Week 21 Pharmacology

Antacids

Weak bases that react with gastric acid to neutralise –> salt + water
Effect varies depending upon – rate of dissolution, water solubility, rate of reaction with acid, rate of gastric emptying
Sodium bicarbonate –> CO2 –> belching, abdo distention, potential metabolic alkalosis
Calcium carbonate
MgOh, AlOH – no CO2 so no belching, metabolic alkalosis uncommon. Can cause diarrhoea(Mg) or constipation(Al)
Renally excreted

Cimetidine, ranitidine, nizatidine
PK – rapidly absorbed, first pass metabolism, 50% bioavail, t 1/2 1-4hrs, hepatic metabolism, glomerular filtration and tubular secretion
PD – competitve inhibitors of parietal cell H2 receptors –> supress basal and post prandial acid secretion in a dose dependent manner, esp nocturnal acid secretion. Volume of gastric acid secretion and pepsin is reduced. Inhibit secretion via histamine and by direct gastrin or ACh. Block 60-70% acid secretion in 24hrs.
Uses – GORD, PUD, dyspepsia
SE – diarrhoea, headache, fatigue, myalgias, constipation
Cimetidine inhibits binding of dihydrotestosterone to androgen receptor and inhibits metabolism of estradiol, increases prolactin –> gynaecomastia, impotence, gallactorrhoea. It also inhibits some Cyt P450.

Esomeprazole, omeprazole, pantoprazole, rabeprazol
PK – Admin as oral prodrug that is absorbed in intestine, lipophilic, weak bases, food decreases bioavail to 50% so give on empty stomach, t 1/2 1.5 hrs, rapid first pass and systemic hepatic metabolism, negligible renal clearance, long duration of action.
PD – activated in parietal cell canaliculus –> inhibits H+/K+ ATPase irreversibly when they are active. Block 90-98% acid secretion.
SE – diarrhoea, headache, abdo pain, reduce B12 abs, ? Dec Ca abs

Metoclopramide.
- Dopamine2 receptor blockade
- Centrally in chemoreceptor trigger zone in medulla – potent antinausea and antiemetic
- Peripheral D2 block – Prokinetic- increase oesophageal peristalsis, enhance gastric emptying. No effect on small intestine or colonic motility.
- SE – EPS, dystonia, restlessness, parkinsons

Prochlorperazine.
- Antipsychotic agents, antiemetic and sedative(H)
- PD – inhibit D and musc receptors.
- SE – EPS, hypotension, antimuscarinic effects

Ondansetron
- 5HT receptor antagonist centrally in vomiting centre and chemoreceptor trigger zone but mainly peripherally on intestinal vagal and spinal afferent nerves
- Good for vomiting from vagal stimuli or post op or chemo, not very good at motion sickness(no effect on D or musc receptors, not pro motility)
- PK – T1/2 4-9hrs, hepatic metabolism and eliminated by renal and hepatic excretion

(we don’t see these as viva questions)