GIS15 Aggressive factors and ulcer healing drugs

Question 1

Name three aggressive factors for peptic ulcer except gastric acid.

Answer 1

Pepsin
NSAIDS
Alcohol
Stress: NE => sympathetic activation
Smoking: nicotin => (+) acid and pepsin secretion

Question 2

Name three defensive factors for peptic ulcer.

Answer 2

Mucus
Bicarbonate
Blood flow
Prostaglandins: + HCO3, + blood flow, - acid (+ PGE1 receptor on parietal cells => - cAMP), + mucus (act on mucous cell)
Nitric oxide: + blood flow
Growth factors

Question 3

Why is famotidine used to replace cimetidine nowadays?

Answer 3

Famotidine: higher potency & duration of action => take smaller doses & lower frequency

Cimetidine:
(-) dihydrotestosterone -> androgen receptors => impotence, gynecomastia in men
(-) cytochrome P450 to greater extent

Question 4

Why is it not advisable to take cimetidine together with phenytoin?

Answer 4

H2 antagonists:
(-) cytochrome P450 in liver (drug metabolising enzymes)
=> drug toxicity
e.g. phenytoin, theophylline, warfarin

Question 5

Why are muscarinic antagonists rarely used nowadays as ulcer healing drugs?

Answer 5

Less effective
Many side effects:
-> blurred vision, dry mouth, cardiac arrhythmias, urinary retention

Question 6

What is the common side effect of sodium bicarbonate and calcium carbonate?

Answer 6

Belching

Question 7

Name a unique side effect of sodium bicarbonate.

Answer 7

Exacerbate fluid retention in px with HF, HT & renal insufficiency (due to sodium)

Also short-acting

Question 8

Name a unique side effect of calcium carbonate.

Answer 8

Hypercalcemia, renal calculi
Constipation

Question 9

Why are magnesium hydroxide and aluminium hydroxide commonly administered together in proprietary formulations?

Answer 9

Mg(OH)2 => diarrhoea
Al(OH)3 => constipation

Question 10

Why is hypermagnesemia very rare?

Answer 10

Poor absorption of Mg

Question 11

MOA of sucralfate

Answer 11

Sucralfate = sucrose sulphate + aluminium hydroxide

Acid => release of Al => remaining molecule -ve charged => bind to +ve charged glycoprotein in mucus => viscous gel formed adheres to epithelial cells including area of ulceration
=> protect stomach luminal surface
=> X degraded by acid & pepsin
+ more time for wound healing

Question 12

What systemic side effects does sucralfate have?

Answer 12

None
Not absorbed

Question 13

Why is sucralfate not taken together with antacids?

Answer 13

Sucralfate requires acidic environment for activation => antacids reduces its efficiency

Question 14

Should sucralfate be taken after a meal?

Answer 14

No
Take on empty stomach
May bind to food => lower efficacy

Also bismuth

Question 15

What drugs may sucralfate bind to?

Answer 15

Quinolones, phenytoin, warfarin
=> limited absorption

Question 16

MOA of bismuth

Answer 16

1. Combine with mucus glycoproteins to form a barrier => protect ulcerated area against acid & pepsin
2. (+) mucus, bicarbonate, prostaglandin secretion
3. Antimicrobial against H. pylori

Question 17

Why may a patient taking bismuth be mistaken for having GI bleeding?

Answer 17

Bismuth => darkening of stool

Also teeth and tongue

Question 18

In which group of patients is bismuth contraindicated?

Answer 18

RF px
Prolonged use => toxicity => encephalopathy (ataxia, headache, confusion, seizures)

Question 19

MOA of amoxicillin

Answer 19

(-) transpeptidase
=> (-) cell wall synthesis

Question 20

Side effects of amoxicillin

Answer 20

Hypersensitivity (rash, fever, anaphylactic shock)
GI disturbance (alter gut bacterial flora)

Same as clarithromycin

Question 21

MOA of clarithromycin

Answer 21

(-) 50S subunit of ribosome
=> (-) translocation (A->P) during protein synthesis

Question 22

MOA of tetracycline

Answer 22

(-) 30S subunit of ribosome
=> (-) attachment of tRNA to A site

Question 23

A patient with peptic ulcer due to H. pylori infection shows tooth discolouration, enamel dysplasia and photosensitivity after taking an antibiotic. What is the antibiotic?

Answer 23

Tetracycline

Also reduced bone growth (for <8 y/o), nausea and vomiting

Question 24

Why is metronidazole selectively toxic for anaerobic organisms and H. pylori?

Answer 24

Nitro group of metronidazole is chemically reduced by PFOR, which is expressed in anaerobic but not mammalian systems

Redox product disrupts DNA helical structure => (-) DNA synthesis

Question 25

Side effects of metronidazole

Answer 25

Metallic taste
Occasionally sensory neuropathy

Question 26

Side effects of metronidazole

Answer 26

Metallic taste
Occasionally sensory neuropathy (e.g. numbness of fingers)