Pharmacology

1. Pharmacology Oral Conditions & Their Treatment

2. I. Infectious Lesions • Acute Necrotizing Ulcerative Gingivitis (ANUG) Definitions: • a.k.a Vincent’s infection or trench mouth • develops with bacteriologic (spirochetes) and environmental (stress, debilitation) factors • spreading ulcer with distinctive odor; begins at the interdental papillae

3. I. Infectious Lesions • Acute Necrotizing Ulcerative Gingivitis (ANUG) Treatment: • good oral hygiene • mouthwashes – hydrogen peroxide or saline rinses (flushing), if bacterial type of infection (saline rinse) • aspirin or acetaminophen if pain or ↑ temperature exists • food supplements if difficulty eating • vitamin supplements if vitamin deficiency • antibiotics ONLY IF immunosuppressed or systemic infection exists → penicillin VK or metronidazole • topical chlorhexidine gluconate – rinse effective on g+, g- and Candida organisms\ • DRAMATIC RESPONSE to oral prophylaxis with scaling

4. I. Infectious Lesions • Herpes Infections Primary herpetic gingivostomatitis • Read p259-261 (Herpes review) • SHOULD KNOW-Treatment options • -acyclovir as ex. • Candidiasis • Read p261 • SHOULD KNOW-Treatment options

5. I. Infectious Lesions • Angular Cheilitis / Cheilosis Definitions: • cracks in the corners of the mouth • appearance: redness, fissures, erosion, ulcers & crusting; WITH or WITHOUT pain • most cases → mixed infection → Candida albicans plus g+ bacteria • occurs as a result of drooling • treatment: treat the secondary infection

6. I. Infectious Lesions • Angular Cheilitis / Cheilosis Treatment: • if Candida – topical antifungal agents such as nystatin, clotrimazole, miconazole • if inflammation – antifungal mixed with a topical steroid such as Mycolog (Mycostatin + Kenalog) • if bacterial overgrowth – systemic penicillinase-resistant penicillins such as dicloxacillin • newerantibiotic mupirocin (Bactroban) – topical antibiotic that ↓ likelihood of adverse reactions & is as effective as penicillinase-resistant penicillins • mupirocin + topical antifungal agent can be used together if indicated

7. I. Infectious Lesions • Alveolar Osteitis Definitions: • a.k.a. “dry socket” • occurs as a result of tooth extractions but uncommon (only in 2-3% of cases) • most common in the lower molar areas • caused by loss or necrosis of the blood clot formed at extraction site thus, exposing the underlying bone → severe pain!

8. I. Infectious Lesions • Alveolar Osteitis Predisposing Factors: • BCP’s & the menstrual cycle, smoking (negative pressure) and diabetes Symptoms: • infection, swelling, ↑ temperature, lymph-adeno-pathy and a foul odour Treatment: • saline rinses, debridement, dry socket pack & analgesics • antibiotics – ONLY IF infection present or in patients at high risk of infections (treatment not prophylaxis)

9. II. Immune Reactions • Recurrent Aphthous Stomatitis (RAS) Definitions: • a.k.a. “canker sore” • common oral lesion occurring in about 20% of the population • unknown etiology – involvement of the immune system suspected • presents as a few small to many large ulcers (can also coalesce into giant ulcers) • 3 different types: minor, major & herpetiforme • minor most common – flat, white lesion on the mucosa • hypotheses on etiology: allergenic / hypersensitivity, genetic, hematologic, hormones, infection, nutrition, trauma & stress • also some question OTC toothpastes that contain sodium lauryl sulfate *Know table 14-2* Dentifrices that do not contain sodium lauryl sulfate

10. II. Immune Reactions • Recurrent Aphthous Stomatitis (RAS) Treatment: • corticosteroids – reduce inflammation • example: fluocinonide and betamethasone • carboxymethylcellulose paste (Orabase) – hardens into a plasticlike plaster (steroids in this paste) • severe cases, systemic steroids given • amelorex (Aphthasol) - topical • ↓ duration of both healing & pain • diphenhydramine (die-fen-hydra-mine) • preferred due to its L.A. action • antihistamine • immunosuppressives • last resort to treat severe aphthous • example: azathioprine (Imuran) & cyclosporin (Sandimmune)

11. II. Immune Reactions • Lichen Planus Definitions: • skin condition with frequent oral lesions on the mucous membranes • oral lesions present without skin lesions in 65% of cases • 3 types: striated, plaquelike & erosive • hypertrophic type (erosive) the most prevalent – white lace-like pattern Symptoms: • varying pain from no pain to extreme pain depending on the presence of ulcerations Etiology: • unknown • hypotheses – viral infection, an autoimmune disease & hypersensitivity reaction to an unknown agent (toothpaste)

12. III. Miscellaneous Oral Conditions • Geographic Tongue Definitions: • world map like lesions on tongue with lesions appearing to be the continents • ringed lesions with erythema – centers are white • changes in patterns over time & may also disappear at times Etiology: • unknown; relations to hormonal changes, stress, infection, psoriasis, or autoimmune diseases • burning becomes severe with spicy foods or alcohol Treatment: • reassurance and avoidance of irritating food & alcohol

13. III. Miscellaneous Oral Conditions • Burning Mouth or Tongue Syndrome Definitions: • a.k.a. glossodynia & glossopyrosis • oral cavity appears normal but patient reports discomfort described as pain or burning sensation that ↑ in severity through the day • painful tongue with or without observable alterations on the tongue • caused by local or systemic conditions • redness, burning, stinging, or itchiness can occur Etiology: • unknown; hypotheses – xerostomia, candidiasis, acid reflux, nutritional deficiency, immunologic, hormonal changes, allergic reaction, inflammatory process, psychogenic or idiopathic reaction • depression or chronic disease may play a role Treatment: • depends on practitioner’s beliefs of cause

14. IV. Inflammation • Pericoronitis Definitions: • inflammation of the tissue around the crown of the tooth • most common location: partially erupted third molars (wisdom teeth) • food & bacteria trapped between the operculum and the tooth – painful & swelling Treatment: • debridement with saline irrigation and warm saline rinses • extraction if indicated • repeated episodes could occur with partially erupted third molars • analgesics: for discomfort • infection: in debilitated patients could spread rapidly thus, treat with antibiotics

15. IV. Inflammation • Postirradiation Caries Definitions: • changes in saliva after irradiation therapy & lack of proper plaque control can rapidly ↑ rate of dental caries • cervical decay evident after the first year Treatment: • meticulous oral hygiene, frequent cleanings, artificial saliva's, self-administered fluoride gel 4 time daily (extreme cases) in a bite guard

16. IV. Inflammation • Root Sensitivity, recession Definitions: • sensitivity of exposed root surfaces precipitated by heat, cold, sweet or sour foods; even scaling • occlusal trauma – adjustment is treatment • periodontal surgery, extensive root planing, or accumulation of plaque can also cause sensitivity Treatment: • difficult to manage; glycerin, sodium fluoride, stannous fluoride, adrenal steroids • desensitizing toothpastes help some patients but research lacking

17. IV. Inflammation • Actinic Lip Changes Definitions: • long-term exposure of lip to the sun → irreversible tissue changes known as actinic cheilitis • near vermillion border & could lead to malignancy Treatment: • sunscreen (higher that 15 protection) • if keratotic changes – antineoplastic agent that promotes sloughing( example: 5-fluorouracil)- (5-FU) • topical steroid may be used to relieve irritation produced by 5-FU • Common cream, used daily

18. V. Drug-Induced Oral Side Effects • Xerostomia Sjögren’s syndrome Definitions: • dry mouth • may result from a drug (e.g. atropine), a disease, aging or radiation • many drug groups can produce xerostomia such as anticholinergics and other drugs with anticholinergic side effects • can produce ↑ in incidence of caries (especially Class V lesions)

19. V. Drug-Induced Oral Side Effects • Xerostomia Treatment: • caries prevention • fluoride trays & gels • artificial saliva • home care • fluoride rinses or trays • water & sugarless gum; NO sugar gum or candy • change medication or reduce dose • depending on indications for use • Pilocarpine a cholinergic agent - P+; increases saliva (sialorrhea,sialosis, and sialism)

20. V. Drug-Induced Oral Side Effects • Sialorrhea • a.k.a. sialosis or sialism • certain drugs can increase in saliva; example: pilocarpine • Hypersensitivity-Type Reactions • may be hyperimmune responses to an antigenic component of the drug • contact stomatitis – localized with gum or candy & diffuse with toothpaste • buckle mucosa & lateral borders of tongue involved • cinnamon flavoured products can produce this response • potential for reaction depends on: particular drug, frequency and route of administration (topical Ab’s more likely to cause rx), patient’s immune system

21. V. Drug-Induced Oral Side Effects • Oral Lesions That Resemble Autoimmune-Type Reactions • Lupus-like reactions: • oral lesions occurring with lupus erythematosus • also produced with antiarrhythmic & anticonvulsant drugs • Erythema multiforme-like: • drugs such as anticonvulsants can produce lesions that resemble this • Stains • primary or adult dentition • tetracyclines are main group of drugs causing stains • chlorhexidine rinse as well as liquid iron can cause extrinsic stains

22. V. Drug-Induced Oral Side Effects • Gingival Enlargement • a.k.a. gingival hyperplasia • can occur most commonly with: • phenytoin (Dilantin): half the patients exhibit this reaction; oral hygiene must be meticulous • cyclosporin (Sandimmune): antirejection drug – kidney transplant & other transplants • calcium channel blockers (CCB): used for hypertension & congestive heart failure (CHF) • other: carbamazepine (Tegretol) – anticonvulsant

23. VI. Common Agents Used to Treat Oral Lesions • Corticosteroids • used for inflammation or immune response • depending on severity of lesions, topical corticosteroids selected based on their potency • weak, intermediate or potent used in turn until agent is effective • hydrocortisone cream 1% is popular OTC • if topical ineffective or condition severe, systemic corticosteroids may be used • most common: prednisone • if chronic systemic corticosteroids need to be used then adverse reactions must be managed: • osteoporosis, fluid retention, diabetes, hypertension, moon face &buffalo hump

24. VI. Common Agents Used to Treat Oral Lesions • Palliative Treatment • designed to make patient more comfortable • topical or systemic agents to ↓ pain in oral cavity (sometimes can be used together for pain management) • systemic analgesics can often provide relief from a painful oral lesion • topical local anesthetics could cause reduction of sensations of throat leading to possible choking • isolated lesions: paint on the anesthetic with cotton swab

25. Pharmacology - CVD

26. Introduction • cardiovascular disease (CVD): various diseases of the heart & blood vessels • leading cause of death; 25% of top 200 drugs from this group • examples: hypertension (↑ blood pressure), angina pectoris, cerebrovascular accident (CVA), congestive heart failure (CHF) & hypercholesterolemia (↑ cholesterol) • medical histories are a VERY important identifier of CVD & the accompanying list of one or more medications

27. I. Dental Implications of CVD • Contraindications To Treatment • certain circumstances dictate that dental procedures may be delayed until CVD under better control • absolute contraindications are highlighted on page 273 (Box 15-1) • these absolute contraindications apply only to uncontrolled or severe CVD

28. I. Dental Implications of CVD ii.Vasoconstrictor Limit majority of CVD can have L.A. with vasoconstrictor – epinephrine; severity of the disease must be considered endogenous epinephrine could be released anyways, if we have poor pain management, so epinephrine in L.A. may be useful limit epinephrine to cardiac dose (0.04 mg) in severely affected patients use slow rate of injection & appropriate aspiration techniques

29. I. Dental Implications of CVD • Infective Endocarditis • if rheumatic heart disease or other valvular or degenerative disease discovered on medical history, risk of producing infective endocarditis present • prophylactic antibiotics should be considered

30. I. Dental Implications of CVD • Cardiac Pacemakers • an electrical device implanted into patient’s chest to regulate heart rhythm • if not shielded properly, some devices used in dentistry (ex. cavitron) may interfere with activity of pacemaker; get medical clearance • patients DO NOT require prophylactic antibiotics • Periodontal Disease & CVD • studies show that presence of periodontal disease predicts an ↑ in morbidity & mortality resulting from CVD

31. II. Cardiac Glycosides Definitions • the heart is a pump: adequate circulation of blood to meet oxygen needs of body • when needs ↑ (ex. exercise), normal heart adjusts the output • Congestive Heart Failure (CHF): a “failing” heart; the heart does not provide adequate cardiac output to provide for the oxygen needs of the body • occurs when heart suffers injury (myocardial infarction, arrhythmias, valvular abnormalities, rheumatic heart disease) • enlargement takes place (ok at first but later too much enlargement) thus, too much blood to pump out – tachycardic • usually, left side fails first → blood backs up into lungs → pulmonary edema → dyspnea & orthopnea • dental patients – semi-reclined position • if right side failure → systemic congestion → peripheral edema (pedal edema)

32. Antiarrhythmic Agents Definitions • arrhythmia & dysrhythmia used synonymously to mean “abnormal rhythm” • results from abnormal impulse generation or abnormal impulse conduction • cardiac diseases such as arteriosclerosis & heart block can produce arrhythmias • antiarrhythmic agents used to prevent arrhythmias • various types of arrhythmias – divided into: • supraventricular (atrial) • ventricular • can cause tachycardia or bradycardia

33. Antiarrhythmic Agents • Antiarrhythmic Agents • work by depressing parts of the heart that are beating abnormally • examples of specific action of these drugs: • ↓ velocity of depolarization • ↓ impulse propagation • inhibition of aberrant impulse propagation • digoxin – not classified as an antiarrhythmic drug but used as one; toxic doses can cause ventricular arrhythmias

34. Antiarrhythmic Agents • Adverse Reactions • antiarrhythmic agents are difficult to manage therefore, only used in patients with arrhythmias that prevent proper functioning of the heart

35. Antianginal Agents Definitions: angina pectoris: common cardiovascular disease characterized by pain or discomfort in the chest radiating to the left arm or shoulder; sometimes radiating to the neck, back & lower jaw (can be confused with a toothache) coronary arteries do not supply enough O2 to the myocardium for its current work anginal pain precipitated by stress, physical exercise or emotional (anxiety of dental appt.) pharmacologic effects of antianginal agents - ↓ C.O., ↓ peripheral vascular resistance or both; thus, O2 requirement of heart ↓ - reduces pain anginal episode can occur at any time & have emergency procedures ready antianginals reduce symptoms only; not curative

36. Antianginal Agents • Nitroglycerine-Like Compounds • nitroglycerine (NTG) – most frequently used nitrate for management of angina induced by stress or exercise • also used to manufacture dynamite • vasodilator – relaxation of vascular smooth muscle throughout the body • ↓ O2 demand • tolerance can occur unless a nitrate-free period is observed daily

37. Antianginal Agents • Nitroglycerine-Like Compounds Sublingual Nitroglycerin • used to treat acute anginal attacks • rapid onset (minutes); lasts up to 30 mins. • sublingual tablet - Nitrostat • sublingual spray - Nitrolingual • dental patients usually bring these agents with them or should be reminded to do so & should be kept ready on the bracket table • dental office emergency kit should contain these meds

38. Antianginal Agents • Nitroglycerine-Like Compounds Adverse Reactions • severe headaches (vasodilation) • flushing • hypotension (enhanced by alcohol & hot weather) • light-headedness • syncope • localized burning or tingling at site of administration (with sublingual NTG)

39. Antianginal Agents • Nitroglycerine-Like Compounds Storage • NTG degraded by heat & moisture; NOT by light • should be stored in original brown glass container; tightly closed; do not refrigerate • unopened bottle: active until expiration • opened bottle: date opened should be written on outside of the bottle & the medication should be discarded between 3-6 months • NTG spray: until expiration date (no air in bottle)

40. Antianginal Agents • Nitroglycerine-Like Compounds • long-acting NTG-like products such as isosorbide dinitrate used for prophylaxis of anginal attacks • tablets & topical ointment, patch products available • with long-term, regular use, tolerance develops – 8-12 hour “vacation” everyday needed to prevent this

41. Antianginal Agents • Calcium Channel Blocking Agents • CCB’s inhibit movement of Ca+ during contraction of cardiac & smooth muscle • some CCB’s ↓ myocardial contractility (↓ C.O.) & others ↑ coronary vasodilation • also used for arrhythmias & hypertension • adverse reactions include constipation & hypotension • nifedipine – gingival enlargement (like Dilantin) & dysgeusia • frequent appt’s & meticulous oral hygiene • examples: • vera-pam-il (Calan, Isoptin) • dil-tia-zem (Cardizem) • ni-fed-ipine (Procardia, Adalat)

42. Antianginal Agents • Dental Implications Treatment of acute anginal attack • be prepared! Have emergency kit with NTG in supply & not expired • place NTG on bracket table • if needed, sublingual NTG should be administered while seated upright • one tablet at once, 5 mins later – another one and 5 mins later – another one • if this does NOT help, go to emergency • do not inhale if using spray-type NTG

43. Antianginal Agents • Dental Implications Prevention of anginal attacks • pretreatment with an anxiolytic (benzodiazepine or N2O) or with sublingual NTG • anxiolytic - ↓ anxiety & ↓ stress on heart; N2O relaxes as well • NTG – give as a premedication to anxiety-provoking dental procedure such as L.A. Myocardial Infarction (MI) • if anginal attack not relieved by 3 doses of SL NTG, MI could be suspected → take to emerg

44. Antihypertensive Agents Definitions: Categories for hypertension: • essential • 85-90% of cases; treated with antihypertensive drugs • a.k.a. idiopathic or primary; unknown cause • secondary • 10% of cases; associated with other disease such as endocrine or renal disease; treat initial cause/disease • steroids, NSAIAs, BCPs, decongestants & antidepressants can produce • malignant • small # of cases (5% of people with primary or secondary hypertension); BP very high or rapidly rising • evidence of retinal or renal damage exists

45. Antihypertensive Agents Stepped-Care Regimen • pharmacologic management of HT involves stepped-care approach • Step 1 • lifestyle changes: ↓smoking, ↓stress, ↓weight, ↓salt, ↑exercise • Step 2 • therapy with “Big 5” group of antihypertensive drugs • several drugs from different groups can be used; ↓side effects • diuretics (> 50 yo’s) and peripheral vascular disease • β –Blockers (< 50 yo’s) and ischemic heart disease • Step 3 • ↑ dosage; combined with other drugs – vasodilators/adrenergic blockers • Step 4 • mixing 2-3 drugs already mentioned

46. Antihypertensive Agents Dental Considerations: regardless of medication usage, BP of each HT patient should be measured & recorded patients should be questioned about compliance re: their antihypertensive medication abrupt discontinuation could cause rebound hypertension – BP rises to higher level than it was before treatment

47. Antihypertensive Agents • Diuretic Agents 3 types: • Thiazide Diuretics • Loop • Potassium-sparing

48. Antihypertensive Agents • Diuretic Agents • Thiazide Diuretics Adverse Reactions: • hypo-kal-emia - ↓K+ - could cause arrhythmias; if patient taking digoxin, potential for arrhythmias exacerbated • hyper-uricemia -↑uric acid in blood – watch out for patients with gout • hyper-glycemia – watch out for diabetics • hyper-lipid-emia - ↑fats/lipids • hyper-ca-lcemia - ↑ Ca+ • anorexia - ↓appetite / food aversion • oral: xerostomia, oral lichenoid eruptions • reversible on discontinuation of meds (with time) • NSAIAs (usually used by patients for arthritis) ↓ antihypertensive effect of HCTZ – takes few days to manifest so a few days of NSAIA okay for acute pain; HT meds have to be adjusted for chronic usage • limit epinephrine to cardiac dose • thiazides potentiate action of other antihypertensives → hypotension

49. Antihypertensive Agents • β-Adrenergic Blocking Agents • suffix of drugs -olol • propranolol – blocks both β1 & β2 receptors • selective β-blockers (β1 > β2) have advantages in patients who may have asthma • less likely to produce a drug interaction with epinephrine • these drugs lower BP by ↓C.O. • usually used in step 2 therapy – alone or in combination with other antihypertensive drugs

50. Antihypertensive Agents • Calcium Channel Blocking Agents Pharmacologic Effects: • smooth muscle – vascular smooth muscle relaxed, dilation of coronary & peripheral arteries & arterioles → reduces preload • cardiac muscle - ↓HR, ↓contractility & conduction