L8 RENAL 2025_formatted_text

DENT 3005: Introduction to Pharmacology¹

Renal and genitourinary 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

1. Understand the mechanism of diuretics
2. Broadly understand the function of the kidney and chronic kidney disease
3. Broadly understand BPH, drugs used and dental implication of these drugs
4. Recognise oral and dental side effects of diuretic drugs
5. Recognise dental implications of renal disease
6. Understand drugs interactions with dental medications
7. Applied knowledge to clinical scenarios

Functions of the kidney⁴

• Filtration of Blood
• Regulation of Blood Pressure
• Electrolyte Balance
• Acid-Base Balance
• Erythropoiesis Regulation
• Detoxification

Nephron Sites of Action⁵

Glomerulus

• 120 ml min⁻¹

Proximal convoluted tubule

• Acids Bases
• Lumen
• HCO₃ (reabsorption)
• Na⁺ (60%)
• Cl⁻ (45%)
• H₂O
• ① Carbonic anhydrase inhibitors
• ② Osmotic diuretics

Loop of Henle

Thin descending loop

• H₂O

Thin ascending loop

• H₂O

Thick ascending loop

• K⁺
• Ca²⁺
• Mg²⁺
• Cl⁻
• Na⁺ (25%)
• ③ Loop diuretics

Distal convoluted tubule

• Na⁺ (10%) Cl⁻
• Ca²⁺
• ④ Thiazides

Collecting Ducts

• Cortex
• Medulla
• PTH sensitive (ADH)
• K⁺H⁺
• Na⁺ (5%)
• (ADH)
• H₂O
• ⑤ K⁺ sparing
• ⑥ Aldosterone antagonists

Diuretics⁶

Classes of diuretics – Mechanism and sites of action

Medication	Mechanism of Action	Site of Action
Loop diuretics (e.g. frusemide, bumetanide)	Inhibit Na⁺/K⁺/2Cl⁻ symport (NKCC2)	Thick ascending loop of Henle
Thiazide diuretics (e.g. hydrochlorothiazide, indapamide)	Inhibit Na⁺/Cl⁻ symport	Distal convoluted tubule
Potassium-sparing diuretics (aldosterone antagonists, e.g. spironolactone)	Aldosterone antagonists	Collecting duct
Pteridine derivatives (e.g. amiloride)	Inhibit Na⁺ entry through epithelial sodium channels (ENaC)	Collecting duct
Carbonic anhydrase inhibitors (e.g. acetazolamide)	Inhibit carbonic anhydrase	Proximal convoluted tubule
Osmotic diuretics (e.g. mannitol)	Increase in tubular fluid osmolality	Proximal convoluted tubule

Diuretic Classes and Dental Implications⁷

Thiazide & related anti-diuretics

• MOA: inhibit reabsorption of Na & Cl
• Dental implications
  • NSAIDs: may reduce renal function

Generic name	Brand Name
Hydrochlorothiazide	Dithiazide
Chlorthalidone	Hygroton
Indapamide	Natrilix

Potassium sparring diuretics

• MOA: inhibit reabsorption of Na in the distal tubule
• Dental implications
  • NSAIDs: may increase risk for hyperkalemia & reduce renal function
  • Dry mouth

Generic name	Brand Name
Amiloride	Kaluril
Triamterene	Only available w/ hydrochlorothiazide

Aldosterone antagonists⁸

• MOA: antagonize Aldosterone → inhibit Na absorption in distal tubule
• Dental implications
  • Orthostatic hypotension & drug interaction w/ NSAIDS

Generic name	Brand Name
Eplerenone	Inspra
Spironolactone	Aldactone, Spiractin

Loop diuretics

• MOA: inhibit reabsorption of Na & Cl in ascending limb of loop of Henle
• Dental implications
  • Orthostatic hypotension & drug interaction w/ NSAIDS

Generic name	Brand Name
Bumetanide	Burinex
Ethacrynic acid	Edecrin
Frusemide	Lasix, Urex

Potassium sparing effect⁹

• Retention of K while promoting the excretion of sodium and water
  • Prevent potassium loss
• AIP – Aldosterone-induced protein
• ROMK - Renal outer medullary potassium channel
• NR3C2 - Nuclear hormone receptor
• Both Amiloride and Spironolactone lead to mild natriuresis with a K+ sparing effect
• Adverse effect = Hyperkalemia

Diagram illustrating the mechanism of potassium-sparing diuretics in the principal cell of the nephron.

Diuretics: Dental implications¹⁰

• K+ imbalance
  • Hypo and Hyperkaliemia → More prominent in thiazide and loop diuretics
• Cardiac precautions e.g. Local anesthetic w/ adrenaline
  • Ensure safe delivery of LA
• Triple whammy: consider other drugs w/ adverse renal effects (NSAIDs)
• Dry mouth (Xerostomia)
  • Dental caries
  • Difficult swallowing (Dysphagia)
  • Taste alteration (Dysgeusia)

Chronic kidney disease¹¹

• Chronic Kidney Disease (CKD) is a progressive condition
• Risk factors: diabetes, Hypertension, History of kidney disease
• Drug therapy
  • Anti-hypertensives
  • Diuretics
  • Phosphate binders
  • Vitamin D
  • Erythropoietin injection and iron

Chronic kidney disease Staging¹²

Table 1 - Relationship between glomerular filtration rate and stage of chronic kidney disease*

Kidney function stage	eGFR (mL/min/1.73 m²)
1	≥90
2	60–89
3a	45–59
3b	30–44
4	15–29
5	<15 or on dialysis

https://www.nps.org.au/australian-prescriber/articles/how-to-adjust-drug-doses-in-chronic-kidney-disease

Renal disease: Dental implications¹³¹⁴

• Compromised kidney function

  • Impaired drug metabolism, bleeding risks, susceptible to infections

• Altered drug clearance

  • Prolonged effect/toxicity

• Altered platelet function

  • Bleeding risks: monitor use of NSAIDs

• Weakened immune response

  • Educate OH and preventative dental tx

• Renal osteodystrophy

  • Weakened bones: jaw?

• If patients are taking high doses of corticosteroids for a long duration of time [i.e. polymyalgia rheumatica]

• Schedule the dental session in the morning

• Try to avoid nephrotoxic medications → If necessary → Dose / Frequency adjust

  • NSAID - Can cause bleeding tendencies
  • Aspirin - Increases platelet dysfunction

• LA, paracetamol, codeine

Benign prostatic hyperplasia¹⁵

• Non-cancerous enlargement of the prostate gland
• The prostate surrounds the urethra, and as it enlarges → compress the urethra → urinary symptoms
• Driven by hormonal changes
  • Increase in dihydrotestosterone (DHT) levels → LUTS
    • Frequent urination (especially at night)
    • Difficulty starting urination
    • Weak urine stream
    • Incomplete bladder emptying
    • Urgency to urinate
• $\alpha$1-adrenoceptor antagonists
  • Smooth muscle relaxation → urinate

Incontinence¹⁶

• Neurogenic Bladder: this condition refers to bladder dysfunction that results from a neurological impairment. It can affect bladder control and the ability to store or void urine properly
• Incontinence: this is the inability to control urination, leading to involuntary leakage of urine
• Oxybutynin: muscarinic receptor antagonist, reduce involuntary contractions of bladder muscle [Anticholinergic effect - Dry mouth]

Anti-muscarinic medications¹⁷

• Competitive antagonists of acetylcholine at muscarinic receptors – reduction in parasympathetic activity
• Dental relevance = Dose-dependent effect → Salivary secretion is reduced
• Symptoms
  • Unpleasant dryness
  • Difficulty swallowing
• Examples
  • Oxybutynin
  • Atropine
  • Scopolamine
  • Ipratropium
  • Benztropine

flowchart TD
    A[Anticholinergic effects]
    B[Urinary retention]
    C[Dry throat, dry mouth, constipation]
    D[Feeling hot, decreased sweating]
    E[Tachycardia]
    F[Blurred vision, dry eyes]
    G[Sedation, dizziness, confusion, hallucinations]

    A --> B
    A --> C
    A --> D
    A --> E
    A --> F
    A --> G

Anti-muscarinic drugs: Dental implications¹⁸

• Dry mouth 😊

References¹⁹

• 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. Cardiovascular, Genitourinary; [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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