6. ANTACIDS
• The principal target of this class of drugs is the neutralization of the acid
secreted by parietal cells, maintaining the pH of the stomach ≥ 4
Evangelista,
2007 3/7/2023 6
7. HISTAMINE (H2) RECEPTORS ANTAGONIST
• Acid secretion can be stimulated by three principal
“secretagogues”: histamine, acetylcholine and gastrin
• Vagal stimulation and gastrin induce histamine releases
activated parietal cell H2 receptors increase proton pump
activity H+ into lumen
• Burimamide dan metiamide 60’s
• Cimetidine (400 mg bid) substitution imidazole ring
ranitidine (good compliance and 5-10x more potent, 150 mg bid)
• Insert thiazole in imidazole ring famotidine and nizatidine
3/7/2023 7
8. PROTON PUMP INHIBITORS (PPIS)
• Activation parietal cells triggers H+/K+ ATPase pump increases hydrogen ion
into the lumen of stomach 20-40 mEq/hour
• 1st PPIs omeprazole
• Modification of omeprazole lansoprazole, pantoprazole, rabeprazole
• PPIs doesn’t affect gastric motility
• PPIs better than H2 receptor antagonist in GERD and Zollinger-Ellison syndrome
(gastrinoma tumor that secretes gastrin)
3/7/2023 8
10. CONCERNS USE OF H2 RECEPTOR
ANTAGONIST AND PPIS
• Inhibition of cytochrome 450 prolongation t ½ of drugs with low
therapeutic index (such as warfarin, phenytoin, tacrolimus, ciclosporin, theophylline,
and others).
• PPIs Induction enzyme metabolism for antiplatelet (clopidogrel)
• Long-term proton PPIs treatment lead hypomagnesemia-induced seizure
• H2 receptor antagonist induce mental confusion in elderly (toxic dose/impairment
of renal)
3/7/2023 10
13. POTASSIUM-COMPETITIVE ACID
BLOCKER
• Vonoprazan (10-20 mg/day)
Inhibits H+, K+-ATPase in gastric
parietal cells at the final stage of the
acid secretory pathways
3/7/2023 13
Akazawa et al., 2016
14. CYTOPROTECTIVE AGENTS
• Misoprostol
• Sucralfate
Stimulate mucus production and enhance blood flow throughout the lining of the
gastrointestinal tract
3/7/2023 14
18. FIVE KEY RECEPTORS IMPLICATED IN
VOMITING
• Muscarinic (M1)
• Dopaminergic (D2)
• Histaminergic (H1)
• 5-hydroxytriptamine or 5-HT3 (serotonin)
• Neurokinin NK1 (substance P)
3/7/2023 18
19. FIVE KEY PRECIPITANTS IN VOMITING
• Toxic material in the lumen of the gastrointestinal tract
• Visceral pathology
• Vestibular disturbance
• Central nervous system stimulation
• Toxins in the blood or cerebrospinal fluid (CSF).
3/7/2023 19
21. Prokinetic agents mechanism of action is complex and involves vagal and central 5-
HT3 and D2 receptor antagonism with prokinetic properties via gut dopamine receptor
antagonism and 5-HT3-receptor agonist activity (Singh et al, 2016)
3/7/2023 21
22. Novel and non traditional therapies for nauesa (Singh et al, 2016)
3/7/2023 22
27. ACUTE DIARRHEA
• Bismuth subsalicylate (BSS) have dose responses activity against bacteria and
viruses (dose 2,1 g/day)
BSS has intestinal mucosa cytoprotective
• Prebiotics and probiotics not recommended to treatment and prevention, even two
meta analysis suggest marginal benefits of probiotics (Lactobacillus)
3/7/2023 27
29. DRUGS USED IN CHRONIC DIARRHEA
(LEE, 2015)
• Opiates loperamide (2 mg bid, max 16 mg/day)
Agonist for the μ receptors in the myenteric plexus of the intestinal wall
inhibits release of acetylcholine decreased peristaltic activity,
reduces fluid and electrolyte loss, decreases fecal volume, and increases stool consistency
• Probiotics efficacy depends on strain, dose, and viability of microorganism used
The advantages of probiotics mechanisms of action against pathogens and interaction
with the host’s natural defense systems
3/7/2023 29
30. DRUGS USED IN CHRONIC DIARRHEA
(LEE, 2015)
• Absorbent Diosmectite, Kaolin Pectite
Improve stool consistency by absorption of toxins, bacteria, and viruses,
reinforcement of the intestinal mucus barrier with the reduction
of penetration of luminal antigens through the mucus layer,
and reduction of inflammation
• Antispasmodics reduce smooth muscle contractility of the gut
Directly affecting Mebeverine
Anticholinergics/antimuscarinic Scopolamine, hyoscine,
3/7/2023 30
32. CONSTIPATION
• Constipation can be divided into:
- slow-transit constipation
- dysfunctional constipation that is treated with biofeedback and
medications
- constipation-predominant irritable bowel syndrome (IBS)
3/7/2023 32
33. NON PHARMACOLOGY THERAPY -
LIFESTYLE MODIFICATION
• Bowel movement habits
• Dietary management high
fiber intake, water intake, fruits
3/7/2023 33
34. PHARMACOLOGY THERAPY (PORTALATIN
AND WINSTEAD, 2012)
• Laxatives
- bulk laxatives fiber intake
- psyllium high water binding capacity, fermented in colon
- metylcellulose synthetic fiber polymer
absorbs water into lumen increases fecal mass, promoting motility
- calcium polycarbophil hydrophilic resin
3/7/2023 34
39. ACUTE PANCREATITIS CAUSE (SUNDAR
ET AL., 2019)
• Inflammatory disorder of pancreas which is characterized by severe
epigastric pain and increased/irregular secretion of pancreatic
enzymes, associated with involvement of multiple systems
• Key drivers of the inflammatory response in acute pancreatitis
circulating cytokines and chemokines.
• Pro-inflammatory cytokines such as tumor necrosis factor alpha (TNF-
α) and interleukins
3/7/2023 39
44. Pharmacological agents in clinical studies acute pancreatitis (Kambhampati et al., 2014)
3/7/2023 44
45. CHRONIC PANCREATITIS
(BANKS ET AL., 2010)
• Chronic pancreatitis results from irreversible scarring of the pancreas
resulting from prolonged inflammation.
• Six major etiologies for chronic pancreatitis have been identified:
- toxic/metabolic - idiopathic
- genetic - autoimmune
- recurrent and severe acute pancreatitis - obstruction
• common symptom pain localized to the upper-to-middle abdomen,
food malabsorption, and eventual development of diabetes.
3/7/2023 45
46. PHARMACOTHERAPY
• Drug to treat abdominal pain
• Pancreatic enzymes to treat steatorrhea
- pancreatin dan pancrelipase
• Insulin to correct diabetes mellitus
3/7/2023 46
48. INFLAMMATORY BOWEL DISEASE
• Chronic inflammatory disorder in GI tract
• Include Crohn’s disease and ulcerative colitis
• Etiology is unknown
• Interleukin,TNF-α, interferon play roles in pathogenesis of IBDs
3/7/2023 48
49. CONVENTIONAL THERAPY
(HEMPERLY ET AL., 2018)
• Glucocorticoids
Increase the transcription of genes coding for anti-inflammatory proteins or
repress inflammatory gene expression (prednisone, budenoside)
• Aminosalycilates
Sulfasalazine resides with the 5-ASA moiety that interacts with pathways of
inflammation and apoptosis
3/7/2023 49
51. MAIN NON ANTI-TNF PHARMACOLOGICAL DRUGS THAT SHOW
BENEFICIAL EFFECTS IN IBD THERAPY IN RANDOMIZED
CLINICAL TRIALS (PAGNINI ET AL., 2019)
3/7/2023 51
53. HEPATIC DISEASES
• Cirrhosis, acute liver function, acute on chronic liver function
- Usually need adjustment drug dosage
- liver diseases significant alter in PK PD medication
(Peppard et al., 2018)
- pain management
acetaminophen lower dose, tramadol, pregabalin, nortryptilin
(Chandok and Watt, 2010)
3/7/2023 53
54. HEPATITIS
• Hepatitis A and E caused food or water infection
Need rest, fluid rehydration, usually resolves in few weeks without
antiviral
• Hepatitis C, B, and D caused blood infection
Treated with antiviral medication
3/7/2023 54
57. CHRONIC HEPATITIS B
• Interferon α β γ
naturally occurring protein produced in response to viral infection
• Combination of nucleoside analogues (Razonable, 2011)
Inhibition DNA polymerase
Adefovir, entecavir, lamivudine, telbivudine, emtricitabine, tenofovir
3/7/2023 57
58. HEPATITIS C
• Ribavirin
Ribavirin competitive inhibitor of inosine monophosphate
dehydrogenase reduced viral nucleic acid inhibit protein
produced
• Interferon α in combination with ribavirin
3/7/2023 58
59. HEPATITIS D
• Interferons use is unsatisfactory (Yurdaydin et al., 2019)
• New compound established in clinical trial
- hepatocyte entry inhibitor myrcludex B
- farnesyl transferase inhibitor lonafarnib
- nucleic acid polymers
- pegIFN lamda
3/7/2023 59
60. REFERENCES
• AkazawaY, Fukuda D, Fukuda Y. 2016.Vonoprazan-based therapy for Helicobacter pylori eradication:
experience and clinical evidence. Therapeutic Advances in Gastroenterology 9(6):845-852.
• Aggarwal A, and Bhatt M. 2014. Commonly used gastrointestinal drugs. Handbook of Clinical Neurology chapter
43: 633-643
• Banks PA, Conwell DL,Toskes PP. 2010. The management of acute and chronic pancreatitis. Postgraduate institute
for medicine: Clinical Rountable Monograph
• Chandok A and Watt KDS. 2010. Pain management in the cirrhotic patient: the clinical challenge. Mayo Clin Proc
85(5): 451-458
• Denholm L and Gallagher G. 2018. Physiology and pharmacology of nausea and vomiting. Anaest Intens Care
2018: 1-4
• Evangelista S. 2007. Overview on gastrointestinal pharmacology Vol. I. Encyclopedia of Life Support Systems
• Hemperly A, Sandborn WJ, Casteele NV. 2018. Clinical pharmacology in adult and pediatric inflammatory bowel
disease. Inflamm Bowel Dis 00: 1-17 3/7/2023 60
61. REFERENCES
• Kambhampati S, Park W, Habtezion A. 2014. Pharmacologic therapy of acute pancreatitis.World J Gastroenterol
20(45): 16868-16880
• Kumar U and Sneha S. 2020. Role of Somatostatin in the Regulation of Central and Peripheral Factors of Satiety
and Obesity. International Journal of Molecular Sciences 21(7): 2568.
• Kuna L, Jakab J, Smolic R, Raguz-Lucic N,Vcev A, and Smolic M. 2019. Peptic ulcer disease: A brief review of
conventional therapy and herbal treatment options. J Clin Med 8(179): 1-19
• Lee KJ. 2015. Pharmacologic agents for chronic diarrhea. Intest Res 13(4): 306-312
• Pagnini C, Pizarro TT, and Cominelli F. 2019. Novel pharmacological therapy in inflammatory bowel diseases:
beyond anti-tumor necrosis factor. Front Pharmacol 10: 671-681
• Peppard WJ, Killian AJ, Biesboer AN. 2018. Pharmacological considerations in acute and chronic liver disease.
Hepatic Critical Care: 211-232
• Portalatin M, and Winstead N. 2012. Medical management of constipation. Clin Colon Rectal Surg 25(1): 12-20
3/7/2023 61
62. REFERENCES
• Razonable RR. 2011. Antiviral drugs for viruses other than human immunodeficiency virus. Mayo Clin Proc
86(11): 1009-1026
• Riddle MS, DuPont HL, Connor BA. 2016. ACG clinical guideline: Diagnosis, treatment, and prevention of
acute diarrheal infections in adults. Am J Gastroenterol 30; 1-21
• Singh P,Yoon SS, and Kuo B. 2016. Nausea: a review of pathophysiology and therapeutics. Ther Adv
Gastroenterol 9(1): 98-112
• Sundar V, Kumar KAS, Manickam V, and Ramasamy T. 2020. Current trends in pharmacological approaches
for treatment and management of acute pancreatitis – a review. J Pharm Pharmacol 72: 761-775
• Yurdaydin C, Abbas Z, Buti M, Cornberg M, Esteban R, Etzion O. 2019.Treating chronic hepatitis delta: the
need for surrogate markers of treatment efficacy. Journal of Hepatology 70: 1008-1015
• Yibirin M, De Oliveira D,Valera R, Plitt AE, Lutgen S. 2021. Adverse Effects Associated with Proton Pump
Inhibitor Use. Cureus 13(1): e12759. doi:10.7759/cureus.12759
3/7/2023 62
