Pharmacology Of Inflammation

Front 1

Effects of Prostaglandins on Cardiovascular system

Back 1

1. Blood Pressure – PGE and PGI2 decrease while Thromboxane A2 (TXA2) increases

2. Heart – PGE and PGI2 dilate coronary vessels, TXA2 constricts them

3. TXA2 stimulates platelet aggregation

4. PGI2 (prostacyclin) inhibits platelet aggregation

5. PGE2 and PGI2 can maintain patency of ductus arteriosus and Alprostadil (PGE1) used clinically to maintain maternal/fetal blood flow

Front 2

Effects of Prostaglandins on Renal system

Back 2

Effects of Prostaglandins on Renal system

1. PGE and PGI2 cause vasodilatation, natriuresis, diuresis, and renin release

Front 3

Effects of Prostaglandins on Respiratory system

Back 3

Effects of Prostaglandins on Respirator system

1. PGE and PGI2 dilate bronchioles

2. Thromboxane A2 and PGF2a constricts bronchioles

3. PGE2 can be used as aerosol in bronchial asthma, but brief duration limits clinical usefulness

Front 4

Effects of Prostaglandins on Gastrointestinal System

Back 4

Effects of Prostaglandins on Gastrointestinal System


1. PGE2 and PGI2 inhibit gastric acid and pepsin secretion, increase mucous secretions

2. Misoprostrol (PGE1 analog) marketed and approved to promote ulcer healing

Front 5

Effects of Prostaglandins on Reproductive System

Back 5

Effects of Prostaglandins on Reproductive System


1. PGE2 relaxes non-pregnant but contracts pregnant uterus

2. PGF2a contacts pregnant and non-pregnant uterus

3. PGF2a causes lysis of corpus luteum

4. PGE2 and PGF2a used as a contraceptive, to induce abortion, and to control post-partum hemorrhage

Front 6

Prostaglandin role in Fever and Pain?

Prostaglandins and Tolerance?

Back 6

Prostaglandin role in Fever and Pain

Role in Pain and inflammation:
1. PGs synthesized and found in synovial fluid in inflammation
2. PGs produce pain or hyperalgesia (i.e. increased sensitivity to painful stimuli)

Fever
1. Central administration of PGs, especially into the hypothalamus, produces fever

Tolerance - the human body never develops tolerance to prostaglandins

Front 7

6 Clinical Uses of Prostanoids

Back 7

6 Clinical Uses of Prostanoids

1. Facilitate labor by promoting ripening and dilation of the cervix (Dinoprostone)
2. Gastric protection (misoprostol)
3. Improve harvesting and storage of platelets (PGG, PGI2)
4. Impotence (Aloprostadil)
5. Dilate pulmonary vessels (epoprostenol (PGI2))
6. Maintenance of patent Ductus Arteriosus (Aloprostadil)

Front 8

Pharmacology of Nonsteroidal Anti-inflammatory Drugs
Therapeutic Effects?
Untoward Actions?

Back 8

Pharmacology of Nonsteroidal Anti-inflammatory drugs

Therapeutic Effects:
1. Pain Relief (Analgesic)
2. Reduce Fever (Antipyretic)
3. Anti-inflammatroy (except Acetominophen)
4. Prophylactic to reduce the risk of MI

Untoward actions/Side Effects
1. Gastric Irritation
2. Altered respiration
3. Disturbance in Acid/Base balance
4. increased bleeding
5. Prolongation of gestation
6. Potential Renal damage

Note that NSAIDs provide symptomatic relief but do not affect the underlying disease

Front 9

Aspirin Toxicity

Back 9

Aspirin Toxicity
1. Gastric Distress - Epigastric distress, nausea, vomiting; gastric ulceration, hemorrhage, exacerbate ulcers
2. Inhibits platelet aggregation and prolongs bleeding
3. Toxic concentrations of aspirin may suppress circulation
4. Reyes Syndrome
5. Hepatotoxicity
6. Acute Renal insufficiency in patients with underlying disease
7. Low doses decrease urate excretion - Gout patients

Front 10

Reyes Syndrom - Define?

Back 10

Reyes Syndrome

Persistent of recurrent vomiting, listlessness, irritability, combativeness, disorientation or confusion, delirium, convulsions, loss of consciousness - prognosis is linked to severity of brain swelling.

Front 11

Aspirin Poisoning
Primary Effects?
Secondary Effects?

Back 11

Aspirin Poisoning

Primary Effects
1. CNS - Tinnitus, mental confusion, hearing loss, convulsions and coma
2. GI - Nausea and vomiting
3. Hyperthermia (Uncoupling of oxidative phosphorylation), dehydration
4. Stimulation of respiratory centers

Secondary Effects
1. Respiratory Alkalosis
2. Metabolic Acidosis
3. Water and electrolyte loss
4. Cardio and respiratory arrest with severe intoxication

Front 12

Respiratory Effects of Aspirin
Therapeutic Effects?
Toxic Effects?

Back 12

Respiratory Effects of Aspirin

Therapeutic Effects
1. Stimulates respiration secondary to increased O2 consumption and CO2 production
2. Directly stimulates respiration
3. Results in respiratory alkalosis
4. To compensate for increased renal excretion of bicarbonate and return pH toward normal

Toxic Doses
1. Depresses Respiration resulting in increased CO2
2. True metabolic acidosis
- Displacement of bicarbonate
- Decreased Renal excretion of organic acid
- Increased lactic acid production secondary to increased carbohydrate metabolism

Front 13

Contraindications to Aspirin

Back 13

Contraindication to Aspirin
1. Ulcer patients
2. Patients allergic to aspirin
3. Patients with clotting disorders
4. Pregnancy
5. Gout
6. Viral infections in children and young adults - Reyes