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The Gastrointestinal System 2023 > Pharmacology of the GI Tract > Flashcards

Pharmacology of the GI Tract Flashcards

1
Q

What are the main types of metabolism that occur in the liver?

A
  • Carbohydrate metabolism
  • Fat metabolism
  • Protein metabolism
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2
Q

What are some common substances stored in the liver?

A

Vitamin A, B12, E, D and K

Copper

Iron

Glycogen

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3
Q

The liver produces which coagulation factors?

A

II, VII, IX and X

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4
Q

Which main plasma protein is produced in the liver?

A

Albumin

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5
Q

Which substance, when released stimulates bile to be released from the sphincter of Oddi?

A

CCK

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6
Q

When chyme is present in the duodenum, which two factors cause smooth muscle contraction?

A

CCK

Vagal impulses

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7
Q

How are bile salts formed?

A

When bile acids react with sodium or potassium

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8
Q

Which antibody class is present in bile?

A

IgA

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9
Q

What is bilirubin?

A

The breakdown product of the porphyrin component of haemoglobin

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10
Q

Which excretions from the body is bilirubin responsible for colouring?

A

Faeces - brown

Urine - yellow

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11
Q

What is jaundice?

A

The increase in blood levels of bilirubin

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12
Q

What is cholelithiasis?

A

Formation of gallbladder stones

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13
Q

For patients who cannot undergo surgery, which drug can be given to aid with dissolving the gallstones?

A

Ursodeoxycholic acid

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14
Q

Why is morphine not a suitable painkiller for gallstone-related pain?

A

It constricts the sphincter of Oddi and increases intrabiliary pressure worsening any problems present

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15
Q

Which drugs can be given for gallstone pain?

A
  • Buprenorphine
  • Pethidine
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16
Q

How may biliary spasm be relieved?

A
  • Atropine
  • GTN
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17
Q

Why are hardly any bile salts lost in the faeces?

A

Enterohepatic recycling

Bile salts in the ileum are taken up by sodium coupled transporters

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18
Q

Which transporters will transport bile salts back into hepatocytes, after their uptake from the terminal ileum?

A

Sodium coupled transporters

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19
Q

What happens when bile salt concentration is reduced?

A

More is propared from cholesterol

(this indirectly lowers plasma LDL levels)

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20
Q

Give examples of bile acid sequestrates, or resins

A
  1. Colesevelam
  2. Colestipol
  3. Colestyramine
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21
Q

What is the purpose of resins?

A

They can bind to bilse salts and prevent their reabsorption

This will indirectly lower cholesterol because more bile salts must be synthesised from cholesterol in the body

LDL receptor activity of liver cells increases to achieve this

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22
Q

How many phases does drug metabolism generally contain?

A

2

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23
Q

Why is it dangerous to stop smoking during drug treatment?

A

Smoking inceases liver enzyme activity, so more drug is required to have an effect

If smoking is stopped, the liver activity is reduced and less drug is required so continuing the same dose could lead to overdoses and serois side effects

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24
Q

Name a large family of enzymes in the liver able to participate in drug metablism

A

The cytochrome p450 family of mono-oxygenases

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25
Q

What is hepatic encephalopathy?

A

In severe hepatic failure, blood ammonia levels increase resulting in coma

This is because detoxification of ammonia to urea does not occur sufficiently

26
Q

What are two therapeutic options for hepatic encephalopathy as a result of raised blood ammonia levels?

A

Lactulose - reduces pH allowing ammonia to become ammonium ions which are not absorbed

Antibiotics - suppress colonic flora from producing ammonia in the first instance e.g. rifaximin, neomycin (not used due to side effects)

27
Q

What is the name of the area of the medulla that receives inputs from blood-borne drugs or hormones?

A

Chemoreceptor trigger zone (CTZ)

28
Q

What are the three man pathways that can induce vomiting?

A

Central pathway - unpleasant sights, smells, memories or anticipation (essentially this is unnecessary vomiting)

Vagal pathway - any toxins in the GI ract can stmulate the vagal pathway - receptos in the pharynx can be stimulated for example through choking

Vestibular pathway - this involves the vestibulocochlear nerve which is associated with balance and conditions such as tinnitus or even motion sickness can induce this pathway

29
Q

What the substances within the body that act on receptors in the brain (CTZ) to induce vomiting?

A
  • S - Substance P (NK1 receptors)
  • O - Opiates or analgesia (opiate/analgesic receptors)
  • D - Dopamine (D2 receptors)
  • A - Acetylcholine (Muscarinic cholinergic receptors)
  • S - Serotonin (5-HT3 receptors)
  • H - Histamine (H1 receptors)

Remember SODAS H

30
Q

Which receptors are present in the vestibular nuclei that can induce vomiting?

A

M1 and H1 receptors

(acts directly on vomiting centre)

31
Q

Which receptors are present int he pharynx and GI tract?

A

5HT3 receptors

(act on CTZ and vomiting centre)

32
Q

Which receptors are present on the CTZ?

A
  • D2
  • 5HT3
  • Opioid
  • H1
  • M1

When stimulated, the vomiting centre is then acted upon

33
Q

Toxic material in the gut lumen will lead to release of what?

A

5-HT by enterochromaffin cells

34
Q

What effect does 5-HT have when released into the gut lumen?

A

It willlead to depolarisation of sensory afferent terminals in the mucosa when 5HT3 receptors are bound

Vagal afferents will then stimulate the CTZ, nucleus tractus solitaris amd the vomiting centre

35
Q

What causes the physical act of vomiting?

A

Retrograde (backwards) peristalsis from the ileum to stomach

All sphincters are relaxed

Breathing is suspended

Abdominal muscles compress the stomach

36
Q

In relation to motor outputs associated with vomiting what do vagal efferents contribute?

A
  • Oesophageal shortening
  • Stomach proximal relaxation
  • Small intestine retrograde contraction
37
Q

In relation to motor outputs associated with vomiting what do somatic motor neurones contribute?

A
  • Anterior abdominal muscle contraction
  • Diaphragmatic contraction
38
Q

In relation to motor outputs associated with vomiting what do autonomic and somatic efferents contribute?

A
  • Increased heart rate and force
  • Increased salivation
  • Pallor, cold sweating skin
  • Sphincters of bladder and anus constrict
39
Q

In relation to to acid balance, what is a severe side effect of excessive vomiting?

A

Excessive acid loss

This leads to hypochloraemic metabolic alkalosis

40
Q

How will the body try to counteract a hypochloraemic metabolic alkalosis from excessive vomiting and why is this bad?

A

Excreting potassium by kidneys to try and balance the alkalosis

This can cause hypokalaemia

41
Q

In which two forms can dopamine antagonists be used as anti-emetics?

A
  • Rectal suppositries
  • Buccal tablets
42
Q

Give examples of dopamine antagonists that function as anti-emetics

A
  • Prochlorperazine
  • Droperidol
  • Haloperidol
43
Q

Why is metoclopramide useful and to which drug class does it belong?

A

It is a dopamine receptor antagonist

(it acts on the GI tract to increase forward peristalsis)

44
Q

What are the most potent anti-emetic drugs?

A

5HT3 receptor antagonists

45
Q

Give examples of 5HT3 receptor antagonists

A
  • Ondansetron
  • Dolasetron
46
Q

Where are 5HT3 receptors present?

A

GIT and CNS

47
Q

What are 5HT3 receptor antagonists useful for?

A

Chemotherapy induced nausea and vomiting

Radiation-induced emesis

Post-operative nausea and vomiting

48
Q

What is a frequent side effect of 5HT3 receptor antagonists?

A

Headache

49
Q

H1 antihistamines block H1 receptors in whcih areas of the body to stop vomiting?

A

Vestibular nuclei

NTS

50
Q

Which types of sickness can H1 receptor antagonists block well?

A

Motion sickness, morning sickness, post-operative nausea and vomiting

51
Q

Give examples of H1 receptor antagonists for use as anti-emetics

A
  • Promethazine
  • Cyclizine
  • Cinnarizine
52
Q

What are side effects of H1 receptor antagonists?

A

Lethargy

Depression

53
Q

Anticholinergics are used primarily for what?

A

Motion sickness

54
Q

Where can anticholinergics act to induce an anti-emetic effect?

A

CNS

NTS

Vomiting centre

55
Q

What are side effects of anticholinergics?

A

Blurred vision, urinary retention, dry mouth, sedation

56
Q

Give examples of anticholinergics for emesis control

A

Hyosine

Dicycloamine

57
Q

When first line drugs fail to give a response adequate to prevent emesis, which second line drugs can be used as adjuvants?

A
  • Neurokinin 1 receptor antagonists
  • Corticosteroids
  • Benzodiazepines
  • Cannabinoids
58
Q

Which triple drug therapy is opten utilised for chemotherpay induced emesis?

A

5HT3 receptor antagonist + dexamethasone + aprepitant

59
Q

What causes pregnancy associated nausea and vomiting?

A

Human chorionic gonadotropin

(produced by placenta)

60
Q

What is the first line treatment for pregancy induced vomiting?

A

Changes in diet, use of ginger or pyridoxine, wrist acupressure

61
Q

What is hyperemesis gravidarum?

A

Pregnancy induced sickness that cannot be stopped any way other than pharmacologically

62
Q

How is hyperemesis gravidarum treated?

A

First line - Antihistamine (promethazine, cyclizine)

Second line - Prochlorperazine, metoclopramide (D2 receptor antagonists)

The Gastrointestinal System 2023 (27 decks)

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