Lecture 34 Clinical Pharmacology of Alimentary Flashcards
What drugs are used for acid suppression
o Antacids
o H2-receptor antagonists
o Proton pump inhibitors
What drugs are used to control GI motility
o Anti-emetics
o Anti-muscarinics/other anti-spasmodics
o Anti-motility
What drugs are used for IBD
o Aminosalicylates
o Corticosteroids
o Immunosuppressants
o Biologics
What drugs affect intestinal secretions
o Bile acid sequestrants and ursodeoxycholic acid
What is the action and use of antacids
Contain magnesium or aluminium and neutralised gastric acid
What is the action of alginates and give an example of one
Forms viscous gel that floats on stomach contents and reduces reflux
What is the action of H2-receptor antagonists and what’s its use
– Block histamine receptor thereby reducing acid secretion
– Indicated in GORD/Peptic ulcer disease
Ranitidine
What is the action and use of a PP inhibitor and name an example
– Block proton pump and thereby reduce acid secretion
– Indicated in GORD/peptic ulcer disease
– Oral or IV administration
Omeprazole
– Triple therapy for treatment of PU/DU associated with H pylori
What is the function of Prokinetic agents
Increase gut motility and gastric emptying
What drugs are used to treat vomiting
Anti-muscaranics Anti-histamines Dopamine antagonists 5HT3 antagonists Cannabinoids
Where does anti-histamines act on
Vestibular nuclei
Medulla
Where does anti-muscaranics act on
Medulla
Where does dopamine antagonists act on and what does it involve
Chemoreceptor trigger zone
Pharynx and GIT
involves parasympathetic nervous system control of smooth muscle and sphincter tone (via ACh)
Where does 5HT3 act on
Chemoreceptor trigger zone
Pharynx and GIT
Where does cannabinoids act on
Chemoreceptor trigger zon
How do anti-spasmodics help relieve symptoms of IBS, renal colic
- Anti-cholinergic muscarinic antagonists (hyoscine buscopan, mebeverine)
- inhibit smooth muscle constriction in the gut wall, producing muscle relaxation and reduction spasm.
- Direct smooth muscle relaxants
- Calcium-channel blockers (peppermint oil) reduce calcium required for smooth muscle contraction
Name the 4 types of laxatives and how they work
– Bulk (e.g. Isphagula) – Osmotic (e.g. Lactulose) – Stimulant (e.g. Senna) – Softeners (e.g. Arachis oil) – Work by increasing bulk or drawing fluid into gut
Issues with laxatives
– Obstruction – Route of administration • Oral or Rectal – Need for other measures • Osmotic laxatives will not work without adequate fluid intake – Misuse
Concerns or contraindications for corticosteroids
- Osteoporosis
- Cushingoid features including weight gain, DM, HT,
- Increased susceptibility to infection
- Addisonian crisis with abrupt withdrawal
What are the mechanisms of immunosuppressants
– Prevents the formation of purines required for DNA synthesis so reduces immune cell proliferation
Whats the mechanism of Biologics
– Prevents action of TNFα (key cytokine in inflammatory response)
Mechanism of Cholestyramine
– Reduces bile salts by binding with them in the gut and then excreting as insoluble complex
Mechanism of Ursodeoxycholic Acid
– Inhibits an enzyme involved in the formation of cholesterol, altering amount in bile and slowly dissolving non-calcified stones
Drug effect on absorption
o Tend to reduce absorption, but not always depending on drug properties
o Rate more affected than total absorption
How can distribution of drug be affected
– Low albumin (decreased binding and increased free drug concentration)
• e.g. Phenytoin
How can metabolism affect drug action
– Liver enzymes (variability in effects but generally toxicity)
– Increased gut bacteria (metabolise drugs so increased dose needed)
– Gut wall metabolism (disease may reduce first pass metabolism)
• e.g. Morphine
– Liver blood flow (drugs with a high extraction ratio)
How can excretion affect drug action
– Biliary excretion (increased toxicity if hepatobiliary disease)
• e.g. Spironolactone
What ways can NSAIDs causes mucosal injury & bleeding
Reduced mucosal flow Reduce mucus & bicarbonate secretion Impaire platelet aggregation Epithelial damage Reduced angiogenesis Increases leukocyte adherence
What is involved with changes to gut bacteria
– Mainly antibiotics
– Loss of OCP activity
– Reduced vitamin K absorption (increased prothrombin time)
– Overgrowth of pathogenic bacteria (e.g. Clostridium difficile)
Name drugs that can cause acute hepatitis
Paracetamol
Isoniazid
Ritonavir
Troglitazone
Name drugs that can cause chronic hepatitis
Diclofenac
Methyldopa
Minocycline
Nitrofurantoin
Name drugs that cause acute cholestasis
ACE inhibitors
Co-amoxiclav
Chlorpromazine
Erythromycins
Names drugs that cause mixed pattern or atypical hepatitis
Phenytoin
Sulfonamides
Name drugs that can cause nonalcoholic steatohepatitis
Amiodarone
Tamoxifen
Name a drug that can cause fibrosis/cirrhosis
Methotrexate
Name drugs that can cause microvascular stenosis
NRTIs, Valproic
Name a drug that can cause veno-occlusive disease
Cyclophosphamide
Risk factors for induced liver injury
- Age (elderly at risk)
- Sex (female at risk)
- Alcohol consumption
- Genetic factors
- Malnourishment
What classification is used for liver disease classification
Child-Pugh classification Bilirubin Albumin PT Encephalopathy Ascites
Child-Pugh classification >9
C
Child-Pugh classification 7-9
B
Child-Pugh classification <7
A
Particular drugs to avoid in liver disease
• Warfarin/anti-coagulants
– In liver disease, clotting factors are already low
• Aspirin/NSAIDs
– Can increase bleeding time, in combination with deficiency in clotting factors;
– NSAIDs can worsen ascites due to fluid retention
• Opiates/benzodiazepines
– May precipitate encephalopathy by increasing sedation
