Please enable JavaScript.
Coggle requires JavaScript to display documents.
Pharmacology for Upper GIT (Antacids (Weak bases which are used to…
Pharmacology for Upper GIT
Proton Pump Inhibitors
OMEPRAZOLE
Irreversibly blocks H+/K+ ATPase on parietal cells
Inactive pro-drug, is protonated at acid pH to active derivative. So inactive when swallowed but it becomes activated in the stomach
S.E: Hypomagnesaemia, osteoporotic fracture, pneumonia and vitamin B12 deficiency
Single oral dose-->long-lasting acid secretion inhibition
Mainstay of acid suppression: Triple therapy for peptic ulcer, gastrooesophageal reflux, prophylaxis against ulcer development and Zollinger-Ellision syndrome
Treatment for peptic ulcers
H2 receptor antagonists
Competitive inhibitors of histamine
Two mechanisms: 1. Histamine blocked from binding to parietal cells2. Gastrin and ACh have reduced effects on parietal cells when the H2 receptors are blocked.
Less acid suppression compared to Proton Pump Inhibitors because only histamine is blocked. This means gastrin and ACh will be able to function
CIMETIDINE
: Inhibits cytochrome P450 enzymes present in the liver which is responsible for the metabolism of drugs, causes confusions and drowsiness with headaches and rashes.
RANITIDINE
: Little of no inhibition of P450 and no antiandrogenic activity
Muscarinic antagonists
PIRENZEPINE
- Has high incidence of anti-cholinergic SE
Mucosal barrier fortifying agents- cycloprotectives
MISOPROSTOL
: Semi-synthetic PG which promotes mucus prodcution and inhibits acid secretion by binding onto the PG receptor (EP3) on the parietal cells.SE: Diarrhoea, uterine contractions. Used for patients with an ulcer who need NSAIDs.
PGs which are cycloprotectives. NSAIDs inhibit COX-1 which then decreases PG synthesis. So increases the chances of ulceration
SUCRALFATE
: It is a polymer of aluminium and sucrose and it binds to ulcer base which has a mucosal protecting action. PG and bicarbonate production is stimulated.
BISMUTH
: It binds to the ulcer base and precipitates at acid pH to protect the mucosa so PG and bicarbonate production will be stimulated.
Antacids
Weak bases which are used to neutralise gastric acid and raise the gastric pH. Used as symptom relief in peptic ulcer disease and also in indigestion, dyspepsia, heart-burn and gastrooesophageal reflux disease. However it does not facilitate peptic ulcer healing.
SODIUM BICARBONATE:
Causes rapid neutralisation but very high doses could result in alkalosis. Also results in the production of carbon dioxide--> bloating.
CALCIUM CARBONATE
: The calcium ions cause gastrin release. It also results in carbon dioxide production
MAGNESIUM
: Magnesium Hydroxide causes rapid neutralisation and produces diarrhoea. Mg2Si3O8 results in rapid neutralisation and produces constipation
ALUMINIUM
: Al(OH)3 is a slow neutraliser and produces constipation
So a combination of Mg(OH)2 and Al(OH)2 co-dried gel can be used which would result in the constipation and diarrhoea cancelling out
Gastrooesophageal reflux disease is due to the damage to the oesophagus by gastric acid. PPI(first line) and higher doses are used 4-8 weeks. H2 antagonists will be used if needed and antacids for mild symptoms.
Heart burn can be treated with rafting agents such as alginates which would cause swelling and thickening in contact with stomach due to the reaction with acid. These agents will float over the contents of the stomach providing a mechanical barrier for reflux. So when reflux occurs, the viscous form will contact the oesophageal mucosa first.
Stimulants of upper GIT motility
METOCLOPRAMIDE
: Dopamine antagonist which prevents smooth muscle releaxation produced by dopamine action of the D2 receptors. Also inhibits ACh release by activating pre-junctional D2 receptors which indirectly inhibits the musculature and the presynaptic 5-HT4 receptors. Stimulates gastri emptying and increases the lower oesophageal sphincter tone.
DOMPERIDONE
: Peripheral D2 antagonist which does not cross the blood-brain barrier. It stimulates gastric emptying and enhances contraction in the stomach and increases the lower oesophageal tone. Both of them speed up the transit of stomach contents.
Anti-emetics
Anticholinergics
: Muscarinic antagonists with SE such as sweating and blurred vision. Used mainly for motion sickness.
HYOSCINE
Antihistamines
: H1 antagonists and some also have anti-cholinergic activity with SE such as sedation.
CYCLIZINE
is used in for motion sickness.
Dopamine antagonists
: D2 antagonsits which depresses the chemoreceptor trigger zone activity. It decreases vomiting due to drugs such as chemotherapy drugs. E.g:
PROCHLORPERAZINE
(acts on muscarinic and H1 receptors),
HALOPERIDOL
(Butyrophenones),
METOCLOPRAMIDE
and
DOMPERIDONE
Serotonin receptor antagonists
: Acts as antagonists on the 5-HT3 receptors and depresses the chemoreceptor trigger zone and also the visceral afferents from GIT. It decreases vomiting due to drugs.
ONDANSETRON
: Oral or IV and has SE such as constipation and headaches
Cannabinoids
: Delta-9THC antagonists acting on the CB receptor and decreases vomiting due to drugs.
NABILONE
: Has SE such as drowsiness and psychological effects.