Antihypertensives , Anticoagulants, and Antidepressants:

1. Antihypertensives, Anticoagulants, and Antidepressants: Important Dental Implications Ann R. Witham, D.V.M.

2. Learning Objectives: What you will (hopefully) be able to do after this talk • How to perform risk assessment • How to know when to refer • How to manage and prevent complications when treating patients on: • Antihypertensive medications • Anticoagulants • Antidepressants

3. Hypertension: The Silent Killer. Hypertension defined: • Chronic illness, affects > 1 billion worldwide • One of leading risk factors for cardiovascular disease mortality • Systolic BP of 140 mm Hg or diastolic BP ≥ 90 mm Hg • BP readings elevated on at least 2 occasions with or without provocation

4. Two Main Types of Hypertension • Primary: 90-95% of all • Secondary: caused by • vascular diseases • Cushing’s syndrome • Sleep apnea, hormonal dysfunction, substance abuse, alcohol consumption, contraceptive use, and chronic kidney disease

6. Risk Factors for Primary Hypertension? • How many can you name? • Shout out!

7. Risk Factors • Diabetes • Reduced nephron number • Family history • Age • Contraceptive use/menopause • Excessive alcohol consumption • Dyslipidemia • High sodium diet • Physical inactivity • Low education • Socioeconomic status • Obesity • Race • Personality traits/depression • Hypovitaminosis D • Tobacco use • Stress

8. BP = Cardiac Output x Peripheral Resistance BP = (Heart Rate x Stroke Volume) x Peripheral Resistance To alter BP, you must alter either HR, SV, or PR.

10. Key Regulators of Blood Pressure • Sympathetic nervous system • Renal system related to blood volume • Renin angiotensin aldosterone mechanism Antihypertensive drugs act on one or more of these control mechanisms.

11. Consequences of Hypertension • Damages vasculature. • Damages major organs ( including kidneys), eventually causes HF • Increased morbidity and mortality

12. Main Categories of Antihypertensives • Diuretics – • Beta-blockers • Angiotensin-converting enzyme inhibitors (ACEI’s) • Angiotensin II receptor blockers • Calcium channel blockers (CCB’s) • Alpha blockers • Alpha 2 agonists • Vasodilators • Others!!

13. Diuretics • How do they work? • Increase urine production  decrease blood volume  decrease stroke volume (SV)  decrease blood pressure

14. Diuretics • Act by increasing the amount of sodium ions and water that are excreted by the kidneys into the urine • Three major classes of diuretics • Thiazides • Loop diuretics • Combinations

16. Thiazides: Adverse Effects and Drug Interactions • Hypotension • Hypokalemia (increases chance for arrhythmias, especially with digoxin toxicity) • Hyperglycemia, hyperlipidemia, hypercalcemia • Gout (hyperuricemia): inhibits uric acid secretion • NSAIDs can reduce antihypertensive effect of thiazides • Crossover allergies with sulfa antiinfective drugs possible because thiazides are sulfonamides • Caution with epinephrine in patients taking thiazides and digoxin

17. Loop Diuretics • Pharmacologic class: loop diuretic • Prevents chloride reabsorption in loop of Henle; greatly increases urine output. • Increases K+, Mg+2, Ca+2 and uric acid excretion • Prototype: furosemide (Lasix) • Indications • Hypertension • Edema

18. Potassium-Sparing Diuretics • Pharmacological class: K+-sparing diuretic • Used in combination with thiazides • Counteracts the effects of thiazides on potassium loss • Pharmacologic effects: decreases K+ excretion while increases Na+ excretion (increasing urine production) • Prototype: spironolactone (Aldactone) • Combination drugs: • HCTZ with triamterene (Dyrenium) = (Dyazide, Maxzide) • HCTZ with spironolactone (Aldactone) = (Aldactazide) • Indications: • hypertension • hypokalemia

20. Antiadrenergic Drugs- alpha and beta blockers • Act by inhibiting sympathetic activity • Decrease HR and contractility Decrease cardiac output  decrease blood pressure • Sympathetic NS controls blood pressure by • Increasing HR • Vasoconstriction • Increasing contractility of heart • Examples: • Alpha adrenergic blockers • Beta adrenergic blockers

21. Alpha Adrenergic Blockers • Competitive inhibitors of norepinephrine and epinephrine at alpha adrenergic receptors. • Leads to vasodilation of arteries/arterioles • Decrease PR! • Examples: • prazosin (Minipress) • terazosin (Hytrin) • doxazosin (Cardura)

22. Beta Adrenergic Blockers • Competitive inhibitors of NE and Epi at beta adrenergic receptors • Leads to decreased HR and decreased contractility of heart • Examples: • propranolol (Inderal) • atenolol (Tenormin) • metoprolol (Lopressor) • esmolol (Brevibloc) • retaxolol (Kerlone) • penbulolol (Levatol) • sotalol (Betapace) • risoprolol (Zebeta)

23. ACE Inhibitors = Angiotensin Converting Enzyme Inhibitors • Used in persons with normal renal function • Pharmacologic effects: • Inhibits formation of angiotensin II, thus decreasing vasoconstriction = causing vasodilation • Decreases aldosterone secretion  decreasing sodium retention and water retention = causing sodium elimination and water elimination, decreasing blood volume and decreasing blood pressure

24. Blood Pressure Regulation • Renin-Angiotensin System (Renin-Angiotensin-Aldosterone) This endocrine pathway works to maintain blood volume in order to maintain BP. • Kidney (JG Apparatus cells) detect decrease in blood volume  secrete Renin into blood. • Renin, an enzyme, converts circulating Angiotensinogen to Angiotensin I. • As Angiotension I circulates in the blood through the lungs, an enzyme on the surface of pulmonary capillary endothelial cells, Angiotensin Converting Enzyme (ACE), converts Angiotensin I to Angiotensin II: an active hormone. Renin ACE Angiotensinogen Angiotensin I Angiotensin II

25. Blood Pressure Regulation • Renin-Angiotensin-Aldosterone System (continued) Effects of Angiotensin II • Increased secretion of aldosterone by adrenal cortex. • Increased secretion of ADH by posterior pituitary. • Increased vasoconstriction (___ PR) • Increased thirst center activity. (__ Body fluids  __ SV)) RESULTS: Increased reabsorption of Na+ in the DCT & CT of renal tubule. Increased reabsorption of water in the DCT & CT of renal tubule. INCREASES BLOOD VOLUME  INCREASED SV HR x SV x PR  BP

26. Angiotensin II causes the secretion/production of which 2 hormones? • Renin and aldosterone • Aldosterone and ADH • Angiotensin I and renin • Cortisol and insulin • Estrogen and testosterone

28. ACE Inhibitors- • Side effects • Hypotension • Dry cough • others include loss of taste, rash, jaundice, hyperkalemia, renal damage • Examples: all end in –pril • enalapril (Vasotec) • captopril (Capoten • lisinopril (Zestril) • quinapril (Accupril) • ramipril (Altace) • moexepril (Univasc) • fosinopril (Monopril) • renzapril (Lotensin

29. Calcium Channel Blockers • Mechanism: inhibits entry of calcium into cells. • Bottom line: Decrease heart rate & contractility and decrease vasoconstriction  Decrease CO and PR Decrease blood pressure • Also leads to decreased vasoconstriction • Decreased HR • Decreased contractility

30. Calcium Channel Blockers: Pharmacologic Effects/ Indications • Coronary and peripheral vasodilation • Decreased HR • Decreased contractility Clinical Indications: HTN arrhythmias angina

31. Calcium Channel Blockers • Examples: “rap” and “dip” • verapamil (Isoptin) • nifedipine (Procardia) • diltiazem (Cardizem) exception • nisoldipine (Sular) • amlodipine (Norvasc) • nicardipine (Cardene) • felodipine (Plendil)

32. Angiotensin II antagonists e.g. Losartan (COZAAR) Mechanism: prevents Ang II from binding to its receptor Effects - same as ACE inhibitor without the bradykinin effect Adverse effects – same AE’s as ACE inhibitor without the dry cough and angioedema

33. Match the antihypertensive to its category, just for fun! • Lisinopril ______ • Verapamil ______ • Prazosin ______ • Metoprolol ______ • Furosemide ______ • Spironolactone ______ • Hydroclorothiazide ______ • Losartan ______ • Calcium channel blocker • Potassium sparing diuretic • Loop diuretic • ACE inhibitor • Beta blocker • Angiotensin II blocker • Alpha-1 blocker • Thiazide diuretic

34. Which are the most common ones??

35. Management of Dental Patients Taking Antihypertensive Drugs • Adverse Effects: • Xerostomia • Dysgeusia • Gingival enlargement (Calcium channel blockers) • Orthostatic hypotension • Lichenoid reactions

37. Drug Interactions of Concern • Common drug interactions with antihypertensives often occur with drugs the dental professional prescribes. • Local anesthetics with or without epinephrine • Conscious sedation of anxious patients • NSAIDS and antifungals are commonly prescribed

38. Hypertensive Crisis- Emergency • Medication noncompliance is one of most significant factors • Thorough history, always take BP reading. Severe increase >180/120 mm Hg or acute rise after previously normal baseline can be caused by • Neurologic deficits due to stroke • Nausea/vomiting from hypertensive encephalopathy and increased intracranial pressure • Chest discomfort from MI or aortic dissection • Back pain from aortic dissection • Dyspnea from pulmonary edema • Pregnancy hypertension; pre-ecclampsia

39. Complications associated with use of vasoconstrictors • Epinephrine – hemostatic agent with local anesthetics • Also used in retraction cord to improve overall vision and control hemorrage in taking impressions for crown and bridge • Risks of using epinephrine in hypertensive population • Acute hypertensive or hypotensive episodes, angina pectoris, arrhythmias, and MI • Epi in local anesthetics can affect hemodynamics of a patient. (recent study, 2015) • 1:80,000 can affect SBP and DBP as well as heart rate • 1:100,000 can exacerbate SBP and heart rate • 1:200,000: exacerbate heart rate

40. Continued, vasoconstrictor complications • Continued: consider concentrations of 1:200,000 before tooth extraction to prevent significant hemodynamic changes • Use of impregnated retraction cord has been discouraged in patients with uncontrolled hypertension • 0,04 mg epi total dose for those with CV disease.

41. Drug interactions with vasoconstrictors • Epinephrine interacts with some antihypertensive agents • Beta blocker + epi  possible hypertension and relex bradycardia • Diuretics produce hypokalemia; with epi can be exacerbated, causing arrhythmia • Epinephrine + cocaine  blood pressure spikes and fatal dysrhythmias.

42. Bleeding Issues • Elevated BP can cause excessive bleeding • In patients who are on anticoagulants, if INR (international normalized ratio) value is <4, no need to stop anticoagulant therapy before minor surgery. • For aspirin or other antiplatelet drugs like clopidogrel, continue with procedure even if minor surgery • Various hemostatic agents can be used in the above cases

43. Racial/Ethnicity disparity-associated hypertension • Prevalence of hypertension in African Americans is highest in the world, 41.4% of hypertensive patients. • Cause? • Access to care, poor diagnoses • Poor treatment/medication noncompliance • Socioeconomic status • Still it’s duty of health care provider to aid in prevention and education of hypertension

45. Your client’s BP is 181/120. This person is experiencing: • Stage I hypertension • Stage II hypertension • Pre-hypertension • Normal blood pressure • Hypertensive crisis • ”White coat” hypertension

46. Break

47. Pharmacology of Antidepressants:Clinical Considerations

48. Introductory information on antidepressant use • Widespread use: 21% of the 1,800 patient dental records reviewed showed antidepressant use. (Josephe et al, 2003). Watch for increased evidence of oral lesions! • Used in patients of all ages! • Used to treat many psychiatric diseases (depression, affective disease, insomnia, anxiety, panic syndrome, bipolar) • Used to treat other medical conditions like rheumatoid arthritis, dietary disorders, fibromyalgia, migraine, trigeminal neuralgia, premenstrual tension (Keene et all, 2003)

49. Clinical Depression – sometimes confused with other causes Major depression, situational depression • postpartum depression, premenstrual dysphoric syndrome, seasonal affective disorder • side effects of some drugs (glucocorticoids, levodopa, oral contraceptives) mimic depression • B-vitamin deficiencies, thyroid disorders, Alzheimer’s disease may be misdiagnosed as depression • alcoholism and drug abuse may be misdiagnosed as depression or can be contributing factors to the development of depression

50. Depression