Presenter. Dr. Ronald Lucchino
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1 Adverse Drug Reactions in Adults with Down Syndrome Presenter Dr. Ronald Lucchino
2 PURPOSE To increase staff awareness that older adults with DD may have higher levels of medication in the blood for longer periods of time, leading to increased risk of ADRs. This higher level and increased time is caused by: 1. Age related changes in the metabolism of medication(s) - influenced by gender, culture, and ethnic background 2. Increasing the number of medications increases the risk of drug to drug interactions 3. Use of non-prescription medications
3 WHY A CONCERN The adult IDD population is growing older with similar aging concerns as in the general population. A critical area of concern for both populations is the increase in medication use and the negative affects on functioning. There is more awareness of this concern in the general population than in the aging adult ID population.
4 Historically, in drug research, as in other fields of public health research, subjects have largely been males from the general population. Findings emerging in the past few years, however, clearly are establishing the importance of studying issues specific to women and different cultures in areas of drug research. This also is true in the adult IDD population. Unfortunately very little research on medications has been conducted on this population
5 General Consideration of Aging and Medications
6 Age Related Changes Influencing the Affects of Medication Decreased ability to metabolize medications results in: medications in body longer and higher levels in the blood Higher incidence of non-compliance in older adults Take an average 7-10 prescription medications Mask or mimic other diseases or disorders Cultural and gender variations in response to medications
7 Number of Medications vs. Increases in ADRs
8 DOSE CURVES Curve for a 40 year old individual Curve for an 80 year old individual
9 DOSE CURVE FOR A 40 YEAR OLD INDIVIDUAL Toxic - ADR dose Plasma concentration Concentration in blood Therapeutic dose B/2 Minimum concentration Time in blood
10 DOSE CURVE FOR AN OLDER INDIVIDUAL Plasma concentration Concentration in blood Toxic - ADR dose Minimum concentration B/2 Time in blood
11 Cultural Considerations
12 Caucasians experience twice the side effects of Hispanics from the antidepressants Prozac and Paxil. With an earlier class of antidepressants called tricyclics, Hispanics, receiving half the dose, had twice the side effects of Caucasians. Blacks on some anti-psychotic drugs seem more likely than whites to suffer tardive dyskinesia - repetitive, involuntary facial movements Asians who received half the dose of an anti-psychotic drug responded better than Caucasians who received the regular dose.
13 Age Related Biological Changes Affecting Medication Metabolism in the General Adult and ID Populations
14 Oral administration A. Absorption B.Transportation in blood (Plasma bound vs.. unbound) unbound C. Liver D. Kidney E. Lipid/Water compartments injection Plasma level of medication Therapeutic affect Target cells
15 Adult ID Population and Medications
16 The observation that individuals with Down syndrome have a reduced life expectancy has led to the supposition that: a) they may age prematurely and display signs of aging as early as years of age, and b) they may suffer earlier from health problems usually found in the 70 year old general population.
17 Aging Curve: General Population 100 Maximum vitality vitality vitality % vitality minimum vitality death conception birth age 30 senescence
18 Adult Down syndrome Aging Curve Maximum vitality 100 vitality General aging curve vitality % vitality General Aging DD curve minimum vitality Down syndrome death 0 conception birth age 30 senescence
19 Question: With the adult DS experiencing early aging changes with an concomitant increase in chronic health conditions, are they at the same or greater risk for ADR as the general population but at an earlier age?
20 Similarities as the General Population Decreased ability to metabolize medications results in: medications in body longer higher levels in the blood Older adults with ID take on average 11+ prescription medications - drug to drug interactions Hard to determine possible ADRs from their aging changes and the signs associated with the DS disabilities
21 Developmental Disabilities Age associated changes Aging Age related changes Medications
22 Possible Dose Curve for adults with Down syndrome Plasma concentration Concentration in blood Toxic - ADR dose Adult ID General population B/2 Minimum concentration Time in blood
23 Increased risk of ADR in the adult DS population that: may mimic or mask diseases may result in acute dementia overlaying AD reduces functional levels and independence may exacerbating existing disabilities associated with DS Very little research on ADRs in the adult with DS
24 TYPES OF ADRs Biological changes Cardiovascular functioning Constipation or diarrhea Dehydration Dryness of mouth Impaired senses Incontinence or retention Increased or decreased appetite Male impotence Skin - rashes, itching Stomach - nausea Mental changes Acute dementia Apathy Delusion Depression or sadness Increased or decreased sleep Personality change
25 Neurological changes Black-out spells Coma Dizziness Headache High fever/elevated body temperature Numbness Tingling Muscle coordination Convulsions Decreased or loss of muscle coordination Falls/uncoordinated movement Tremors/twitches Restlessness Seizures Unsteady gait
26 Similar ADRs that Mimic Dementia in adult with DS Agitation Anxiety Behavioral changes Cognitive function decline Communication skills decline Confusion Delusions Depression Disorientation to person, place or time Disturbed concentration
27 Euphoria Excitable Reduced muscle coordination Hallucinations - auditory/visual Irritability Memory loss short term long term Nightmares Restlessness/wandering Shuffling/unsteady gait Sadness Loss of interest
28 Examples of ADRs and Medications in the Aging ID Population
29 Medicines are not used to specifically treat the Down syndrome disorder, but to treat the chronic diseases associated with the adult with Down syndrome. This include 23 different acute and chronic categories. A total of 24 categories of medications were identified in treating these chronic conditions in adults with DS.
30 Examples of some of the increased at-risk medication categories in adults with Down syndrome resulting in multiple medications are : Anti-hypertensive Leukemia and other cancers Immune system problems Thyroid problems Bone, muscle, nerve, or joint problems Hearing eye problems Digestive problems Seizures disorders Anti-anxiety/anti-psychotic Cholesterol lowering
31 Percentage of medication in adults with Down syndrome <50 >50 total Anti-anxiety Anticonvulsant Antidepressant Anthypertensive Antipsychotic Antispasmodic Cholesterol lowering Fosamax GERD- related Hormones Hypothyroidism Respiratory Vitamin A Vitamin B Vitamin C 4 6 5
32 Gerard Kerins, Kimberly Petrovic, Mary Beth Bruder and Cynthia Gruman. Oct Medical conditions and Medication use in adults with Down syndrome: A descriptive Analysis. Down Syndrome Research and Practice: 12 (2). www Down Syndrome Research and Practice
33 Specific Examples of ADRs that may Mimic or Mask Dementia and other Health Concerns
34 Anticonvulsant medication Dilantin (phenytoin)
35 ADRs dizziness, headache, atrial fibrillation, hypotension, reduced heart rate - mimicking CVD blurred vision - mimics or masks vision problems in DS adults nausea, vomiting, constipation, weight loss - mimicking GI problems aplastic anemia, leucopenia - masks leukemia associated with DS adults confusion, aggression, slurred speech, depression - mimics or masks Alzheimer s
36 Reduce symptoms of memory loss -Alzheimer s disease - 1. Reduce inflammation Namenda (memantine) - Glutamate inhibitor 2. Increase acetylcholine Aricept, Exelon
37 Namenda (memantine)
38 1. Reduces symptoms by reducing inflammation - reduced the rate of cell death 2. Mid to late stages - works better if given with cholinergic mimics 3. Does not work for all individuals, efficacy may vary with individuals 4. Reduced effectiveness over time
39 Side Affects 1. Common- Dizziness, confusion, sommelence - possibly mimicking acute dementia 2. Not common - hypertension, vomiting, constipation, back pain, rash, fatigue, pain - mimicks apathy or GI problems 3. May affect cimetidine levels - affects GI
40 Aricept (donepezil)
41 1.Reduces symptoms by increasing acetylcholine concentration in the brain compensating neuron loss 2. Early to mid stages - works better if given with memantine 3. Does not work for all individuals, efficacy may vary with individuals 4. Reduced effectiveness over time
42 Side Effects of Aricept (donepezil) dizziness, headache, atrial fibrillation, reduced heart rate - mimicking CVD nausea, vomiting, diarrhea, ulcers, asthma, GI bleeding, abdominal stress, flatulence - mimicking GI problems seizures - mimicking, masking or exacerbating existing seizures in DS and CP insomnia, somnolence, fatigue, agitation, lethargic, nightmares, incontinence - mimics AD
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44 Case Study
45 A male adult (71) with mild ID (Down s syndrome) has been diagnosed with senile dementia. He is confused and is apathetic to the environment around him - he refuses to participate in any activities. He is taking medications for hypothyroidism, ulcer and seizures. Recently he was placed on a medication to help increase his cognitive function and memory. Two weeks after he was started on this medication you noticed some changes from his normal behavior and from his prior symptoms of dementia. He appears to be more: confused, tired, lathargic/apathetic, and problems sleeping, resulting in many short naps. His also appears to have loss his appetite along with black out spells and small muscle tremors.
46 Medications Exelon (rivastigmine) cholinergic mimic Synthroid (levothyroxine) T 4 Zantac (ranitidine) anti-acid H 2 Keppra (levetiracetam) anticonvulsant anticholinergiccognitiveburdenscale.html
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50 Type of Medication: Exelon (rivastigmine) use: Increase memory in AD Adverse Reactions: Common Side Affects Mental CNS Biology GI Urinary confusion, hallucinations, insomnia tremors nausea, anorexia,constipation,cramps Infections At Risk GI vomiting
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53 Type of Medication: Synthroid (levothyrosine) use: Increase metabolism in hypothyroidism Adverse Reactions: Common Side Affects - Synthroid Mental anxiety, insomnia, CNS tremors Biology GI nausea, anorexia, diarrhea, cramps CV tachycardia, palpitations, angina, At Risk CV Biology cardiac arrest Thyroid storms (high level of excitability
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56 Type of Medication: Zantac (ranitidine) use: Gastric acid Adverse Reactions: Common Side Affects Mental CNS Biology GI CV EENT At Risk sleeplessness, lathargic/apathetic, hallucinations, headaches constipation tachycardia blurred vision
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59 Type of Medication: Keppra (levetiracetam) use: Seizures Adverse Reactions: Common Side Affects Mental CNS sleepy, dizziness, headaches At Risk Mental suicidal ideation
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62 REPORTING FORM Patient Name Date form completed Name of person form was sent (A) (B) (C) (D) (Observed changes) (Associated ADRs) (At Risk) (Beers List) List all observed changes from Medications from Medications from Medications on Beer s Column A of Assessment Form Column B Column C list constipation Exelon, Synthroid appetite (nausea, constipation) Exelon, Synthroid, Zantac X swallowing difficult inability to urinate Not drugs but prostate? loss of bladder Exelon black out spell Keppra dizziness Keppra confusion Exelon memory loss sedation uncaring - apathy Zantac disrupted sleep Exelon, Synthroid, Zantac X excess napping Exelon, Synthroid, Zantac X insomnia loss of coordination Exelon, Synthroid, Zantac X seizures tremors Exelon, Synthroid
63 Possible explanation of the increase risk for ADRs that mimic or mask dementia associated in the adult with DS
64 Reducing ADRs in Adult with DS record a baseline activities before medication regime is changed record any observed changes after medication regime is changed record the medications that have associated ADRs to changes observed record all medications that have similar ADRs with observed changes
65 CAUTION AGING INTO MEDICATION Older individuals who are on medications for extended periods of time may begin to experience ADRs from those medications!
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