Question

Samuel is an 82-year-old male brought in by his daughter for complaints of low blood sugar. Samuel has a history of type II diabetes well-controlled with glyburide and diet. He was treated last week at an urgent care for a suspected staph infection to his arm with sulfamethoxazole and trimethoprim. He also takes lisinopril, Lipitor, Flomax, Paxil, Coenzyme Q10, and a multivitamin. His daughter also found old prescriptions for alprazolam, atenolol, and terazosin in his medicine cabinet. With what you know about drug-drug interaction in older adults, what could be the cause of his hypoglycemia? What questions do you need to ask the patient and his daughter about safe medication management? What education should be offered to this patient and his family?

Answer 1

Drug-drug interactions (DDIs) represent an escalating concern for older adults attributed to polypharmacy, multi-morbidity and organ dysfunction. Few studies have evaluated the prevalence of major DDIs and the variability between DDI detection software which confuses management. Drug-related problems are common in older adults and include drug ineffectiveness, adverse drug effects, overdosage, underdosage, and drug interactions

A drug given to treat one disease can exacerbate another disease regardless of patient age, but such interactions are of special concern in older adults. Distinguishing often subtle adverse drug effects from the effects of disease is difficult (see table Drug-Disease Interactions of Concern in Older Adults) and may lead to a prescribing cascade.

A prescribing cascade occurs when the adverse effect of a drug is misinterpreted as a symptom or sign of a new disorder and a new drug is prescribed to treat it. The new, unnecessary drug may cause additional adverse effects, which may then be misinterpreted as yet another disorder and treated unnecessarily, and so on.

Many drugs have adverse effects that resemble symptoms of disorders common in older adults or changes due to aging. The following are examples:

• Antipsychotics may cause symptoms that resemble Parkinson disease. In older adults, these symptoms may be diagnosed as Parkinson disease and treated with dopaminergic drugs, possibly leading to adverse effects from the antiparkinson drugs (eg, orthostatic hypotension, delirium, hallucinations, nausea).

• Cholinesterase inhibitors (eg, donepezil, rivastigmine, galantamine) may be prescribed for patients with dementia. These drugs may cause diarrhea or urinary frequency or urge incontinence. Patients may then be prescribed an anticholinergic drug (eg, oxybutynin) to treat the new symptoms. Thus, an unnecessary drug is added, increasing the risk of adverse drug effects and drug-drug interactions. A better strategy is to reduce the dose of the cholinesterase inhibitor or consider a different treatment for dementia (eg, memantine) with a different mechanism of action.

Drug-drug interactions

• Older adults often take many drugs, they are particularly vulnerable to drug-drug interactions.
• Older adults also frequently use medicinal herbs and other dietary supplements and may not tell their health care providers.
• Medicinal herbs can interact with prescribed drugs and lead to adverse effects.

For example, ginkgo biloba extract taken with warfarin can increase risk of bleeding, and St. John's wort taken with a selective serotonin reuptake inhibitor (SSRI) can increase risk of serotonin syndrome.

Therefore, physicians should ask patients specifically about dietary supplements, including medicinal herbs and vitamin supplements.

• Drug-drug interactions in older adults differ little from those in the general population. However, induction of cytochrome P-450 (CYP450) drug metabolism by certain drugs (eg, phenytoin, carbamazepine, rifampin) may be decreased in older adults
• The change (increase) in drug metabolism may be less pronounced in older adults.
• Many other drugs inhibit CYP450 metabolism and thus increase the risk of toxicity of drugs that depend on that pathway for elimination. Because older adults typically use a larger number of drugs, they are at greater risk of multiple, difficult-to-predict CYP450 interactions.
• Also, concurrent use of ≥ 1 drug with similar adverse effects can increase risk or severity of adverse effects.

What could be the cause of his hypoglycemia?

Mr. Samuel is on glyburide and the drug will not interact with sulfamethoxazole(antibiotic), because this drug is a CYP2C9 inhibitor with unspecified potency. The interaction of these two drugs will cause hypoglycemia.

What questions do you need to ask the patient and his daughter about safe medication management?

• Does the patient experienced similar problem yet before?
• If so, how did you managed?
• At what timings you are taking all these drugs?
• Do you have any other associated symptoms other than low blood sugar?
• Have you mentioned the name of the hypoglycemic agent to the physician you met last week for staph infection?
• Are you keeping all these medications together?
• Had you missed any of these drugs at anytime?
• What you did immediately after hypoglycemia?
• When you were diagnosed with diabetes mellitus?
• From that time, are you on the same medication?

What education should be offered to this patient and his family?

1) Effectively Communicating Signs and Symptoms

• Educate the patient and daughter regarding the receiving medications known to cause hypoglycemia, providing education regarding the associated signs and symptoms
• the importance of follow-up testing, and the need for careful management and close medical supervision is imperative.

2) Patient education

•   MTM interactions
• Comprehensive teaching of appropriate management strategies involving patients and their families and caregivers.

3) Prevention of Drug-Induced Glucose and Insulin Imbalance

A risk-benefit evaluation should be considered for each individual patient, bearing in mind that in a high-risk patient, avoidance of potentially causative drugs may be the best preventive strategy, although not always possible. The following general preventive strategies have been recommended:

• Avoid Concomitant Use of: more than one drug that can cause glucose and/or insulin dysregulation; drugs that could cause pharmacokinetic or pharmacodynamic drug interactions with a potentially causative drug.
• At Each Visit: Inquire about any symptoms of hypoglycemia or hyperglycemia; monitor weight.
• Monitor Fasting Plasma-Glucose Concentration: within the first few weeks following the initiation of high-risk drugs, and regularly thereafter, particularly in the presence of weight changes or preexisting disorders of glucose metabolism; in addition to postprandial plasma-glucose concentration monitoring, for patients taking glucocorticoids.
• Obtain Baseline Fasting Plasma Glucose Level: prior to initiation of potentially causative drugs, especially in patients with risk factors.
• Low Dose and Short Duration: When a potentially offending drug is necessary, use at the lowest effective dose for the shortest duration of therapy, if possible.