L18 GI Pharmocology Flashcards
GORD symptoms, complications and risk factors
Symptoms:
- heart burn
- cough
- laryngitis
- asthma
- dental erosion
Complications:
- Barrett’s oesophagus
- oesophagitis
- ulceration
- haemorrhage
- stricture formation
Risk factors:
- older age
- hiatus hernia
- obesity
- pregnancy
- smoking
- alcohol
Medication that causes GORD
Alpha blockers Anticholinergics Benzodiazepines Beta blockers CCBs Corticosteroids NSAIDs Nitrates Theophylline
GORD management medication
PPIs:
- omeprazole
- lansoprazole
Gastritis symptoms, complications and risk factors
Symptoms:
- burning epiblast tic pain
- nausea and vomiting
- food may increase or decrease pain
Complications:
- GI bleeding
Risk factors:
- H. Pylori
- chronic NSAIDs
- bile reflux
Erosive causes of gastritis
NSAIDs
Alcohol
Bile
Non erosive causes of gastritis
H. Pylori
Treatment of erosive gastritis
Stop or reduce use of NSAIDs or alcohol
Give PPI or a H2 receptor antagonist
Treatment of non erosive gastritis
Triple therapy
- PPI + 2x antibiotic (amoxicillin + clarythromycin or metronidazole)
Quadruple therapy - given if resistant to clarythromycin
- PPI + bismuth + 2x antibiotics
Autoimmune cause of gastritis
Antibodies produced against parietal cells
Treatment for autoimmune gastritis
Cyanocobalamin
Peptic ulcer disorder symptoms, complications and risk factors
Symptoms:
- epigastric pain before (gastric) or after (duodenal) meals
Complications:
- perforation causing peritonitis
Risk factors:
- H pylori
- NSAIDs
Treatment for H pylori negative peptic ulcer disease
Stop NSAIDs
COX 2 inhibitor - celecoxib
PPI
H2 receptor antagonist - IGF unresponsive to PPI
Why is COX2 inhibitors used
Doesn’t effect COX 1 mediated prostaglandin synthesis
Treatment of peptic ulcer disease when NSAIDs need to be taken or elderly
Consider misoprostol (prostaglandin analogue) - inhibits adenylate cyclase decreased cAMP - decreases PPI activity
Treatment of H. Pylori positive peptic ulcer disease
Test for H. Pylori using a urea breath test or stool antigen test
Triple therapy:
- PPI + amoxicillin and clarythromycin or metronidazole
NSAID effect on COX
NSAIDs inhibit COX enzymes therefore less prostaglandins are synthesised from arachidonic acid
COX 1 abundance and regulation
High concentration in:
- platelets
- vascular endothelial cells
- kidney
- stomach
Regulates:
- prostaglandins - decreases platelet aggregation, vasodilation and mucosal protection
- thromboxane - platelet aggregation and vasoconstriction
COX 2 abundance and effects
High concentration:
- at sites of tissue damage
- brain
- kidney
- bones
Regulates:
Prostaglandins - can cause inflammation and fever
Roles of prostaglandins
Vasodilation
Decrease gastric release
Stimulates mucus and bicarbonate release in stomach
Reduce permeability of epithelium to acid back flow
Reduce release of inflammatory mediators
Promotes ulcer healing
Parietal cell non secreting state
Non secreting state:
- proton pump (H+, K+ ATPase) are located in tubulovesicles
- lack K+ permeability therefore no activity
- apical membrane of parietal cells have K+ channels and involutions (canaliculi) and microvilli
Parietal cell secreting state
Tubulovesicles fuse with canalicular membrane forming canaliculi
More proton pumps where K+ exchange can occur
Elongation of microvilli
PPI activation
PPIs are activated by acidic condition of the parietal canaliculus
PPIs are weak bases therefore accumulate in the canaliculi in high concentration
Enteric coating of PPI
Prevents premature activation in stomach
Absorbed in the small intestine and transported to parietal cells
Activated in canaliculi
PPI mechanism of action
Bind covalently to proton pumps irreversibly and block function
- short half life
- long term effect
- requires de novo synthesis of pump enzyme to produce more acid
