DENT 3005: Introduction to Pharmacology¹

Gastrointestinal drugs

Dr Thuy Linh Truong thuy.truong@uwa.edu.au

Acknowledgement of country²

The University of Western Australia acknowledges that its campus is situated on Noongar land, and that Noongar people remain the spiritual and cultural custodians of their land, and continue to practise their values, languages, beliefs and knowledge.

Artist: Dr Richard Barry Walley OAM

Learning Outcomes³

Learning objectives

Understand the classes and mechanisms of major classes of GI drugs
Recognise common GI conditions managed with these drugs
Recognise oral and dental side effects of GI drugs
Understand the oral impact of GI conditions
Understand drugs interactions with dental medications
Applied knowledge to clinical scenarios

Gastrointestinal drugs⁴

Ulcers
- Dyspepsia: chronic/recurrent pain, burning or discomfort centered in upper abdomen
- GORD: chronic & relapsing condition
- PUD: H-pylori most common cause, others medication induced
- Drug therapy: Antacids, H2 antagonists, PPIs, other drugs for ulcer
Laxatives
Anti-emetics
Anti-diarrheal
Inflammatory bowel disease
Obesity
Perianal disorder

Ulcer Medications⁵

Antacids

MOA: neutralize hydrochloric acid secreted by gastric parietal cells
Dental implications: nil
Drug interaction: reduce absorption of many drugs

Generic name	Brand Name
Aluminum hydroxide	Alu-tab
Combo antacids	Mylanta, Rennie

H₂ antagonists

MOA: competitively block H2 receptors on parietal cells, Reduce gastric acid secretion
Dental implication: dry mouth, taste disorder
Drug interaction: reduce absorption of azoles

Generic name	Brand Name
Famotidine	Ausfam, Pepzan
Nizatidine	Nizac, Tazac
Ranitidine	Ausran, Rani

Proton Pump Inhibitors⁶

MOA: irreversibly inactivate proton pump
- Suppress stimulated & basal acid secretion
Dental implications: dry mouth, taste disturbance
- Implant failure???
Drug interaction: reduce absorption of azoles

Generic name	Brand Name
Esomeprazole	Nexium
Lansoprazole	Zopral, Zoton
Omeprazole	Acimax, Losec
Pantoprazole	Somac
Rabeprazole	Pariet

Other drugs for ulcers

Bismuth subcitrate & sucralfate
- MOA: forms acid & pepsin resistant coating at ulcer site
- [Bismuth Sub] ADR: darkening of teeth & tongue
- [Sucralfate]: Dry mouth
Misoprostol
- Prostaglandin E analogue: increase mucus secretion in stomach

Generic name	Brand Name
Bismuth subcitrate	Bismuth subcitrate
Sucralfate	Ulcyte
Misoprostol	Cytotec

Mechanism of Gastric Acid Secretion⁷

flowchart TD
    G(G cell)
    ECL(ECL cell)
    P(PARIETAL CELL)
    AA(AA)
    PGE2(PGE₂)
    HIST(Histamine)
    GASTRIN(Gastrin)
    SST({{Somatostatin}})
    NS(NSAIDs)
    MISO(Misoprostol)
    H2B(H₂ blockers)
    PPI(Proton pump inhibitors)
    ATRO(Atropine)
    ACH(Ach)

    G -- Gastrin --> ECL;
    SST --|Inhibits| G;
    SST --|Inhibits| ECL;
    SST --|Inhibits| P;
    GASTRIN --> ECL;

    ECL -- Histamine --> P;

    AA -->|Inhibited by| NS;
    AA --> PGE2;
    PGE2 --|Stimulates| ECL;
    MISO --|Stimulates| ECL;

    HIST --> P;
    H2B --|Inhibits| P;

    ACH --> P;
    ATRO --|Inhibits| P;

    PPI --|Inhibits| P;

    subgraph Receptors
        SST_R_G[SST₂R]
        CCK_R_ECL[CCK₂R]
        SST_R_ECL[SST₂R]
        EP_23_R[EP₂/₃R]
        H2_R[H₂R]
        SST_R_P[SST₂R]
        CCK_R_P[CCK₂R?]
        M3_R[M₃R]
    end

    G --> SST_R_G;
    GASTRIN --> CCK_R_ECL;
    SST --> SST_R_G;
    SST --> SST_R_ECL;
    SST --> SST_R_P;
    PGE2 --> EP_23_R;
    MISO --> EP_23_R;
    HIST --> H2_R;
    H2B --> H2_R;
    GASTRIN --> CCK_R_P;
    ACH --> M3_R;
    ATRO --> M3_R;

    P -- "H⁺" --> PPI;
    P -- "K⁺" --> PPI;
    P -- "Cl⁻" --> PPI;

    P -- "H⁺" --> H_out;
    P -- "K⁺" --> K_out;
    P -- "Cl⁻" --> Cl_out;

Cell Functions and Drug Targets

G cell

Located in gastric antrum of stomach and duodenum
Produce and secrete gastrin- secretes gastric acid secretion
Gastrin stimulates parietal cells to secrete HCl
Target for: Gastrin, Somatostatin

ECL cell

Located in gastric mucosa
Secrete histamine – stimulates parietal cells to produce HCl
Histamine released by ECL binds to the H2 receptor on parietal cells enhancing acid secretion
Target for: Histamine, Somatostatin

PARIETAL CELL

Located in gastric mucosa
Responsible for secreting HCl and intrinsic factor
HCl – creates an acidic environment – for protein digestion/ activation of digestive enzymes.
Intrinsic factor- for vitamin B12 absorption in small intestine
Secretes: H⁺, K⁺, Cl⁻
Target for: H₂ blockers, Atropine, Proton pump inhibitors

Other Components

NSAIDs: Inhibit AA
Misoprostol: Stimulates ECL
Ach: Stimulates Parietal Cell
AA: Precursor to PGE₂
PGE₂: Stimulates ECL

Cellular Mechanisms of Acid Secretion and Drug Action⁸

Parietal Cell Signaling Pathway

flowchart TD
    A1[Acetylcholine] --> M3R
    A2[Histamine] --> H2R
    A3[Gastrin] --> CCK2R
    M3R --> IP3Ca2_1[IP₃/Ca²⁺]
    CCK2R --> IP3Ca2_2[IP₃/Ca²⁺]
    H2R --> AC[Adelynate cyclase]

    AC --> ATP
    ATP --> cAMP

    IP3Ca2_1 --> PK[Protein Kinase]
    IP3Ca2_2 --> PK
    cAMP --> PK

    PK --> H_plus[H⁺]
    PK --> HKATPase[H⁺/K⁺ ATPase]
    PK --> K_plus[K⁺]
    PK --> Cl_plus[Cl⁻]

    subgraph Parietal Cell
        M3R
        H2R
        CCK2R
        IP3Ca2_1
        IP3Ca2_2
        AC
        ATP
        cAMP
        PK
        HKATPase
        Cl_plus
    end
    
    H_plus --> Acid[Acid(HCl)]
    Cl_plus --> Acid
    K_plus --> HKATPase
    HKATPase --> H_plus
    HKATPase --> K_plus

    PPI(PPI) --> HKATPase
    HKATPase -.-|Inhibited| PPI

Drug Mechanisms in the Stomach

Alginic acid forms a floating protectant vs GERD.
Bismuth subsalicylate coats and has an antimicrobial and antidiarrheal effect—used vs ulcers and traveler’s diarrhea.
Antacids (magnesium, calcium, aluminum salts) raise pH.
Sucralfate binds to and protects the ulcer.
Misoprostol (PGE2) protects vs ulcers from NSAIDs.
H₂ histamine receptor antagonists inhibit H $^{+}$ release by parietal cells.
Proton pump inhibitors (e.g., esomeprazole, lansoprazole) reduce H $^{+}$ release from parietal cells.
Antibiotics (metronidazole, tetracycline, amoxicillin, clarithromycin) inhibit H. pylori, which can cause ulcers.
“Stomach” label points to the stomach organ itself.

Laxatives⁹

Stool softener:
- Docusate, liq paraffin, poloxamer
Stimulant laxative:
- Act on nerve endings in colonic mucosa → increase intestinal motility
- Bisacodyl, senna, sodium picosulfate
Osmotic laxative:
- Non-absorbable sugar → draw water into feces
- Glycerol, lactulose, macrogol, saline laxatives, sorbitol
Other:
- Bulk forming: absorb water in colon → increase fecal bulk
- Methylnaltrexone: Mu opioid receptor antagonist
- Prucalopride: 5HT4 receptor agonist → increase GI motility

Laxative Type	Generic Name
Stool softeners	Docusate
	Liquid paraffin
	Poloxamer
Stimulant laxatives	Bisacodyl
	Senna
	Sodium picosulfate
Osmotic laxatives	Glycerol
	Lactulose
	Macrogol laxatives
	Saline laxatives
	Sorbitol
Other laxatives	Bulk-forming laxatives
	Methylnaltrexone
	Prucalopride

Mechanisms of Action for Laxatives¹⁰

graph TD
    subgraph Bulk-forming
        direction LR
        A[Examples:] --> B(psyllium)
        B --> C(methylcellulose)
        C --> D(polycarbophil)
        D --> E[Increases stool mass]
    end

    subgraph Stimulant (irritant)
        direction LR
        F[Examples:] --> G(bisacodyl)
        G --> H(senna)
        H --> I(castor oil)
        I --> J[Stimulates enteric nerves]
    end

    subgraph Osmotic
        direction LR
        K[Examples:] --> L(magnesium hydroxide)
        L --> M(lactulose)
        M --> N(polyethylene glycol (PEG))
        N --> O[Increases fluid volume]
    end

    subgraph Wetting agents
        direction LR
        P[Examples:] --> Q(docusate)
        Q --> R(mineral oil)
        R --> S[Moistens to ease passage]
    end

    E --> T(Swelling & distending colon)
    O --> T
    T --> U[H₂O Uptake]

    J --> V[Increased motility]
    S --> W[Softer stool]

    U --> X[Stool movement]
    W --> X
    V --> X

    T --> Y(H₂O)
    Z(H₂O) --> T
    
    AA(H₂O) --> S
    BB(H₂O) --> J
    
    J --> CC(H₂O)
    
    Y --> N
    Z --> D
    
    style T fill:#f9f,stroke:#333
    style J fill:#f9f,stroke:#333
    style Z fill:#f9f,stroke:#333
    style Y fill:#f9f,stroke:#333
    style AA fill:#f9f,stroke:#333
    style CC fill:#f9f,stroke:#333

Anti-emetics¹¹

Nausea & vomiting
- Rationale: prevent/ relieve sx
- Prevent complications (dehydration, electrolyte disturbance)
Dopamine antagonists
Sedating antihistamines
- Pheniramine & promethazine: px motion sickness
Anticholinergics
- Hyoscine hydrobromide: px motion sickness
5HT3 antagonists, substance P antagonists, corticosteroids
- Px nausea & vomiting assoc w/ chemotherapy

Dopamine antagonists¹²

MOA: block dopamine receptor in CTZ
Dental implications: dry mouth
Drug interaction: prolongation of QT interval
- +Clarithromycin, erythromycin, fluconazole, moxifloxacin

Generic name	Brand Name
Domperidone	Motilium
Droperidol	Droperidol inj
Haloperidol	Serenace
Metoclopramide	Maxolon
Prochlorperazine	Stemetil

5HT3 antagonists

MOA: block serotonin (5-HT3) receptors in the brain and gut
[Granisetron] ADR: dry mouth, taste disturbance
Dental implications
- Not directly but normally use adjunct in chemotherapy

Generic name	Brand Name
Granisetron	Kytril
Ondansetron	Ondaz
Palonosetron	Aloxi inj
Tropisetron	Tropisetron inj

Sedating antihistamines¹³

MOA: $H_{1}$ receptor and stabilising it in an inactive form
Dental implications: sedation, dry mouth
Drug interaction: nil in dental setting

Generic name	Brand Name
Cyclizine	Nausicalm
Promethazine	Allersoothe, Phenergan

Anticholinergics

MOA: Block muscarinic actions of acetylcholine
Dental implications: sedation, dry mouth
Drug interaction: nil in dental setting

Generic name	Brand Name
Hyoscine hydrobromide	Kwells, Travacalm

Substance P antagonists¹⁴

AKA: Also known as neurokinin-1 (NK1) receptor antagonists
MOA: antagonize substance P/neurokinin-1 receptors.
ADR: hiccups
Drug interaction
- [CYP3A4 inH] azoles, clarithromycin, erythromycin: increase conc of substance P antagonist

Generic name	Brand Name
Aprepitant	Aprepitant
Fosaprepitant	Emend inj
Fosnetupitant (+palonosetron)	Akynzeo inj

Anti-diarrheal¹⁵

Rationale for drug therapy
- Px dehydration & electrolyte disturbance
- Sx relief
- Tx of infection
Acute diarrhea: self limiting
Chronic diarrhea: underlying disease req investigations
Drug therapy choice
- ORS: $1^{st}$ line in children
- Opioid antidiarrheals: short term tx

Generic name	Brand Name
Codeine	Codeine phosphate Actacode linctus
Diphenoxylate + Atropine	Lofenoxal Lomotil
Loperamide	Imodium

Inflammatory bowel disease¹⁶

Crohn’s disease & ulcerative colitis
- Tx rationale: relieve sx & improve QOL, induce & maintain remission, px complications
Corticosteroids
- Budesonide (oral), prednisolone (rectal)
- Adrenal suppression possible w/ budesonide
- Steroids ADRs
5-aminosalycilates
- Mesalazine, Olsalazine, Sulfasalazine

Treatment Comparison

Crohn’s	Ulcerative colitis
5-aminosalicylates	5-aminosalicylates
Azathioprine & mercaptopurine	Azathioprine & mercaptopurine
Corticosteroids	Corticosteroids
TNFa antagonists	TNFa antagonists
	Cyclosporin
MTX
Antibacterials for perianal fissures
- Metronidazole
- Ciprofloxacin

Corticosteroids ADRs¹⁷

Infection
Delayed wound healing
Steroid rosacea
Perioral dermatitis
Skin atrophy
Bruising
Acne
Facial flushing
Pupura
Depigmentation
Telangiectasia
Steroid induced crushing’s

5-Aminosalicylates¹⁸

MOA
- Anti-inflammatory, immunosuppressant. Exact mechanism unknown
- Sulfasalazine: also indicated for RA (see RA lecture)
Indication: UC, Crohn’s
ADR & drug interaction: no dental implication

Generic Name	Brand Name
Mesalazine	Mesasal
	Salofalk
Olsalazine	Dipentum
Sulfasalazine	Pyralin
	Salazopyrin

TNFa antagonists¹⁹

MOA: binds & antagonize TNFa (cytokine involved in inflammatory & immune responses
Common adverse effect include infections
- Persistent fever, other signs of infection, bruising, bleeding → Pt need to contact medical GP urgently
Also indicated for RA (see RA lecture)

Generic name	Brand Name
Adalimumab	Humira inj
Golimumab	Simponi inj
Infliximab	Remicade inj

Drugs for obesity²⁰

Orlistat
- MOA: inH GI lipases
- Fecal urgency/incontinence
Phentermine
- MOA: sympathomimetic w/ CNS stimulatory effect
- CNS overstimulation
  - Restlessness, nervousness, tachycardia, agitation, HTN, dry mouth!
Dietary and lifestyle factors

Generic name	Brand Name
Orlistat	Xenical
Phentermine	Duromine

Total parenteral nutrition²¹

Total parenteral nutrition
- Method of feeding - Bypasses the gastrointestinal tract
- Nutrition is given into a vein
- Used when a person cannot or should not receive feedings or fluids by mouth
Pancreatic enzymes
- Pancreatic enzyme insufficiency: cystic fibrosis
- Amylase, Lipase, Protease
- Irritation of skin around mouth & anus

Generic name	Brand Name
Pancreatic enzymes	Creon
Ursodeoxycholic acid	Ursofalk

Gastrointestinal drugs: Dental implications²²

Drugs for gastric ulcer
- No real dental implications
- However, uncontrolled acid secretions → dental erosions
- Use of NSAIDs: close monitoring, risk Vs benefit
Drug interactions
- Antacids: most interaction avoided by dosing interval of at least 2hrs
- Esomeprazole/omeprazole & diazepam
- H2 antagonists & PPIs: decrease absorption of itra- & ketoconazole → reduce antifungal effect
- Phentermine & tramadol: risks of seroT toxicity

IBD: Dental implications²³

Oral manifestations of Crohn’s disease & UC
- Pyostomatitis vegetans: rare, abscess & pustular lesions
- Recurrent aphthous ulcers: 1 or more
- Atrophic glossitis: red glossy tongue appearance
- Burning mouth syndrome
- Angular cheilitis: scaling & crusting corner of mouth
- Taste disturbance
- Dry mouth
- Halitosis
- Periodontitis


SORE TONGUE	IMPAIRED TASTE	DENTAL CARIES, PERIODONTAL DISEASES
EXTREME DRYNESS AND DISCOMFORT		INFECTIOUS DISEASE
UPPER DIGESTIVE TRACT DISORDERS	DRY MOUTH

References²⁴²⁵

Ritter JM, Flower RJ, Henderson G, Loke YK, MacEwan D, Robinson E, editors. Rang & Dale’s pharmacology. 10th ed. Edinburgh: Elsevier; 2023
Australian Medicines Handbook Online [Internet]. Adelaide (AU): Australian Medicines Handbook Pty Ltd;2000. Gastrointestinal; [updated 2025; cited 2025]. Available from: UWA Onesearch
Pharmaceutical Society of Australia. Australian Pharmaceutical Formulary and Handbook: A Guide to Best Practice. 25th ed. Canberra: Pharmaceutical Society of Australia; 2021
Ali K. Clinical dental pharmacology. 1st ed. Oxford: Wiley-Blackwell; 2023
Bullock S, Manias E. Fundamentals of pharmacology. 8th ed. Frenchs Forest, NSW: Pearson Australia; 2017
MIMS Australia. eMIMSelite: Consumer medicine information, specific clinical monograph [Internet]. Sydney: MIMS Australia; [updated 2025; cited 2025 Apr 17]. Available from: UWA Onesearch

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L9 Gastrointestinal 2025_formatted_text

DENT 3005: Introduction to Pharmacology1

Gastrointestinal drugs

Acknowledgement of country2

Learning Outcomes3

Learning objectives

Gastrointestinal drugs4

Ulcer Medications5

Antacids

H₂ antagonists

Proton Pump Inhibitors6

Other drugs for ulcers

Mechanism of Gastric Acid Secretion7

Cell Functions and Drug Targets

G cell

ECL cell

PARIETAL CELL

Other Components

Cellular Mechanisms of Acid Secretion and Drug Action8

Parietal Cell Signaling Pathway

Drug Mechanisms in the Stomach

Laxatives9

Mechanisms of Action for Laxatives10

Anti-emetics11

Dopamine antagonists12

5HT3 antagonists

Sedating antihistamines13

Anticholinergics

Substance P antagonists14

Anti-diarrheal15

Inflammatory bowel disease16

Treatment Comparison

Corticosteroids ADRs17

5-Aminosalicylates18

TNFa antagonists19

Drugs for obesity20

Total parenteral nutrition21

Gastrointestinal drugs: Dental implications22

IBD: Dental implications23

References2425

Footnotes

Graph View

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