Lower GI Pharmacology

Question 1

What is the clinical definition of Diarrhoea?

Answer 1

Frequent (>3/day) watery/soft stools OR 200g stool/day

Question 2

What are the major infective causes of diarrhoea?

Answer 2

Rotavirus
Invasive bacteria
Adhesive enterotoxigenic bacteria

Question 3

How does Rotavirus lead to diarrhoea?

Answer 3

Damages small bowel villi

Question 4

How do Invasive bacteria lead to diarrhoea?

Answer 4

Damage epithelium

Question 5

How do adhesive enterotoxigenic bacteria lead to diarrhoea?

Answer 5

Adhere to brush border

Increase cAMP - Cl/Na secretion, followed by water

Question 6

What are the common drug related causes of Diarrhoea?

Answer 6

Antibiotics - superinfection
Orlistat - pancreatic lipase inhibitor
Misoprostol - increases cAMP
PPIs - infection
Digoxin toxicity, acarbose, metformin, iron salts

Question 7

What is ORT?

Answer 7

Oral rehydration therapy

Isotonic solution of electrolytes with glucose

Question 8

Why is glucose needed in an ORT?

Answer 8

Allows transport of Na via a symporter

Question 9

How do antibiotics lead to Diarrhoea?

Answer 9

Suppress normal gut flora

Leads to superinfection w/ normally dormant bacterium

Question 10

When should antibiotics be used to treat Diarrhoea?

Answer 10

Infections mostly viral, often self-limiting
Use when causative bacteria identified
Use Ciprofloxacin empirally for traveller’s diarrhoea

Question 11

What are the two most common types of antimotility agents?

Answer 11

Opioids

Anti-muscarinics

Question 12

How do opioids lead to antimotility?

Answer 12

Presynaptic inhibition (u-opioid receptors) of AcH release
Reduces motility
Promotes reabsorption of water

Question 13

What are opioids used for?

Answer 13

Symptomatic relief of diarrhoea

Question 14

What are the possible negative effects of treatment with opioids?

Answer 14

Reduce clearance of infective organisms - prolong infection

Question 15

What are the two most commonly prescribed opioids?

Answer 15

Loperamide - retained largely in the gut, doesn’t penetrate BBB, enterohepatic cycling
Codeine - analgesia

Question 16

How do Alpha-2 adrenoceptor agonists work?

Answer 16

Agonise a2-receptors - causes constipation

CLONIDINE

Question 17

How do antimuscarininc agents work?

Answer 17

Antagonise muscarininc receptors
Decreased activity of PNS - constipation
DICYCLOVERINE

Question 18

What effect do TCAs have on diarrhoea?

Answer 18

Antagonise muscarinic receptors

Constipation as a side effect

Question 19

Define constipation

Answer 19

Altered bowel habits

<3 motions/week

Question 20

How is constipation treated?

Answer 20

Balanced diet w/ roughage

Avoid causative drugs

Question 21

How do osmotic laxatives work?

Answer 21

Enter colon - converted to lactic/acetic acid (bacteria) - raises fluid volume osmotoically
LACTULOSE

Question 22

What non-osmotic laxatives are available?

Answer 22

Magnesium
Bulking agents
Stimulant laxatives

Question 23

How does Magnesium work?

Answer 23

Osmotic effect

Mg2+ release cholecystokinin - increases GI motility

Question 24

How do bulking agents work?

Answer 24

Increase bulk of faeces, trigger release
ISPAGHULA
METHYLCELLULOSE

Question 25

How do stimulant laxatives work?

Answer 25

Senna extracts - enter colon - metabolised to anthracene derivates - stimulate GI activity Dantron - irritant

Question 26

What is Irritable Bowel Syndrome?

Answer 26

Long standing disorder (12/52) Pain/bloating relieved by defecation Episodes of diarrhoea/constipation

Question 27

What are the main pharmacological treatments for IBS?

Answer 27

Lactulose/Loperamide for symptoms Antispasmodic agents Amitryptyline (TCA)

Question 28

How do antispasmodic agents work?

Answer 28

Antimuscarinics - inhibit PNS | Mebeverine - direct relaxant of GI sm, phosphodiesterase inhibitor

Question 29

How does Amitryptyline work?

Answer 29

Antimuscarinic effects | Alters sensitivity of sensory ner

Question 30

What is Inflammatory Bowel Disease?

Answer 30

Ulcerative Colitis AND Chron's Disease

Question 31

Describe UC/Chron's

Answer 31

Distinct inflammatory conditions Relapsing/remitting courses Unclear causes (genetics, microbial, environmental)

Question 32

What are the clinical features of UC/Chron's?

Answer 32

``` Diarrhoea Faecal incontinence Rectal bleeding/bloody diarrhoea Passing of mucus Cramping pains Weight loss Mouth ulcers + anal skin tags (Chron's) ```

Question 33

What are the complications of Chron's disease?

Answer 33

Malabsorption | Folate/iron deficiencies - anaemias

Question 34

What is the main complication of Ulcerative Colitis?

Answer 34

Iron deficiency anaemia

Question 35

What are the shared complications of IBD?

Answer 35

Arthritis Iritis Uveitis Thromboembolism

Question 36

What are the defining characteristics of UC?

Answer 36

Inflammation of rectum, spreads to colon | Superficial, affecting mucosa

Question 37

What are the defining characteristics of Chron's?

Answer 37

May affect any part of GI, usually Ileum/Colon | Activation of T-lymphocytes - transmural inflammation - fistulae

Question 38

What is the mainstay treatment for UC?

Answer 38

5-Aminosalicylates

Question 39

What are the three main 5-Aminosalicylates?

Answer 39

Sulphasalazine - metabolised to 5-ASA (gut flora) Mesalazine - pH change produces 5-ASA 5-ASA

Question 40

How does 5-ASA have its effect?

Answer 40

Inhibits leukotriene/prostanoid formation Scavenges free radicals Decreases neutrophil chemotaxis

Question 41

What are corticosteroids used for?

Answer 41

To induce remission in IBD?

Question 42

What are the main corticosteroids?

Answer 42

Prednisolone | Budenoside - poorly absorbed so fewer s/e

Question 43

How do corticosteroids work?

Answer 43

Anti-inflammatory, immunosuppressive

Question 44

What immunosuppressants are used to treat Chron's?

Answer 44

Azathioprine Cyclosporine Methotrexate

Question 45

What is Inflixmab?

Answer 45

Monoclonal antibody to TNF-a used to treat severe Chron's

Question 46

What are the ADRs associated with 5-ASAs?

Answer 46

Rashes Headaches Diarrhoea

Question 47

What is the specific ADR associated with Mesalazine?

Answer 47

Blood dyscrasia (abnormal materials in blood) - sore throats - fevers - easy brusing/bleeding

Question 48

What dietary changes can be used to treat IBD?

Answer 48

Avoid fatty food Avoid bolus foods (nuts/corn/fruit) Fish oils/probiotic recommened Amino acids/proteins

Question 49

What is the main ADR of Aziothioprine?

Answer 49

Risk of pancreatitis Risk of myelosuppression Requires FBC monitoring (6-8 wks)

Question 50

What is Methotrexate used for?

Answer 50

Immunosuppressant used for Chron's disease

Question 51

What is the main ADR associated with Methotrexate?

Answer 51

Interaction w/ NSAIDs leading to toxicity

Question 52

What is the dosing schedule for Methotrexate?

Answer 52

Once weekly

Question 53

How should Methotrexate be monitored?

Answer 53

FBC Renal function LFT Report fever/cough/dyspnoea

Question 54

What is Ciclosporin?

Answer 54

Immunosuppressant used to induce remission in Chronh's

Question 55

What is the main ADR associated with Ciclosporin?

Answer 55

When given w/ steroids increased risk of P. carinii | Prophylactic co-trimoxazole is used

Question 56

What antibiotics should be used when treating IBD?

Answer 56

Metronidazole + Ciprofloxacin for 3/12 | prophylaxis?

Question 57

What is the main ADR associated with Infliximab?

Answer 57

Infusion reactions (20%)