Pharmacology of GORD

Question 1

What are NSAIDs?

Answer 1

Non-steroidal anti-inflammatory drugs

Question 2

What is the drug target of NSAIDs?

Answer 2

Cyclo-oxygenase (COX) enzyme

Question 3

What is the primary mechanism of action of NSAIDs?

Answer 3

1) Inhibit COX enzyme which inhibits production of prostanoids from arachnoid acid
2) Prostanoids act through large number of prostanoid receptors to produce many effects
3) Unwanted affects due to COX 1 inhibition

Question 4

What are the main side effects of NSAIDs”? (8)

Answer 4

-Gastric irritation, ulceration and bleeding
-Gastric perforation in extreme cases
-Reduced creatinine clearance and possible nephritis
-Chronic renal failure in prolonged analgesic abuse over years
-Bronchoconstriction in susceptible individuals
-Skin rashes and allergies, dizziness and tinnitus
- Adverse cardiovascular effects may occur with prolonged use/pre-existing CV risk
-Aspirin linked with rare but serious post-viral encephalitis in children

Question 5

What is nephritis?

Answer 5

Inflammation of kidneys

Question 6

What patients tend to get bronchoconstriction with NSAIDs use?

Answer 6

Asthma patients

Question 7

What are some examples of cardiovascular effects? (3)

Answer 7

-Hypertension
-Stroke
-Myocardial infarction

Question 8

What is post-viral encephalitis (Reye’s syndrome)?

Answer 8

Inflammation of the brain following a viral infection

Question 9

What are the main uses of NSAIDs generally? (3)

Answer 9

-Analgesics for relief of mild to moderate pain
-Antipyretic to reduce fever
-Anti-inflammatory drug for control of chronic inflammatory drugs

Question 10

What is the main use of aspirin?

Answer 10

Anti-aggregatory agent to inhibit platelet aggregation in stroke/MI risk patients

Question 11

What are examples of NSAIDs? (3)

Answer 11

-Ibuprofen
-Naproxen
-Diclofenac

Question 12

What is the drug target of proton pump inhibitors (PPIs)?

Answer 12

H+/K+ ATPase (proton pumps)

Question 13

What is the primary mechanism of action of PPIs?

Answer 13

1) Irreversible inhibitors of H+/K+ ATPase in gastric parietal cells
2) They are weak bases and accumulates in acid environment of canaliculi of the parietal cells
3) This concentrates their actions there and prolongs their duration of action
4) Omeprazole plasma half life is 1 hour but single daily dose affects affects acid secretion for 2-3 days
5) Proton pump inhibitors inhibit basal and stimulated gastric acid secretion by >905

Question 14

What are the main uncommon side effects of PPIs? (4)

Answer 14

-Headache
-Diarrhoea
-Bloating
-Abdominal pain and rashes

Question 15

What is a more serious side effect of PPIs?

Answer 15

May mask gastric cancer symptoms

Question 16

What is a serious side effect of omeprazole?

Answer 16

Inhibitor of cytochrome P2C19 and reduces activity of p450 enzymes

Question 17

What type of drugs are PPIs?

Answer 17

Pro-drugs which activate at low pHs

Question 18

What is the most common way to administer PPIs?

Answer 18

Given as capsules of enteric-coated granules so do not degrade due to low pH

Question 19

What are examples of PPIs? (2)

Answer 19

-Omeprazole
-Lansoprazole

Question 20

What is the drug target of histamine (H2) receptor antagonists?

Answer 20

Histamine H2 receptor

Question 21

What is the primary mechanism of action of histamine receptor antagonists?

Answer 21

1) Competitive H2 receptor antagonists
2) Inhibit stimulatory action of histamine released from enterochromaffin-like (ECL) cells on gastric parietal cells
3) Inhibit gastric acid secretion by 60%

Question 22

What is the main side effect of general histamine receptor antagonists?

Answer 22

-Diarrhoea, dizziness, muscle pains and transient rashes

Question 23

What side effects can cimetidine cause?

Answer 23

-Inhibits cytochrome P450
-May retard metabolism and potentiate effects of a range of drugs including oral anticoagulants and TCAs

Question 24

What is the dose of ranitidine given?

Answer 24

-2x daily dose
-This is due to plasma half life being 2-3 hours and is well tolerated

Question 25

What is the drug target of paracetamol?

Answer 25

Not sure but a few sites have been proposed:
-5HT3 receptors
-Cannabinoid reuptake proteins
-Peroxidase

Question 26

What is the primary mechanism of action of paracetamol?

Answer 26

-Not known properly

Question 27

What is the proposed primary mechanism of action of paracetamol through peroxidase?

Answer 27

-At peripheral sites
-May inhibit peroxidase enzyme involved in converting arachidonic acids to prostaglandins

-Ability to inhibit peroxidase can be blocked by excessive peroxidase build up like inflammation

Question 28

What is the proposed primary mechanism of action of paracetamol through 5TH3?

Answer 28

Activation of descending serotonergic pathways via 5TH3 receptors

Question 29

What is the proposed primary mechanism of action of paracetamol through cannabinoid receptors?

Answer 29

-Inhibits reuptake of endogenous endocannabinoids
-Increased activation of cannabinoid receptors
-May contribute to activation go descending pathways

Question 30

What are the main symptoms of a paracetamol overdose?

Answer 30

-Liver damage and less frequent renal damage
-Nausea and vomiting early features of poisoning (settles in 24 hours)
-Onset of high subcostal pain after 24 hours indicates hepatic necrosis

Question 31

What are the main functions of paracetamol?

Answer 31

-Anti-pyretic
-Analgesic
-NOT anti-inflammatory