Clinical GI pharmacology

Question 1

This covers drugs for:

Answer 1

Acid Suppression
Motility
Laxatives
IBD Medications
Drugs affecting secretions

Question 2

What drug types are used for acid suppression?

Answer 2

Antacids - Neutralize acid

H2-receptor antagonists - Block histamine2 receptor

Proton pump inhibitors - Block pumping out of H+ ions.

Question 3

What are the types of antacid?

Answer 3

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)

Question 4

Example of a H2-receptor antagonist?

Answer 4

Ranitidine
Oral or IV

Question 5

Give an example of a proton pump inhibitor and when theyre used?

Answer 5

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.

Question 6

What are the risks of PPIs?

Answer 6

Predispose to:
- C. Diff infection
- Hypomagnesaemia
- B12 Deficiency

Question 7

What are the types of drugs affecting gut motility?

Answer 7

• Anti-emetics
• Anti-spasmodics (inc. Anti-muscarinics)
• Anti-motility
• Pro-kinetic

Question 8

What are the types of anti-spasmodics used for GI motiltiy?

Answer 8

• Anti-cholinergic muscarinic antagonists
• Direct smooth muscle relaxants
• Ca channel blockers (lowers Ca for muscle contraction)

Question 9

How do anti-motility drugs work?

Answer 9

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.

Question 10

How do anti-emetics help with GI issues?

Answer 10

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).

Question 11

What are the categories of laxative?

Answer 11

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

Question 12

List the drugs for IBD

Answer 12

• Aminosalicylates e.g. Mesalazine
• Corticosteroids e.g. Prednisalone
• Immunsuppresants e.g. Azathioprine
• Biologics e.g. Anti-TNFalpha antibodies Infliximab

Question 13

What are the side effects of corticosteroids?

Answer 13

Fucking loads incl:
- Osteoporosis
- Cushing’s Disease
- Predispose to infection
- Addisonian crisis on abrupt withdrawel

Question 14

How does azathioprine work?

Answer 14

Prevent purine formation needed to make DNA thus reducing immune cell proliferation

Question 15

How does Anti-TNFalpha Antibodies work??

Answer 15

By inhibiting the action of TNFalpha which is a key cytokine of inflammation

Question 16

What are the contraindications/side effects of Biologics?

Answer 16

Increases risk of infection particularly TB so its also a contraindication.

Contraindicated in MS, pregnancy or breast feeding.

Can increase risk of malignancy

Question 17

What are some drugs used for intestinal secretions?

Answer 17

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)

Question 18

ADME = Absorption - Distribution - Metabolism - Excretion.

What are the factors affecting GI drugs in each category?

Answer 18

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

Question 19

List some common ADRs of GI drugs:

Answer 19

• Diarrhoea/constipation
• GI bleeds from low dose aspirin, NSAIDs or warfarin
• Antibiotics
• Drug induced liver injury

Question 20

What are the types of drug induced liver injury

Answer 20

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.

Question 21

How do antibiotics have GI ADRS?

Answer 21

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

Question 22

How do we consider the severity of liver disease?

Answer 22

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

Question 23

Few more tips

Answer 23

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)

Question 24

Why should you be wary of benzodiazapines in liver disease?
And Aspirin/NSAIDs/Warfarin/anticoagulants

Answer 24

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.