Git drugs Pharmacology

1. Ita Armyanti
FARMAKOLOGI dan BIOETIKA PSPD FK
UNTAN
8/30/2022
GIT-drugs/2013
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Pharmacology : GIT- drugs

2. KAPITA SELEKTA
GASTROINTESTINAL
 Drugs used in acid peptic diseases
 Drugs stimulating gastrointestinal motility
 Laxatives
 Antidiarrheal agents
 Drugs used in the treatment of Irritable Bowel Syndrome
 Drugs used to treat inflammatory bowel disease
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6. Gastric acidity and Peptic Ulcer
Disease
Factors that
Increase Acidity
Factors that
Protect Against
Acidity
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7. Peptic Ulcer Disease
Imbalance between defenses and aggressive factors
Defensive factors:
1.Mucus: continually secreted, protective effect
2.Bicarbonate: secreted from endothelial cells
3.Blood flow: good blood flow maintains mucosal
integrity
4.Prostaglandins: stimulate secretion of bicarbonate and
mucus, promote blood flow, suppress secretion of gastr
acid
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8. Aggressive factors:
1.Helicobacter pylori: gram negative bacteria, live in
stomach and duodenum, may breakdown mucus layer
=> inflammatory response to presence of the bacteria
also produces urease  forms CO2 and ammonia
which are toxic to mucosa
2.Gastric Acid: needs to be present for ulcer to form
=> activates pepsin and injures mucosa
3.Decreased blood flow: causes decrease in mucus
production and bicarbonate synthesis, promote gastric
acid secretion
4.NSAIDS: inhibit the production of prostaglandins
5.Smoking: nicotine stimulates gastric acid
production
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9. Classes of Agents
1. Proton Pump Inhibitors
2. Histamine H2-Receptor
Antagonists
3. Prostaglandin Analogs
4. Cytoprotectants
5. Antacids
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11. 1. Proton Pump Inhibitors
(PPI’s)
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12. PPIs
1. Most potent suppressors of acid secretion
2. 24-48 hr effects on acid suppression
Irreversible inhibitor of proton pump; blocks 98%
of acid secretion in all forms of ulcer and
hypersecretory Zollinger-Ellison syndrome.
The drug is given in gelatin coated capsule to resist
breakdown in stomach acid. It reaches the intestine,
well absorbed, enters blood stream,reaches the parietal
cell.
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13. PPIs
Irreversibly inhibit H+/K+ATPase function to:
Block gastric acid secretion
Decrease pepsin concentration
Increase gastric pH
Secretion of acid only resumes when new
proton pumps are deployed
Steady-state inhibition (affecting 70% of
pumps) may take 2-5 days
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14. PPI Pharmacology
 Activated only when pH decreases below 4
 Occurs only in parietal cell
 Achieved only when parietal cell activation occurs
(after meals)
 Most effective after a prolonged fast when large
amounts of active proton pumps are present (i.e.
breakfast)
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15. Available PPIs
 Esomeprazole (Nexium)
 Lansoprazole (Laproton. Lapraz)
 Omeprazole (Protop, Pumpitor, OGB)
 Pantoprazole (Pantozol) (iv)
 Rabeprazole (Pariet)
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16. PPI Metabolism
 Rapidly absorbed and Highly protein bound
 Extensively metabolized in the liver by the
P450 system (CYP2C19 and CYP3A4)
 Sulfated metabolites are excreted in the urine
or feces
 Hepatic disease reduces the clearance of
lansoprazole  reduce dose
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17. Common PPI Side Effects
 Headache (2.9-6.9%) vs. Placebo
(2.5-6.3%)
 Diarrhea (3%) vs. Placebo (3.1%)
 Abdominal pain (2.4-5.2%) vs. Placebo
(3.1-3.3%)
 Constipation (1.1-1.5%) vs. Placebo (0-0.8%)
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18. Drug-Drug Interactions
Ketoconazole and Digoxin absorption is
decreased due to reduced acidity.
Omeprazole may inhibit diazepam and
phenytoin metabolism
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19. 2. Histamine H2-Receptor
Antagonists (H2RAs)
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20. H2RAs
 Reversibly compete with histamine for
binding to H2 receptors on the basolateral
membrane of parietal cells
 Less potent than PPIs but still suppress acid
by 70% over 24 hrs
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21. Available H2RAs
H2 receptor blockers:
Cimetidine (OGB, iv)
First H2-blocker available Inhibits
P450 Drug interaction
Ranitidine (OGB, iv)
Does not inhibit P450  fewer side
effects
Famotidine ((Famocid, Gaster:iv®)
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22. Pharmacokinetics
 Rapidly absorbed after oral administration
 Serum concentrations peak in 1-3 hr
 Therapeutic levels maintained up to 12 hrs
 Small percentage is protein bound
 10% to 35 % metabolized by the liver
 Drugs and metabolites primarily excreted by kidney
(**reduce doses in renal disease)
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23. 1. inhibit 90% acid secretion in basal state as
well as food-induced and nocturnal acid
production.
2. they are helpful in healing gastric and
duodenal ulcers and prevent their recurrence.
Have benefits in preventing increased gastric
acid secretion in Zollinger-Ellison syndrome.
3. Cimetidine Has several side effects, not a
choice now - Under Prescription.
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24. Common H2RA Side Effects
 All less than 3%
 Diarrhea
 Headache
 Drowsiness
 Fatigue
 Muscular pain
 Constipation
 Much less common
 Confusion, delirium in the elderly
 Associated with thrombocytopenia
 Cimetidine anti-androgen effects
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25. Drug-Drug Interactions
1. Inhibits CyP450: Inhibits the metabolism
of various drugs that are concomitantly
taken: phenytoin, warfarin, theophylinne,
BZD.
2. These adverse effects are relatively least
with ranitidine and famotidine
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26. 3. Prostaglandin Analogs:
Misoprostol
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27. Protective Effects of Prostaglandins
 PGE2 and PGI2 synthesized by gastric mucosa
 Acid-reducing effects
 Bind to EP3 receptors on parietal cellsDecrease
acid production
 Cytoprotective effects
 Stimulation of mucin and bicarbonate
 Increase mucosal blood flow
 Contrast with NSAIDS which diminish
prostaglandin formation by inhibition of
cycloxygenase and lead to
ulcer formation 8/30/2022
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28. Misoprostol: Cytotec
 Synthetic analog of PGE1
 Enhanced potency
 Increased oral bioavailability
 Inhibit basal acid secretion (85-95%)
 Inhibit stimulated acid secretion (75-
85%)
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29. Pharmacokinetics
 Rapidly absorbed
 Rapidly de-esterfied to misoprostol acid--
the active metabolite
 Therapeutic effect peaks at 60-90
minutes
 Lasts 3 hours (qid dose required)
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30. Side Effects
 Diarrhea ± abdominal cramps as high as
30%
 Begins within 2 weeks and often resolves
spontaneously in 1 week
 Can exacerbate inflammatory bowel disease
 Contraindicated during pregnancy
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31. 4. Sucralfate: Carafate
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32. Sucralfate
 Aluminium Sulfated polysaccharide, Acid
activated
 Administered on an empty stomach 1 hr
before meals
 Stimulates local prostaglandin synthesis,
adsorbs pepsin
 AH2 & antacids  reduce bioavailability
 Not absorbed  essentially free of side effects
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33. Common Side Effects
 Constipation (2%)
 Aluminium  hyphosphatemia: Avoid in
renal failure
 May impair absorption of other drugs :
tetrasiklin, warfarin, digoksin, fenitoin  2
hr interval
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34. 5. Antacids
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36. Antacids
 Sodium bicarbonate (NaHCO3)
 CaCO3
 Mg2+ hydroxides
 Al3+ hydroxide
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37. Antacids
 Given orally 1-3 hrs after meals and bedtime
 Mg+2 based preparations increase motility 
Diarrhea
 Al+3 based preparations relax smooth muscle
 Constipation
 Ca+2 based preparations release CO2 
Belching, nausea, distension, and flatulence.
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38. Common Side Effects
 Aluminum toxicity with renal disease 
Osteoporosis, enchephalopathy,
osteomalacia
 Hypercalcemia
 Phosphate retention
 Calcium precipitation in the kidney
 Impair absorption of some drugsTake 2
hrs before or after other drugs : INH,
tetrasiklin 8/30/2022
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39. Antibiotic ulcer therapy:
Combinations must be used:
1.Bismuth (Scantoma, Stobiol®) – disrupts cell wall of H.
pylori
2.Clarithromycin – inhibits protein synthesis
3.Amoxicillin – disrupts cell wall
4.Tetracyclin – inhibits protein synthesis
5.Metronidazole – used often due to bacterial resistance to
amoxicillin and tetracyclin, or due to intolerance by the
patient
Standard treatment regimen for peptic ulcer:
Omeprazole + amoxicillin + metronidazole
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40. Laxatives
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41. Constipation
 Abnormally infrequent and difficult passage of
feces through the lower GI tract
 Symptom, not a disease
 Disorder of movement through the colon
and/or rectum
 Can be caused by a variety of diseases
(hemorrhoid, multipara) , drugs (opium,
aluminium antacids) or psikis
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42. Laxatives :
 Bulk forming
 Emollient
 Hyperosmotic
 Saline
 Stimulant
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43. Laxatives:
Mechanism of Action
Bulk forming
 High fiber
 Absorbs water to increase bulk
 Distends bowel to initiate reflex bowel
activity
 Examples:
 psyllium (Mulax)
 Methylcellulose, polycarbophil
 Agar-agar (>>hemiselulosa, tdk diabsorbsi &
dicerna) 8/30/2022
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44. Laxatives:
Mechanism of Action
Emollient
 Stool softeners and lubricants
 Promote more water and fat in the stools
 Lubricate the fecal material and intestinal
walls
 Examples:
 Stool softeners: docusate sodium
 Lubricants: mineral oil
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45. Laxatives:
Mechanism of Action
Hyperosmotic
 Increase fecal water content
 Result: bowel distention, increased
peristalsis, and evacuation
 Examples:
 polyethylene glycol
 sorbitol
 glycerin
 lactulose
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46. Laxatives:
Mechanism of Action
Saline
 Increase osmotic pressure within the intestinal tract,
causing more water to enter the intestines
 Result: bowel distention, increased peristalsis, and
evacuation
 Saline laxative examples:
 magnesium sulfate (Epsom salts, garam Inggris)
 magnesium hydroxide
 magnesium citrate
 sodium phosphate
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47. Laxatives:
Mechanism of Action
Stimulant
 Increases peristalsis via intestinal nerve
stimulation
 Examples:
 castor oil
 senna
 cascara
 bisacodyl
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48. Laxatives: Side Effects
 Bulk forming :Impaction, Fluid overload
 Emollient : Skin rashes, Decreased absorption of
vitamins (ADEK  parafin )
 Hyperosmotic : Abdominal bloating, Rectal
irritation
 Saline :Magnesium toxicity (with renal
insufficiency), Cramping, Diarrhea, Increased thirst
 Stimulant : Nutrient malabsorption, Skin
rashes,Gastric irritation, Rectal irritation
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49. Antidiarrheals
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50. Causes of Diarrhea
Acute Diarrhea
Bacterial
Viral
Drug induced
Nutritional
Protozoal
Chronic Diarrhea
Tumors
Diabetes
Addison’s disease
Hyperthyroidism
Irritable bowel
syndrome
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51. Antidiarrheals
 Drugs that decrease peristalsis, thereby
allowing fluid absorption from the
intestinal contents
 Examples:
 Anticholinergics
 Protectants/adsorbents
 Opiate-related agents
 Probiotics
 Metronidazole
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52.  Anticholinergics are used to treat tenemus
and vomiting
 Examples:
 Atropine
 Aminopentamide
 Isopropamide
 Propantheline
 Methscopolamine
 Side effects include dry mucous
membranes, urine retention, tachycardia,
and constipation
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53.  Protectants/adsorbents coat inflamed intestinal
mucosa with a protective layer (protectants) or
bind bacteria and/or digestive enzymes and/or
toxins to protect intestinal mucosa from
damaging effects (adsorbents)
 Examples:
 Bismuth subsalicylate (bismuth + aspirin-like
product)
 Kaolin/pectin
 Activated charcoal
 Side effects include constipation
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54.  Opiate-related agents control diarrhea by
decreasing both intestinal secretions and the
flow of feces and increasing segmental
contractions
 Examples:
 Diphenoxylate
 Loperamide
 Paregoric
 Side effects include CNS depression, ileus,
urine retention, bloat, and constipation
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55.  Probiotics seed the GI tract with beneficial
bacteria; use is based on the theory that some
forms of diarrhea are caused by disruption of
the normal bacterial flora of the GI tract
 Must be refrigerated to maintain the viability
of the bacteria
 Examples:
 Plain yogurt with active cultures
 Variety of trade-name products
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56.  A theory regarding the development of
diarrhea is that anaerobic bacteria may
increase due to disruption of normal GI
flora
 One way to treat this is to use an antibiotic
effective against anaerobic bacteria
 Metronidazole is an example of an
antibiotic used to treat diarrhea
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57. Cost-effectiveness studies of Zinc
supplementation…
 zinc supplementation significantly improved
the cost-effectiveness of standard
management of diarrhoea for dysenteric as
well as non-dysenteric illness.
 Sufficient evidence to recommend the
inclusion of zinc into standard case
management of both types of acute
diarrhoea
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58. The new WHO-UNICEF recommended policies
for health professionals on the treatment of
diarrhoea
1. Counsel mother to begin administering suitable home
fluids immediately upon onset of diarrhoea in a child
2. Treat dehydration with new low osmolarity ORS solution
(or with intravenous electrolyte solution in cases of severe
dehydration)
3. Emphasize continued feeding or increased breastfeeding
during, and increases feeding after, the diarrhoeal episode
4. Use antibiotics only when appropriate, i.e., in the presence
of bloody diarrhoea or shigellosis, and abstain from
administering anti-diarrhoeal drugs
5. Provide children with 20 mg per day of zinc
supplementation for 10-14 days (10 mg per day for
infants under six months old)
6. Advise mothers of the need to increase fluids and continue
feeding during future diarrheoal episodes
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59. Zinc and Low-osmolarity ORS:
effective, safe and available
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60. APA ITU
TABURIA ?
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61. pelengkap gizi makanan balita sehari-hari
yang mengandung 12 macam vitamin dan 4
macam mineral yang dibutuhkan anak untuk
tumbuh kembang secara optimal
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62. Taburia berbentuk serbuk
Taburia mengandung:
1. Vitamin A
2. Vitamin B1, B2,B6,
B12
3. Vitamin C
4. Vitamin D3
5. Vitamin E
6. Asam Folat
7. Niasin
8. Selenium
9. Yodium
10. Besi
11. Seng 8/30/2022
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63. KEPADA SIAPA TABURIA
DIBERIKAN?
Anak usia 6 bulan sampai 2 tahun
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64. Petunjuk penggunaan taburia :
1. Sebelum memberikan taburia, sebaiknya cuci
tangan terlebih dahulu dengan sabun
2. Tambahkan satu bungkus Taburia pada makanan
padat anak siap santap (nasi, lauk pauk, bubur,
ubi,jagung,kentang dll)
3. Pilih kapan / waktu balita makan paling banyak.
Dianjurkan pada makan pagi
4. Taburia sebaiknya tidak dicampur dengan
makanan yang terlalu berair, seperti minuman
susu, teh, atau sayuran berkuah seperti sup, sayur
bening dll karena mineral tidak larut sehingga
dikhawatirkan tidak habis dikonsumsi.
5. Tidak boleh dicampur pada makanan yang panas
(lapisan lemak akan pecah dan beberapa zat gizi
akan rusak) 8/30/2022
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65. Yang perlu diketahui bila mengkonsumsi Taburia
Selama mengonsumsi Taburia, ada kemungkinan tinja
anak berwarna hitam. Hal ini bukan masalah karena
warna hitam itu disebabkan oleh zat besi yang
dikandung Taburia.
Adakalanya terjadi susah buang air besar. Hal ini dapat
diatasi dengan anak meminum air putih matang yang
lebih banyak.
Anak bisa mengalami diare/mencret-mencret, bila
mengkonsumsi makanan yg tidak disiapkan dengan
sanitasi yg baik
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