Download Prevention of premature discontinuation of dual antiplatelet therapy

COURSE TITLE:
Pharmacologic Management of the Geriatric Patient: Oral
Health Care Considerations
COURSE INSTRUCTOR:
Ann Eshenaur Spolarich, RDH, PhD
COURSE CREDITS:
3 CEUs
COURSE DATE:
April 28, 2017
_____________________________________________________________________________
COURSE DESCRIPTION: The purpose of this course is to review characteristics and disease
trends among the aging population, and oral disease risks associated with medications and
common systemic diseases. Most patients take multiple medications, many of which have oral
complications and drug interactions of significance to dentistry. Medication therapies, oral drug
and disease complications, drug interactions and dental practice management considerations will
be discussed. Recommendations for treatment modifications and oral hygiene self-care programs
will be provided.
LEARNING OBJECTIVES:
Upon completion of this continuing education program, course participants will be able to:
1.
Describe common oral disorders observed in the elderly population, including
xerostomia, taste and smell disorders, orofacial muscular disorders, and lichenoid drug
reactions.
2.
Discuss changes in pharmacokinetics associated with normal aging.
3.
Describe the Beers Criteria for potentially inappropriate medication use in older adults.
4.
Identify drugs that are associated with an increased risk for falling.
5.
Identify drugs that are associated with risk for alteration of the QT interval.
6.
Discuss considerations with antibiotics, benzodiazepines, sedatives and opiate use in
older adults.
7.
Discuss indications and adverse events associated with drugs used for dementia and
Parkinson’s disease.
8.
Discuss potential uses and risks associated with antipsychotic medications in older adults.
9.
Describe different classes of blood altering medications with indications for use.
*These course materials may not be duplicated without the written consent of the course
instructor.
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I.
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II.
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Pharmacokinetics of Normal Aging
Decreased absorption due to increased stomach acidity (*why elderly use antacids)
Decreased liver function; more drug unchanged (more “active” drug)
Decreased lean body mass
Increased body fat (drug storage)
Decreased total body water (drug more concentrated in blood)
Decreased plasma proteins (more unbound “active” drug)
Less binding capacity (decreased plasma proteins), less metabolism (decreased liver function) and
decreased renal function allow for normal doses of drug to act at overdose levels in the geriatric
patient
Give lower dose
Liver diseases = in most cases, drug metabolism is reduced due to diminished function of the
cytochrome P-450 system; dosing must be reduced
Renal diseases = results in renal impairment of drug excretion; dosing must be modified on the
basis of renal clearance values of the drug
Benzodiazepines
Commonly abused
Prescribers rarely understand addictive quality of these meds with related complications in elderly
patients
Patients receive prescriptions from multiple providers
Patients develop “benzo-abstinence syndrome” due to unavailability of drug or during
hospitalization for other medical problem
Indications for BDZs
 Chronic anxiety
o Should assess for depression
o Prescribe antidepressants with slow discontinuation of BDZs
 Depression
 Sleep disturbance
o Chronic insomnia significant problem in elderly
o Rarely improves with long-term use of BDZs
o Nightly use of BDZs lose effectiveness after 3-6 mos (tolerance)
o Requires steadily increasing doses to initiate sleep
 Long-term use produces significant physical dependence or addiction
Complications of BDZs
 Exacerbates chronic medical problems
o COPD, GERD
 Increases length of stay and morbidity in hospitalized patients
 Higher rates of MVA and falls
 Significant additive effect with other sedative hypnotic drugs (opiates, alcohol)
 Prolonged half-life predisposes to easy intoxication
 Withdrawal syndrome occurs after stopping (similar to alcohol withdrawal)
 Withdrawal often happens following admission to hospital for other medical reason (e.g. surgery)
 Treatment for BDZ abuse:
o Detoxification and withdrawal
o Appropriate therapy for psychiatric problems
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o Long-term addiction treatment (e.g. AA, NA)
If less than 2 years of life remaining, remain on BDZs but monitor dosages
Most have very long half-lives
Most are metabolized to active compounds
Repeated dosing results in accumulation of drug in the body
triazolam (Halcion) – shortest half-life of oral meds
o fast onset of action
o *no kinetic data reported with multiple titration doses (used for oral conscious sedation)
 “unlabeled” use
o elderly experience greater sedation and increased psychomotor impairment
 much higher risk for oversedation
III. *Beers Criteria
 3 lists of medications that pose potential risks outweighing potential benefits for people 65 and
older
 Medications that are potentially inappropriate because:
o pose high risks of adverse effects
o limited effectiveness in older patients
o alternatives are available
 Medications that are potentially inappropriate for those with certain diseases or disorders:
o drugs may exacerbate health problems
 Medications to be used with caution:
o more risks than benefits
o may be the best choice for a particular individual if administered with caution
o medications need to be tailored to the unique needs of each patient
 Benzodiazepines are to be avoided for treatment of:
o Insomnia
o Agitation
o Delirium
 Flumazenil = BDZ antagonist = “blocker” drug
 Will not block CNS effects from alcohol, barbiturates, general anesthetics or opiates
 May not reliably reverse respiratory depression/hypoventilation
o Establish airway
o Provide ventilation
 BDZ reversal may cause seizures = be prepared to manage
IV.
Opiates in Older Adults
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Not all pain responds to same medications
When should treatment be intensified?
Unresolved pain or continued complaints of pain despite escalating doses of prescription opioids:
o Disease progression
o Self-medication of co-morbid psychiatric and/or physical complaints
o Diversion
o Pseudo-addiction = providing analgesia stops behaviors
Altered CYP450 enzymes
Reluctance to report adequate pain relief
o Fear that care will be reduced
o Fear that clinician will stop searching for underlying cause of pain
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Misconceptions or misunderstanding regarding opioid treatment
*Avoid concurrent use of opiates and benzodiazepines whenever possible
Alternative Interventions to Pain Management
 Musculoskeletal pain = acetaminophen or NSAIDS
 Neuropathic pain = tricyclic antdepressants or anti-epileptics; topical anesthetics for localized
neuropathic pain
o Sympathectomy = weak evidence
 Neuralgia = local anesthetics + steroids; botulinum toxin
 Joint pain = steroids, hyaluronic acid
 Cognitive behavioral therapy
 Physical activity
 Assistive devices
 Transcutaneous electrical nerve stimulation (Tens units)
 Massage
Should we use opiates in older adults?
 Frequent occurrence of both cancer and non-cancer persistent pain
o opioid analgesics are appropriate for moderate to severe persistent pain
 Challenges: factors involved in making appropriate choices, monitoring the beneficial effects of
pain relief and managing side-effects
 Goals of using opioids = improved function and quality of life
Opiates and End of Life Care
 Pain management in the elderly is undertreated
 Challenges with pain management:
o co-morbidities
o polypharmacy
o cognitive dysfunction
 In the geriatric population, the assessment of pain requires measurement of:
o pain intensity
o delineation of opioid responsiveness
o clarification of the impact of pain on patient’s
 psychological
 social
 spiritual
 existential domains
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Drugs and Falls
Many drugs increase risk for falling
o Antihypertensives (orthostatic hypotension)
o Antidepressants
o Sedative hypnotics
o Antipsychotics
o Benzodiazepines
o Opiates
o NSAIDS
o *Alcohol
Risk assessment and prevention
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VI.
Drugs that Alter the QT Interval
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Drugs that prolong the QT interval:
o Fluoroquinolone antibiotics
 moxifloxacin (Avelox)
 ciprofloxacin (Cipro)
 levofloxacin (Levaquin)
o Macrolide antibiotics
 azithromycin (Zithromax)
 clarithromycin (Biaxin)
o Azole antifungals
 fluconazole (Diflucan)
 ketoconazole
 itraconazole (Sporanox)
o Epinephrine
Lexicomp® Database 2013; Mosholder AD, Mathew J, Alexander JJ, Smith H, Nambiar S. Cardiovascular
risks with azithromycin and other antibacterial drugs. N Engl J Med. 2013 May 2;368(18):1665-8.
VII.
Considerations with Antibiotics
Clarithromycin/Azithromycin
 Caution in liver disease = hepatotoxic
o Can lead to hepatitic failure, death
 Discontinue immediately if symptoms of hepatitis:
o Malaise, nausea, vomiting, abdominal colic, fever
 Alters QT interval of the heart = caution with vasoconstrictor
o Elderly at greater risk
o Avoid if uncorrected hyperkalemia or hypomagnesemia
o Avoid if bradycardia
o Avoid if taking Class I or Class III antiarrhythmics
o Contraindicated in patients with ventricular arrhythmias (including torsade de pontes)
Pseudomembranous Colitis
 Greatest number of antibiotic-associated cases of C diff diarrhea are from cephalosporins
 Also clindamycin
o *may occur with many antibiotics
VIII.
MAJOR TRANQUILIZERS/ANTIPSYCHOTICS
A.
Pharmacology and Use
-Older term: neuroleptic drugs
-A chemically diverse but pharmacologically similar class of drugs used to treat a variety of
conditions
-Used in the treatment of:
-Psychotic disorders – Schizophrenia, paranoia
-Acute delirium and dementia
-Manic episodes during induction of lithium
-Movement disorders – Huntington’ disease, Tourette’s syndrome, ballismus
-Intractable hiccups
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-Severe nausea and vomiting
-Individual drugs bind to a variety of receptors and act as antagonists:
-dopaminergic, alpha1 and alpha2 adrenergic, serotonergic (5-HT), muscarinic,
H1 histamine, sigma opioid
-Blockade of dopaminergic transmission in various areas of brain is thought to be responsible for
their major effects
-Antipsychotic action = blockage in prefrontal cortex and limbic areas
-Extrapyramidal side effects = blockade in basal ganglia
-Antiemetic effects = blockade in chemoreceptor trigger zone of the medulla
-All antipsychotics have high therapeutic index
-Not addictive
B.
Side Effects
-Extrapyramidal side effects:
Parkinsonism – akinesia (difficulties in initiating movement), tremor, rigidity
Caused by blockade of D2 receptors in basal ganglia
-Akathisia = restless legs syndrome; Caused by D2 receptor blockage in basal ganglia
-Dystonia – sustained muscular contraction
-Tardive Dyskinesia – abnormal movements, particularly of face and tongue, but may also be of
trunk and limbs
-Noticeable after at least 6 months of chronic treatment
- begins with spastic, thrusting tongue movement, body restlessness, changes in HR &
respiration
*Most extrapyramidal side effects are treatable with anticholinergic drugs
Sedation and autonomic side effects are caused by blockade of histamine, cholinergic and
adrenergic receptors
-orthostatic hypotension
-blurred vision
-dry mouth
-nasal congestion
-constipation
-urinary retention
C.
Drug Interactions of Significance to Dentistry
-Antipsychotics potentiate the actions of
-sedatives
-analgesics
-antihistamines
-Antipsychotics potentiate the respiratory depression caused by opioids
-Antacids = decrease absorption of antipsychotics
-Anticonvulsants = decrease plasma levels of antipsychotics
-Antipsychotics may alter efficacy of antihypertensive medications
*monitor vital signs
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TYPICAL ANTIPSYCHOTICS
chlorpromazine (Thorazine) = Schizophrenia,
nausea/vomiting, intractable hiccups,
combativeness
fluphenazine (Prolixin) = management of
psychotic disorders and schizophrenia; improves
outcomes in patients with psychoses who are
nonadherent with oral antipsychotics
haloperidol (Haldol)
RX for schizophrenia and Tourette’s; severe
behavioral problems in children
-EPS of TMJ
pimozide (Orap) = suppression of severe motor and
phonic tics with Tourette’s
-prolongs QT interval: consult physician prior to
administering vasoconstrictor
prochlorperazine (Compro, Compazine) =
antiemetic; psychosis, anxiety
-EPS side effect: torticollis (neck muscle spasm)
promethazine (Phenadoz, Phenergan,
Promethegan) = antiemetic, antihistamine,
sedative, motion sickness, post-operative pain,
anesthetic
-EPS side effect: tardive dyskinesia, Parkinson’s
syndrome, akathisia is most common in elderly
patients
thiothixene (Navane) = psychotic disorders in
children, rapid tranquilization of agitated child;
patients with dementia
-prolongs QT interval: consult physician prior to
administering vasoconstrictor
ATYPICAL ANTIPSYCHOTICS
aripiprazole (Abilify) = Commonly used agent in
schizophrenia, treatment and stabilization of
bipolar disorder
-Low risk of EPS
-Does not cause as much weight gain as other
antipsychotics, but may be less effective than
others
clozapine (Clozaril) = Schizophrenia; severe OCD,
childhood psychosis, attempted suicide, substance
abuse recovery
Side effect: agranulocytosis – susceptibility to
infection, hypersalivation (others cause
xerostomia), weight gain, reduced risk of EPS
olanzapine (Zyprexa) = Schizophrenia, bipolar
disorder, acute agitation
olanzapine and fluoxetine (Symbyax) = treatment
of depressive episodes associated with bipolar
disorder
paliperidone (Invega) = Schizophrenia
quetiapine (Seroquel) = Schizophrenia, acute
manic episodes and/or depressive episodes with
bipolar disorder (monotherapy or with lithium)
risperdone (Risperdal) = Commonly used agent in
schizophrenia, acute mania and/or
irritability/aggression with bipolar disorder,
behavioral problems with dementia, Tourette’s
ziprasidone (Geodon) = schizophrenia, acute manic
or mixed episodes with bipolar disorder with or
without psychosis, acute agitation with
schizophrenia
-prolongs QT interval: consult physician prior to
administering vasoconstrictor
EPS = extrapyramidal effects
Why are Cholinesterase Inhibitors typically used?
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Indirect-Acting Cholinergic Drugs
Also known as “cholinesterase inhibitors”
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These drugs stop the breakdown of acetylcholine (via cholinesterase), which allows for the
concentration of acetylcholine to build up = acetylcholine remains active and stimulates the
PANS
These drugs produce PANS stimulation
Dementia with Alzheimer’s disease
Investigational for mild to moderate dementia with Parkinson’s disease
Examples:
o donepezil (Aricept)
o rivastigmine (Exelon)
o galantamine (Razadyne)
Side Effects of Direct-Acting and Indirect-Acting Cholinergic Drugs
 nausea, vomiting, diarrhea (by increasing GI activity)
 salivation, sweating (increased gland secretions)
 bronchoconstriction
 constricted pupils
 Paralysis at high doses (effect at neuromuscular junction)
 CNS = confusion
Anticholinergic Drugs for Parkinson’s Disease
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benztropine (Cogentin)
trihexyhenidyl (not in U.S.; Canadian drug)
Anticholinergic Drugs (Parasympatholytics)
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Prevent the action of acetylcholine at the postganglionic PANS nerve endings
“blocker” drugs or antagonists
Block the receptor site for acetylcholine
Do not prevent release of ACH
Acetylcholine cannot act on receptors in smooth muscle, glands or the heart
Also called antimuscarinic drugs (block muscarinic receptors but not nicotinic receptors)
Pharmacologic Effects of Anticholinergic Drugs
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Reduce PANS activity
o Skin = decrease sweating
o GI = decrease salivation, decreased gut motility
o Urinary tract = urine retention
o Respiratory = bronchodilation
o CNS = decreased concentration/memory; sedation; possible hallucinations and coma
Adverse Reactions to Anticholinergic Drugs
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Frequently are extensions of their pharmacologic effects
Xerostomia
Blurred vision, photophobia
Tachycardia
Fever
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Urinary and GI stasis
Hyperpyrexia (elevated temperature)
Hot, dry flushed skin (lack of sweating)
Toxicity = CNS excitation = delirium, hallucinations, convulsions, respiratory depression
ORAL HEALTH CONSIDERATIONS FOR NEUROPSYCHIATRIC CONDITIONS
- most neuropsychiatric medications cause xerostomia
-watch for opportunistic infections
-loss of protective effects: viral, fungal, bacterial infections
-traumatic aphthous ulcers
- lack of interest in performing daily self-care
- increased demineralization, caries and gingival disease
- lack of interest/motivation to seek treatment
- caution with epinephrine = Monitor vital signs!
-use vasoconstrictors cautiously with all classes of antidepressants except SSRIs
-tricyclics and monoamine oxidase inhibitors
-venlafaxine (Effexor) – depression, anxiety, OCD, ADHD
--all drugs for ADHD
-some antipsychotics = consult drug reference guide
-SSRIs = bruxism: increased extrapyramidal effects
-burning mouth syndrome = observed in depression and anxiety; tricyclics
X.
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.
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1.
2.
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.
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 nonadherence/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 (many Canadian brand names) – 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-Sement elevation MI managed
medically
Dosing: 300 mg loading dose; 75 mg daily (with aspirin 81-325 mg daily)
Problems:
Drug interactions
Slow onset of action
Wide variability in patient response
Includes “no” response
prasugrel (Effient) *new drug approved in July 2009
Approved for patients with acute coronary syndromes undergoing PCI
Indications: Reduces rate of thrombotic cardiovascular events (eg, stent thrombosis) in patients
with unstable angina, non-ST-segment elevation MI, or ST-elevation MI (STEMI) managed with
percutaneous coronary intervention
Loading dose of 60 mg followed by maintenance dose of 10 mg
Manufacturer labeling states to also take 75-325 mg aspirin once daily upon recommendation of
provider
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Prevention of premature discontinuation of dual antiplatelet therapy in patients with coronary
artery stents: a science advisory from the American Heart Association, American College of
Cardiology, Society for Cardiovascular Angiography and Interventions, American College of
Surgeons, and American Dental Association, with representation from the American College of
Physicians.
Grines CL, Bonow RO, Casey DE Jr, Gardner TJ, Lockhart PB, Moliterno DJ, O'Gara P, Whitlow P; American
Heart Association; American College of Cardiology; Society for Cardiovascular Angiography and Interventions;
American College of Surgeons; American Dental Association; American College of Physicians. William Beaumont
Hospital, Royal Oak, Michigan, USA. J Am Dent Assoc. 2007 May;138(5):652-5.
Abstract
BACKGROUND: and Overview. Dual antiplatelet therapy with aspirin and a thienopyridine has been
shown to reduce cardiac events after coronary stenting. However, many patients and health care providers
prematurely discontinue dual antiplatelet therapy, which greatly increases the risk of stent thrombosis,
myocardial infarction and death. CONCLUSIONS AND CLINICAL IMPLICATIONS: This advisory
stresses the importance of 12 months of dual antiplatelet therapy after placement of a drug-eluting stent
and educating patients and health care providers about hazards of premature discontinuation. It also
recommends postponing elective surgery for one year, and if surgery cannot be deferred, considering the
continuation of aspirin during the perioperative period in high-risk patients with drug-eluting stents.
PMID: 17473044
3 Recommendations from Advisory Statement (listed above):
Those concerned about peri/postprocedural bleeding must be aware of catastrophic risks of premature
discontinuation
-Consult cardiologist to discuss optimal patient management strategies
Elective procedures with significant risk of peri/postoperative bleeding should be deferred until
patient has completed an appropriate course of thienopyridine therapy:
-12 months after DES implantation if they are not at high risk of bleeding
-Minimum of one month for bare-metal stent implantation
Patients with DES who are to undergo subsequent procedures that mandate discontinuation of drug
therapy, aspirin should be continued if at all possible
-Restart thienopyridine as soon as possible after the procedure because of concerns of late stent
thrombosis
ANTICOAGULANT MEDICATIONS
 Coumarin derivatives/Vitamin K Antagonist
o warfarin
 Heparin (anticoagulant)
 Heparinoid (anticoagulant)
o danaparoid (Orgaran) *Canadian drug – prevention of DVT following orthopedic
surgery or in patients with non-hemorrhagic stroke
 Low Molecular Weight Heparin (anticoagulants)
o dalteparin (Fragmin) – prevention and treatment of DVT/VTE; unstable angina
o enoxaparin (Lovenox) – acute coronary syndromes; DVT prophylaxis
o nadroparin (Fraxiparine) *Canadian drug - acute coronary syndromes; DVT prophylaxis
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tinzaparin (Innohep) *Canadian drug – treatment of DVT/PE; prevent DVT/PE following
orthopedic surgery; prevent clotting in indwelling IV lines and circuit during
hemodialysis
Direct Thrombin Inhibitors (anticoagulants)
o argatroban – px/tx of thrombosis with heparin-induced thrombocytopenia (HIT); adjunct
to PCI if at risk for HIT
o bivalirudin (Angiomax) – with ASA for unstable angina receiving PCI; undergoing PCI
with risk for HIT
o dabigatran etexilate (Pradaxa) – prevention of stroke and systemic embolism with
nonvalvular atrial fibrillation; postop thromboprophylaxis for hip/knee replacement
o desirudin (Iprivask) *US drug – prophylaxis of DVT for hip replacement
Factor Xa Inhibitors (anticoagulants)
o apixaban (Eliquis) - thromboprophylaxis for hip/knee replacement; nonvalvular atrial
fibrillation
o fondaparinux (Arixtra) – thromboprophylaxis for hip/knee replacement; unstable angina;
non-ST segment elevation MI
o rivaroxaban (Xarelto) – thromboprophylaxis for hip/knee replacement; treatment of
DVT; nonvalvular atrial fibrillation; treatment of PE
o
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ANTITHROMBINS
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Antithrombin III
o given to those with an antithrombin III deficiency
Heparin - enhances the inhibition rate of clotting proteases by antithrombin III impairing normal
hemostasis and inhibition of factor Xa.
Low molecular weight heparins - strongly inhibit factor Xa; higher ratio of antifactor Xa to
antifactor IIa activity than unfractionated heparin.
Heparin
 Naturally-produced anticoagulant (anti-thrombin)
 Synthetic version given by IV
 Indications: prevention and treatment of thromboembolic disorders
 Anticoagulant for dialysis procedures
 Heparin Lock flush used to clear IV lines
 Produces immediate anticoagulation effect
 Patient admitted to hospital is started on heparin and warfarin: heparin produces initial effect
Low Molecular Weight Heparins
 Use: prevention of DVT with or without PE (following hip and knee replacement); reduce risk for
PE; acute coronary syndromes: acute unstable angina; non-ST-elevation MI; non-Q-wave MI
 Mechanism: Inhibit factor Xa and IIa (thrombin)
COUMARIN DERIVATIVES
 warfarin (Coumadin, Jantoven)
 interferes with liver synthesis of vitamin-K dependent clotting factors
 effects occurs in 4 to 5 days
 when patient is admitted to hospital with stroke, there is a 1 to 2 day overlap period with heparin
following warfarin administration to prevent hypercoagulable state
o Heparin produces immediate effect
o Takes 4-5 days for effects of warfarin to occur
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Indications for warfarin:
o Prophylaxis and treatment of TE disorders (venous and pulmonary) and embolic
complications that arise from atrial fibrillation or cardiac valve replacement
o Adjunct to reduce risk of systemic embolism (recurrent MI, stroke) after MI
Investigational: prevention of recurrent TIA
Many things can upset a patient’s level of anticoagulation from warfarin:
o Fever
o Flu
o Diarrhea or vomiting
o Use of many drugs, including antibiotics
o Change in diet (consumption of green leafy vegetables increases vitamin K intake =
promotes clotting)
 Need vitamin K to synthesize clotting factors in liver
 Warfarin shuts off production of these clotting factors
**Key messages: warfarin causes the greatest number of drug interactions
o Always check compatibility prior to issuing a prescription
o Always ask about the INR and monitor INR status across time to examine trends in
anticoagulation control
THROMBIN INHIBITORS
dabigatran (Pradaxa)
 Thrombin inhibitor
 Prodrug = lacks anticoagulant activity
o converted in vivo to active dabigatran
 specific, reversible, direct thrombin inhibitor that inhibits both free and fibrin-bound thrombin
 prevents thrombin-mediated effects, and by inhibiting thrombin-induced platelet aggregation
 Dabigatran inhibits coagulation by preventing thrombin-mediated effects, including cleavage of
fibrinogen to fibrin monomers, activation of factors V, VIII, XI, and XIII
 Indications:
 Prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation
 Postoperative thromboprophylaxis after total hip or knee replacement
o Knee replacement – up to 10 days
o Hip replacement – up to 35 days
 compared to warfarin (Coumadin)
 advantages: no monthly monitoring; fewer drug-drug and drug-diet interactions
 disadvantages: very expensive; twice daily dosing
 in studies, patients who took Pradaxa had fewer strokes than those taking warfarin
o RE-LY trial = Randomized Evaluation of Long-Term Anticoagulation Therapy
 adverse effects: bleeding, GI effects
*new antidote for dabigatran = idarucizumab (humanized antibody fragment (FAB))
Indications for Direct Antithrombins (Thrombin Inhibitors)
 Prevent/reduce ischemia with unstable angina
 Prevent DVT following hip replacement
 Prevent/treat thromboembolism
 Treatment of heparin-induced thrombocytopenia (HIT)
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COMMON ORAL PROBLEMS IN ELDERLY PATIENTS
Disease or Drug Induced Xerostomia
Caries and Demineralization
Tooth Sensitivity
Periodontal Disease
Fungal Infections
Viral Infections
Pain and Ulcerations
Food Packing/Decreased Oral Clearance
Oral signs and symptoms associated with drug-induced xerostomia
Caries
Enamel erosion
Dentinal hypersensitivity
Opportunistic infections
Oral ulcerations/stomatitis
Dry, cracked, bleeding lips
Angular cheilitis
Difficulty speaking, chewing,
swallowing
Enamel demineralization
Cemental abrasion on exposed root surfaces
Increased gingivitis and periodontal infection
Increased viral infections
Taste alteration
Fissured, sore tongue
Friable oral mucosa
Difficulty wearing dentures or appliances
Drug classes that produce neural effects on the salivary glands
The following are examples of anticholinergic drugs that reduce the volume of serous saliva:
Antidepressants
Antiemetics
Anti-parkinsonian drugs
Antihistamines
Antipsychotics
Antihypertensives
Antispasmodics
The following are examples of sympathomimetic drugs that produce a viscous, mucinous saliva:
Amphetamines
Appetite suppressants
Bronchodilators
Decongestants
Sources: Sreeby LM, Schwartz SS: A reference guide to drugs and dry mouth, 2 nd ed, Gerodontol 14:33-47, 1997;Porter SR,
Scully C, Hegarty AM: An update of the etiology and management of xerostomia, Oral Surg Oral Med Oral Pathol Pral Radiol
Endod 97:28-46, 2004; Nähri TO, Meurman JH, Ainamo A: Xerostomia and hyposalivation: causes, consequences and
treatment in the elderly, Drugs & Aging 15:103-116, 1999.
Drug classes associated with causing xerostomia
Antiacne agents
Antianxiety agents
Anticholinergics/Antispasmodics
Anticonvulsants
Antidepressants
Antidiarrheals
Antiemetics
Antihistamines
Antihypertensives
Anti-inflammatory analgesics
Antinauseants
Anti-parkinsonian agents
Antipsychotics
Anorexiants
Bronchodilators
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Decongestants
Diuretics
Narcotic Analgesics
Sedatives
Muscle Relaxants
Source: USP DI® Drug Information for the Healthcare Professional, vol 1, ed. 24, Englewood, CO, Micromedix, Inc., 2004.
Taste and Smell Disorders
Drugs that alter taste
Alcohol detoxification agents
Alzheimer’s medications
Analgesics (NSAIDS)
Anesthetics (general and local)
Anorexiants
Antacids
Antianxiety agents
Antiarthritics
Anticholinergics
Anticonvulsants
Antidepressants
Antidiabetics (oral hypoglycemics)
Antidiarrheals
Antiemetics
Antifungals
Antigout medications
Antihistamine (H1) antagonists
Antihistamine (H2) antagonists
Antihyperlipidemics
Antiinfectives
Anti-inflammatory/antiarthritics
Antimigraine agents
Antiparkinson agents
Antipsychotics
Antithyroid medications
Antivirals
Anxiolytics/sedatives
Asthma preventives
Bronchodilators
Calcium-affecting drugs
Cancer chemotherapeutics
Cardiovascular medications
CNS stimulants
Decongestants
Diuretics
Glucocorticoids
Gallstone solubilization agents
Hemorheologics
Immunomodulators
Immunosuppressants
Irritable bowel syndrome medications
Methylxanthines
Nicotine replacement drugs
Ophthalmics
Proton pump inhibitors
Retinoids, systemic
Salivary stimulants
Skeletal muscle relaxants
Vitamins
Source: Gage TW, Pickett FA: Mosby’s dental drug reference, ed. 7, St. Louis, 2005, Elsevier Mosby.
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Systemic drugs associated with lichenoid drug reactions
Category
Agents
Analgesic agents
NSAIDs, propoxyphene/acetaminophen, acetaminophen/codeine
Antianxiety drugs
benzodiazepines
Antiarrhythmics
quinidine
Anticonvulsant drugs
Depakote
Antineoplastic drugs
levamisole
Cardiovascular agents
beta-adrenergic blockers, angiotensin II antagonist, calcium
channel blockers, cardiac glycoside, methyldopa, thiazide
diuretics, potassium supplements
Gastric acid secretion inhibitors H2-antagonists
Hormone replacement
thyroid hormone, insulin, sulfonylureas, metformin, oral
contraceptives, estrogen, progesterone
Photographic Dyes
Uricosuric agent
allopurinol
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