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Pharmacy Stage 2 > GI tract > Flashcards

GI tract Flashcards

1
Q

Label GI tract, see week 5 gastric secretion lecture

A

see week 5

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2
Q

Name 8 gastrointestinal disorders.

A 
Gastroesophageal Reflux Disease (GORD) 
Peptic Ulcer Disease (PUD)
Duodenal Ulcer
Nausea 
Emesis 
IBS 
Diarrhoea 
Constipation
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3
Q

Main sites for therapeutic intervention in GI System?

A 
Mouth 
Oesophagus 
Stomach
Liver 
Small Intestine
Pancreas
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4
Q

3 salivary glands?

A

parotid
submandibular
sublingual

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5
Q

Function of mouth in digestive system?

A

ingestion and fragmentation of food

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6
Q

Mouth diseases?

A

Oral ulceration
Stomatitis
Leukoplakia
Dysphagia

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7
Q

What is Oral Ulceration?

A

breakdown of membrane in the mouth leading to a break in the oral epithelium, exposing nerve endings in the underlying connective tissue.
Caused by physical or chemical injury, infections, drugs, malignancy, systemic disease.

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8
Q

What is stomatitis?

A

Inflammation of the lining of any of the soft tissues of the mouth.
Caused by poor oral hygiene, poorly fitted dentures, heat burns, drugs, allergy, infection.

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9
Q

What is leukoplakia?

A

Painless white patches on side of tongue or cheeks.

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10
Q

What is dysphagia?

A

Difficulty swallowing

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11
Q

How does oesophagus propel food towards stomach?

A

Contracts rythmicaly

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12
Q

2 Functions of the Upper Oesophageal Sphincter (UOS)?

A

1) Prevents air entering oesophagus

2) Prevents oesophagopharyngeal reflux.

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13
Q

What is the function of the Lower Oesophageal Sphincter (LOS)?

A

To prevent gastroesophageal reflux.

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14
Q

How does the LOS prevent gastroesophageal reflux?

A

Has high intraluminal pressure which keeps it closed until food needs to be dumped into the stomach.

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15
Q

What causes GORD (gastroesophageal reflux disorder)?

A

Obesity, Medication, Spicy, acidic or fatty foods, Smoking

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16
Q

3 diseases of the oesophagus?

A

GORD
Hiatal herna
Motility disorders

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17
Q

What causes Barret’s Oesophagus (premalignant state)?

A

When GORD becomes consistent, cells become very damaged and can get malignant potential.

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18
Q

What is hiatal hernia?

A

The protrusion of an organ, typically the stomach, through the oesophageal opening in the diaphragm.

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19
Q

Describe 4 types of motility disorders of the oesophagus.

A

1) Achalasia – Inadequate LOS relaxation
2) Diffuse oesophageal Spasm – Uncoordinated contraction
3) Hypercontraction
4) Ineffective oesophageal Motility – Hypocontraction.

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20
Q

What is dyspepsia?

A

A group of symptoms that arise from the upper GI tract
•Symptoms includes heartburn, abdominal discomfort, eructation, nausea
•Alone or in combination with other upper GI disorders

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21
Q

What is peptic ulceration?

A

Benign lesion of the gastric / duodenal mucosa at the site where the mucosa exposed to acid and pepsin.

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22
Q

What are the symptoms of peptic ulceration?

A
  • Often asymptomatic, or symptoms similar to dyspepsia

* But if it gets serious, then symptoms include: Epigastric pain, vomiting, symtpoms worse at night

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23
Q

What are the dangers of peptic ulceration?

A

Danger of:
•Haemorrhage
•Perforation
•Damage adjacent organ • Melena (black, tarry stools from GI bleeding)

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24
Q

What does blood red stool and black stool due to peptic ulceration represent?

A

Blood red- ulcer in lower GI tract

Black- ulcer in GI tract

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25
Q

What is GORD?

A

Exposure of ‘unprotected’ oesophageal epithelium to acid

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26
Q

How does GORD happen?

A

Transient LOS relaxation in absence of swallowing, which is a response to the stimulation of gastric vagal mechanoreceptors and oesophageal hypomotility.

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27
Q

Describe the 3 distinct types of GORD.

A

1) Non-erosive reflux disease (“heartburn”)
2) Erosive oesophagitis - acute inflammatory response
3) Barrett’s oesophagus (metaplasia of mucosa) - cancer risk

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28
Q

Name the 4 types of acid secreting cells found in the OXYNTIC GLAND AREA. ( Oxyntic gland area found in the body and fundus areas of the stomach).

A
  • Mucous cells
  • Chief cells
  • Enterochromaffin-like cells (ECL cells)
  • Parietal cells
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29
Q

What do chief cells secrete and why?

A

Pepsinogen- for protein digestion.

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30
Q

What do mucous cells secrete and why?

A

Bicarbonate/Mucus for gastro-protection.

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31
Q

What do ECL secrete and why?

A

Histamine for regulation of gastric secretion (stimulate acid secretion)

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32
Q

What do parietal secrete and why?

A
  • HCl for hydrolysis of proteins and to kill bacteria that enters the stomach.
  • Intrinsic factor for Vitamin B12 absorption.
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33
Q

Name the 3 types of cells found in the PYLORIC GLAND AREA in the pyloric region.

A
  • Mucous cells
  • G cells
  • D cells
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34
Q

What do G cells secrete and why?

A

Gastrin for regulation of gastric secretion (stimulates acid secretion).

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35
Q

What do D cells secrete and why?

A

Somatostatin for regulation of gastric secretion (off switch for acid secretion).

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36
Q

What cell type is found on the surface of the pyloric region of the stomach and why?

A

Surface mucosa cell. It secretes a thick, protective, alkaline-rich mucus. This is the gastric mucosal barrier.

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37
Q

How are the cells in the stomach stimulated?

A

By mechanical and chemical irritation and parasympathetic inputs.

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38
Q

How can the gastric mucous barrier be damaged?

A

By bacterial and viral infection, and certain drugs (NSAIDs, e.g. aspirin)

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39
Q

Describe how acid secretion from parietal cells is stimulated.

A

Translocation of H+/K+-ATPase (“proton pump”) to the apical membrane.

Resting parietal cell:
H+/K+-ATPase are in cytoplasmic vesicles

Stimulated cell:
1)H+/K+-ATPase vesicles fuse with the plasma membrane and move to the surface of the cell
2) Surface area of the cell increases and membrane pumps are activated
»»»acid secretion….

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40
Q

What are the 3 positive regulators of gastric acid secretion?

A
  • Acetylcholine (from the enteric neurons)
  • Histamin (ECL cells)
  • Gastrin (G cells)
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41
Q

Name a negative regulator of gastric acid secretion.

A

Somatostatin (D cells)

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42
Q

How is gastrin release from G cells stimulated?

A

By the stomach expanding.

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43
Q

Describe 2 ways somatostatin inhibits acid secretion.

A

1) Directly inhibits parietal cell secretion

2) Inhibits gastrin and histamine release

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44
Q

Describe 2 ways which gastrin release is stimulated.

A

1) When stomach expands

2) When stomach exposed to high levels of peptides. (remember HCl breaks down peptides).

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45
Q

How does acetylcholine stimulate gastric acid secretion?

A

Ach from the cholinergic nerve (postganglionic parasympathetic).
Direct parietal cell stimulation via muscarinic M3 receptors on parietal cells.

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46
Q

How does histamine stimulate gastric acid secretion?

A
  • Direct parietal cell stimulation via Histamine H2 receptor

* Paracrine activity (hormone cell signalling to near by cells)

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47
Q

How does gastrin stimulate acid secretion?

A
  • Endocrine action
  • Stimulates histamine release -ECL cells
  • Directly stimulates parietal cell proliferation via cholecystokinin B (CKKB/CCK2) receptor
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48
Q

Which signalling pathway is used by Ach and Gastrin on parietal cells to stimulates acid secretion?

A

CA2+ DEPENDANT PATHWAY.
…act through G-coupled receptors.
Phospholipase-C (PLC) and IP3 pathway causes increases in Ca2+ and diacylglycerol.

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49
Q

Which signalling pathway is used by histamine on parietal cells to stimulates acid secretion?

A

cAMP DEPENDANT PATHWAY.

Histamine acts through G-coupled receptor to increase cyclic AMP (cAMP).

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50
Q

Most powerful stimulus for HCl secretion?

A

Histamine.

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51
Q

3 Phases of acid secretion stimulation?

A

1) Cephalic Phase:
2) Gastric Phase:
3) Intestinal Phase:

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52
Q

Describe the cephalic phase of acid secretion.

A

Sight/Smell/Thought of food. Hungry. Stomach gurgles. Acid released in preparation as body thinks u r receiving food.

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53
Q

Describe the gastric phase of acid secretion.

A

Food in stomach stimulates further acid secretion…

Mechanoreceptor neural reflex caused by stretching in stomach.

Peptides in food stimulate G-cells to secrete gastrin, which stimulates HCl secretion from parietal cells.

Food ↑ pH, which prevents D-cells activity: Less somatostatin, less inhibition of parietal cells secreting acid.

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54
Q

Describe intestinal phase of acid secretion.

A

Chyme (gastric juices and partly digested food) enters duodenum.

pH detected in duodenum>feedback lowers pH

Duodenal stimulation of hormones

↓Food ↓ pH, stimulates D-cell activity: somatostatin secreted which inhibits parietal cells from secreting HCl.

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55
Q

Explain the pH changes, rate of acid secretion and changes in volume of the stomach from eating a meal up to four hours after the meal.

A
  • Food in the stomach buffers acid and raises the pH
  • Suppresses somatostatin from D cells causing gastrin and HCl release
  • Stomach distention (swelling), digestion trigger huge secretion volume and HCl.
  • As food leaves stomach, acid increases, pH falls. Stimulates D cells, HCl production inhibited by somatostatin. Stomach distention decreases.
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56
Q

Why might it be important in pharmacy for a drug to be taken before or after a meal?

A

Food increases pH and buffers acid. This affects drug absorption site because where in the GI tract a drug is absorbed depends on the pH.

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57
Q

How does ?

A

• Stomach distention via vagovagal reflex increase parietal cell acid production by…

1) Direct stimulation of ECL cell to release histamine
2) Direct stimulation of G cells to release gastrin via GRP
3) Inhibition of somatostatin release from D cells in antrum.

  • Pyloric antrum exposure to peptides stimulates G cells to release gastrin, which increases parietal cell HCl release by direct stimulation and by increasing ECL histamine release.
  • High acid feeds back to stimulate D cells to release somatostatin and inhibits gastrin release to limit acid secretion
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58
Q

Mechanism of HCl Secretion from parietal cell?

A

1) CO2 diffuses into parietal cell from plasma and hydrated to carbonic acid by carbonic anhydrase.
2) H2CO3 dissociates into H+ and HCO3-
3) H+/K+-ATPase actively transport H+ out, K+ in • Na+ also actively reabsorbed
4) K+ back into gastric lumen via K+ channel, resulting elevated K+ of gastric juice.
5) Cl- exits into lumen passively from cell via Cl- channel
6) Extracellular H+ generates osmotic gradient across membrane>outward H20 diffusion

> > > Gastric juice: 160mM HCl, 15mM KCl, small NaCl

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59
Q

Function of the basolateral membrane Na+/K+ ATPase and the HCO3- and CL- exchanger?

A

• Na+/K+ ATPase maintains intracellular Na+ and K+
• Exchanger promotes HCO3- exit into blood and Cl- uptake by parietal cell. Cellular pH is maintained•
Slight rise blood pH = “alkaline tide”,
•Negative gastric arter-venous CO2 gradient

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60
Q

Prostaglandin E2 inhibit or promote acid secretion?

A

inhibit.

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61
Q

What causes somatostatin secretion from D cells?

A

drop in pH in duodenum by chyme enterance.

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62
Q

What do PGE2 do?

A

increase blood flow (to take nutrients away from stomach), bicarbonate release, mucus secretion and cell regeneration. Decrease H+ secretion.

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63
Q

How does mucosal protection layer form?

A
  • Vagal stimulation and irritation stimulate gastric mucous cells to secrete mucin, a glycoprotein that is part of the mucosal barrier
  • Gastric surface epithelial cells secrete HCO3- when stimulated by ACh, HCl, and PGs
  • HCO3- accumulates near cell surface
  • Mucus protects gastric surface epithelium by trapping HCO3- rich fluid near apical border of epithelia
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64
Q

Why is a continual production of mucins required?

A

Because mucins get cleaved by pepsin.

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65
Q

How does HCO3- rich fluid near apical border of epithelia protect the epithelium surface?

A

HCO3- neutralizes HCl that comes near epithelium.

creates “micro-environment” to stop acid damage

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66
Q

How is the gastric epithelium surface protected from acid?

A
  • Mucinscleaved by pepsin, so continual production required
  • Rich in bicarbonate; creates “micro-environment” to stop acid damage
  • Impermeable apical cell membrane tight junctions limit H+ ion diffusion
  • Locally produced prostaglandins (PGE2 and PGI2) > reduces HCl secretion, increases mucus and bicarbonate secretion
67
Q

What inhibits HCO3- secretion?

A

inhibited by adrenergic input (prominent in stress!)

68
Q

What are the genetic factors and family history reasons linked to peptic ulcers?

A

Excessive acid production
Weaker mucosa/intrinsic defect in mucosal barrier
Abnormal mucus production

69
Q

What are the causes of peptic ulcers linked to lifestyle?

A

Caffeine, Smoking, Alcohol, NSAIDs, Stress

70
Q

Symptoms are a poor guide to peptic/duodenal ulcer location. However if the condition gets worse, what are the symptoms?

A

> Gastric ulcer pain made worse by food
More likely than duodenal ulcer to associate with weight loss, anorexia and nausea (don’t eat as much, stomach still making acid so balance disrupted)

71
Q

Name a difference between gastric and duodenal ulcers.

A
  • Gastric ulcers normally inflammatory response of parietal cells
  • Duodenal ulcers normally associate with high acid / low bicarbonate.
72
Q

Name a major cause of peptic ulcers.

A

Gastric and duodenal infection with Helicobacter pylori

73
Q

Why are NSAIDs linked to peptic ulcers?

A

Long term use of NSAIDs • NSAIDs block COX enzymes and decrease prostaglandin production. Prostaglandins increase mucus secretion, bicarbonate release, mucus secretion and cell regeneration. Decrease H+ secretion.
>this leads to excess acid production and thinner gastric mucus layer for protection.

74
Q

Gastric Ulceration: Lead to normal or decreased acid secretion. Why?

A
  • Usually caused by damage to whole gastric area
  • Atrophic gastritis (thinned mucosa)
  • Less able to secrete acid, increased pH
75
Q

Duodenal Ulceration: Lead to increased acid secretion. Why?

A
  • Gastric inflammation elevated in antral/pyloric region

* Relative sparing of gastric body(acid-secreting) region • Increased gastrin release and increased acid secretion

76
Q

Development of peptic ulcer is associated with shift in balance between ……………………….. and ……………………….

A

Mucosal-damaging and mucosal-protecting mechanisms.

77
Q

Non-steroidal anti-inflammatory drugs (NSAIDs; e.g.aspirin) reduce prostaglandin formation (COX 1 inhibition) and may trigger ………… and ………….?

A

• Gastric ulceration • Bleeding

78
Q

Gastric damage due to long-term NSAID treatment (e.g. rheumatoid arthritis) can be prevented how?

A

with a stable PGE1 analogue (i.e. misoprostol).
:( - polypharmacy
one drug to cover the damage of another, then another drug to cover damage of that one and so on and so on..

79
Q

Aspirin causes Irreversible inhibition COX enzymes and Direct Gastric Toxicity. How do you prevent this?

A

ENTERIC COAT THE TABLETS TO PREVENT ALL THIS AND HAVING TO GIVE SECOND DRUG THIRD DRUG ETC.

80
Q

Treatment of Dyspepsia & Gastric Disorders?

A

Neutralisation:
• Antacids (neutralize HCl)
• Alginates (forms a ‘raft’ that floats on top of stomach contents)
• Sucralfate (mucosal protectants)

Reduction of Acid Secretion:
• Proton Pump Inhibitors
• Histamine H2-Receptor Antagonists
• Prokinetics

81
Q

What are antacids?

A

Antacids are weak bases (mostly weak inorganic bases): neutralise excess acid in stomach to comfort level and reduce foaming to prevent heartburn.
Quick but short term
• Buffer gastric acid, increasing the pH
• Raising gastric pH from 1.3 to 1.6 neutralises 50% of gastric acid.
• Raising gastric pH from 1.3 to 2.3 neutralises 90% of the gastric acid.
TREATMENT-Often combined with Alginates and anti-foaming agents

82
Q

Antacids prevent the over-production of acid. True/False?

A

False

83
Q

What do anti-foaming agents do?

A

Anti-foaming agents reduce surface tension of stomach acid to prevent bubbles, causing them to coalesce, producing de-foaming action.

84
Q

What are systemic antacids?

A
  • Useful in short-term therapy
  • Rapid onset
  • Prolonged use causes an overload on the kidneys e.g. sodium bicarbonate
85
Q

What are non-systemic antacids?

A
  • Remain in gastrointestinal tract; useful in long-term therapy
  • Most of the dose remains in the gastrointestinal tract e.g.
  • Calcium-based antacids: Tums, Rennies[CaCO3]
  • Magnesium-based antacids: Milk of Magnesia [Mg(OH)2]
  • Aluminum-based antacids: Mylanta [Al(OH)3]
  • Bicarbonate-based antacids: Alka Seltzer [NaHCO3]
86
Q

Interactions of Antacids?

A

Pharmacokinetic and Pharmacodynamicinteractions:
• Binding of other drugs to the antacid causing reduced bioavailability
• Chemical inactivation of other drugs
• Increased gastric pH (alkaline), decreasing drug absorption and excretion

87
Q

Adverse Effects of antacids?

A

Antacids are relatively harmless but they can have minor contraindications:
• Magnesium hydroxide has laxative properties.
• Magnesium antacids: Not used in renal failure, due to reduced Mg excretion
• Aluminum hydroxide: cause constipation (Used with Mg to counteract)
•Calcium carbonate : may cause renal calculi (stones) and constipation
• Carbonates may generate CO2 leading to bloating and flatulence.
• Sodium Bicarbonate (Systemic): Highly soluble, short duration. May cause metabolic alkalosis. Na+ content may cause problems in hypertension or renal insufficiency.

88
Q

What are Alginates?

A

• Polysaccharide found in the cell walls of brown algae. • Forms protective barrier on top of gastric contents • Usually combined with an antacid.

89
Q

How does Gaviscon work?

A
  • Combination of antacids (Sodium Bicarbonate, Calcium Carbonate) and Alginate
  • Ingestion: reacts rapidly with acid to form raft of alginic-acid gel, near neutral pH, which floats on top of stomach contents>impeding gastro-oesophageal reflux.
90
Q

Muscarinic M1 and M3 receptor antagonists, histamine H1 receptor antagonists, proton pump inhibitors and prostaglandin (PGE2) analogues can be used to REDUCE ACID SECRETION in treatment of dyspepsia and GORD. True or False?

A

FALSE.
DO NOT give antimuscarinic drugs, otherwise u r gonna paralyze patient.
histamine antagonists u can use
proton pump inhibitors u can use e.g. omeprazole.

91
Q

Antacids, Alginates and Sucralfate are used to treat the SYMPTOMS of dyspepsia and GORD. True or False?

A

True.

92
Q

What are proton pump inhibitors?

A
  • Act upon parietal cells which release H+ (protons) during HCl production.
  • PPI Do not neutralize excess acid but inhibit production of HCl.
93
Q

Give some examples of PPI drugs.

A
  • Lansoprazole -Omeprazole
  • Rabeprazole
  • Pantoprazole
  • Esomeprazole [S-isomer of omeprazole]
94
Q

Mechanism of action of Proton Pump Inhibitors?

A

PPI=WEAK BASES.
1) Activated form irreversibly binds to cysteines of the H+/K+ ATPase to inhibit the active (i.e. membrane inserted) proton-pump
• (but pumps in tubulovesicles are not inhibited)

2) Prevents movement of H+ from parietal cell into stomach.
»>Achlorhydria “ALL gastric acid secretion blocked”.
To return to normal acid secretion, must synthesize new H+/K+ ATPase>(this takes time).

95
Q

why do PPIs have to be absorbed from the GI tract and enter the systemic circulation, even though the target is the GI tract?

A

Has to bypass stomach because you’d only be blocking the surface pumps and not all of the pumps from inside.

96
Q

How does PPI reach target and gets activated?

A

PPI = WEAK BASE
1) Absorbed from GI tract and delivered via the systemic circulation> to the secretory gastric canaliculi.
• (Enteric coated to resist gastric metabolism and allow GI absorption)
• Prodrugs: inactive at neutral pH, but activated in strongly acidic environment (i.e. the canaliculus).

97
Q

OMEPRAZOLE ACTIVATION AND ACTIVITY?

A
  • Diffuse into the parietal cells of the stomach and accumulates
  • Activated by proton catalyzing (pH<5) to form sulfenic acid (active form)
  • Active drug irreversibly binds to the sulfhydryl groups of cysteines on H+/K+ pump
  • Charged drug molecule cannot diffuse out of parietal cells
  • Irreversible inactivation of the H+/K+ pump
  • Inhibits acid production, irrespective of stimulating factor
98
Q

Pharmacokinetic considerations of PPIs?

A
  • Inhibition of acid secretion: 10-14 hr duration after a pre-breakfast dose. This greatly exceeds plasma half-life of PPIs. [T½ for most PPIs e.g.lansoprazole, 1 to 1.5 hr]. (Before drug dose reduced to half).
  • Timing of dosing important – drug must be present in plasma at an effective concentration whilst proton pumps are active - just before you eat.
  • PPI are effective orally once daily, but not all pumps are inactivated and nocturnal acid breakthrough (NAB) may occur (small period when stomach still producing acid).
  • Full effect only achieved after repeated dosing -(takes time to ensure every single pump is inactivated and a new one made, a bit like laser treatment).
  • Unwanted effects uncommon but concerns raised about long term treatment
99
Q

Suggest why histamine and acid production is high during an infection.

A

Mast cells, located throughout mucosa, secrete a steady basal level of histamine.
On top of histamine being released from ECL cells, during an infection there is an increase in mast cells activation and so increased histamine production. More histamine bind to H2 receptor on parietal cells>cAMP pathway> acid production

100
Q

Name two Histamine H2 receptor blockers and describe how the second blocker has improved drug properties.

A
  • Cimetidine (Tagamet®) – First H2-blocker available – Inhibits P450 => Drug interaction
  • Ranitidine (Zantac®) – Does not inhibit P450 => fewer side effects . IMPROVED.
101
Q

Histamine H2 receptor antagonists: mechanism of action?

A
  • Act as competitive (reversible) antagonists of H2 receptors on basolateral membrane of parietal cells
  • Completely block the histamine-mediated component of acid secretion and reduce secretion evoked by gastrin and ACh
  • Effective against basal and stimulated gastric acid production
  • Effective once/twice daily by oral administration
102
Q

PPIs are less potent than H2 receptor antagonists. True or false?

A

False. PPI are more potent.

103
Q

Pharmacokinetics considerations of H2 receptor antagonists?

A

Pharmacokinetics:
• Rapidly absorbed after oral administration
• Serum concentrations peak in 1-3 hr
• Therapeutic levels maintained up to 12 hr

104
Q

Drug interactions of H2 receptor antagonists?

A
  • Cimetedine: inhibits hepatic P450s: modulates drug metabolism
  • May inhibit absorption of drugs requiring acidic environment for absorption
  • SMOKING has been shown to decrease the effectiveness of H2 blockers
105
Q

PGE2 and PGI2 synthesized by gastric mucosa bind to which receptors on parietal cells?

A

Bind to EP3 receptors on parietal cells -decrease acid production

106
Q

what are the •Cytoprotective effects of PGE2 AND PG12?

A

-Stimulate mucin and bicarbonate production

107
Q

Give an example of a synthetic prostaglandin E1 (PGE1) analogue used to treat GERD and dyspepsia. Descibe the characteristics of this analogue.

A

Misoprostol
• Enhanced potency and increased oral bioavailability
• Inhibit basal secretion (~85%) and Inhibit stimulated secretion (~75%)

108
Q

Pharmacokinetics of misoprostol?

A
  • Rapidly absorbed and de-esterified to active metabolite

* Therapeutic effect peaks at 60-90 minutes, lasts ~3hrs (4x day dose)

109
Q

Adverse effects of misoprostol?

A
  • Diarrhoea± abdominal cramps
  • Can exacerbate inflammatory bowel disease
  • Contraindicated during pregnancy
110
Q

What is sucralfate?

A

only used for extreme cases.
>Treatment of Benign gastric and duodenal ulceration
>Complex of aluminum hydroxide and sucrose octasulphate
– Dissociates in gastric acidic environment to anionic form
– Forms complex gel with mucus and forms cross-linked viscous polymer
– Acts as acid buffer and impairs diffusion of H+
- Stimulates PG-synthesis and bicarbonate secretion

111
Q

Pharmacokinetics of sucralfate?

A
  • Only slightly absorbed from gut
  • Essentially free of side effects, but may cause constipation
  • Absorbed fraction excreted unchanged by kidney
112
Q

What are prokinetics?

A

Dopamine receptor antagonist
• Enhances gastric motility
• Increases rate of gastric emptying
• Increases gastro-oesophageal tone

Rarely used because of severe side effects (only in extreme cases):
• Fatigue • Tremors • Parkinsonism • Tardive Dyskinesia • Severe cardiac events

113
Q

What is dyspepsia?

A

Derived from the Greek word, that means ‘hard or difficult digestion’
•  Subjective feeling of pain or discomfort located primarily in the upper abdomen
•  ‘A group of symptoms that alert doctors to consider disease of the upper GI tract, and states that dyspepsia itself is not a diagnosis’

114
Q

9 regions of abdomen?

A

HLi, epigastric, umbilical, hypogastric

115
Q

Causes of dyspepsia?

A

h pylori , stress, spicy food, smoking, alcohol,drugs like corticosteroids, potassium supplements, bisphosphonates, and NSAIDs e.g. diclofenac.

116
Q

What is acute and chronic dyspepsia?

A

acute-few weeks

chronic-all the time

117
Q

Clinical assessment: Describe investigated and uninvestigated dyspepsia.

A

Investigated dyspepsia: investigate with camera (endoscopy) in stomach
uninvestigated dyspepsia: no endoscopy.

118
Q

When should you investigate dyspepsia with endoscopy?

A

If there are ‘alarm’ symptoms present (signs of cancer): •  Chronic GI bleeding (black stool - called melaena)
•  Dysphagia (difficulty swallowing)
•  Progressive unintentional weight loss
•  Persistent vomiting
•  Iron deficiency / anaemia
•  Epigastric mass
•  Suspicious barium meal result
•  In patients aged 55 years and older with unexplained and persistent recent- onset dyspepsia alone, a referral should be made (more likely to have cancer at 55)

119
Q

What is a barium meal?

A

barium sulphate- drink > coats all of internal organs.
barium sulphate is radiopaque so xrays cant penetrate it. pic on right- black mass could be carcinoma.
if get this then another endoscope.

120
Q

What to do with investigated dyspepsia?

A

Treat any underlying pathology (PUD or malignancy.

121
Q

Many investigated dyspepsia don’t reveal any problems. What are they called? and what action next?

A

-known as functional, idiopathic dyspepsia.
–  Treat and test for H. pylori
–  Offer PPI or H2RA for 4 weeks
–  If symptoms recur, re-start the PPI or H2RA at lowest dose possible
–  Avoid long-term, frequent use of antacids

122
Q

H. Pylori tests?

A

stool or breath tests
stool dipstick to detect h pylori antigen in feces sample.

(h pylori reaction- produces urease which converts urea and water to co2 and ammonia).
breath test : breath in radioactive urea
h pylori urease will breath out radioactive co2. -
-breath test :) non invasive and relatively accurate and simple.

123
Q

What action to take with Uninvestigated Dyspepsia?

A
  • Offer H. pylori ‘test and treat’ to people, making sure to leave an appropriate wash out period :
    (PPI or antibiotics before test can affect reading. leave appropriate washout period before carrying out the test. at least 4 weels for antibiotics and 4 days for PPI. can give antacid instead in that period-they don’t cause false readings on test.)
  • Offer full-dose PPI therapy for 4 weeks
  • If symptoms return, step down PPI to the lowest dose needed to control symptoms. Even PRN therapy?
  • Offer H2RA therapy if there is an inadequate response to a PPI .
124
Q

How long do PPI and H2RA take to work?

A

12 hours

125
Q

Safety of long-term PPI use?

A

not safe start reducing them slowly.
–  Rebound hypersecretion( reduced gastric acidity caused by PPIs induces hypergastrinemia and growth of histamine-releasing enterochromaffin-like cells, which leads to an increased acid secretory capacity once the PPI therapy is discontinued )
–  Osteoporotic fractures(decreased calcium absorption)
–  Hypomagnesaemia(low Mg>patient confused)
–  Community- and hospital-acquired pneumonia
–  Drug interactions?(clopidogrel + omaprazole )

126
Q

what is GORD?

A

Is the retrograde passage of gastric contents from the stomach into the oesophagus
•  Symptoms include heartburn, pyrosis, regurgitation of gastric contents into the throat, early satiety, belching, hiccups and nausea and vomiting
•  Therapeutic goals are to relieve symptoms, promote oesophageal healing, and avoid long-term complications

127
Q

How can GORD become Barret’s oesophagus?

A

stomach contents gone back up osophagus
squamous cells at bottom of osophagus - change to gland cells.
gland cells can become cancer- barraets osophagus- more likely to get osaphageal cancer.

128
Q

H pylori testing is required for GORD. TRUE OR FALSE?

A

FALSE

129
Q

What action to take for mild, infrequent symptoms of GORD?

A

–  Lifestyle advice

–  Antacid and alginate:GAVISCON

130
Q

What action to take for frequent symptoms of GORD?

A

–  Lifestyle advice
–  Offer people with GORD a full-dose PPI for 4-8 weeks
–  If symptoms reoccur after initial treatment, offer a PPI at the lowest possible dose to control symptoms (even PRN) -WHE REQUIRED
–  Offer H2RA therapy of there is an inadequate response to a PPI

131
Q

Describe what prokinetic drugs do and why best not to recommend for treating GORD?

A

increase pressure of lower osephagus sphincter to close it.
but try not to recommend bc too toxic.
• Metoclopramide •  Bethanechol •  Cisapride??
•  Increase LOS pressure
•  Stimulate the motility of GI tract without altering gastric acid secretion
•  Ineffective at healing erosive oesophagitis
•  Now seldom used in the treatment of GORD

132
Q

Lifestyle Modifications to treat GORD?

A

•  Avoid medication that relax the LOS- theophylline.
•  Avoid foods that relax the LOS -spicy foods, fat foods
•  Lose weight-over weight, more pressure on sphincter to open.
•  Avoid tight clothing
•  Stop smoking
•  Raise the head of the bed by 6 to 8 inches -gravity more pressure on sphincter to open.
raise, then less of this.
•  Avoid eating within 3 hours of bedtime

133
Q

Dyspepsia and GORD are the same thing. True or false?

A

false. dyspepsia is a group of symptoms - discomfort of upper abdomen.
GORD is acid reflux disorder up into oesophagus.

134
Q

Eradication therapy ‘triple therapy’ can increase the risk of C. difficile. true or false?

A

true. clostridium difficile linked to ‘triple’ regime containing clarithromycin and metronidazole to eradicate h pylori.

135
Q

Rebound hypertension is a risk when stopping a long-term PPI. true or false?

A

false. its rebound hypersecretion -
( reduced gastric acidity caused by PPIs induces hypergastrinemia and growth of histamine-releasing enterochromaffin-like cells, which leads to an increased acid secretory capacity once the PPI therapy is discontinued )

136
Q

Prokinetic agents reduce the pressure of the Lower Oesophageal Sphincter (LOS) . true or false?

A

false. they increase pressure of LOS.

137
Q

what are gastric ulcers?

A
  • Localised erosions of the mucous membranes of the stomach and the duodenum.
  • Potentially fatal if untreated.
  • Caused by stress, infection (H. pylori) and reaction to drugs (NSAIDS).
  • Aggravated by gastric acid (HCl/digestive enzymes) in the stomach.
138
Q

Gastric ulcer therapy?

A
  • Medication to lower levels of gastric acid.
  • Histamine (H2) antagonists and proton pump inhibitors (PPIs).
  • Antibacterial agents to treat H. Pylori.
  • Herbal remedies.
139
Q

• Parietal cells are highly enervated . true or false?

A

true. Autonomic nervous system (ANS) stimulated release of neurotransmitter (ACh)

140
Q

LEARN LECTURE SLIDE 34 MECHANISM OF PPI ON WEEK 6 CASE STUDY GI

A

LEARN LECTURE SLIDE 34 MECHANISM OF PPI ON WEEK 6 CASE STUDY GI

141
Q

What are the accessory organs within the mouth?

A

Salivary glands
Teeth
Oral cavity

142
Q

How many litres of HCL secreted per day by parietal cells?

At what pH?

A

Secrete 1-2L of 150-160mM HCl per day (pH 0.8-1)

143
Q

What is nausea?

A

the subjective feeling of the need to vomit. It includes an unpleasant sensation in the mouth and stomach and can be associated with salvation, sweating, dizziness, and tachycardia.

144
Q

What is vomiting?

A

the forceful expulsion of the stomach contents through the mouth, but is preceded by the relaxation of the oesophageal sphincter, contraction of the abdominal muscles, and temporary suspension of breathing

145
Q

What Is retching?

A

the rhythmic contraction of abdominal muscles without actual emesis

146
Q

Causes of vomitting and nausea and retching?

A
  • medication/drugs: e.g. cancer chemotherapy, (and opioids. dose increased- more nausea/vomiting, antidepression medication, dopamine agonist, emergency hormonal contraception (EHC))
  • anxiety
  • pregnancy
  • brain tumour
  • migrane
  • diabetes type 1 >diabetic ketoacidosis
  • Ca2+ increased levels - (e.g. by thiazides drugs)
  • obstruction in GI tract e.g. tumour - preventing food going down, peristalsis )
  • meningitis
  • food poisoning-E.coli, salmonella
  • motion sickness-boat, car etc.
147
Q

Is it harder to treat vomiting

A

can treat from being sick- antiemetic

but difficult to treat nausea- feeeeling sick

148
Q

Complications of vomiting?

A
  •   Dehydration - oral rehydration therapy to treat. Skin pinch test to check. elastic skin-hydrated.
  •   Electrolyte imbalances-reduced sodium and potassium, and alkalosis
  •   Malnutrition - cant keep any food down, cant absorb nutrients u need. crucial for children- wont thrive and more likely to get infections and aching muscles
  •   Aspirational pneumonia- stomach contents going into lungs. Serious. that’s why to not eat before surgery.
  •   Oesophageal tear - a lot of pressure on bottom of oesophagus- serious. needs managing quick.
149
Q

Treatment Approach to vomiting?

A

Anti-emetics should only be prescribed when the cause of vomiting is known because otherwise they may delay diagnosis
BUT need to treat underlying problem too, e.g. diabetic ketoacidosis.
If an anti-emetic is indicated, the drug is chosen according to the aetiology of the vomiting

150
Q

what is motion sickness?

A

brain thinks is something wrong

  • protective thing
  • once happens-difficult to cure
  •   A disagreement exists between visually perceived movement and the vestibular system’s sense of movement
  •   Prevention is better than the cure
151
Q

treatment for motion sickness?

A

what works: hyoscine-works on muscarinic receptors.
promethazine
cinnarizine
hyoscine most effective.

-majority of anti-emetic drugs don’t really work for motion sickness
•  Domperidone, metoclopramide, 5HT3 receptor antagonists, NK1 receptor antagonists and the phenothiazines have not been shown effective in preventing motion sickness

  •   Anticholinergic agents and antihistamines that cross the blood brain barrier effectively prevent and treat motion sickness
  •   A role for non-sedating antihistamines? non sedating ones don’t work, just sedating ones bc need to cross CNS blood brain barrier
152
Q

anticholinergic side effects?

A

•  Drowsiness •  Blurred vision •  Dry mouth •  Constipation •  Urinary retention - e.g. in men BPH - penign prostatic hyperplasia

all anti motion sickness drugs make u drowsy

153
Q

Chemotherapy Induced Nausea and Vomiting (CINV) .

what are the different kinds? what are the factors affecting CINV?

A

Different kinds of CINV:
•  Acute
•  Delayed
•  Anticipatory - E.G. can be after finished and cancer cured, just seeing the nurse who treated u can make u become sick.

Factors affecting CINV:
•  Type of chemotherapy regimen
•  ‘Patient-based factors’ - WOMEN MORE LIKELY TO EXPERIENCE CINV, if u have history of motion sickness, if u drink less alcohol or no alcohol - more likely, being younger- more CINV
•  Genotypic factors

154
Q

What drug is considered by many oncologists as the most significant in the last forty years?? (for CINV)

A

ondansetron. - but also cardiogenic and bad constipation
- its an antiemetic . acts on serotonin (5HT)

before this was discovered, would give cancer patients metoclopramide - D2 RECEPTOR antagonist. increases peristalsis. if give high enough e.g. 120mg also has effect on 5HT. but problem with high dose is causes bad movement disorders (EPS- extrapyramidal symptoms ) . e.g. too much movement. also its cardiogenic - should only use for 5 days.

anticholinergic drugs reduce peristalsis. so never give D2 receptor antagonist and anticholernic drugs together.

155
Q

Give 4 examples of EPS associated with high dose metoclopramide.

A

Akathisia
pill rolling
dystonia
tardive dyskinesia

156
Q

Drugs used for CINV?

A
  •   Ondansetron and palonosetron (selective 5HT3 receptor antagonists)
  •   Aprepitant (a neurokinin-1 [NK1] receptor antagonist)
  •   Dexamethasone (a corticosteroid)
  •   Metoclopramide (a D2 receptor antagonist)
157
Q

genetic factors effecting CINV:

A

diff people have diff CYP 2D6 and CYP 3A4.
lazy 2D6 - good for ondansertron
efficient 2d6 - use diff drug.

158
Q

how to treat morning sickness?

A

promethazine.

159
Q

how to treat Hyperemesis Gravidarum?

A

pregnant- v bad morning sickness.

go to hospital and given antiemetics and supplementation for electrolytes and vitamin B

160
Q

Postoperative Nausea and Vomiting Postoperative nausea and vomiting (PONV) is a common complication of surgery . risk factors?

A

•  Patient-based factors - (how long u have surgery- longer- more risk
female- more risk)
•  Type of anaesthetic
•  Surgical

161
Q

complications of PONV?

A
  •   Increased hospital stay
  •   Stress on surgical closure
  •   Aspirational pneumonitis
162
Q

NAUSEA AND VOMITING in Palliative Care-CAUSES?

A

•  Chemicals •  Gastric stasis •  Bowel obstruction •  Raised intracranial pressure •  Psychological factors •  Unknown

Patients with nausea/vomiting absorb drugs poorly by the oral route. Prescribe subcutaneously for at least 24 hours if there is vomiting, obstruction and/or poor symptom control

163
Q

True or False?

  1.   Metoclopramide should be used with cyclizine
  2.   Ondansetron commonly causes constipation
  3.   The treatment of choice for motion sickness is hyocine
  4.   High dose metoclopramide is associated with extrapyramidal symptoms
A 
1) FALSE- metocl. increases peristalsis
cyclIzine slows peristalsis- antimuscarinic.
2) true
3)true
4) true

Pharmacy Stage 2 (8 decks)

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