, and the salicylate esters of organic acids,

(the substitution is made in the hydroxyl group).

Acetylsalicylic acid derivatives are obtained as: lysine acetylsalicylate (salt

soluble for parenteral use that after its absorption releases acetylsalicylic acid), the

benorilate (ester of AAS and paracetamol) and the ether.

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This work has a teaching purpose. The Faculty of Pharmacy is not responsible for the information contained therein.

6

Lysine acetylsalicylate Benylate Eterilate

Other derivatives of acetylsalicylic acid are: sodium salicylate, choline trisalicylate and

magnesium, salsalate or diplosal (salicylsalicylic acid that after its absorption is doubled

in two molecules of salicylate), diflunisal, salicylazasulfapyridine or sulfasalazine,

phosfosal (Ofosphorylated ester of salicylic acid) and salicylamide.

Salicylamide Salicylate

sodium

Diflunisal Salsalato

Sulfasalazine Fosfosal Choline and magnesium trisalicylate

Formulations:

Acetylsalicylic acid can also be found in other types of formulations

Galenic as:

Buffer-effervescent formulations: Produce some protection of the mucosa

Gastric They were designed to increase the solubility and, therefore, increase the

absorption speed and minimize local irritation of the gastric mucosa.

They contain the association of AAS, citric acid and sodium bicarbonate. In water it

releases the CO2, which produces the effervescence and disintegration of the tablet,

form acetylsalicylate sodium, citrate and bicarbonate acting as a system

buffer that sets the pH to 5.5-6.5.

Controlled release formulations: They were designed with the purpose of

reduce gastric irritation, prolong absorption time and duration of

effect.

Mechanism of action of acetylsalicylic acid

The mechanism is due to the inhibition of the activity of cyclooxygenase, an enzyme that

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converts arachidonic acid from cell membranes into cyclic endoperoxides

unstable to transform into thromboxanes and prostaglandins.

AAS irreversibly inhibits COX-1 and COX-2 cyclooxygenases by acetylation

covalent of a serine residue in:

- Position 530 in COX-1 with total inactivation of enzymatic activity.

- Position 516 in COX-2 (active center of the enzyme) with partial loss of

activity of cyclooxygenase (but the synthesis of 15-HETE (15-

hydroxyeicosatetraenoic).

This inhibitory effect of cyclooxygenase is what gives rise to the therapeutic effects and

adverse reactions.

- Antithrombotic effect: COX-1 present in platelets produces thromboxane

A2 which is a vasoconstrictor. COX-1 is very sensitive and therefore doses are needed

AAS losses. By inhibiting COX-1, there is a decrease in aggregation platelet, with the consequent increase in bleeding time. This effect

it disappears at 36 hours after the last dose is taken.

- Anti-inflammatory effect: There is an inhibition at the peripheral level of the action of

COX-1 and 2. It is believed that inflammation is mediated by COX-2 since it is

Enzyme is induced by cytosines. By inhibiting COX-2 there is a decrease in

prostaglandins E and F responsible for vasodilation and capillary permeability, so

that increase the mobility of fluids and leukocytes that cause inflammation,

redness and pain.

- Analgesic effect: ASA decreases pain because it reduces the synthesis of

prostaglandins. It is an indirect effect on the central nervous system.

- Antipyretic effect: In the hypothalamus, the synthesis of prostaglandins is inhibited.

It produces peripheral vasodilatation and sweating.

Substitution in the carboxyl group or in the hydroxyl modifies the potency or toxicity

of the AAS.

The ortho position of the hydroxyl group is important for the activity of the AAS.

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PHARMACODYNAMIC INTERACTIONS

Concomitant administration of ASA with other NSAIDs / corticosteroids / anticoagulants

oral / thrombolytic and antiplatelet agents / alcohol increases the risk of

Gastrointestinal ulcers and hemorrhages because ASA displaces drugs

and prostaglandins PGI2 and PGE2, which are cytoprotectors, are inhibited.

Also, the synthesis of thromboxane A2 is suppressed, which inhibits aggregation

platelet

ACE inhibitors: The antihypertensive effect of the IECAS is reduced due to the

inhibition of prostaglandins with vasodilator effect. The AAS has an effect

indirect effect on the renin-angiotensin system, with which the hyponatremic effects,

antihypertensives and vasodilators will be modified. There will be a decrease in

glomerular filtration.

Beta-blockers: The antihypertensive effect of the IECAS is reduced due to the

inhibition of prostaglandins with vasodilator effect. Decrease the flow

renal blood, and the retention of salts and fluids.

Antidiabetics: AAS inhibits the synthesis of prostaglandin E2, which increases the

insulin secretion and blood glucose levels are lowered. I also know

produces a displacement of sulfonylureas that leads to a hypoglycemic effect

of this.

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OBJECTIVES

Bibliographic review of the biopharmaceutical and pharmacokinetic aspects of acid

acetylsalicylic.

Realization of an introduction in which the different aspects will be reviewed and

characteristics, as well as the mechanism of action of acetylsalicylic acid.

Understanding of its pharmacokinetics and obtaining conclusions.

MATERIAL AND METHODS

Retrospective study through bibliographic review on the Internet. Bases have been used

of data such as AEMPS-CIMA and Vademécum to consult the technical data sheets of

medicines that contain acetylsalicylic acid.

General and specific pharmacology texts have also been used.

in the bibliography section

BIOPHARMACEUTICAL ASPECTS:

The route of administration of the most used AAS is the oral route with which it is obtained

adequate therapeutic efficacy.

There are multiple pharmaceutical forms intended for oral administration:

-Compressed. They can be 100, 125, 250, and 500 mg (Aspirin® and generic)

(chewable and effervescent tablets are also found).

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-Compressed gastro-resistant. They can be 75, 100, 300 mg (Adiro® and generic).

- Soft EFG capsules of 75 mg.

- Long-lasting hard capsules. They can be 150 and 300 mg (Tromalyt)

- 500 mg granule (Aspirin®).

The bioavailability of the active principle will depend on the pharmaceutical form used.

More soluble forms such as buffered aspirin and effervescent will be absorbed

more quickly, being the time in which the maximum concentration (tmax) is reached

30 minutes The disintegration will be shortened and the motility of the wall will be favored

Gastric The maximum plasma levels will be reached at short times.

In contrast, controlled release formulations utilize

microencapsulation of AAS with suitable polymers to achieve a slow

dissolution and release of the active substance in the small intestine, and therefore, a

slow absorption In this case, the tmax will be between 2-4 hours, and the concentration

maximum will decrease and adequate plasma levels will be maintained for

longer.

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PHARMACOKINETIC ASPECTS:

SSA presents a complex pharmacokinetics depending on multiple factors.

First, the dosage and duration of treatment depends on clinical use: (i)

antiaggregant (very low doses and chronic consumption), as (ii) analgesics-antipyretics

(intermediate doses and punctual or discontinuous consumption) or as (iii) anti-inflammatory

(high doses and chronic consumption).

On the other hand, the galenic form used, conditions, as has been commented

previously, biopharmaceutical behavior.

They also influence, the different behavior of the AAS and the derivatized salicylate ion, and

the existence of a saturable metabolism, which affects the plasma half-life (in

dose-dependent form).

Oral absorption:

Although acetylsalicylic acid is slightly absorbed in the stomach, it does

mainly in the duodenum, because the latter has a greater surface area.

The absorption depends on three factors:

- Method of administration. Already commented previously.

- Gastric pH. At low pH, the proportion of AAS in a non-ionized state increases. Rate

absorption will depend on the liposolubility of the non-ionized fraction and its

concentration. The increase of the pH favors the dissolution.

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When the drug is dissolved or available, the non-ionized fraction will pass into the interior

of mucous cells by simple or passive diffusion.

Within the cell, the equilibrium moves towards the ionized fraction and therefore,

will increase the intracellular concentration of the drug.

- Gastric emptying speed. The absorption rate of the AAS will be higher if

there is a rapid gastric emptying due to the absence of food (although it is not

recommendable). In the presence of food, the absorption speed will be lower, but

not the total amount of AAS absorbed.

DISTRIBUTION:

Absorbed AAS suffers first-pass effect in the intestinal wall (esterases)

intestinal) and in the liver (first pass liver effect). Of the total amount

absorbed, a part reaches the systemic circulation in an unaltered form where it is hydrolyzed

to acetic acid and salicylate, detected in plasma for a short period of time.

The plasma protein binding (UAP) of AAS is 80-90%. It joins mainly

to serum albumin in a non-linear way.

The fraction that does not bind to plasma proteins, is distributed homogeneously to

all tissues by passive diffusion through interstitial water. In muscle tissue,

in the brain and synovial fluid, the maximum concentration is less than

plasma In addition, it crosses the placenta and is excreted in breast milk.

Aspirin and its metabolite, salicylate, will also be found in the liquid

cerebrospinal fluid, saliva and peritoneal fluid. The LCR accesses through a saturable system of

low capacity.

Aspirin acetylates serum albumin by reaction with the -amino group of the

lysine Also, acetylates other proteins, hormones, DNA and hemoglobin.

Depending on the dose administered, different plasma levels will be reached:

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- For an intermittent antipyretic and analgesic effect, it will be enough to reach

plasma levels of 50 to 100 μg / mL.

- For an analgesic-anti-inflammatory effect (4-6 g / day), plasma levels

they should be in the range 125-350 μg / mL.

The AAS has an apparent volume of distribution of 170 mL / kg for doses

intermediate (0.5 g) and 500 mL / kg for high therapeutic doses due to saturation

the binding to plasma proteins

Metabolism:

Acetylsalicylic acid is hydrolyzed in stomach, blood and liver (about 75%),

presenting a plasma half-life between 15 and 20 minutes.

ASA is deacylated to form salicylic acid, an active metabolite that turns

metabolize, especially in the liver, through three processes:

- Conjugation with glycine. To form saliciluric acid. This is the process

faster and if it is saturated (at doses greater than 650 mg of ASA) the elimination

it will be of zero order and toxicity may occur. Approximately 75% of the

Salicylic acid is excreted as saliciluric acid.

- Conjugation with glucuronic acid. To form the ether and ester conjugates

(salicylglucuronic acid (5%) and salicylglucuronide acid (10%)). When

Ingests 1 g or more of AAS, saturates the ether conjugate and the kinetics will be of order

zero. This leads to an increase in the half-life of the salicylate in plasma. The

Conjugated derivatives are water-soluble organic acids that do not have ease

to diffuse through the wall of the renal tubule. They filter in the glomerulus, they are

secreted by a carrier of organic acids and do not undergo tubular reabsorption

by passive diffusion processes.

- Oxidation to gentisic acid. This active metabolite possesses an activity

analgesic, anti-inflammatory and antipyretic less powerful than the compound

original (<1%).

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Due to the saturation characteristics of the metabolism process discussed

previously, the plasma half-life of salicylic acid will depend on the dose

administered. At low doses, an average plasma half-life of 3 to 6 is manifested

hours, while at high doses the half-life increases to values between 15 and 30 hours.

Also, as a consequence of the above, at low doses, the

plasma concentration follows a deletion function of order 1. At high doses,

as a part of the metabolic pathways are saturated, the plasma concentration

it increases disproportionately and a non-linear elimination manifests itself.

The same applies to the percentages of salicylic acid and its metabolites excreted in

urine, so that the general data indicated above vary with the dose

administered.

Dosage (mg) Salicylic acid

(%)

Salicylic acid

(%)

Salicylic glucuronides

and phenolic acyl (%)

200 3 83 17

750 5 70 24

1500 17 59 24

3000 14 50 30

Excretion:

A percentage of salicylate less than 10% is eliminated in urine. Salicylate suffers

glomerular filtration processes, secretion and partial tubular reabsorption. The latter is

a passive process involving only the non-ionized fraction of the salicylate.

The excretion of salicylates will be increased when the alkalinization of the

urine because it increases the degree of ionization. This excretion is considered close to

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two%.

Pharmacokinetic interactions

The main consequence of the concomitant use of acetylsalicylic acid with other

drugs is the increase or decrease in plasma concentrations of these

drugs that can lead to toxicity.

Lithium and uricosurics: AAS decreases lithium excretion, increasing

plasma concentrations thereof.

Methotrexate: ASA affects the processes of filtration, secretion and tubular reabsorption

of methotrexate. Decreases the tubular secretion of methotrexate (increases the

plasma concentrations thereof), delaying its elimination.

Antacids: Increase renal excretion of ASA due to alkalinization of urine

and reduce plasma concentrations.

Anticonvulsants: Higher doses of ASA can displace phenytoin from its union

to plasma proteins, increasing their free plasma concentrations. This effect

favors the plasma clearance of phenytoin.

AAS displaces plasma proteins from its binding and inhibits hepatic metabolism

of valproic acid, which produces an increase in plasma concentrations of

same.

Zidovudine: AAS competitively inhibits glucuronidation or directly

hepatic metabolism of this active principle, which increases the concentrations

plasma levels of zidovudine.

CLINICAL USE

Orally:

Treatment or symptomatic relief of occasional mild or moderate pain in

> 16 years old (A)

Treatment of fever in> 16 years (A).

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Platelet antiaggregant: prophylaxis of acute myocardial infarction (AMI)

or reinfarction in patients with unstable angina pectoris or AMI, thrombophlebitis, phlebotomy and arterial thrombosis, postoperative thromboembolism in patients with biological valvular prostheses or arteriovenous shunts. Prevention of stroke in> 16 years (A).

Non-rheumatic inflammation: musculoskeletal pain, sports injuries,

bursitis, capsulitis, tendinitis, acute tenosynovitis (E: off-label).

Rheumatoid arthritis, juvenile idiopathic arthritis, osteoarthritis, fever

rheumatic (E: off-label).

Kawasaki disease (E: off-label).

Rectal route:

Its absorption is more irregular but may be useful in patients who do not

tolerate in another way.

DOSAGE AND ADMINISTRATION GUIDELINES

Pain treatment (oral or rectal): 10-15 mg / kg / dose every 4-6 hours up to a maximum of 4 g / day.

Juvenile idiopathic arthritis (JIA): in children under 25 kg at 80-100 mg / kg / day

in 3-4 shots. Maximum dose 130 mg / kg / day up to a maximum of 4 g / day.

At> 25 kg 1 g every 6-8 hours.

AAS 2 of 5

Rheumatic fever: Dosage 75-100 mg / kg / day in 4 doses (2 weeks) and

then reduce to 60-70 mg / kg / day (4-6 weeks)

Kawasaki disease: 80-100 mg / kg / day divided every 6 hours for a maximum of 14 days (until the fever has disappeared

less for 48 hours); then decrease the dose to 3-5 mg / kg / day

once a day at least 6-8 weeks.

Antiplatelet treatment: 100-300 mg / day. Antithrombotic treatment:

Its effect lasts more than 7 days.

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Shunt of Blalock-Taussig, endovascular stents, cerebrovascular disorders: 1-5 mg / kg / day.

Fontan surgery: 5 mg / kg / day.

Prosthetic valves: 6 -20 mg / kg / day.

CONTRAINDICATIONS

Gastrointestinal ulcer, recurrent gastric discomfort, history

of gastrointestinal hemorrhage after treatment with NSAIDs.

Hypersensitivity (asthma, angioedema, urticaria or rhinitis) to AAS or any other NSAID.

Children and adolescents under 16 years of age with fever (possible syndrome)

de Reye), gastrointestinal ulcer, hemophilia and other blood dyscrasias.

Contraindicated in severe renal or hepatic failure.

PRECAUTIONS

In children under chronic treatment with ASA it is advisable to check their

immune status against the chickenpox virus and advise immunize

with 2 doses of vaccine (minimum interval of 4 weeks) in case

be negative Also annual influenza vaccination.

Asthma and allergic disease.

Renal and hepatic impairment.

Usual alcohol intake (risk of gastric bleeding).

G6PD deficiency, urticaria, rhinitis, arterial hypertension.

Do not take before (1 week) or after dental extraction or surgery, or

in case of gout, metrorrhagia or menorrhagia.

Risk of hemorrhage, ulceration and perforation of the upper digestive tract.

Avoid associating with drugs that increase the risk of bleeding.

Its use should be avoided at least 2 weeks before surgery to avoid

risk of bleeding

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Do not use systematically as a precaution against vaccination discomfort.

Avoid using concomitant heparin especially if there is thrombocytopenia.

AAS 3 of 5

SIDE EFFECTS

Anti-inflammatory doses are associated with a high incidence of effects

adverse effects, can produce mild chronic salicylicity characterized by

tinnitus and deafness. Stop treatment if these symptoms appear.

Hypoprothrombinemia, rhinitis, paroxysmal bronchial spasm, designs, gastrointestinal hemorrhage, abdominal pain, nausea, dyspepsia, vomiting,

Gastroduodenal ulcer, urticaria, rash, angioedema.

In general, its use in children under 16 years of age should be avoided, except

in specific indications (for example in JIA), due to the risk of Reye syndrome and should be avoided especially if a viral infection or fever is suspected.

Possible liver damage especially due to overdose.

Hypotension, tachycardia, edema, fatigue insomnia, nervousness, agitation,

confusion, hyperkalemia, acidosis, hypernatremia, dehydration, rhabdomyolysis, prolonged pregnancy, blood dyscrasias.

Toxic dose intoxication treatment.

Toxic dose> 150 mg / kg / day. Lethal dose 300-500 mg / kg / dose.

At toxic doses, the cyclooxygenase enzyme of the complex is inhibited

prostaglandinsintetasa what entails different manifestations:

Central nervous system (CNS): Hyperventilation, hyperpyrexia, hyperpnea, seizures and even coma.

Digestive: Erosion of mucosa and hemorrhage due to inhibition of platelet aggregation

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CONCLUSIONS

• ASA is used at low doses as a platelet antiaggregant and at intermediate doses such as analgesic and antipyretic. It is not used as an anti-inflammatory, nor as uricosuric.

• Because ASA is a potent ulcerogenic it will be convenient to administer it with food.

• AAS inhibits COX to give rise to the different therapeutic effects.

• Joint taking of ASA and other drugs can lead to drug interactions.

• Bioavailability depends on the preparation and the pharmaceutical form used. The absorption will be faster in the most soluble dosage forms. UNIQUE DOSE ABSORPTION (tmax) COMPRESSED (100-125-250-500 MG) 1-2 h GASTRO-RESISTANT TABLETS (75-100-300 MG) 3-5 h (fasting) or 3h later if taken with food CAPSULES BLANDAS (75 MG) 40 min PROLONGED HARD CAPACITIES (150-300 MG) 2-4 h (decreases Cmax) EFFERVESCENT TABLETS (500 MG) 17 min (increases Cmax) CHEWABLE TABLETS (500 MG) 20 min GRANULATED (500 MG) ) 25 min

• When taking food the absorption will be delayed but the amount absorbed will be the same.

• The pharmacokinetic behavior (distribution and elimination) vary depending on the posology and other aspects discussed. - In any case it is metabolized mainly in the liver. - Two of the metabolization processes are easily saturated when a high dose of ASA is administered, giving rise to kinetics of order 0. - The highest proportion of metabolite excreted corresponds to saliciluric acid and the lowest to gentisic acid. - When urine is alkaline (pH> 7) the elimination of metabolites increases.

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Jácome Roca Alfredo. Hoffman and aspirin. History of medicines. 1st edition.

Colombia. Editorial Kimpres Ltda. 2003. p. 147-150.

Flórez Jesús, Armijo Juan Antonio, Mediavilla Africa. Analgesic anti-inflammatory drugs and non-steroidal anti-inflammatory drugs. Antiarthritics. In: Feria M.

Human pharmacology 6th edition. Barcelona. Masson S.A. 2013. p. 355-368.

Furst Daniel E, Ulrieh Robert W, Altamirano Cissy Varkey. Anti-inflammatory drugs

non-steroidal, antirheumatic disease modifiers, analgesics not

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Masters Susan B, Trevor Anthony J. Basic and clinical pharmacology. 12th edition. Saint

Francisco: McGraw-Hill; 2013. p. 606-625.

Burke Anne, Smyth Emer, FitzGerald Garrett A. Analgesic-antipyretic agents and

anti-inflammatories; pharmacotherapy of gout. In: Brunton Laurence L. editors. Editors

associates: Lazo John S, Parker Keith L. The pharmacological bases of therapeutics.

11th edition. Mexico DF. McGraw-Hill INTERAMERICANA EDITORES, S.A. 2007. p.

671-692.

Goth Andrés. Non-steroidal antipyretic anti-inflammatory analgesics. In: Vesell

Elliot S., Salva Miquel J.A. Medical pharmacology 11th edition. Ed. Doyma. 1984. p.

343-346.

Esplugues J. Antitérmicos analgesic (I). In: Orts-Buchón A. Vila-Pastor J.

Therapeutic perspectives with their pharmacological basis. Vol. 5: Nervous system

central. 2nd edition. Valencia. Editorial: Fundación García Muñoz-saber section. 1981. p.

418-435.

Rowland Malcolm, Tozer Thomas N. Clinical Pharmacokinetics: Concepts and

applications. 3rd edition. USES. Ed.Williams and Wilkins. nineteen ninety five.

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Real Spanish Pharmacopoeia. 3rd edition. 2003

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