Adverse drug reactions
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Introduction
Adverse drug reactions (ADRs)are the 4th-6th leading cause of death. However, up to half of these are preventable, with mis-dosing the most common error.
10-20% of hospital admissions of seniors are because of ADRs. 10-25% of community-dwelling seniors experience side-effects from meds, and this number increases to over 50% of nursing home patients.
Over 1:9 visits to the emergency department are due to ADRs (Zed et al, CMAJ, 2008)
Common ADR's include:
- confusion due to benzodiazepines, anticholinergics, amitriptyline
- falls due to postural hypotension and sedation
- decreased appetite due to iron, metformin, SSRIs
- constipation due to verapimil, iron, anticholinergics
Drug Toxicity
Therapeutic index = TD50/ED50
Mechanisms of toxic effects:
- extension of pharmacological effect (ie insulin-induced hypoglycemia)
- same mechanism, but different tissue (ie digoxin can increase contractility, but also arrhythmias in conducting tissue)
- different receptor systems (ie TCAs and anti-cholinergic effects)
ADRs in the elderly
"Start low, go slow"
Adverse drug reactions are more common in the elderly for a number of reasons:
- polypharmacy and multiple co-morbidities leads to drug/disease interactions
- ie NSAIDs and CHF
- ACE and CRF
- less body reserves
- a GI bleed can go bad very quickly
- postural hypotension can lead to falls
- altered pharacokinetics and dynamics
- altered renal function
- increased gastric pH
- increased body fat
- decreased body water (digoxin's vicious circle)
- altered hepatic metabolism
- decreased albumin (ie for carrying phenyltoin)
ADRs can be overlooked, especially in the elderly, due to:
- attribution to underlying disease, ie edema and CHF
- atypical presentation
Medications and Pregnancy?
There is not a black and white answer to the question "is this medicine safe for my baby"
There is good evidence of safety with TCAs, fluoxetine, sertraline, paroxetine, and citalopram. There are still more questions with venlafaxine, buproprion, and mirtazapine.
There is evidence that psychotherapy is just as effective as medications.
Teratogens are especially important before 15-20 weeks gestation
- there is a 3% risk in the general population of congenital anomalies
There can also be obstetrical complications
Specific Adverse Drug Reactions
- serotonin
syndrome
- neuroleptic
malignant syndrome
- hypertensive
crisis
- discontinuation
syndromes
Serotonin Syndrome
aka serotonin toxicity or serotonin storm
Life-threatening overstimulation of serotonin
clinical triad: cognitive, autonomic, somatic
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moderate |
- tachy
- fever
- diarrhea, with hyperactive bowel sounds
- diaphoresis with normal skin colour
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severe |
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- antidepressants: MAOI's, TCA's, SSRI's, SNRI's, buproprion
- opioids
- CNS stimulants: coacine, meth, amphetamines
- 5-HT1 agonists
- psychedilecis
- herbs: St John's Wort, Yohimbe, Ginseng, Ginko
Rule out with CK, myoglobin,
Neuroleptic Malignant Syndrome
due to massive dopamine blockade
onset is slower, developing over days
people tend to be akinetic, with rigitiy, with decreased LOC and mutism
- fever
- encephalopathy
- unstable vitals
- elevated envymes (CPK)
- muscle rigidity
treat by withdrawing meds and provide supportive therapy
Hypertensive Crisis
life threatening emergency
MAOI interactions: medicines and tyramine-containing foods
blood pressure rises due to increase levels of amines
Discontinuation Syndromes
Not life-threatening
- flu-like syndrome
- insomnia
- nausea
- imbalance
- sensory disturnaces
- hyperarousal