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drugs affecting the salivary function / dental implant courses

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drugs affecting the salivary function / dental implant courses

  1. 1. By:- INDIAN DENTAL ACADEMY Leader in continuing Dental Education www.indiandentalacademy.com
  2. 2. Contents  Introduction  Formation of saliva  Salivary secretion control  Functions of saliva  Affect of drugs on salivary function  Mechanism of action  References www.indiandentalacademy.com
  3. 3.  Salivary glands are specialized secretory apparatus.  They show varying differentiation, structure & arrangement in different species.  In human beings, all salivary glands arise from the ectoderm of the oral cavity. www.indiandentalacademy.com
  4. 4.  Based on size; salivary glands divided into 2 types 1. Major salivary glands 2. Minor salivary glands: 600-1000 minor salivary glands present throughout oral cavity and oropharynx.  Salivary glands produce 1-1.5 lit. of saliva per day.  In total saliva 60% by submandibular, 35% by parotid, 4% by sublingual, 1% by minor salivary glands www.indiandentalacademy.com
  5. 5. 1. Parotid Gland 2. Submandibular 3.Sublingual Gland Anatomical location of major salivary glands www.indiandentalacademy.com
  6. 6.  Based on type of secretion; – 2 types 1. Serous 2. Mucous  Parotid is pure serous.  Submandibular is mixed but predominately serous.  Sublingual also mixed but predominately mucous. www.indiandentalacademy.com
  7. 7.  Minor salivary glands classified according to their anatomical location.  Labial & Buccal glands — mixed in nature  Glassopalatine — pure mucous in nature  Palatine — pure mucous in nature  Lingual – Anterior — chiefly mucous in nature Posterior — pure mucous in nature Post. Lingual serous — pure serous www.indiandentalacademy.com
  8. 8. Definition Saliva is complex fluid composed of a wide variety of organic and inorganic constituents that collectively act to modulate the oral environment Edger WM 1992 www.indiandentalacademy.com
  9. 9. Formation of saliva occurs in 2 stages  The basic functional unit of salivary gland is terminal secretory unit called “acini” / “secretory end piece”  First stage – Primary saliva – produced by cells of secretory end pieces & intercalated ducts  It is isotonic fluid containing most of the organic components & water.  Second stage – primary saliva is modified as it passes through the striated & excretory ducts, mainly by reabsorption & secretion of electrolytes  The final saliva that reaches the oral cavity is hypotonic. www.indiandentalacademy.com
  10. 10. Formation of saliva www.indiandentalacademy.com
  11. 11. Saliva secretion control  The physiologic control is mediated through ANS; particularly parasympathetic nervous system.  The control of secretion is also linked to changing taste & smell.  Each of these is capable of modifying the amount & consistency of saliva though gustatory stimulus is more important than masticatory stimulus.www.indiandentalacademy.com
  12. 12.  Postganglionic fibers of both sympathetic and parasympathetic divisions innervate the secretory cells.  Myoepithelial, arteriolar smooth muscle cells, intercalated & striated duct cells also receive direct innervation.  Unmylinated nerve invested by cytoplasmic processes of Schwann, forms a plexus in the connective tissue surrounding the terminal secretory units. www.indiandentalacademy.com
  13. 13. Cortex Fear Anticipation of feeding Hypothalamu s Salivary Nuclei Superior Inferior (Pons ) (Medulla) Vomiting Center (Medulla ) Trigeminal Nuclei TMJ Periodontiu m Muscles Mastication Submandibul ar Sublingual Parotid Gland Smel l Nu.of Tractus Solitarius Taste - - VII IX IXVII + + + + www.indiandentalacademy.com
  14. 14. Composition  Saliva is made up of approximately 99% water & 1% inorganic ions, secretory proteins & other components  Secretory proteins- α-Amylase, ribonulease, kallikrein, histatin, cystatin, sialoperoxidase, lysozyme, lactoferin, mucins.  Organic components like glucose, amino acids, urea, uric acid & lipid molecules www.indiandentalacademy.com
  15. 15.  Immunoglobulins - secretory IgA, IgG, IgM  Electrolytes are sodium, potassium, chlorine, bicarbonate, phosphate, calcium, magnesium, thiocynate, & flouride ions.  Other components like epidermal growth factor, insulin, cyclic AMP, binding proteins & serum albumin. www.indiandentalacademy.com
  16. 16. Functions Protection & Lubrication:  Pellicle formation,  Bolus formation,  Forms a barrier against proteolytic & hydrolytic enzymes in plaque, potential carcinogen from smoking & desiccation from mouth breathing. Buffering action:  PH maintenance – Bicarbonate, Phosphate, basic proteins.  Neutralization of acids www.indiandentalacademy.com
  17. 17. Maintenance of tooth integrity:  Calcium & Phosphate ions – post-eruptive remineralization, increasing surface hardness and resistance to demineralization.  Remineralization of initial caries lesions; enhanced by presence of flouride ion in the saliva. Antimicrobial property:  Physical barrier – Mucins,  Immune defense – Secretory IgA,  Non immune defense – Sialoperoxidase, lysozyme, lactoferin, mucins,www.indiandentalacademy.com
  18. 18. Digestion:  Bolus formation – water, mucin,  Starch, triglyceride – Amylase, lipase. Taste:  Solubilization of food –water, lipocalins,  Maintenance of taste buds –epidermal growth factor & carbonic anhydrase VI. Tissue repair: Wound healing, epithelial regeneration – growth factors, biologically active peptides and amines. www.indiandentalacademy.com
  19. 19. Sulfonamides Ranitidine Nifedipine Clonidine Clozapine Methyldopa Phenytoin Iodine Warfarin www.indiandentalacademy.com
  20. 20. Anti Cholinergics Atropine, Scopolamine Anti-Depressants TCA– Imipramine, Amitryptilline SSRI– Fluoxetine, Setraline Anti-Histamines Diphenhydramine Pheniramine Cinnarizine Cetrizine, Loratadine Anti Neoplastic drugs Cyclophosphamide, Methotrexate, Radioiodine, Vinblastine Anti Microbial agent Ofloxacinwww.indiandentalacademy.com
  21. 21. Antiparkinsonian drugs Levodopa Proton pump inhibitors Omeprazole CNS Stimulant Amphetamine Codiene derivatives Tramadol Anti Helminthic Thiabendazole Anti HIV Protease Inhibitors Amprenavir, Indinavir N.R.T.I. Didanosinewww.indiandentalacademy.com
  22. 22. Cholinergic drugs Pilocarpine, Cevimeline Anti-cholinesterase drugs Tacrine, Rivastigmine, Edrophonium Antibiotics Kanamycin, Imipenem Gentamicin, Tobramicin Analgesics Mefenamic acid Muscle relaxants Succinylcholine General anesthetics Ketamine Thiazide derivative Diazoxidewww.indiandentalacademy.com
  23. 23. Benzodiazepine Alprazolam Anti-Arrhythmic drug Amiodarone Anti -Anxiety drugs Buspirone Anti-Depressants Venlafaxine Anti-Epileptic drug Lamotrigine Anti-Psychotic drugs Risperidone Mood stabilizers Lithium Demulcents Methylcellulose, Propylene glycolwww.indiandentalacademy.com
  24. 24.  Ofloxacin inhibits rat salivary gland functions, which might be observed as a side-effect in humans.  Properties of fluoroquinolones to alter intracellular cAMP & calcium levels and their ability to suppress DNA, RNA and protein synthesis of acinar cells might be possible reasons for the observed changes Fundam Clin Pharmacol. 2001;15:307-11 www.indiandentalacademy.com
  25. 25.  Atropine competitively blocks the acetylcholine action ( M3 blockade) thereby decrease the salivary flow.  Anti Histamines – Antagonize muscarinic actions of acetylcholine; which decrease the salivary flow.  Anti Cholinesterases like Tacrine, Edrophonium increases the salivary flow by increasing brain acetylcholine levels. www.indiandentalacademy.com
  26. 26.  Omeprazole causes reduction of plasma secretin and cholecystokinin levels recognised inhibitors of salivation  Omeprazole may convert acidic gastro- esophageal reflux into alkaline reflux thus reducing the volume of saliva stimulated by the esophago -salivary reflex www.indiandentalacademy.com
  27. 27.  The mechanism of hyposalivation by psychotrophic drugs is not yet clear.  They have many endogenous substance receptors in the salivary glands that mediate the salivary flow rate, such as substance P & vasoactive intestinal peptide receptors.  The blocking of α-adrenergic receptors can also lead to decrease in salivary flow rate and alterations in the saliva composition. www.indiandentalacademy.com
  28. 28.  Antidepressants block the effects of acetylcholine on the muscarinic M3 receptors, resulting in a decreased salivary flow rate.  Antidepressants mainly TCAs modify the salivary component concentration, e.g. total proteins, α -amylase, glycoproteins, calcium & potassium.  The benzodiazepines [BZD] decreases the salivary flow rate through the BZD receptors in the salivary glands & by indirect action on the salivary glands through the central BZD receptors. www.indiandentalacademy.com
  29. 29.  Clozapine is have potent anticholinergic effects  Development of transient salivary gland swelling on clozapine therapy  Salivary gland swelling may be a possible cause for the inhibition saliva flow J clinical psychiatry 1995, vol. 56;11:511- 513 www.indiandentalacademy.com
  30. 30.  Theophylline, a phosphodiesterase inhibitor, is known to induce enlargement of the salivary glands.  This enlargement has been thought to be associated with enhanced cellular levels of cyclic AMP as a result of inhibition of phosphodiesterase, finally increase the saliva flow J Toxicologic Pathology Vol. 16 (2003) ;4: 215 www.indiandentalacademy.com
  31. 31. THANK YOU www.indiandentalacademy.com
  32. 32. Good Morning www.indiandentalacademy.com
  33. 33. Management of Xerostomia & Sialorrhea www.indiandentalacademy.com
  34. 34. XEROSTOMIA Xerostomia is defined as subjective feeling of oral dryness resulting from decreased salivary flow. BURKET’S www.indiandentalacademy.com
  35. 35. 1. Iatrogenic causes: Drugs;  Anti Cholinergics ( Atropine, Hyoscine)  Anti Depressants (TCA’s, SSRI, Lithium. )  Anti Hypertensives  Anti Histamines  Anti Emetics  Phenothiazines  Proton pump inhibitors  Cytotoxic drugs  Opioids  BZD s  Diuretics  Decongestants www.indiandentalacademy.com
  36. 36. 2. Salivary Gland Disorders A. Damage to salivary glands Auto immune diseases a. SjŐgren’s syndrome b. SLE c. Scleroderma d. Sarcoidosis B. Infections ( HIV, HCV, HTLV-1) C. Obstructive salivary glandwww.indiandentalacademy.com
  37. 37. 3. Therapeutic irradiation 4. Dehydration: Decreased water intake Water loss thro’ skin (Burns) Diarrhoea Blood loss Emesis 5. Ageing 6. Diabetes 7. Vitamin deficiency www.indiandentalacademy.com
  38. 38. 8. Interference with Neural transmission:  Psychological disorders  Alzheimer’s disease  Paralysis of facial nerve 9. Decrease in mastication 10. Depression www.indiandentalacademy.com
  39. 39. TREATMENT OPTIONS 1. Preventive therapy ( Topical Fluorides, Regular dental visits ) 2. Symptomatic treatment (sipping water frequently, room humidifiers, oral rinses & gels, artificial saliva) 3. Salivary stimulation Topical Systemic 4. Treatment of underlying systemic disorders www.indiandentalacademy.com
  40. 40. Mechanical stimulants  Eating foods which require Mastication  Artificial Sweeteners Chemical stimulants  Mucopolysaccharide solutions containing Citric Acid Electrical stimulants (TENS) www.indiandentalacademy.com
  41. 41. Artificial Salivary Substitutes  Aqueous Ionic solutions Carboxy methyl cellulose Mucin containing sol Glycoprotein containing solutions  Gel based substitutes Pharmacological stimulants www.indiandentalacademy.com
  42. 42. Proposed systemic sialogogues  Pilocarpine  Cevimeline  Bethanechol  Anetholetrithion e  Guaifensin  Bromhexine  Neostigmine  Yohimbine  Potassium iodide  Nicotinic acid  Malic acid  Vit A www.indiandentalacademy.com
  43. 43. Pilocarpine Hydrochloride  Obtained from Pilocarpus Jaborandi plant  Fox et al (1998), reported a clinical trial in primary Sjögren’s syndrome patients with pilocarpine 1. Subjective improvement of xerostomia 2. Improvement of parotid & submandibular flow rates  First medication approved by Food & Drug Administration for the treatment of xerostomia in patients with SS www.indiandentalacademy.com
  44. 44.  Parasympathetic Agent  Muscarinic Agonist  Causes pharmacological stimulation of Exocrine glands  Acts by stimulating functional salivary gland tissue  Hence not much effective in patients with little remaining functional gland tissue www.indiandentalacademy.com
  45. 45. Indications:  Mainly causes pupillary constriction & reduction of IOP Hence used in:  Primary open angle glaucoma  Angle closure glaucoma  Oral dose: 5-10 mg 1 hr before eating  Onset of action is 30 min  Duration of action: 2-3 hrs www.indiandentalacademy.com
  46. 46. Contraindicated in patients:  Gall bladder disease  Narrow angle glaucoma  Acute iritis  Renal colic SIDE EFFECTS  Sweating  GI upset  Bradycardia  Increased pulmonary secretions  Increased smooth muscle tone  Blurred vision Risk to individuals with:  Heart disease  Asthma  Angina pectoris  Chronic bronchitis  COPD  History of MI www.indiandentalacademy.com
  47. 47. Cevimeline hydrochloride  Cholinergic agonist  Binds to Muscarinic receptors  Stimulates remaining functional salivary gland tissue  Binds more specifically to M3 receptors than to M1 & M2  Because it specifically targets the salivary glands, side effects are less severe  Hence better tolerated than Pilocarpine  Approved by FDA for treatment of xerostomia in SS patientswww.indiandentalacademy.com
  48. 48.  Dose: 30 mg t.i.d  Reported peak blood conc. is 1.5-2 hrs Contraindications:  Uncontrolled Asthma  Narrow angle glaucoma  Cardiac diseases ( alters cardiac conduction & heart rate) www.indiandentalacademy.com
  49. 49. Bethanechol chloride  Cholinergic drug  Used for: Urinary retention Neurogenic atony of bladder  Stimulates Parasympathetic nervous system  Everett (1975), published a study in which Bethanechol was given to alleviate the Anticholinergic side effects of TCA & reported symptomatic improvement www.indiandentalacademy.com
  50. 50. Contraindications:  Bronchial asthma  Hyperthyroidism  Peptic ulcer disease  Bradycardia  Hypotension  Mechanical obstruction of GI / Urinary tract www.indiandentalacademy.com
  51. 51.  Dose: 10-25 mg 3-4 times daily  Onset of action of GI effects is 30 min  Duration of action is 1hr Tab. Urotone – 25mg Tab. Urotonin - 25mg Common cholinergic side effects:  Sweating, GI upset, Miosis  Decreased BP & reflex tachycardia  Bronchial obstruction & Asthmatic attacks www.indiandentalacademy.com
  52. 52. Bromhexine  Alkaloid derived from Adhatoda vasica  Mucolytic agent  Used for treatment of chronic bronchitis & COPD  Acts by increasing quantity of secretions while decreasing their viscosity  Does not appear to be an effective treatment for xerostomia (In clinical trials) www.indiandentalacademy.com
  53. 53. Mucolytic Agents  Guaifensin & Potassium iodide  Used to treat respiratory infections  Decrease the viscosity of saliva  Improve the symptoms of oral dryness by improving flow through salivary ducts  No controlled clinical trials have been demonstrated  Dosage; Acolyt syrup, Acocotin-7.5mg www.indiandentalacademy.com
  54. 54.  Alpha Interferon  Hydroxychloroquine  NSAIDS  Corticosteroids  Methotrexate ALTERNATIVE MEDICINES  Herbal medications  Acupuncture therapy www.indiandentalacademy.com
  55. 55. Alpha interferon  Alteration in salivary cytokines are seen in SS  These abnormal salivary cytokine levels may contribute to progressive destruction of salivary gland tissue in SS  Recombinant human alpha interferon may function as a Biological response modifier  Improves salivary gland function in Auto immune related xerostomia  Clinical trials with weekly IM injections of alpha interferon demonstratedwww.indiandentalacademy.com
  56. 56. Sialorrhea Sialorrhea is defined as an excessive secretion of saliva BURKET’S www.indiandentalacademy.com
  57. 57. Causes for sialorrhea 1. Medication 2. Infant teething 3. The secretory phase of menstruation 4. Heavy metal poisoning 5. Oraganophosphorous poisoning 6. Nausea 7. Gastro Esophageal Reflux Disease 8. Obstructive esophagitis 9. Neurologic & neuromuscular diseases www.indiandentalacademy.com
  58. 58. Management  Depending upon etiology of sialorrhea 3 treatment modalities are present; 1. Physical therapy 2. Medications 3. Surgical intervention www.indiandentalacademy.com
  59. 59. Physical therapy  It can be used to improve neuromuscular control.  Speech & swallowing therapy should be attempted prior to medical & surgical intervention.  Patient cooperation is essential, so this therapy reported very low success rate. www.indiandentalacademy.com
  60. 60. Medications  If patient is experienced sialorrhea secondary to pharmaceutical treatment, alternative medications should be evaluated,  If therapeutic regimen cannot be altered, compatible xerostomic agents should be considered.  Cholinergic muscarinic receptor antagonists can be used www.indiandentalacademy.com
  61. 61.  Drugs like atropine, scopolamine can be advised.  These drugs are contraindicated when there is H/o cardiac problem, closure glaucoma, prostate hypertrophy, paralytic ileus / pyloric obstruction. Preparations & Dosages:  Atropine sulfate – 0.6 – 2mg i.m., i.v. ( Children 10µg/ kg )www.indiandentalacademy.com
  62. 62.  Sublingual administered atropine reduces hypersalivation  Hyson et al (2002), delivered 1 drop of atropine (1%wt / vol solution containing 0.5 mg) sublingually twice a day.  Transdermal Therapeutic System [ TTS]; It is a self adhesive dermal patch delivering scopolamine, usually applied to prevent nausea. www.indiandentalacademy.com
  63. 63.  Zeppetella (1999), successfully used scopolamine via nebulization in patients who had not improved with transdermal patch.  With nebulized delivery system scopolamine is absorbed faster & can be used on “as required” basis.  It is helpful in patients with problematic bronchial secretions.  Reinish et al (1997) reported that Amisulpride (400mg/d up-titrated from 100mg/d over week) produced significant improvement in www.indiandentalacademy.com
  64. 64. Minimally invasive methods Injection of botulinum toxin A:  BTX/A (7.5-15 units) is injected in the salivary gland it inhibit acetylcholine release mainly at neurosecretory junctions.  It binds SNAP-25 protein forming a complex that impairs neuronal excytosis by inhibiting fusion of the presynaptic vesicles containing the neurotransmitter www.indiandentalacademy.com
  65. 65. Photocoagulation of salivary ducts  It is aimed to minimize surgical complications.  Chang & Wong used Nd:YAG laser (1064nm) for intraductal laser photocoagulation of bilateral parotid ducts at 7/10 watts during 10 seconds.  Concepts of laser-tissue interaction of intraductal laser photocoagulation are based on partial destruction of parotid gland & occlusion of parotid ducts.  Postoperatively transient facial swelling iswww.indiandentalacademy.com
  66. 66. Tongue acupuncture  Wong et al, hypothesized that tongue acupuncture stimulate the rich neural network in the tongue, which is connected to salivary glands & tongue muscles via the cranial nerve nuclei; & improve salivary secretion and swallowing mechanism.  Children easily tolerated the treatment with significant improvement of hypersalivation & no complications  This technique may be an alternative / adjunctive option for children with intractablewww.indiandentalacademy.com
  67. 67. Surgical methods  Neurectomy – sectioning the parasympathetic pathway reduces the flow of saliva.  The tympanic plexus and Chorda tympanic nerves can be sectioned unilaterally or bilaterally, and either alone in combination with submandibular gland removal.  Chorda tympani neurectomy reduces the salivary flow rate of the submandibular / sublingual complex but it seems to be poor www.indiandentalacademy.com
  68. 68.  Chorda tympani neurectomy always produces a loss of taste in the anterior 2/3rds of the tongue.  Contraindicated in patients who already have hearing problems.  Hearing loss is the possible complication  Despite an initially high success rate, the long term results of neurectomies used alone are relatively disappointing www.indiandentalacademy.com
  69. 69. Salivary duct and gland procedures  One of the earliest surgical management of sialorrhea is;  Bilateral parotid duct relocation from buccal vestibule to tonsillar fossa or posterior part of tonsillar pillar to initiate the swallowing reflex.  Bilateral duct ligation of parotid glands combined with submandibular gland removal gives goodwww.indiandentalacademy.com
  70. 70.  The purpose of duct ligation is to obtain gland atrophy.  Submandibular duct relocation performed alone or in combination gives success rate of 75% - 89%.  Occasional post operative complications such as ranula formation, pain & numbness. www.indiandentalacademy.com
  71. 71. References  The pharmacological Basis of Therapeutics Goodman & Gilman 10th Edition  Pharmacology & Pharmacotherapeutics Satoskar 20th Edition  Essentials of Medical Pharmacology KD Tripathi 6th Edition www.indiandentalacademy.com
  72. 72.  Oral Histology & Embryology Orban 12th Edition  J Contemp Dent Practice 2008; 9: 001- 032  O O O E 2008;106:58- 65  British Dental Jour 1992;172:305- 312 www.indiandentalacademy.com
  73. 73.  Burket's Oral Medicine 11th Edition  Salivary gland dysfunction: A review of systemic therapies OOOE 2001;92:56-62  An update of etiology and management of xerostomia OOOE 2004;97:28-46  Drooling of saliva: A review of etiology and management options OOOE 2006;101:48-57 www.indiandentalacademy.com
  74. 74. Thank You www.indiandentalacademy.com