Pharmacology Flashcards
What can GORD lead to?
Ulcerative oesophagitis which can lead to cancer
Common antacid therapies
- gaviscon: float on stomach contents
- Antacid tablets coat oesophagus and neutralise acid in stomach
- H2 receptor antagonists: inhibitor of H2 receptor - prevent histamine action on parietal cell
GI causes of nausea and vomiting
- outflow obstruction
- dysmotility
- mucosal inflammation
- infections
Other causes of nausea and vomiting
Chemical - drugs, radiotherapy, toxins
Vestibular - motion sickness, cerebellar tumour
CNS - anxiety, raised ICP
Pregnancy
4 Main sources of afferent input that are associated with the pathophysiology of nausea and vomiting
- chemoreceptor trigger zone
- vestibular system
- vagal and spinal afferent serves from GI tract
- CNS
Mechanism of action of metoclopramide
¥ Enhances response to acetylcholine in the upper GI tract
¥ Blocks dopamine receptors in the CTZ
¥ At higher doses also blocks CTZ serotonin receptors
Adverse effects of metoclopramide
- Extra pyramidal symptoms – more common in younger patients (and female)
- Rarely causes tardive dyskinesia, higher risk with longer treatment
Mechanism of action of domperidone
- effective at the CTZ
- blocks dopamine receptors in the upper GI tract resulting in increased motility
Mechanisms to cross the blood brain barrier (3)
- transmembrane diffusion
- transport systems
- transcellular pathway
Examples of serotonin antagonists
Ondansetron, granisteron, palonosetron
Major and minor effects of serotonin antagonists
Major - effect - block released serotonin in upper GI tract
Minor - acts at the vomiting centre
Short term and long term side effects of steroids
Short term - increased BSL, hunger, increased BP, psychosis
Long term - osteoporosis, steroid induced DM, myopathy, thin skin
Action of hycosine
Anticholinergic at muscarinic receptors
- minor histamine and serotonin antagonism
Treating nausea and vomiting in pregnant women
Cat A: metoclopramide, pyridoxine
Cat B1: Odansetron
Cat C: Prochlorperazine
If medication is required for children with acute gastroenteritis (nausea/vomiting), what should be given?
Odansetron
Accompanying signs and symptoms to nausea and vomiting
- abdominal pain, distention, peritonism
- diarrhoea
- fever, neck stiffness
- vertigo
- focal neurology
3 Pharmacokinetic changes in hepatic insufficiency
- bioavailability
- protein binding, and therefore distribution
- hepatic clearance
- phase 1 (cytochrome p450)
- phase 2 (glucourinidation and sulphation)
How does liver disease affect flow dependent clearance?
Chronic hepatic disease
scarring obstructed blood vessels shunting drug in portal and arterial blood bypasses hepatocytes increased bioavailability and reduced clearance of flow dependent drugs
Flow dependent drugs
- nitrates
- opiates
- beta-adrenoceptor blockers
- calcium channel blockers
- lignocaine
Enzyme dependent drugs
- Most anti-convulsants
- Warfarin
- Benzodiazepines
- Theophylline
- Most NSAID’s
- Amiodarone
Effects of hepatic disease on enzyme dependent drugs
- impaired clearance
- alcohol induces some P450 isoenzymes
Liver failure and reduced albumin
Hypoalbuminaemia: reduced bound fraction of highly albumin bound drugs
Results in increased extravascular water volume and reduced intravascular water volume – altered distribution volume for highly water soluble drugs
How does hepatic disease effect anticoagulant use?
Reduced clotting factor synthesis = increased effectiveness of anticoagulants and increased bleeding risk
CONTRAINDICATED
How does hepatic disease effect sedative use?
- increased sensitivity to sedatives - bento’s and opiates
- increased risk of over sedation and hepatic encephalopathy
TAKE WITH CARE
How does hepatic disease effect diuretic use?
- Reduced plasma albumin reduced plasma osmotic pressure
- Increased tissue fluid and reduced plasma volume
- Reduced renal flow
- Increased renin increased angiotensin II increased aldosterone
- Na+ and H2O retention and K+ loss
AVOID K+ DEPLETING AGENTS
Therapeutic goals in inflammatory bowel disease
- manage exacerbations swiftly
- suppress chronic inflamm
- surveillance for complications
- manage GIT complications as well as extra intestinal disease
Role of aminoslicylates in IBD
- maintaining remission in UC, limited in Crohn’s
Role of corticosteroids in IBD
- potent anti-inflammatory
- used for moderate and severe relapses of UC and Crohn’s
Action and adverse effects of thiopurines
- result in immunomodulation via induction of T cell apoptosis Adverse affects antiproliferative • Antiproliferative actions: bone marrow failure (↓WCC, ↓platelets) • Hepatotoxicity • Allergic skin rash • Teratogenicity risk
Role of anti-TNF-alpha antibodies in IBD (infliximab, adalimumab)
TNF-alpha regulates immune cells
Osmotic laxatives used in constipation
- increase water content of stools
• Polyethylene glycol (PEG) Movicol – lower dose as aperient ColonLytely - larger doses as bowel prep
• Magnesium citrate
Epson salts, some Mg absorbed
• Sodium phosphate
Risk of electrolyte disorders (↑PO4, ↓Ca, ↓K), used in enemas
• Nonabsorbable carbohydrates Lactulose/sorbitol
Stimulants used in constipation
Encourage bowel motility
• Senna
Converted into active Sennosides A & B by colonic bacteria
• Docusate sodium (Coloxyl) Detergent, also stool softener
• Sodium picosulphate Picoprep
• Bisacodyl
Oral and suppository formulations
Drugs used in diarhoea
Mu opioid receptor antagonists: Diphenoxylate, loperamide, codeine sulfate
Bulking agents: plant fibre, guar gum
