Pharmacology Of The Lower GI Tract

Question 0

Emesis physiology

Answer 0

Discomfort, dry mouth (salivary inhibition) 
Yawning (sympathetic distress)
Reappearance of saliva
Pyloris closes
Tone of stomach increases
Deep breath 
Contraction of abdominal muscles 
Forced expiration

Question 1

Emesis definition and causes

Answer 1

Appropriate or inappropriate gastric emptying 
Stimulated by:
Toxins
Motion sickness
Smells
Migraines 
Oregnancy

Question 2

Emesis neurology

Answer 2

Visceral afferent 5HT3 receptors detect stimulation of stomach/pharynx and toxins
Stimulate H1 and M receptors in nucleus of solitary tract
Stimulate vomiting centre M receptors
Nervous output
Toxins and 5HT3 receptors can also stimulate chemoreceptors
Trigger zone D2 and 5HT3 receptors-> vomiting centre

Question 3

Motion sickness neurology

Answer 3

Motion detected by labyrinth
Stimulates vestibular nuclei H1 and M receptors
Stimulates chemoreceptors that trigger zone D2 and5Ht3 receptors
Etc

Question 4

H1 receptor antagonists

Answer 4

Anti emetic
Promethazine, cyclizine 
Act on vestibular nuclei-> effective in motion sickness 
Also have anti muscarinic effects 
Used in pregnancy

Question 5

Anti muscarinic agents

Answer 5

Anti emetic
Hyoscine
Effective in motion sickness and stomach irritation
Anti muscarinic side effects

Question 6

Dopamine antagonists

Answer 6

Anti emetic
Mentocloperamide
Acts in CT 2 but has unwanted side effects in CNS
effective against anti cancer drug induced Emesis

Question 7

5-hyroxytryptamide antagonists

Answer 7

Anti emetic 
Ondansetron,Metocloperamide 
Block 5-HT3 receptors in gut and CNS 
Particularly effective against anti cancer drugs 
Post pop nausea

Question 8

Diarrhoea

Answer 8

> 3 watery stools per day or 209g of stool per day, Bristol stool scale
Causes:
Rotavirus-> damages small bowel villi
Invasive bacteria->damage epithelium
Cytotoxins->damage mucosa
Adhesive enterotoxigenic bacteria-> adhere to brush border-> increase cAMP-> Cl and Na secretion followed by water
May be secondary to drugs
Antibiotics can cause super infection-> by increased chance of colonisation by pathogenic bacteria
Oralistat-> inhibits pancreatic lipase-> steatorrhea
Misoprostol->uncertain, inflammatory type response
PPI’s-> infection

Question 9

Diarrhoea treatment

Answer 9

Oral rehydration therapy-> solution of electrolytes to replace loss! must be isotonic
Contains glucose for Na transport
Antibiotics-> of little value, normally viral
do a stool sample to identify bacteria first
Ciproflaxin for travellers diarrhoea
Probiotics-> reduce duration of diarrhoea infection

Question 10

Anti motility agents, opioids

Answer 10

Codeine and loperamide
Reduce tone and peristaltic movement of GI muscle-> increased transit time-> promotes water reabsorption
Presynaptically inhibit release of ACH
Act on u receptors on presynaptic nerve->inhibit ACH
Cause K efflux-> hyper polarisation-> no Ca influx
Symptomatic relief but not cure
Loperamide doesn’t cross blood brain barrier and is enterhepaticly recycled so retained in gut

Question 11

Antimotilty agents, antimuscarinics

Answer 11

Dicylorerine
Tricyclic antidepressants->anti muscarinic side effect
Act on muscarinic receptors in gut

Question 12

Constipation

Answer 12

Less than 3 poos per week
Try balanced diet with lots of roughage first
May be drug induced

Question 13

Osmotic laxatives

Answer 13

Lactulose->enters colon unchanged-> converted by bacteria-lactic and acetic acid-> increase fluid volume through osmosis
Macrogls

Question 14

Magnesium

Answer 14

Laxative
Osmotic effect to increase fluid volume
Also realises CCK-> stimulates gut motility

Question 15

Bulking agents

Answer 15

Laxative
Speed up small intestines and colon transit time
Ispaghulla
Methyl cellulose

Question 16

Stimulant laxatives

Answer 16

Senna extracts
Enter colon-> metabolised-> anthracem derivatives-> stimulate gut motility
Danton, irritant

Question 17

Irritable bowl syndrome

Answer 17

Present for at least 3 days pert month in the last 3 months
Abdo pain
Bloating-> relieved by defection
Changes in bowl habit
Episodes of diarrhoea and or consitpation

Question 18

IBS treatments

Answer 18

Lactulose or loperamide for symptoms
Antispasmodic agents:
antimuscarinics
mebervine (OCT)-> direct relaxant of GI smooth muscle 
Amitriptyline:
Low dose
Provides some pain relief
Antimuscarinic effects 
Alters sensitivity of nerves in low GI

Question 19

Inflammatory bowel disease

Answer 19

Chrons-> mouth to anus
Pain and bloody diarrhea
Ulcerative colitis->rectum to colon

Question 20

IBS treatment

5-ASA’s

Answer 20

5-amionosalicylates:
Mainly for UL
Sulphosalazine-> metabolised in colon by gut flora-> 5-amionosalicylates and sulphapyridine
5-ASA-> inhibits leukotriens and prostanoid formation-> scavenge free radicals-> decrease neutrophil chemo taxis

Question 21

IBD treatment,corticosteroids

Answer 21

Induce remission of IBD
Prednisone-> glucocorticoid with anti inflammatory immunosuppressive actions
Budesonide-> poorly absorbed-> less side effects

Question 22

Other IBS treatment

Answer 22

Bowel rest
Probiotics
Fish oils
Immunosuppressants->azathicprine, cyclosporine 
Methotrexate for severe chrome