Clinical GI pharmacology Flashcards
This covers drugs for:
Acid Suppression Motility Laxatives IBD Medications Drugs affecting secretions
What drug types are used for acid suppression?
Antacids - Neutralize acid
H2-receptor antagonists - Block histamine2 receptor
Proton pump inhibitors - Block pumping out of H+ ions.
What are the types of antacid?
Most contain Mg or Al and function by neutralizing gastric acid.
Alginates arnt like the rest, they form a viscous gel floating on the stomach contents which prevents reflux. (Gaviscon)
Example of a H2-receptor antagonist?
Ranitidine
Oral or IV
Give an example of a proton pump inhibitor and when theyre used?
Omeprazole
Oral or IV
Theyre used for GORD, peptic ulcer disease and as triple therapy with 2 antibiotics for Peptic/duodenal ulcers associated with H pylori.
What are the risks of PPIs?
Predispose to:
- C. Diff infection
- Hypomagnesaemia
- B12 Deficiency
What are the types of drugs affecting gut motility?
- Anti-emetics
- Anti-spasmodics (inc. Anti-muscarinics)
- Anti-motility
- Pro-kinetic
What are the types of anti-spasmodics used for GI motiltiy?
- Anti-cholinergic muscarinic antagonists
- Direct smooth muscle relaxants
- Ca channel blockers (lowers Ca for muscle contraction)
How do anti-motility drugs work?
Loperamide (immodium) or opioids
They activate opiate receptors to inhibit Ach release. This in turn lowers smooth muscle contraction and raises anal sphincter tone.
Look out they can cause constipation.
How do anti-emetics help with GI issues?
They are prokinetic agents, i.e. they increase gut motility
& gastric emptying.
Probably by blocking the dopamine receptors that inhibit post-synaptic cholinergic receptors. (A roundabout way of stimulating cholinergic receptors to increase smooth muscle contraction)
E.g. Domperidone (a dopamine antagonist).
What are the categories of laxative?
Bulk e.g. Isphagula - Draws in water leading to bulkier stool which stimulates a bowel movement
Osmotic e.g. Lactulose - Helps the intestine retain water to soften and bulk the stool
Stimulant e.g. Senna - Directly stimulates gut motility
Softeners e.g. Arachis Oil - Softens faeces
List the drugs for IBD
- Aminosalicylates e.g. Mesalazine
- Corticosteroids e.g. Prednisalone
- Immunsuppresants e.g. Azathioprine
- Biologics e.g. Anti-TNFalpha antibodies Infliximab
What are the side effects of corticosteroids?
Fucking loads incl:
- Osteoporosis
- Cushing’s Disease
- Predispose to infection
- Addisonian crisis on abrupt withdrawel
How does azathioprine work?
Prevent purine formation needed to make DNA thus reducing immune cell proliferation
How does Anti-TNFalpha Antibodies work??
By inhibiting the action of TNFalpha which is a key cytokine of inflammation
What are the contraindications/side effects of Biologics?
Increases risk of infection particularly TB so its also a contraindication.
Contraindicated in MS, pregnancy or breast feeding.
Can increase risk of malignancy
What are some drugs used for intestinal secretions?
Ursodeoxycholic acid
- Treats gallstones and Primary Biliary Cirrhosis
- Inhibits the enzyme that forms cholesterol so lowering the amount in bile and already formed stones
Cholestyramine:
- Used for Pruritis from biliary cause
- Reduces bile salts by binding with them in the gut and then excreting as insoluble complex
- May affect absorption of other drugs so should be taken separately
- May affect fat soluble vitamin absorption so may decrease vitamin K levels (affecting clotting and warfarin)
ADME = Absorption - Distribution - Metabolism - Excretion.
What are the factors affecting GI drugs in each category?
Absorption:
- pH
- Gut Length
- Transit Time
Distribution:
- Low Albumin from liver disease -> Decreased binding and increased free drug concentration -> Toxicity
Metabolism:
- Liver enzymes & Disease
- Gut Bacteria. The bigger the microbiota, the greater the metabolism, the larger the necessary dose
- Liver blood flow, affects drugs with a high extraction ratio
Excretion:
- Biliary Excretion.
Drugs are more toxic if theres hepatobiliary disease as they arnt excreted properly
List some common ADRs of GI drugs:
- Diarrhoea/constipation
- GI bleeds from low dose aspirin, NSAIDs or warfarin
- Antibiotics
- Drug induced liver injury
What are the types of drug induced liver injury
Intrinsic Hepatotoxicity
- Predicatble, Dose-depandant, acute
- Type A ADR (augmented)
Idiosyncratic Hepatotoxicity:
- Unpredictable, Not dose-dependant
- Type B ADR (Bizarre)
- Ranges from asymptomatic LFT rise to Liver failure
- Most commonly hepatitis or cholestasis
Risk factors for Drug induced liver injury include age, female, alcohol, genetics and malnourishment.
How do antibiotics have GI ADRS?
Alter the gut bacteria messing with digestion, absorption and other drug
- Makes Oral contraceptive pill useless
- Can also lead to overgrowth of pathogens like C. Diff.
- Can lead to reduced Vit K absorption which increases prothrombin time
How do we consider the severity of liver disease?
Child-Pugh Classification, includes:
- Bilirubin level
- Albumin level
- Prothrombin Time
- Encephalopathy
- Ascites
Each split into 3 levels of abnormality scoring 1, 2 & 3.
An A grade = <7
B = 7-9
C = >9
Few more tips
Whe someone has liver disease be careful with any drug metabolied there or excreted by the biliary system
Along with any drug that could worsen effects of liver disease such as benzodiazepines and encephalopathy or aspirin/NSAID/Warfarin/Anti-coagulants (since liver disease means clotting factors are already low)
Why should you be wary of benzodiazapines in liver disease?
And Aspirin/NSAIDs/Warfarin/anticoagulants
Benzodiazapines could worsen existing encephalopathy from liver disease..
Aspirin/NSAIDs/Warfarin/Anticoagulants could cause clotting problems but liver disease has already lowered the clotting factors in the blood.
