Pharmacologic Management of the Geriatric Patient: Practice Considerations for Oral Healthcare Professionals

Special Care in Dentistry, New Orleans April 20, 2013

Ann Eshenaur Spolarich, RDH, PhD

Where do I find good information about drugs and herbs?

Lexi-Comp www.lexi.com

Drug Information Handbook for Dentistry; Authors: Wynn R, Crossley H and Meiller T

Lexicomp Online; Lexi-Interact Online (subscriptions)

Oral Soft Tissue Diseases; Authors: Newland RJ, Meiller T, Wynn R, Crossley H

Dental Drug Reference with Clinical Implications; 2nd edition; Authors: Frieda Atherton Pickett and Geza Terezhalmy; Lippincott Williams & Wilkins

National Center for Alternative and Complementary Medicine http://nccam.nih.gov/

Natural Standard Research Collaboration (subscription) http://www.naturalstandard.com/

1. hydrocodone and acetaminophen 2. hydrocodone and acetaminophen

3. levothyroxine sodium 4. lisinopril

5. Lipitor 6. simvastatin

7. Plavix 8. Singulair

9. azithromycin 10. Crestor

11. Nexium 12. levothyroxine sodium

13. metoprolol tartrate 14. hydrocodone and acetaminophen

15. Synthroid 16. Lexapro

17. Proair HFA 18. ibuprofen

19. trazodone HCl 20. amoxicillin

INDICATIONS / DRUGS
pain relievers / hydrocodone and acetaminophen, ibuprofen
hypercholesterolemia / Lipitor, simvastatin, Crestor
hypertension / lisinopril, metoprolol
adverse thromboembolic events / Plavix
endocrine disorders / levothyroxine, Synthroid
antibiotics / amoxicillin, azithromycin
antidepressants / Lexapro, trazodone
GERD, reflux or hypersecretory disease / Nexium
respiratory disease / Singulair, ProAir HFA

Source: Top 200 Medications for 2011. Source: IMS Health. Available at:

http://www.pharmacytimes.com/publications/issue/2012/July2012/Top-200-Drugs-of-2011

Popular Herbs and Supplements

·  A national survey conducted in 2007 found that 17.7% of American adults had used "natural products" in the past 12 months

o  dietary supplements other than vitamins and minerals

·  The most popular products used by adults for health reasons in the past 30 days were:

fish oil/omega 3/DHA (37.4%)

o  glucosamine (19.9%)

o  echinacea (19.8%)

o  flaxseed oil or pills (15.9%)

o  ginseng (14.1%)

·  52% of adult respondents said they had used some type of supplement in the last 30 days

multivitamins/multiminerals (35%)

vitamins E and C (12-13%)

o  calcium (10%)

B-complex vitamins (5%)

Barnes PM, Bloom B, Nahin R. Complementary and alternative medicine use among adults and children: United States, 2007. CDC National Health Statistics Report #12. 2008.

Supplement Use in Seniors

·  130 study participants (mean age 71.4 years)

·  prevalence of polypharmacy: 72.3% (n = 94)

o  38.5% (n = 50) taking five or more medications

§  major polypharmacy

o  16.2% (n=21) reported taking two or more herbs

§  polyherbacy

o  26.2% (n=34) reported taking two or more vitamin/mineral supplements

o  6.9% (n=9) reported using two or more nutraceuticals

·  46.2% (n = 60) at risk of having at least one potential drug-drug interaction

·  31.5% (n = 41) at risk of having at least one possible drug and herbal-supplement interaction

Loya, AM,González-Stuart, A,Rivera, JO. Prevalence of Polypharmacy, Polyherbacy, Nutritional Supplement Use and Potential Product Interactions among Older Adults Living on the United States-Mexico Border: A Descriptive, Questionnaire-Based Study. Drugs & Aging. May 5 2009; 26(5):423-436.

Supplement Use in Older Adults

·  Herbal product(s) and dietary supplements used

Glucosamine or glucosamine/chondroitin

o  Garlic

o  Echinacea

o  Gingko biloba

o  Herbal tea

o  Cod liver oil

o  St John's wort

o  Ginseng

o  Saw palmetto

o  Other

·  A total of 90 different herbs or supplements were used by participants

Marinac JS, Buchinger CL,Godfrey LA, Wooten JM, Sun C, Willsie SK. Herbal Products and Dietary Supplements: A Survey of Use, Attitudes, and Knowledge Among Older Adults. JAOA January 2007;107 (1):13-23.

Herbal Dietary Supplement (HDS) and Medication Interactions and Contraindications

·  Identified 1,491 pairs of HDS-drug interactions

o  213 HDS

o  509 medications

·  Greatest number of documented interactions with medications:

o  St. Johns wort

o  magnesium

o  calcium

o  iron

o  ginkgo

·  Of a total of 509 drugs, most were used for:

o  CNS disorders (100)

o  cardiovascular system disorders (90)

o  systemic anti-infectives (75)

·  Greatest number of reported interactions with HDS:

o  warfarin: most HDS interactions (100+)

o  insulin

o  aspirin

o  digoxin

o  ticlopidine

·  HDS products containing herbs were more likely to have documented interactions with medications and contraindications than vitamins, minerals and other types of dietary supplements.

·  152 identified contraindications

·  Most frequent contraindications involves:

·  gastrointestinal (16.4%)

·  neurological (14.5%)

·  renal/genitourinary diseases (12.5%)

·  59 HDS were contraindicated for use among patients with specific disease states

·  Highest number of documented contraindications:

·  flaxseed ( Linum usitatissimum)

·  echinacea ( Echinacea purpurea)

·  yohimbe ( Pausinystalia yohimbe)

Tsai HH, Lin HW, Simon Pickard A, Tsai HY, Mahady GB. Evaluation of documented drug interactions and contraindications associated with herbs and dietary supplements: a systematic literature review. Int J Clin Pract. 2012:66(11):1056-1078.

·  Flaxseed contraindications:

o  acute/chronic diarrhea

o  esophageal stricture

o  inflammatory bowel disease

o  hypertriglyceridemia

o  prostate cancer

Ulbricht CE. Natural Standard Herbs & Supplement Reference: Evidence-Based Clinical Review. St Louis, MO: Mosby/Elsevier, 2005.

·  Echinacea contraindications:

o  rheumatoid arthritis

o  systemic lupus erythematosus

o  leukosis

o  multiple sclerosis

o  tuberculosis

o  HIV infection

Cassileth BR. Herb-Drug Interactions in Oncology. Lewiston, NY: BC Decker, Inc., 2003; Mahady GB. Botanical Dietary Supplements: Quality, Safety and Efficacy. Lisse, The Netherlands: Swets & Zeitlinger Publishers, 2001.

·  Yohimbe contraindications:

o  anxiety

o  bipolar disorder

o  depression

o  mania and schizophrenia

o  benign prostate hypertrophy

o  kidney disease

Ulbricht CE. Natural Standard Herbs & Supplement Reference: Evidence-Based Clinical Review. St Louis, MO: Mosby/Elsevier, 2005; National Center for Complementary and Alternative Medicine. Herbs at a Glance. http://nccam.nih.gov/health/herbsataglance

It is estimated that > 50% of patients with chronic diseases or cancers use HDS

Miller MF, Bellizzi KM, Sufian M, Ambs AH, Goldstein MS, Ballard-Barbash R. Dietary supplement use in individuals living with cancer and other chronic conditions: a population-based study. J Am Diet Assoc. 2008;108:483-94.

HERBAL MEDICATIONS AND BLEEDING

Many herbal preparations act like anti-platelet and anticoagulant medications

THE G’S (Ginkgo, Ginseng, Garlic, Glucosamine, Ginger)

Ability to antagonize PAF (Platelet Activating Factor) = potentially increase bleeding

Garlic

Uses: anti-lipidemic, antimicrobial, anti-asthmatic, anti-inflammatory

Components implicated in bleeding: volatile oil and ajoene

-ajoene is an unsaturated sulfoxide disulfide that is a component of allicin

-allicin: a sulfinyl compound that gives garlic its strong odor and flavor

-effect of ajoene on platelets is irreversible: lasts for life of the platelet and potentiates the effect of other platelet inhibitors (e.g. aspirin)

-several sulfur containing compounds isolated from garlic have also demonstrated significant inhibition of human platelet aggregation

Effect: antiplatelet

-garlic oil exerts its effect on the archidonic acid pathway

-interrupting the synthesis of thromboxane

-stimulating the synthesis of prostacyclin

-decreases platelet aggregation and increases bleeding

-dose dependent effect

-occurs with both dietary garlic and garlic supplements

-alliin/allicin inhibit the production and/or release of chemical mediators: platelet activating factor (PAF) and adenosine = decreases platelet function (strongest sources of allicin is natural garlic clove)

Ginkgo

Uses: prevent decreased cerebral functions and peripheral vascular insufficiency associated with Alzheimer’s disease or age-related dementia

Components implicated in bleeding: terpenoids (terpene ginkgolides)

-potent antagonists of PAF

-long-lasting effects and rapid onset with oral dosing

Effect: ginkgo increases prothrombin time and decreases platelet activity

-many case reports of severe bleeding episodes with ginkgo use

-patients taking warfarin and aspirin are at risk for severe spontaneous bleeding with ginkgo use at recommended doses

Ginseng

Uses: anti-cancer, slows aging, prevent heart attack, improve digestion, reduce hypertension, strengthen immunity, CNS stimulant

Components implicated in bleeding: ginsenosides

Effect: inhibit PAF, platelet aggregation, thrombin and thromboplastin

-antagonizes the effects of warfarin (decrease effectiveness)

-potentiate bleeding when combined with aspirin, NSAIDS, warfarin, heparin

Ginger

Uses: relive motion and morning sickness, decreases pain and inflammation with arthritis, relieves upset stomach

Components implicated in bleeding: pungent principles (gingerol, shogaol, zingerone), volatile oils (bisabolene, zingiberene, zingiberol) and proteolytic enzymes

Effect: reduces platelet thromboxane and inhibits platelet aggregation

-mixed reports in the literature: effects may be most significant with raw ginger

Feverfew

Uses: anti-inflammatory (rheumatoid arthritis), Preventive for migraine headache, Muscle soreness

Components implicated in bleeding: sesquiterpene lactone, parthenolide

Effect: inhibits platelet aggregation

Fish Oils

Uses: skin disorders, cardioprotection, diabetes, headache, immune support, memory, PMS, ulcerative colitis, many others

Components implicated in bleeding: various derivatives of omega-3

Effect: Inhibit ADP-induced platelet aggregation. Increased bleeding time is suggested to be due to either less thromboxane (TXA2) or higher prostacyclin I3 levels (anti-aggregatory effects). Contradictory studies about effects on fibrinolysis and vascular plasminogen levels.

St. John’s wort

Use: manage mild to moderate depression

Components implicated in bleeding: hypericin: induces cytochrome P450 liver enzymes

Effect: induction reaction of drugs in the liver

-reduces anticoagulant effect of warfarin (increases clotting)

-decreases the effects of many medications

Vitamin E

Use: fat soluble vitamin used as a dietary supplement

Antioxidant: prevents the oxidations of vitamins A and C; protects polyunsaturated fatty acids in membranes from attack by free radicals; protects RBCs against hemolysis

Effect: may alter the effect of vitamin K on clotting factors, increasing hypoprothrombinemic (prothombinopenia) response to warfarin = delayed clotting of blood or spontaneous hemorrhage

HERB / COMMON USES / SOME SIDE EFFECTS AND INTERACTIONS
Echinacea / Common cold; cough and bronchitis; wound and burn care; urinary tract infection / Hepatotoxic, especially when used with other hepatotoxic drugs; may decrease effectiveness of corticosteroids
Feverfew / Migraine prophylactic; fever reduction; see above / Inhibits platelet activity; avoid use with warfarin; 5-15% of users may develop aphthous ulcers or GI tract irritation
Garlic / See above / Potentiates effects of warfarin; May decrease effectiveness of certain HIV protease inhibitor drugs
Ginseng / See above / Antiplatelet properties; Avoid use with other stimulants: risk for tachycardia and hypertension
Kava-Kava / Anxiolytic / Serious risks for hepatotoxicity; potentiates alcohol, benzodiazepines, barbiturates = caution with sedation and general anesthesia
Licorice / Gastric disorders; cough and bronchitis / Glycyrrhizic acid in licorice may cause hypertension and hypokalemia; contraindicated with chronic liver disease, renal insufficiency, hypokalemia
St. John’s wort / Depression and anxiety / Decreases effectiveness of drugs for HIV: protease inhibitors and non-nucleoside reverse transcriptase inhibitors; induces liver enzymes (altered drug metabolism); prolongs effects of general anesthesia (anecdotal reports)
Valerian / Mild sedative; mild anxiolytic / Potentiates effects of barbiturates
Vitamin E / Antioxidant; CVD prevention; wound healing; fibrocystic breast syndrome / Increased bleeding risk with other antiplatelet and anticoagulant medications; may affect thyroid function in otherwise healthy person; may enhance hypertension in hypertensive patients (≥ 400 IU per day)

Source: American Society of Anesthesiologists. Considerations for Anesthesiologists: What you should know about your patients’ use of herbal medicines and other dietary supplements. 2003. Available at: www.ASAhq.org.

Dental Considerations

- Synergistic interactions may occur with antiplatelet drugs: aspirin, thienopyridines, NSAIDS

- Monitor patients who take warfarin (Coumadin) for herbal use and INR

-Cross-reference all herbal and prescription medications in a drug database to ensure compatibility prior to prescribing

DRUGS THAT ALTER BLEEDING

ANTIPLATELET MEDICATIONS

-aspirin = antiplatelet drug

-blocks cyclo-oxygenase, an enzyme associated with clot formation

-inhibits platelet aggregation

-prevents thrombus formation on atherosclerotic plaques

-lowers risk of MI in those with increased risk for atherosclerosis/thrombogenesis

-lowers risk of MI and stroke in those with previous history of MI and stroke, unstable angina, post-coronary artery bypass grafting

-one enteric coated 325 mg tablet of aspirin daily or 81 mg low dose aspirin

Sudden Discontinuation of Aspirin

Discontinuing the use of aspirin increases mortality risk 1

Large clinical trial (n=1358) with hospitalized patients with an acute coronary syndrome 2

3 groups: never taken an oral antiplatelet agent (n=930), Hx of prior use (n=355), recently discontinued use (n=73)

Among recently discontinued aspirin group, mostly due to physician recommendation prior to surgery, there was a higher 30 day rate of death or MI and adverse bleedings than among prior users

No difference in the incidence of death or MI at 30 days between nonusers and prior users.

Recent withdrawal displayed worse clinical outcomes than nonusers.

1.  Ho PM, Spertus JA, Masoudi FA, et al. Impact of medication therapy discontinuation on mortality after myocardial infarction. Arch Intern Med. 2006 Sep 25;166(17):1842-7.

2.  Collet JP, Montalscot G, Blanchet B, et al. Impact of prior use or recent withdrawal of oral antiplatelet agents on acute coronary syndromes. Circulation. 2004 Oct 19;110(16):2361-7. Epub 2004 Oct 11.

A meta-analysis reviewing data from over 50,000 patients showed that aspirin non-adherence/withdrawal was associated with a three-fold higher risk for major adverse cardiac events. 3

Risk was even greater among patients with coronary stents.

Risk was amplified by a factor of 89 in patient who had undergone stenting.

3. Biondi-Zoccai GG, Lotrionte M, Agostoni P, et al. A systematic review and meta-analysis on the hazards of discontinuing or not adhering to aspirin among 50,279 patients at risk for coronary artery disease. Eur Heart J. 2006 Nov;27(22):2667-74. Epub 2006 Oct 19.

other anti-platelet medications:

aspirin and dipyridamole (Aggrenox)

cilostazole (Pletal)

ticlopidine (Ticlid) – used for those who are intolerant to aspirin, when aspirin therapy has failed, and coronary stent implantation

Lowers risk of stent thrombosis

Low risk of bleeding complications compared to other strategies

clopidogrel (Plavix)

Replaced use of ticlopidine

Lower rates of major adverse cardiac events and mortality compared with ticlopidine

Better safety-tolerability profile

Lower risk of neutropenia

Indications: reduce rate of TE (MI, stroke, vascular death) in patients with recent MI or stroke; reduce rate of TE in patients with unstable angina managed medically or with PCI (with or without stents); reduces rate of death and TE in patients with ST-Segment elevation MI managed medically

Dosing: 300 mg loading dose; 75 mg daily (with aspirin 81-325 mg daily)