Drug Interactions - Adverse Effects Flashcards
Drug allergy - characteristics
Delay after initial exposure
Precipitated with small doses of drug
Does not resemble normal pharmacology
Classic symptoms of allergic response
Drug allergy factors can be
Host related
Drug related
Drug related factors
Nature of drug
Degree of exposure
Route of admin.
Cross sensitisation i.e reactivity to similar drugs
Degree of exposure
Dose, duration, frequency, repeated administration
Penicillins rate of reaction
More frequent parenteral rather than orally
Host related factors
Age (20-49 at higher risk) Sex - more common in women Genetic factors Diseases Previous exposure
Anaphylaxis
Acute response
Potentially fatal
Incidence of anaphylaxis (drug related)
3/100000 - deaths are 1-2/100000
Mechanisms of anaphylaxis
release of inflammatory mediators from mast cells –> oedema and tissue damage
Inflammatory mediators
Histamines and prostaglandins
Signs of anaphylaxis
Skin
Swelling
Runny nose
Symptoms of anaphylaxis
Gastrointestinal
Respiratory
Incontinence
CNS
Anaphylaxis in dentistry
Deaths occur from penicillin, aspirin, LA
Treatment of anaphylaxis in dentistry
Adrenaline
Anti histamine
Steroids
Bronchodilator
Stephen Johnson syndrome
Bizarre type B reaction e.g to anti-gout med (allopurinol)
Pain relievers
Antibiotics
Anti-epileptic medication
Drug-drug interaction mechanisms (3)
Pharmaceutical
Pharmacodynamic
Pharmacokinetic (Absorption, Distribution, Metabolism, Excretion)
e.g 1 LA and vasoconstrictor e.g Lidocaine and adrenaline
Adrenaline enhances effect of lidocaine by slowing absorption from site of action into circulation
Result of LA and VC interaction
Prolonged anaesthesia
Reduced bleeding
Reduced system toxicity
Pharmacodynamics e.g warfarin
Increased risk of anticoag - inhibits Vit K recycling by depleting active form in liver
Pharmacokinetic
Not for water soluble drugs
Drugs usually metabolised in liver and are digested by cytochrome P450 enzymes
Involves enzyme inhibitors which increase blood levels and inducers which reduce blood levels
Adverse events occur in
10-20% of hospitalised patients
Type A reaction
Pharmacological/toxic effect of a drug
Type B reaction
Idiosyncrasy and drug allergy
Types of pharmaceutical in dentistry (4)
Sedative
LA
Analgesic
Antibiotics
Therapeutic index
A ratio that compares the blood concentration at which a drug becomes toxic and the concentration at which the drug is effective.
Higher TI
Drug is safer
Lower TI
Drug needs to be monitored more carefully
Circumstances of adverse drug effects (2)
Accidental/deliberate overdose
Normal therapy side effects
Site of action (2)
Localised e.g aspirin –> ulcers, GI irritation
Systemic - most reactions
Time Course (3) and give examples
Acute toxicity - single intake e.g morphine
Sub-acute toxicity - repeated exposure for hrs/days - tetracycline
Chronic toxicity - repeated exposure for m/y - carcinogenesis
Factors affecting adverse effects (3)
Circumstances
Site of action
Time course
Type A mechanism (Augmented)
Exaggerated therapeutic response Secondary unwanted actions More predictable effects Dose dependent Low mortality Decrease dose to stop run
Type B mechanism (bizarre)
Pharmacologically unpredictable/idiosyncratic
Immunologic (allergic/anaphylactic)
Idiosyncratic (abnormal adverse reactions where mechanism not understood)
Type A concerns - major/minor and examples of cause
Resp. depression (narcotics) Cardiac toxicity (overdose of IV)
Diarrhoea (antibiotics)
Dry mouth (antidepressants)
Drowsiness (CNS drugs)
Risk factors of reaction (6)
Childhood Elderly Pregnancy Lactation Renal failure (poor filtration) Haemodialysis
Pharmacokinetic stages (4)
Absorption
Distribution
Metabolism
Excretion
Absorption e.g tetracycline is reduced by
chelation of drugs/foods/vitamins/divalent cations e.g Ca2+
Distribution (abnormal)
Sequestration of tetracycline in bone leads to depression of bone growth in children and irreversible staining of enamel
Metabolism
Interactions are usually due to effects on drug metabolising enzymes
Results in inhibition or induction of that enzyme
Metabolism can be altered by (give example) (2)
Disease e.g renal/hepatic dysfunction
Inherited factors
Excretion (controlled by, factors affecting, results)
Glomerular filtration, tubular secretion and tubular reabsorption
Kidney function, protein binding, urine pH and urine flow
Accumulation of drugs eliminated by kidneys
Type B reaction characteristics
No dose relation Uncertain mechanism Pseudo allergy Not reproducible e.g anaphylaxis Immunoallergic reactions Cause uncertain Low incidence High mortality Treatment needs to stop if occurs
Anaphylaxis signs and symptoms
Swelling of lips/tongue/throat CNS dysfunction Fast/slow heart rate and low BP Skin itching, hives and flushing Respiratory - shortness of breath, wheezing GI - cramping, vomiting, diarrhoea
Erythromycin example
Increases effect of?
Mechanism?
Warfarin, carbamazepine, theophylline, cyclosporin
Inhibit CYP450
Midazolam example
Increased plasma conc by
Erythromycin, grapefruit juice, omeprazole
Inhibits CYP3A –> sedation
St John’s Wort
Herbal drug for anxiety Enhances metabolism and reduces plasma levels therefore efficacy Affects oral contraceptive Immunosuppressant Midazolam
Lidocaine and liver
Lidocaine is CYP3A4 substrate
Clearance limited by hepatic blood flow
HBF reduced by propranolol
Hepatic enzyme metabolism inhibited by cimetidine
LA
Safety
Mechanism
XS
Safe is used within dosage
Inhibits neuronal activity
Initially stimulates CNS then depresses (in XS)
XS leads to addictive effect
Mortality due to LA - max dose
MD more rapidly reached with 3% mepivacaine than 2% lidocaine
Adrenaline a/beta agonists
a1
b2
vasoconstriction - skin and mucous membrane
vasodilation - skeletal muscles
Benzodiazepines (examples)
Diazepam/Temazepam
Benzodiazepines
Mechanism
Inhibit CYP3A4 Increased plasma or Induction decreased plasma
