Lower GI Pharmacology Flashcards
What is the clinical definition of Diarrhoea?
Frequent (>3/day) watery/soft stools OR 200g stool/day
What are the major infective causes of diarrhoea?
Rotavirus
Invasive bacteria
Adhesive enterotoxigenic bacteria
How does Rotavirus lead to diarrhoea?
Damages small bowel villi
How do Invasive bacteria lead to diarrhoea?
Damage epithelium
How do adhesive enterotoxigenic bacteria lead to diarrhoea?
Adhere to brush border
Increase cAMP - Cl/Na secretion, followed by water
What are the common drug related causes of Diarrhoea?
Antibiotics - superinfection Orlistat - pancreatic lipase inhibitor Misoprostol - increases cAMP PPIs - infection Digoxin toxicity, acarbose, metformin, iron salts
What is ORT?
Oral rehydration therapy
Isotonic solution of electrolytes with glucose
Why is glucose needed in an ORT?
Allows transport of Na via a symporter
How do antibiotics lead to Diarrhoea?
Suppress normal gut flora
Leads to superinfection w/ normally dormant bacterium
When should antibiotics be used to treat Diarrhoea?
Infections mostly viral, often self-limiting
Use when causative bacteria identified
Use Ciprofloxacin empirally for traveller’s diarrhoea
What are the two most common types of antimotility agents?
Opioids
Anti-muscarinics
How do opioids lead to antimotility?
Presynaptic inhibition (u-opioid receptors) of AcH release
Reduces motility
Promotes reabsorption of water
What are opioids used for?
Symptomatic relief of diarrhoea
What are the possible negative effects of treatment with opioids?
Reduce clearance of infective organisms - prolong infection
What are the two most commonly prescribed opioids?
Loperamide - retained largely in the gut, doesn’t penetrate BBB, enterohepatic cycling
Codeine - analgesia
How do Alpha-2 adrenoceptor agonists work?
Agonise a2-receptors - causes constipation
CLONIDINE
How do antimuscarininc agents work?
Antagonise muscarininc receptors
Decreased activity of PNS - constipation
DICYCLOVERINE
What effect do TCAs have on diarrhoea?
Antagonise muscarinic receptors
Constipation as a side effect
Define constipation
Altered bowel habits
<3 motions/week
How is constipation treated?
Balanced diet w/ roughage
Avoid causative drugs
How do osmotic laxatives work?
Enter colon - converted to lactic/acetic acid (bacteria) - raises fluid volume osmotoically
LACTULOSE
What non-osmotic laxatives are available?
Magnesium
Bulking agents
Stimulant laxatives
How does Magnesium work?
Osmotic effect
Mg2+ release cholecystokinin - increases GI motility
How do bulking agents work?
Increase bulk of faeces, trigger release
ISPAGHULA
METHYLCELLULOSE
How do stimulant laxatives work?
Senna extracts - enter colon - metabolised to anthracene derivates - stimulate GI activity
Dantron - irritant
What is Irritable Bowel Syndrome?
Long standing disorder (12/52)
Pain/bloating relieved by defecation
Episodes of diarrhoea/constipation
What are the main pharmacological treatments for IBS?
Lactulose/Loperamide for symptoms
Antispasmodic agents
Amitryptyline (TCA)
How do antispasmodic agents work?
Antimuscarinics - inhibit PNS
Mebeverine - direct relaxant of GI sm, phosphodiesterase inhibitor
How does Amitryptyline work?
Antimuscarinic effects
Alters sensitivity of sensory ner
What is Inflammatory Bowel Disease?
Ulcerative Colitis AND Chron’s Disease
Describe UC/Chron’s
Distinct inflammatory conditions
Relapsing/remitting courses
Unclear causes (genetics, microbial, environmental)
What are the clinical features of UC/Chron’s?
Diarrhoea Faecal incontinence Rectal bleeding/bloody diarrhoea Passing of mucus Cramping pains Weight loss Mouth ulcers + anal skin tags (Chron's)
What are the complications of Chron’s disease?
Malabsorption
Folate/iron deficiencies - anaemias
What is the main complication of Ulcerative Colitis?
Iron deficiency anaemia
What are the shared complications of IBD?
Arthritis
Iritis
Uveitis
Thromboembolism
What are the defining characteristics of UC?
Inflammation of rectum, spreads to colon
Superficial, affecting mucosa
What are the defining characteristics of Chron’s?
May affect any part of GI, usually Ileum/Colon
Activation of T-lymphocytes - transmural inflammation - fistulae
What is the mainstay treatment for UC?
5-Aminosalicylates
What are the three main 5-Aminosalicylates?
Sulphasalazine - metabolised to 5-ASA (gut flora)
Mesalazine - pH change produces 5-ASA
5-ASA
How does 5-ASA have its effect?
Inhibits leukotriene/prostanoid formation
Scavenges free radicals
Decreases neutrophil chemotaxis
What are corticosteroids used for?
To induce remission in IBD?
What are the main corticosteroids?
Prednisolone
Budenoside - poorly absorbed so fewer s/e
How do corticosteroids work?
Anti-inflammatory, immunosuppressive
What immunosuppressants are used to treat Chron’s?
Azathioprine
Cyclosporine
Methotrexate
What is Inflixmab?
Monoclonal antibody to TNF-a used to treat severe Chron’s
What are the ADRs associated with 5-ASAs?
Rashes
Headaches
Diarrhoea
What is the specific ADR associated with Mesalazine?
Blood dyscrasia (abnormal materials in blood)
- sore throats
- fevers
- easy brusing/bleeding
What dietary changes can be used to treat IBD?
Avoid fatty food
Avoid bolus foods (nuts/corn/fruit)
Fish oils/probiotic recommened
Amino acids/proteins
What is the main ADR of Aziothioprine?
Risk of pancreatitis
Risk of myelosuppression
Requires FBC monitoring (6-8 wks)
What is Methotrexate used for?
Immunosuppressant used for Chron’s disease
What is the main ADR associated with Methotrexate?
Interaction w/ NSAIDs leading to toxicity
What is the dosing schedule for Methotrexate?
Once weekly
How should Methotrexate be monitored?
FBC
Renal function
LFT
Report fever/cough/dyspnoea
What is Ciclosporin?
Immunosuppressant used to induce remission in Chronh’s
What is the main ADR associated with Ciclosporin?
When given w/ steroids increased risk of P. carinii
Prophylactic co-trimoxazole is used
What antibiotics should be used when treating IBD?
Metronidazole + Ciprofloxacin for 3/12
prophylaxis?
What is the main ADR associated with Infliximab?
Infusion reactions (20%)
