Pharmacology of GIS.power Point for Nursing

Pharmacology pwoer Point For Generic Nursing

1. Pharmacology
of GIS
By Eyuel D.

2. 2

3. 1. Regulation of Gastric acid secretion
2.Classification of drugs used in peptic ulcer
3.Mechanism of action, Uses & Adverse effects of:
H2 Blockers
Proton pump inhibitors
Antacids
Ulcer protectives
4.Drugs for eradication of H.pylori

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4.  A localized lesion of the mucous membrane of the
stomach (gastric ulcer) or duodenum (duodenal ulcer),
typically extending through the muscularis mucosa.

Two main causes: )
infection (gram-negative) or
2.Use of



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5. 5
Protective factors vs hostile factors
Pathogenesis of PUD:

6. Alcohol
Smoking
Diet
Stress
Genetic factors
Diseases:

Nausea, Vomiting, Anorexia
Upper abdominal pain
Weight loss
Heart burn
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7. Gastric secretions:
and ( ).
(Chief cells).
(mucus-secreting cells)


Gastrointestinal hemorrhage
 Pyloric stenosis
 Chronic iron deficiency anemia
 Perforation, Peritonitis

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8. Parietal cells secrete acid in response to:
1.Histamine (local hormone): H
2 receptors
2.Gastrin (hormone) activates gastrin receptors
3.Ach (neurotransmitter): M
3 receptors
4.Proton pump (H+/ K+ ATPase)

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9. Basolateral parietal cells membranes contain
receptors for:
1. stimulation
2. stimulation
stimulation

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11. 1.Eradicating the H. pylori infection,
2.Reducing secretion of gastric acid with the use of
or
3.Providing agents that protect the gastric mucosa from
damage, such as and .
4.Neutralizing the acid by
Antimuscarinic drugs
H2 receptor antagonists
Proton pump inhibitors
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12.  Sucralfate
 Prostaglandin analogues
 Colloidal bismuth

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14. Selectively inhibit gastric acid secretion
No effect on gastric motility
Less side effects of cholinergic blockade
No effect on CNS
1.Adjuvants to H2 receptor blockers
2. se nocturnal pain in peptic ulcer
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15. B. H2 receptor blockers:

Cimetidine
Ranitidine
Famotidine
Nizatidine

Mechanism of action:
They competitively & reversibly block H
2 receptors on
the parietal cells.

 Highly selective, No action on H
1 or H
3 receptors

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16. Pharmacokinetics:
Good oral absorption

Famotidine is the most potent drug.
Exposed to first pass metabolism (except nizatidine
that has 100 % bioavailability).

Duration of action (4-12 h).
Metabolized by .

Excreted mainly in .

Cross placenta & excreted in milk
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17. 17

18. Pharmacological actions:
1.Reduce basal and food stimulated-acid secretion.
2.Block 90% of nocturnal acid secretion (which
depend largely on histamine) & 60-70% of total 24 hr
acid secretion. Therefore, it is better to be taken
before night sleep.

3.Reduce pepsin activity.
4.Promote mucosal healing & se pain
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Modest impact on (As it
depends on )

19. 1.Acute ulcer healing
Duodenal Ulcer (6-8 weeks).
Benign gastric ulcer (8-12 weeks).
2.Gastroesophageal Reflux Disease (GERD)
3.To reduce incidence of in
intensive care unit ()
(large dose)
5.As needed basis for rapid relief from dyspepsia


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20. 1.GIT disturbances (Nausea & Vomiting).
2.CNS effects:
(elderly, hepatic /renal
dysfunction).
and hypotension (rapid I.V.)
(Only Cimetidine) se
metabolism of warfarin, phenytoin,
benzodiazepines
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 H2 receptors mediate & .

21. 5.Endocrine effects (Only Cimetidine)
Galactorrhea (Hyperprolactinemia )
Antiandrogenic actions (gynecomasteia –
impotence) due to inhibition of
dihydrotestosterone binding to androgen
receptors.
6.Rarely: thrombocytopenia

Precautions:
Dose reduction of H2 RAs in severe renal or
hepatic failure and elderly.

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22. C. Proton Pump Inhibitors


Omeprazole
Lansoprazole
Pantoprazole
Rabeprazole
Dexlansoprazole

Mechanism of action:

Irreversible inhibition of
that is responsible for in gastric
acid secretion from the parietal cell.


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23. 23
PPIs……

24. Pharmacodynamics:

Produce marked inhibition of and
-acid secretion.



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25. They are –taken orally.
Are given as capsules

(Unstable in acidic medium).

Rapidly absorbed from the intestine


Activated in the acidic medium of the secretory
parietal cell canaliculus.


Inactivated at neutral pH ( # combined with H2
blockers or antacids).
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PPIs……

26. Long duration of action ( 12 -24 hrs).
Once daily dose is sufficient

Given 1 hr before meal.
Bioavailability is reduced by food (50%).
Are metabolized in the liver by CyP-450.


Dose reduction is required in severe liver failure.
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PPIs……

27. 1. Eradication of H. pylori (combined with
antimicrobial drugs).


2. Hypersecretory conditions as Zollinger Ellison
syndrome and gastrinoma ( ).

3. Resistant severe peptic ulcer ( 4-8 weeks).
used for acute therapy only if H2RAs fail or
cannot be used

4. Reflux esophagitis.
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28. GIT disturbances (N & V).
Achlorhydria (absence of Hcl secretions).
Hypergastrinaemia.
Gastric mucosal hyperplasia


Vitamin B12 deficiency
increased risk of fractures


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29. : is a spiral-shaped bacterium that accounts:
 >90% of duodenal ulcers and up to
 80% of gastric ulcers.

Causes chronic mucosal inflammation.
 Produces that causes tissue damage and ulcer.

Eradication is important to prevent recurrence of ulcer.


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30. 30

31. Helicobacter pylori is the major etiological
factor in peptic ulcer disease (PUD).

All individuals with PUD must be evaluated for H.
pylori.

 Patients with H. pylori should be treated.

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32. How is an H. pylori-induced ulcer treated?

A combination of antibiotics and acid-reducing
medicines is the most effective treatment.
1. PPIs or H2 receptor blockers
2.Antibiotics
 Clarithromycin
 Tetracycline or amoxicillin
 Metronidazole if patient allergic to
penicillin.
3. Bismuth subsalicylate (Pepto-Bismol).

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33. Triple therapy:

Is first-line therapy
consisting of:
1.Proton pump
inhibitors (PPIs)
2.Clarithromycin
3.Amoxicillin.


Quadruple therapy:
(Bismuth-based regimen)

Consisting of:
1.Proton pump inhibitors
(PPIs)
2.Bismuth subcitrate
3.Metronidazole
4.Tetracycline
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34. 34
DURATION DOSE REGIMEN



10 to 14 days
20 mg bid
500 mg bid
500 mg bid
Omeprazole
Metronidazole
Clarithromycin
20 mg bid
1g bid
500 mg bid
Omeprazole
Amoxicillin
Clarithromycin

14 days
20 mg bid
525 mg qid
250 mg qid
500 mg qid
Omeprazole
Bismuth subsalicylate
Metronidazole
Tetracycline

35. Drugs used to relief gastric pain associated with hyper
secretion of HCl

Mechanism of Action:
 Neutralization of HCl
 Inhibition of pepsin (inactive at PH 5)

1. Relief pain of peptic ulcer
2. Dyspepsia
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36. All antacids ↓absorption of other drugs:
tetracycline, fluoroquinolones, iron

Should not be given within 2hrs of doses of the
previous drugs

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37. 1.Rebound hyperacidity.
2.Systemic alkalosis
3.Stomach distension due to CO2 liberation  pain
sensation
4. Sodium load  salt and water retention ( in cardiac
patients).
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HTN, CHF, and renal failure
because of its high .

38. CaCO3 + HCl  CaCl2 + H2O + CO2

Disadvantages:
1. Liberation of CO2 stomach distension ( )
2. 10% is absorbed
3. Rebound hyperacidity (stimulate gastrin release)
4. Systemic alkalosis
5. Milk alkali syndrome (hypercalcemia renal
failure)
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 Should not be used for long-term treatment!!!.

39. :
Al (OH)3 + HCl  AlCl3 + H2O

Advantages:
1. Longer duration of action.
2. Gradual neutralization of
HCl no rebound hyperacidity
3.Adsorbs pepsin.
4.Minimal change in acid base
balance.
5.No stomach distention
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(but
fast onset of action)

40. (
)
Combine and to achieve a
balance b/n the agents’ adverse effects on the bowel

Drug interactions:
Antacids alter the bioavailability of many drugs:
1.The se in gastric pH produced by antacids
ses absorption of acidic drugs and
se absorption of basic drugs.
2.The metal ion in some preparations can chelate
other drugs (e.g., digoxin and TTC) and prevent
their absorption.
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42. Salt of sucrose complexed to sulfated aluminium
hydroxide
Concurrent antacids, H
2 antagonist avoided
( as it needs acid for activation )

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1. Sucralfate:

43. Orally, poor systemic absorption.
Duration (6 h), Excreted in feces.
Avoid co-administration of antacid or H2 blocker.
Better taken on empty stomach (1 hr. before meals)

 Benign gastric and duodenal ulcer.
 Chronic gastritis.

Constipation and dry mouth.
Interferes with absorption of some drugs: TTC, TCAs,
theophyline,.
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44. 44

45. Prevention of peptic ulcer.
Abdominal cramps (sever colic pain)
2. Diarrhea
3. Uterine contraction (
4. Vaginal bleeding
5.

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46. 1.Coats ulcer
2. stimulates mucus & bicarbonate secretion
3. Direct bactericidal activity against H. pylori
4. Prevents proton diffusion into the ulcer


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47. 1.Black stool & tongue
2.Teeth discoloration.
3.Bismuth is radiopaque and may interfere with
radiological examinations.
Not used for long periods – bismuth toxicity
1.Triple therapy for eradication of H. pylori.
2.Traveller’s diarrhea
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48. Summary
oTest for H. pylori prior to beginning therapy.
oComplete H.pylori eradication is required to prevent
relapse

oAcid-reducing medications are prescribed in case of
PUD without H. pylori infections.

Treatment should be initiated with a PPI–based three-
drug regimen.

The selection of H. pylori eradication regimen should be
based on efficacy, safety, antibiotic resistance and cost.

 If a second course of H. pylori therapy is required, the
regimen should contain different antibiotics.

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49. PUD with H. pylori infections can be treated with:






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Summary….

50. 50 50

51. 51

52. •Classify the main different classes of antiemetic
drugs according to their mechanism of action.
•Know the characteristic pharmacokinetics &
dynamics of different classes of antiemetic drugs.
•Identify the selective drugs that can be used
according to the cause of vomiting.
•Learn the adjuvant antiemetics.
•Describe the major side effects for the different
classes of antiemetics.
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55. •Nausea and vomiting may be manifestations of
many conditions.
•A useful mnemonic for remembering causes of
nausea and vomiting is .
estibular
bstruction (opiates)
ind (dysmotility)
nfection (irritation of gut)
oxins (taste and other senses)
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56. Respond to inputs from:
Vestibular system
Periphery (Pharynx, GIT)
Higher brain stem and cortical structures
CTZ stimulation
Muscarinic, histaminergic, serotoninergic receptors
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57. CTZ includes nucleus ambiguous, nucleus
of solitary tract and nucleus of the vague
CTZ is physiologically outside BBB (chemical
stimuli in blood, CSF)
D2, 5HT3 receptors.
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59. Drugs morphine, apomorphine, digitalis, L-dopa,
bromocryptine, estrogen, emetine
Chemicals
Radiation
Uremia

GIT irritation, myocardial infarction, renal or biliar stones
emotional factors,
nauseating smells or sights
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60. (transdermal patches)
Motion sickness
Not in chemotherapy-induced vomiting

Motion sickness
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61. Effective against vomiting due to gastroenteritis,
medications, surgery and toxins, uremia.
dystonic reactions, sedation, and postural
hypotension
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62. Long duration of action
half life 4-9 h
taken once daily
Very effective in vomiting due to:
Chemotherapy
postoperative vomiting and
after radiotherapy

63. Nabilone, dronabinol
Sedation, hallucination and dysphoria
Used as appetite stimulant
May cause euphoria

Dexamethasoneand methylprednisolone
Highly effective in acute emesis
Mechanism not known
Hyperglycemia , insomnia

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64.  Hyoscine: For short Journey
 Diphenhydramine: For Long Journey
 Avoid all drugs in the first trimester
 Pyridoxine (B6)
 Promethazine ( late pregnancy)
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65.  Ondansetron-Dopamine antagonists
 Dexamethazone
 Nabilone
Dopamine antagonists
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66. 66
Drugs used in
the treatment of
constipation

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86. Common stimulant purgatives:
Drugs Type Site of Action Onset of Action
Cascara
Anthraquinone

colon 8-12 hours
Senna Anthraquinone colon 8- 12 hours
Aloe vera Anthraquinone colon 8-12 hours
Bisacodyl Diphenylmethane colon 6-8 hours
Castor Oil ricinoleic acid small intestine 2-6 hours
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92. Purgatives Site of action Onset time
Bulk purgatives Small & large
intestine
12-72 h
Saline purgatives Small & large
intestine
1-3 h
Lactulose colon
12-72 h
Mineral oil colon
6 – 8 hours
Docusate Small and large
intestine
12 – 72 hours

Stimulants

Small intestine
Colon
colon
Castor oil
Bisacodyl
anthraquinones
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93. acute & chronic constipation

Oral, 48–72 hours Bulking agents
prevention of straining after
rectal surgery and in acute
perianal disease
oral, 24–72 hours;
rectal, 5 --20 minutes

stool softeners
- chronic constipation
-hepatic encephalopathy
- opioid constipation

oral, 24–72 hours Osmotic laxatives
(lactulose)

short term treatment of
moderate-to-severe
constipation; chronic
constipation; bowel preparation
oral, 0.5–3 hours;
rectal, 30 minutes
Saline laxatives
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