Effects of Systemic and Non-Systemic Drugs on Oral Mucosa: A Prosthodontic Perspective"- A Review.

International Journal of Pharmaceutical Science and Health Care Volume 15, Number 6, 2025 Available online on http://www.rspublication.com/ijphc/index.html ISSN 2249 – 5738 DOI: 10.5281/zenodo.17670474 Original Article ©2025 RS Publicaon, rspublica[email protected] 82 Effects of Systemic and Non-Systemic Drugs on Oral Mucosa: A Prosthodontic Perspective”- A Review. Dr.B. LakshmanaRao 1 , Dr.A. Sathvika 2 , Dr.D. Kundanaveni 3 , Dr.K. Bhanu Prasad 4 . 1. Prof & HOD, Dept of Prosthodontics, Lenora Institute of Dental Sciences, Rajahmundry, A.P, 2. Sr. Lecturer, Dept of Prosthodontics, Lenora Institute of Dental Sciences, Rajahmundry, A.P, 3. Sr. Lecturer, Dept of Prosthodontics, Lenora Institute of Dental Sciences, Rajahmundry, A.P, 4. Sr. Lecturer, Dept of Prosthodontics, Lenora Institute of Dental Sciences, Rajahmundry, A.P. ARTICLE INFO ABSTRACT ©2025 RS Publicaon Paper ID: IJPHC691EDA9FCBE94 Received: 2025-10-22 Published: 2025-11-21 DOI: https://dx.doi.org /10.5281/zenodo.17 670474 Page No: 82-90 The oral mucosa is very sensitive to changes caused by many different types of drugs, such as antihypertensives, antidiabetics, antineoplastics, corticosteroids, antibiotics, antifungals, and analgesics. These drug-related alterations, like dry mouth, mucositis, lichenoid responses, candidiasis, ulcers, and slow wound healing, have a big effect on the diagnosis, treatment planning, and prognosis of removable prosthodontic therapy. Drugs used to treat systemic and non-systemic disorders can change the mucous membranes of the mouth in ways that directly affect removable prosthodontic treatment. To get good results from prosthodontics, it is important to correctly identify drug-related alterations and put in place both preventive and therapeutic treatments. Comprehending medication-induced mucosal alterations and implementing suitable safeguards guarantees increased patient comfort, improved prosthesis retention, and diminished mucosal damage. This review focuses on the most widely used systemic and non-systemic drugs on the oral mucosa and lists the most important therapeutic precautions for taking care of patients who need detachable prosthodontic rehabilitation. Keywords: Oral mucosa, Systemic medications, Non-systemic medications, Removable prosthodontics. Corresponding Author: Dr.B. LakshmanaRao,  Mail: kus[email protected] Internaonal Journal of Pharmaceucal Science and Health Care Available online on hp://www.rspublicaon.com/ijphc/index.html ISSN 2249 – 5738 Cite This Paper: LakshmanaRao Bathala, Dr. A. Sathvika, Dr. D. Kundanaveni and Dr. K. Bhanu Prasad (2025). "Effects of Systemic and Non-Systemic Drugs on Oral Mucosa: A Prosthodonc Perspecve”- A Review.". INTERNATIONAL JOURNAL PHARMACEUTICAL SCIENCE AND HEALTH CARE (IJPHC), vol. 15, no. 6, 2025, pp. 8290. DOI: hps://dx.doi.org/10.5281/zenodo.17670474 International Journal of Pharmaceutical Science and Health Care Volume 15, Number 6, 2025 Available online on http://www.rspublication.com/ijphc/index.html ISSN 2249 – 5738 DOI: 10.5281/zenodo.17670474 Original Article ©2025 RS Publicaon, rspublica[email protected] 83 Introduction Medications induce alterations in the oral mucosa by several pathways, including direct epithelium toxicity, immunological modulation (either hypersensitivity or immunosuppression), salivary hypofunction, vascular or angiogenic effects, pigment deposition, and modifications of the oral microbiome. Clinical manifestations encompass xerostomia/atrophy, candidiasis, mucositis/ulceration, lichenoid lesions, gingival enlargement, angioedema, hyperpigmentation, and mucosal necrosis/slow healing (illustrations and proof provided below). (See the main guideline for treating mucositis.) [1,2] Medications taken for a wide range of systemic and non-systemic illnesses can substantially affect the biological integrity and functional resilience of the oral mucosa. Antihypertensives, anticholinergics, antidiabetics, immunosuppressants, chemotherapeutic agents, NSAIDs, corticosteroids, antibiotics, and psychotropic medications often cause negative changes to the mucosa, such as dry mouth, mucositis, ulcers, slow healing, candidiasis, hyperplasia, and lichenoid reactions. These changes make detachable prosthodontic appliances less comfortable, stable, and long-lasting. [1-3] Major clinical categories, typical drugs, mechanism & management (concise) 1) Oral mucositis / ulceration (severe — chemotherapy, targeted therapy, some non-systemic drugs) Drugs: cytotoxic chemotherapy (5-FU, methotrexate, doxorubicin, etc.), head and neck radiation, and targeted medicines (EGFR inhibitors, mTOR inhibitors). Mechanism: Damage to epithelial cells, an inflammatory cytokine cascade, and a secondary infection. Clinical features: Erythema → painful ulceration, danger of systemic infection, decreased nutrition. Management: Preventive oral care, topical analgesia, and protocolized supportive treatment according to MASCC/ISOO standards (basic oral care, cryotherapy for specific agents, and topical and systemic measures when advised). [1,3] 2) Xerostomia / mucosal atrophy (anticholinergic effect or reduced salivation) Medications include opioids, diuretics, antihypertensives, anticholinergics, some antidepressants (SSRIs, TCAs), and several antipsychotics. Mechanism: Decreased salivary flow leads to dry mucosa, fissuring, burning mouth, and loss of protecting saliva. Management includes careful oral hygiene, saliva stimulants (if the salivary glands are functioning), and controlling the risk of dental cavities. [4] 3) Oral candidiasis (fungal overgrowth) Medications: Inhaled corticosteroids, broad-spectrum antibiotics, systemic corticosteroids, immunosuppressants (e.g., for autoimmune disorders). International Journal of Pharmaceutical Science and Health Care Volume 15, Number 6, 2025 Available online on http://www.rspublication.com/ijphc/index.html ISSN 2249 – 5738 DOI: 10.5281/zenodo.17670474 Original Article ©2025 RS Publicaon, rspublica[email protected] 84 Evidence: Systematic reviews indicate that inhaled corticosteroids significantly elevate the risk of oropharyngeal candidiasis; the utilization of spacers and mouth rinse mitigates this risk. Management: Local antifungal treatment (nystatin, miconazole oral gel) and prophylactic measures (rinse, spacer). [5,6] 4) Gingival enlargement / overgrowth (secondary mucosal problems) Phenytoin (anticonvulsant), calcium-channel blockers (nifedipine, amlodipine), and cyclosporine. Mechanism: Modified fibroblast collagen turnover and localized inflammatory response lead to fibrous hypertrophy, cyst formation, and subsequent mucosal ulceration. Phenytoin-induced gingival overgrowth is extensively reported; its prevalence varies significantly and is affected by oral hygiene and dosage. Management: Enhanced oral hygiene, drug replacement, if possible, periodontal treatment, surgical intervention for severe instances. [6, 7] 5) Lichenoid and lichenoid-like reactions Medications: NSAIDs, ACE inhibitors, oral hypoglycemics (sulfonylureas), gold salts, antimalarials, and other agents. Clinical: White reticular striae and erosive lesions that may resemble oral lichen planus. Causality is challenging to establish; systematic evaluations indicate a scarcity of high-quality data connecting certain medicines to lichenoid lesions. Temporal correlation and withdrawal responses assist in diagnosis. [5,8] 6) Angioedema (oral/facial mucosal swelling) ACE inhibitors are traditional medications that may induce bradykinin-mediated angioedema affecting the lips, tongue, and throat, which can be life-threatening. Nonsteroidal antiinflammatory drugs and other substances may induce histamine-mediated edema. Clinical and Management: Sudden development of painless edema; airway evaluation is essential — discontinue medication, prompt medical intervention required; targeted therapies vary based on underlying etiology. Recent evaluations delineate incidence, risk determinants, and preventive measures. [3,4] 7) Drug-induced oral hyperpigmentation Medications: Minocycline, antimalarials (chloroquine, hydroxychloroquine), some antineoplastics (cyclophosphamide), antiretrovirals (e.g., zidovudine), among several others. Mechanism: Accumulation of drug or drug-metabolite complexes, activation of melanin synthesis, or deposition of hemosiderin. [9] Evidence: Systematic studies and case series indicate numerous implicated agents and inconsistent reversibility following cessation of the agent. International Journal of Pharmaceutical Science and Health Care Volume 15, Number 6, 2025 Available online on http://www.rspublication.com/ijphc/index.html ISSN 2249 – 5738 DOI: 10.5281/zenodo.17670474 Original Article ©2025 RS Publicaon, rspublica[email protected] 85 8) Nicorandil and other ulcer-causing drugs Nicorandil, a vasodilator utilized for angina, is linked to the development of deep, chronic painful oral ulcers; additionally, other medications, whether topical or systemic, may infrequently induce severe ulceration or conditions within the erythema multiforme/Stevens-Johnson spectrum. [2,4] 9) Drug-related mucosal pigmentation or staining (e.g., minocycline) Clinical: Blue-gray or brownish lesions on the palate or gingiva; occasionally, osseous coloring is visible through the mucosa. Frequently linked to prolonged usage. [6] Practical diagnostic approach (short) 1. History: comprehensive drug list (systemic and topical/inhaled), initiation and cessation dates, dosage, local factors (inhaler technique, dental devices), immunological status. 2. Examination: pattern (reticular, ulcerative, pseudomembranous, pigmented), distribution (palate in inhaled steroid candidiasis; gingiva in phenytoin-induced overgrowth), extraoral symptoms (angioedema). 3. Investigations: perform swab/culture for Candida, conduct biopsy if cancer is suspected or uncertainty exists (lichenoid versus lichen planus), and consider a drug withdrawal trial if clinically permissible. 4. Management: address infection, implement topical symptomatic therapy, employ local measures (mouthwash, spacer post-inhalation), seek physician for potential substitution if adverse medication reaction is probable. [8,9] Pattern Typical drugs Key management point Mucositis/ulceration Chemotherapy, EGFR inhibitors, radiotherapy Implement MASCC guideline-based oral care and address pain and infection. [2] Xerostomia Anticholinergics, SSRIs, antihypertensives Salivary replacements, stimulants, and fluoride. Candidiasis Inhaled corticosteroids, broad antibiotics Administer antifungal medication; clean the oral cavity following inhaler usage. [5] Gingival overgrowth Phenytoin, CCBs, cyclosporine Enhance hygiene, evaluate medication modification, and pursue periodontal or surgical intervention. [1] Lichenoid lesions NSAIDs, ACEi, sulfonylureas Evaluate the medicine as a potential cause; perform a biopsy as necessary. [2] Angioedema ACE inhibitors Administer emergency airway management; discontinue ACE inhibitors. [3] Pigmentation Minocycline, antimalarials, some chemotherapies Document; frequently superficial; may endure postcessation. [6] Persistent ulcers Nicorandil Drug withdrawal is frequently necessary.[8] International Journal of Pharmaceutical Science and Health Care Volume 15, Number 6, 2025 Available online on http://www.rspublication.com/ijphc/index.html ISSN 2249 – 5738 DOI: 10.5281/zenodo.17670474 Original Article ©2025 RS Publicaon, rspublica[email protected] 86 Non-systemic (topical) medicines: Inhaled corticosteroids (topical respiratory): local candidiasis—mitigate risk by utilizing a spacer and performing mouth rinse. Topical antiseptics, such as chlorhexidine, may induce mucosal discoloration and alterations in taste with extended usage. Dental restorative metals and contacts may induce localized lichenoid responses or allergic contact stomatitis. Significant clinical insights Numerous drug-induced oral lesions resemble fundamental oral disorders (e.g., lichenoid lesions vs lichen planus). A meticulous drug history is necessary. Certain responses (ACE-I angioedema, severe mucositis, Stevens-Johnson syndrome) may be life-threatening; discontinue the medication and elevate care upon suspicion. Enhancing local oral hygiene frequently mitigates severity or averts secondary issues (e.g., difficulties from gingival overgrowth, candidiasis). [10] Precautions During Removable Prosthodontic Treatment in Patients with Medication-Induced Abused Oral Mucosa Medication-induced mucosal alterations—such as mucositis, xerostomia, candidiasis, lichenoid responses, pigmentation, atrophy, ulceration, angioedema, and impaired healing—necessitate adjustments in the prosthodontic treatment strategy to prevent damage, infection, or deterioration of systemic health. 1. Thorough Medical & Drug History (FIRST STEP) Precautions Acquire a comprehensive list of systemic and topical drugs, including inhalers, sprays, topical gels, and herbal agents. Inquire regarding: History of chemotherapy or radiation; Administration of steroids (systemic or inhaled); Immunosuppressants (cyclosporine, tacrolimus); Antihypertensives (ACE inhibitors leading to angioedema); Anticonvulsants (phenytoin resulting in gingival hypertrophy); Nicorandil (causing ulceration); Antidepressants and anticholinergics (inducing xerostomia) Determine mucosal responses temporally linked to a medication. Consult the physician prior to modifying or discontinuing drugs. Justification: Timely identification prevents stress to impaired mucosa and facilitates accurate diagnosis of lesions. [1,4] International Journal of Pharmaceutical Science and Health Care Volume 15, Number 6, 2025 Available online on http://www.rspublication.com/ijphc/index.html ISSN 2249 – 5738 DOI: 10.5281/zenodo.17670474 Original Article ©2025 RS Publicaon, rspublica[email protected] 87 2. Evaluate Mucosal Status Carefully Before Any Impression or Denture Procedures Look for: Mucositis (caused by chemotherapy, radiation, methotrexate); Xerostomia-induced atrophy (resulting from anticholinergics, SSRIs, antihypertensives); Lichenoid lesions (nonsteroidal anti-inflammatory drugs, angiotensin-converting enzyme inhibitors, oral hypoglycemic agents); Candidiasis (due to inhaled corticosteroids and antibiotics); Ulcers (attributed to nicorandil and NSAIDs); Gingival hyperplasia (phenytoin, nifedipine, cyclosporine); Hyperpigmentation (antimalarial agents, antiretroviral medications, minocycline) Safety Measures Postpone treatment until active mucosal disease is managed, particularly mucositis, ulceration, and candidiasis. For patients undergoing chemotherapy or immunosuppression, refrain from surgeries during episodes of neutropenia, thrombocytopenia, and severe mucositis. Justification: Compromised oral mucosa may deteriorate due to mechanical pressure or friction from impressions or trial dentures. [5] 3. Gentle, Low-Trauma Impression Procedures Precautions Utilize non-irritating imprint materials with minimal pressure, such as light-body elastomers. Refrain from border molding in regions exhibiting ulcers, lichenoid flare-ups, or mucositis. For patients with xerostomia: Utilize saliva substitutes prior to impression taking and employ hydrophilic materials. Justification: The mucosa impacted by medication is delicate; pressure may induce epithelial sloughing or ulceration.[6] 4. Modify Denture Design for Mucosal Protection Precautions Extensive stress distribution employing wide covering to alleviate pressure on delicate mucosa. Employ soft liners (silicone-based) in cases of xerostomia, atrophic mucosa, immunosuppressed individuals, and post-radiation mucosa. Refrain from using abrupt borders, excessive extensions, and pronounced relief zones on ulcerated regions. For individuals with gingival hyperplasia, ensure prostheses do not make traumatic touch with the gingiva. The rationale is that soft, resilient materials mitigate functional stresses on damaged mucosa. [7,9] International Journal of Pharmaceutical Science and Health Care Volume 15, Number 6, 2025 Available online on http://www.rspublication.com/ijphc/index.html ISSN 2249 – 5738 DOI: 10.5281/zenodo.17670474 Original Article ©2025 RS Publicaon, rspublica[email protected] 88 5. Infection Control & Management of Candidiasis Precautions Address candidiasis prior to denture fabrication: Utilize topical antifungals (nystatin, miconazole), implement a denture disinfection protocol, and refrain from wearing the prosthesis overnight. Monitor patients on steroids (inhaled/systemic) or antibiotics cautiously for recurrence. Justification: Immunocompromised or xerostomic individuals are particularly susceptible to fungal infections; dentures may serve as reservoirs. [11] 6. Control of Xerostomia Before Denture Delivery Precautions Advise the use of saliva substitutes, sugar-free lozenges, and regular water consumption. Achieve a high-gloss finish on the denture base to minimize friction. Refrain from using alcohol-containing mouthwashes. Justification: Dehydrated mucosa elevates friction and the likelihood of ulcers beneath dentures. [12] 7. Occlusal & Functional Precautions Precautions Maintain balanced occlusion to mitigate localized stress. Refrain from using dentures that are excessively tight or cumbersome. Implement gradual modifications and observe mucosal tolerance progressively. Justification: Offsets the diminished resistance of mucosa impacted by pharmaceuticals. [13] 8. Frequent Recall & Monitoring Precautions Brief recollection intervals (every 2–4 weeks initially). Verify for: Novel drug-induced lesions, candidiasis, traumatic ulcers, and excessive pressure marks Enhance cleanliness protocols for both dentures and the oral cavity. Justification: Mucosal problems triggered by medication may occur swiftly and unpredictably. [11,12] 9. Special Considerations for Chemotherapy, Radiotherapy & Immunosuppressive Medications Precautions No elective changes or impressions for dentures during peaks of mucositis. Refrain from using dentures during acute episodes of mucositis. For patients following radiation therapy: International Journal of Pharmaceutical Science and Health Care Volume 15, Number 6, 2025 Available online on http://www.rspublication.com/ijphc/index.html ISSN 2249 – 5738 DOI: 10.5281/zenodo.17670474 Original Article ©2025 RS Publicaon, rspublica[email protected] 89 Refrain from overextension, prevent acrylic monomers from contacting ulcerated tissue, and apply soft liners generously. For patients with immunosuppression: Adhere to rigorous denture hygiene measures and postpone invasive procedures. The rationale is because these patients exhibit inadequate healing, a heightened susceptibility to infection, and significant mucosal fragility. [12,13] 10. Interprofessional Collaboration Precautions Engage with treating oncologists, physicians, or psychiatrists while modifying denture plans during chemotherapy. Alleged harmful drug responses, Severe ulceration due to nicorandil or NSAIDs, angioedema associated with ACE inhibitors, and Request drug replacement alone when clinically appropriate. [1,5] Prosthodontic precautions encompass a comprehensive medication history and mucosal assessment, preconditioning of inflamed tissues prior to impressions, utilization of soft liners and tissue conditioners, postponement of denture fabrication during active mucositis, regular follow-up and hygiene reinforcement, and collaboration with physicians regarding drug-induced mucosal disorders. Conclusion: For prosthodontists, identifying medication-induced mucosal disease is essential for developing a safe and successful treatment plan. A comprehensive review of medical and pharmacological history, a detailed mucosal examination, and the identification of high-risk medication classifications are crucial initial stages. Clinical precautions—including pre-prosthetic tissue conditioning, utilization of tissuecompatible impression materials, application of soft liners, maintenance of optimal denture hygiene, scheduling treatment during phases of reduced mucosal inflammation, and collaboration with the patient's physician—mitigate mucosal trauma and enhance prosthesis adaptation. Further considerations encompass the management of xerostomia, the prevention of opportunistic infections, and the postponement of denture manufacturing during active mucositis or ulceration. A tailored, pharmacologically informed strategy improves mucosal health, prolongs prosthesis durability, and guarantees optimal comfort for those needing removable prosthodontic rehabilitation. Combining medical expertise with prosthodontic principles allows practitioners to provide safer, more reliable, and evidence-based care. References: 1. Elad S, Cheng KKF, Correa ME, et al. MASCC/ISOO clinical practice guidelines for the management of mucositis secondary to cancer therapy. Support Care Cancer. 2020;28(10):4559– 4568. 2. Rubin Tomaszewski M. Prediction and prevention of ACE-inhibitor-induced angioedema. Hypertens Res. 2024; DOI: 10.1038/s41440-023-01491-9. International Journal of Pharmaceutical Science and Health Care Volume 15, Number 6, 2025 Available online on http://www.rspublication.com/ijphc/index.html ISSN 2249 – 5738 DOI: 10.5281/zenodo.17670474 Original Article ©2025 RS Publicaon, rspublica[email protected] 90 3. Chacko LN, Bhat K, et al. Phenytoin-induced gingival enlargement: review and clinical management. J Indian Soc Periodontol. 2014;18(3):1–7. 4. Miravitlles M, et al. Systematic review on long-term adverse effects of inhaled corticosteroids: local side-effects including oral candidiasis. Eur Respir Rev. 2021;30:210075. 5. Binmadi NO, Almazrooa SA. Medication-induced oral hyperpigmentation: a systematic review. J Oral Pathol Med. 2020;49(9):786–796. 6. Fortuna G, et al. Drug-induced oral lichenoid reactions: a real clinical entity? A systematic review. J Oral Pathol Med. 2017;46(9):800–807. 7. Healy CM, et al. Persistent nicorandil induced oral ulceration. Br Dent J. 2004;197(9):561–563. 8. Treister NS, et al. Oral mucosal pigmentation secondary to minocycline therapy. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2004;97(1):69–73. 9. Farook FF, et al. An update on mechanisms of phenytoin-induced gingival overgrowth. Open Dent J. 2019;13:430–438. 10. Hong CHL, et al. Basic oral care and mucositis systematic review (MASCC/ISOO group). Support Care Cancer. 2019;27(5):1817–1831. 11. Epstein JB, Thariat J, et al. Oral complications of cancer and cancer therapy. CA Cancer J Clin. 2012;62(6):400-422. 12. Guggenheimer J, Moore PA. Xerostomia: etiology, recognition & treatment. J Am Dent Assoc. 2003;134(1):61-69. 13. Lalla RV, Bowen J, et al. MASCC/ISOO mucositis guidelines summary. 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