Drug interactions - adverse effects Flashcards
Adverse drug effects statistics
2.9 - 3.7% of hospitalizations involve adverse events
4th leading cause of death
Drug poisoning accounting for 1 in 7 deaths among
people in their 20s and 30s in 2014 in UK
Majority of deaths in males
Adverse events occur in 10-20% of hospitalized patients.
7% of those in ambulatory setting
Type A reactions
pharmacological or toxic effect
Type B reactions
iodiosyncrasy and drug allergy
Typical pharmacopeia in dental practice
Sedative
Local anesthetic
Analgesic
Antibiotics
Therapeutic index
The therapeutic index varies widely among substances
GRAPH
Know the TI for drugs we use
Therapeutic index remifentanyl
Opioid analgesic
33000:1
Therapeutic index diazepam
Benzodiazepine sedative, muscle relaxant
100:1
Therapeutic index morphine
Opioid analgesic
70:1
Drugs with low therapeutic index
Anticoagulant i.e. warfarin
Aminoglycoside antibiotics i.e. gentamicin
Anticonvulsants i.e. phenytoin
Circumstances
Accidental or deliberate overdose
Normal therapy -side effects
Site of action
Localized
-aspirin (mouth ulcers, GI irritation)
Systemic
-majority of reactions
Time course
Acute toxicity- single intake/rapid onset
-narcotics (i.e. respiratory depression)
Sub-acute toxicity-repeated exposure (hours/days)
-tetracycline (i.e. renal impairment)
Chronic toxicity- repeated exposure (months/years)
-chemical carcinogenesis
Mechanisms - Type A
For augmented
- exaggerated therapeutic responses
- secondary unwanted actions
- more predictable or anticipated effects
Mechanisms - type B
For bizarre
Pharmacologically unexpected, unpredictable, or idiosyncratic
adverse reactions
-immunologic (Allergic or anaphylactic)
-idiosyncratic (Qualitatively abnormal adverse reactions
that occur in a given individual and whose mechanism
is not yet understood)
Type A reactions - major concerns
Respiratory depression (i.e. narcotic agents) Cardiac toxicity (i.e. overdose of intravascular injection of local anesthetic)
Type A reactions - minor concerns
Diarrhea (Broad spectrum antibiotics)
Dry mouth (Anticholinergics i.e. antidepressant)
Drowsiness (CNS drugs i.e. benzodiazepines)
Higher dose –>
Higher possibility of side effects
Type A reactions - risk situation
Childhood
- Elderly
- Pregnancy
- Lactation
- Renal failure
- Haemodialysis
Type A reactions - pharmacokinetics
Absorption Distribution Metabolism Excretion -each step is a target for adverse effect
Type A reactions - absorption/ distribution (tetracycline)
Absorption reduced by chelation of drugs/food/vitamins/
divalent cations (i.e. milk)
Distribution sequestration of tetracycline in bone (tissue
binding) leading to depression of bone growth in children and
irreversible staining of tooth enamel
No to be prescribed in pregnant women and children under 12
Type A reactions - absorption GRAPH
Antiacids and iron preparation
decrease absorption by
chelation
Type A reactions - metabolism
Some important preventable drug interactions are due to their
effects on drug metabolizing enzymes, resulting in inhibition of
enzyme or induction of enzyme
Diseases may alter drug metabolism (i.e. renal and hepatic
dysfunction)
Abnormal drug metabolism may be due to inherited factors of either
Phase I oxidation or Phase II conjugation
Polypharmacy risk of drug interactions
Type A reactions - excretion
Renal excretion of drugs mainly controlled by: glomerular
filtration, tubular secretion and tubular reabsorption.
Factors affecting renal excretion of drugs include: kidney
function, protein binding, urine pH and urine flow.
Impaired renal function may lead to clinically significant
accumulation of drugs eliminated by the kidneys
Type B reaction
No dose relationship Unexpected Mechanism uncertain Causality uncertain Not reproducible Characteristic, serious Suggestive time relationship Low background frequency Immunoallergic reactions Pseudoallergy Metabolic intolerance Idiosyncrasy
