Pharmacology

Question 1

Aspirin

• Indication
• Toxicity
• Replacements

Answer 1

Use

• Antiplatelet [MI, IHD)
• Analgesic
• Inflammation

Toxicity

• GI
• Tinnitus
• Reye’s syndrome

Question 2

Paracetamol

- Use

Answer 2

Analgesic
Antipyretic

Does not cause significant toxicity or anti-inflammation
- Doesn’t bind to COX 1/2

Question 3

Paracetamol overdose mechanism

Answer 3

Can be caused by 20/30 500mg tablets

Paracetamol metabolised Into NAPq1= hepatic necrosis
- When it can not undergo conjugation in the liver (Phase 2), so undergoes oxidation (Phase 1)

Can be overcome by
- methionine that shunts NAPQ1 into excretion

Question 4

NSAID GI toxicity

Answer 4

Inhibition of prostaglandins (which initially protects gut mucosa)

• Irritation of GI
• Ulcers (gastric and duodenal)
• GI bleeding
• Colitis

Risk of upper GI bleed

• 4.7
• Older NSAIDs= greater risk
• Older, chronic disease
• Steroids
• Previous GI bleed.

Question 5

NSAID nephrotoxicity

Answer 5

Reduces glomerular blood flow

• Decreases GFR
• Na+ retention
• Hyperkalaemia
• Papillary necrosis

Acute renal failure

Question 6

NSAID and bronchoconstriction

Answer 6

Possibly shunting of Arachidonic acid down 5LPO to leukotrienes by COX2 inhibition= bronchoconstriction

Question 7

Main 4 NSAIDs

Answer 7

Further down= more side effects

Ibuprofen

Naproxen

Diclofenac

Indometacin

Question 8

Preventing NSAID toxicity

Answer 8

Consider alternative

• Paracetamol
• Weak opioids

Gastroprotective drug in co-administration
- PPIs

Avoid in renal failure

Question 9

Selective COX-2 inhibitors

Answer 9

Coxibs
- i.e Celecoxib

Safer than normal NSAIDs and comparable effects

However

• Increases MI rates by by small amount
• MI in first 3 months
• May be due to the lack of anti-platelets effects

Only used when needed, i.e GI toxicity

Question 10

Hydrocortisone

Answer 10

Endogenous glucocorticoid
- Modulator of immune response at high doses

Mechanism

• modulates gene expression in T, B and innate cells
• Delay of onset, so much be taken regularly

Question 11

Immunomodulation by steroids

Answer 11

Cell trafficking

• Reduces lymphocytes and monocytes
• Increases neutrophils but with impaired function

Cell function

• Decreases T and B cell responsiveness
• Inhibits COX
• Impairs phagocytes

Does not affect Ab levels of complement

Question 12

steroids uses

Answer 12

Inflammation

Graft rejection

replacement therapy

Question 13

Steroid preparation

Answer 13

Systemic

• Oral
• Injection

Topic

• Skin
• Joint injection
• Inhaled
• Enteric coated
• Rectal

Question 14

Prednisolone

Answer 14

Main oral corticosteroid

• Medium potency
• Anti-inflammatory

Question 15

COX-1

• Function
• Effects of inhibition

Answer 15

Expressed in all tissues
- Esp. stomach, kidneys, platelet, vascular endothelium

• Inhibition leads to anti-platelet activity

Question 16

COX-2

• Function
• Effects of inhibition

Answer 16

Induced in inflammation via IL-1
- i.e injury, infection, neoplasia

Inhibition
- Analgesia, anti-inflammatory

Question 17

COX 3

• Function
• Effects of inhibition

Answer 17

Expressed in CNS

- Inhibited by paracetamol= antipyretic and analgesic

Question 18

Side effects of corticosteroid drugs

Answer 18

Adrenal suppression when prolonged therapy
- Adrenal atrophy, can lead to adrenal crisis

Increased risk to infection

• Phagycoytic defects: s.aureus, candida [earlier risks]
• Cell mediated: TB, varicella, listeria, pneumocystis.