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The Alimentary Canal > GI Pharmacology > Flashcards

GI Pharmacology Flashcards

1
Q

What are important GI functions from a pharmacological perspective?

A

Gastric secretion
Vomiting and nausea
Gut motility and defaecation
Formation and excretion of bile

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2
Q

What are the main drug classes?

A

Acid suppression
Drugs affecting motility
Laxatives
Drugs for treating IBD
Drugs affecting biliary secretions

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3
Q

Describe neural control of GI tract

A

Enteric nervous system
Coordinates contraction of muscles, transport across mucosal lining and intramural blood flow
2 intramural plexuses

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4
Q

Describe the neurons in the enteric nervous system

A

Neurones in plexuses secrete ACh, NA, 5-HT, Purines and NO
Sensory neurons respond to mucosal stroking and distention

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5
Q

Describe parasympathetic and sympathetic control in enteric nervous system

A

Para - fibres are preganglionic, ACh and excitatory
Symp - fibres are post-ganglionic and inhibitory
Act on blood vessels, smooth muscle and some glandular tissue

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6
Q

Describe hormonal control in GI

A

Endocrine - Gastrin and CCK in blood
Paracrine - histamine and somatostatin from cells acting on nearby cells
Paracrine also function as neurotransmitters - substance P

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7
Q

Describe acid secretion in GI

A

Gastric - ECL parietal axis hypothesis
Histamine acts on H2 receptors on parietal cells
Gastrin cause release of gastrin from G cells and vagal input stimulate histamine

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8
Q

How can acid damage the mucosa?

A

GORD, Barret’s, peptic ulcer disease
Needs to be balance between damage and protection
Acid and H.pylori damage

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9
Q

What protects the mucosa?

A

Prostaglandins (PGE2 and I2) inhibit acid and increase mucus production
Nitric Oxide is protective

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10
Q

What do you do if test for H. pylori is postitive?

A

Triple therapy
PPI and 2 antibacterial agents - amoxicillin and metronidazole/ clarithromycin

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11
Q

What do you do if H. pylori test is negative or patient is untested?

A

Acid suppression
Antacids - Maalox which neutralises and Alginates - Gaviscon which forms protective layer

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12
Q

What are some other mucosal protectors?

A

Bismuth - insoluble salt containing salicylic acid which is antibacterial
Sucralfate - hydrolyses in acid so coats mucosa
Misoprostol - reduces acid secretion and supports mucus production

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13
Q

Describe H2-receptor antagonists

A

Ranitidine - given orally or IV
Block histamine receptor reducing acid secretion
Indicated in GORD and peptic ulcer

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14
Q

Describe Proton Pump Inhibitors

A

Omeprazole - orally or IV
Irreversible inhibitor of H-K-ATPase and targets parietal cells
Indicated in GORD and peptic ulcer

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15
Q

What are the adverse effects of acid suppression drugs?

A

C. difficile, B12 deficiency, ECL tumours and AIN - acute interstitial nephritis

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16
Q

What are the motor outputs for vomiting?

A

Somatomotor - diaphragm and abdominal muscle contraction
Autonomic - increased salivation, cold sweating, cutaneous vasoconstriction, proximal gastric relaxation and intestinal retrograde giant contraction

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17
Q

What are the pharmacological options for vomiting?

A

NK1 antagonists
CB1 agonists
H1RA
Antimuscarinics
D2 antagonists
5HT3RA

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18
Q

What are the side effects for drugs used for vomiting?

A

Sedation, movement, prolactin release, GI drowsiness, dizziness, dry mouth, and blurred vision

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19
Q

What drug is used for late phase of cytotoxic emesis?

A

NK1 antagonists

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20
Q

What is a cytotoxic drug used for vomiting?

A

CB1 agonists - nabilone

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21
Q

What drugs are used for motion sickness?

A

H1RA -cyclizine
Anti-muscarinic - hyoscine

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22
Q

What drug is used in pregnancy for vomiting?

A

D2 antagonists - prochlorperazine

23
Q

What is 5HR3RA drug used for?

A

Cytotoxic drugs
Radiation
Post operative
For vomiting

24
Q

What is used for management of nausea?

A

Low dose antidepressants - gabapentin and olanzapine

25
Q

What are some drugs which affect the motility of the GI tract?

A

Purgatives
Agents which increase motility
Anti-diarrhoeal drugs
Anti-spasmatic

26
Q

What do purgatives do?

A

Accelerate the passage of food through the gut
Used for treating constipation

27
Q

What do anti-spasmodic drugs do?

A

Decrease smooth muscle tone

28
Q

What are bulk laxatives?

A

Methylcellulose
Bulky hydrated mass, takes several days to work but no serious adverse effects

29
Q

What are osmotic laxatives?

A

Saline, Lactulose
Poorly absorbed solutes
Osmotic load draws water so takes 2-3 days to work

30
Q

What can high doses of osmotic laxatives cause?

A

Electrolyte disturbances

31
Q

What are faecal softeners?

A

Docusate sodium
Surface active and weak stimulant

32
Q

Explain stimulant purgatives - laxatives

A

Increase the electrolyte secretion by gut mucosa and therefor increase water secretion
Adverse effects are cramps

33
Q

What are some types of stimulant purgatives?

A

Bisacodyl and glycerol - suppositories
Sodium picosulfate - oral
Senna and dantron - stimulate myenteric plexus

34
Q

Explain domperidone - D2 antagonist

A

Mechanism unknown
Increases LOS pressure which increases gastric emptying and duodenal peristalsis

35
Q

Explain metoclopramide

A

Increases gastric motility and emptying

36
Q

What is diarrhoea caused by?

A

Increased motility, increased secretion and reduced absorption
Treatment needs maintenance of fluid and electrolytes

37
Q

What is the treatment of diarrhoea?

A

Anti-infective agents, anti-diarrhoeal agents, anti-spasmodic agents
Main agent to reduce motility is opioids
Anti-muscarinic

38
Q

What is the main opioid used for treatment of diarrhoea and how does it work?

A

Loperamide
Opioid receptors decrease ACh release
reduces smooth muscle contraction and increases anal sphincter tone

39
Q

What is treatment for chronic bowel disease?

A

IBS and IBD
Treatment is symptomatic
May include loperamide and anti-depressants
High residue diet

40
Q

What is the clinical management of IBD?

A

Corticosteroids - anti-inflammatory effects
Given orally, IV or rectally

41
Q

What are the concerns and contradiction of corticosteroids?

A

Osteoporosis
Cushingoid features
Increased susceptibility of infection
Addisonian crisis with abrupt withdrawal

42
Q

What is the chronic treatment of IBD?

A

Amino salicylates - mesalazine and olsalazine
Is anti-inflammatory
Oral or rectal administration
Avoid if allergic and caution of renal impairment

43
Q

What are the adverse effects of amino salicylates?

A

GI upset, blood dyscrasias, renal impairment

44
Q

What are some other drugs for chronic treatment of IBD?

A

Immunosuppressants - Azathioprine, cycloprin, 6-mercaptopurine
Methotrexate - anti-folate
Infliximab - biologics

45
Q

Describe immunosuppressants

A

Prevents formation of purines required for DNA synthesis so reduces cell proliferation
Adverse effects - bone marrow suppression and organ damage

46
Q

What is the role of TNF-alpha in IBD?

A

Inflammatory cells express TNF-alpha which is membrane bound enzyme
Stimulates inflammatory response which causes gut damage and ulceration

47
Q

What are the 3 mechanisms of anti-spasmodics?

A

Used for symptom relief in IBS
Anti-cholinergic muscarinic antagonists
Inhibit smooth muscle constriction in gut wall
Direct smooth muscle relaxants

48
Q

What drug is used for biliary secretion?

A

If not heavily calcified then Ursodeocycholic acid
GTN for spasm
Cholestyramine - bile acid sequestrants

49
Q

How can GI and liver disease effect ADME?

A

Absorption - pH, gut length and transit time
Distribution - reduced albumin
Metabolism - damaged gut wall, less first pass metabolism, infected gut wall
Excretion - build up if cant be excreted by biliary

50
Q

What drugs can cause GI adverse effects?

A

Lose dose aspirin/ NSAIDs
Warfarin

51
Q

How can drugs effects the liver?

A

Intrinsic hepatotoxicity - dose dependant
Idiosyncratic hepatotoxicity - not dose dependant
Asymptomatic increase in LFTS or liver failure

52
Q

What are some risk factors for hepatic drug response?

A

Age, gender, alcohol consumption, genetic factors and malnourishment

53
Q

What is the Child-Pugh classification?

A

Scoring for liver impairment
<7 = A, 7-9 = B, >9 = C
Allows sensible dosing in cases of hepatic impairment

The Alimentary Canal (33 decks)

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