Drug Interactions - Adverse Effects

Question 1

Drug allergy - characteristics

Answer 1

Delay after initial exposure
Precipitated with small doses of drug
Does not resemble normal pharmacology
Classic symptoms of allergic response

Question 2

Drug allergy factors can be

Answer 2

Host related

Drug related

Question 3

Drug related factors

Answer 3

Nature of drug
Degree of exposure
Route of admin.
Cross sensitisation i.e reactivity to similar drugs

Question 4

Degree of exposure

Answer 4

Dose, duration, frequency, repeated administration

Question 5

Penicillins rate of reaction

Answer 5

More frequent parenteral rather than orally

Question 6

Host related factors

Answer 6

Age (20-49 at higher risk)
Sex - more common in women
Genetic factors
Diseases
Previous exposure

Question 7

Anaphylaxis

Answer 7

Acute response

Potentially fatal

Question 8

Incidence of anaphylaxis (drug related)

Answer 8

3/100000 - deaths are 1-2/100000

Question 9

Mechanisms of anaphylaxis

Answer 9

release of inflammatory mediators from mast cells –> oedema and tissue damage

Question 10

Inflammatory mediators

Answer 10

Histamines and prostaglandins

Question 11

Signs of anaphylaxis

Answer 11

Skin
Swelling
Runny nose

Question 12

Symptoms of anaphylaxis

Answer 12

Gastrointestinal
Respiratory
Incontinence
CNS

Question 13

Anaphylaxis in dentistry

Answer 13

Deaths occur from penicillin, aspirin, LA

Question 14

Treatment of anaphylaxis in dentistry

Answer 14

Adrenaline
Anti histamine
Steroids
Bronchodilator

Question 15

Stephen Johnson syndrome

Answer 15

Bizarre type B reaction e.g to anti-gout med (allopurinol)
Pain relievers
Antibiotics
Anti-epileptic medication

Question 16

Drug-drug interaction mechanisms (3)

Answer 16

Pharmaceutical
Pharmacodynamic
Pharmacokinetic (Absorption, Distribution, Metabolism, Excretion)

Question 17

e.g 1 LA and vasoconstrictor e.g Lidocaine and adrenaline

Answer 17

Adrenaline enhances effect of lidocaine by slowing absorption from site of action into circulation

Question 18

Result of LA and VC interaction

Answer 18

Prolonged anaesthesia
Reduced bleeding
Reduced system toxicity

Question 19

Pharmacodynamics e.g warfarin

Answer 19

Increased risk of anticoag - inhibits Vit K recycling by depleting active form in liver

Question 20

Pharmacokinetic

Answer 20

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

Question 21

Adverse events occur in

Answer 21

10-20% of hospitalised patients

Question 22

Type A reaction

Answer 22

Pharmacological/toxic effect of a drug

Question 23

Type B reaction

Answer 23

Idiosyncrasy and drug allergy

Question 24

Types of pharmaceutical in dentistry (4)

Answer 24

Sedative
LA
Analgesic
Antibiotics

Question 25

Therapeutic index

Answer 25

A ratio that compares the blood concentration at which a drug becomes toxic and the concentration at which the drug is effective.

Question 26

Higher TI

Answer 26

Drug is safer

Question 27

Lower TI

Answer 27

Drug needs to be monitored more carefully

Question 28

Circumstances of adverse drug effects (2)

Answer 28

Accidental/deliberate overdose | Normal therapy side effects

Question 29

Site of action (2)

Answer 29

Localised e.g aspirin --> ulcers, GI irritation | Systemic - most reactions

Question 30

Time Course (3) and give examples

Answer 30

Acute toxicity - single intake e.g morphine Sub-acute toxicity - repeated exposure for hrs/days - tetracycline Chronic toxicity - repeated exposure for m/y - carcinogenesis

Question 31

Factors affecting adverse effects (3)

Answer 31

Circumstances Site of action Time course

Question 32

Type A mechanism (Augmented)

Answer 32

``` Exaggerated therapeutic response Secondary unwanted actions More predictable effects Dose dependent Low mortality Decrease dose to stop run ```

Question 33

Type B mechanism (bizarre)

Answer 33

Pharmacologically unpredictable/idiosyncratic Immunologic (allergic/anaphylactic) Idiosyncratic (abnormal adverse reactions where mechanism not understood)

Question 34

Type A concerns - major/minor and examples of cause

Answer 34

``` Resp. depression (narcotics) Cardiac toxicity (overdose of IV) ``` Diarrhoea (antibiotics) Dry mouth (antidepressants) Drowsiness (CNS drugs)

Question 35

Risk factors of reaction (6)

Answer 35

``` Childhood Elderly Pregnancy Lactation Renal failure (poor filtration) Haemodialysis ```

Question 36

Pharmacokinetic stages (4)

Answer 36

Absorption Distribution Metabolism Excretion

Question 37

Absorption e.g tetracycline is reduced by

Answer 37

chelation of drugs/foods/vitamins/divalent cations e.g Ca2+

Question 38

Distribution (abnormal)

Answer 38

Sequestration of tetracycline in bone leads to depression of bone growth in children and irreversible staining of enamel

Question 39

Metabolism

Answer 39

Interactions are usually due to effects on drug metabolising enzymes Results in inhibition or induction of that enzyme

Question 40

Metabolism can be altered by (give example) (2)

Answer 40

Disease e.g renal/hepatic dysfunction | Inherited factors

Question 41

Excretion (controlled by, factors affecting, results)

Answer 41

Glomerular filtration, tubular secretion and tubular reabsorption Kidney function, protein binding, urine pH and urine flow Accumulation of drugs eliminated by kidneys

Question 42

Type B reaction characteristics

Answer 42

``` 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 ```

Question 43

Anaphylaxis signs and symptoms

Answer 43

``` 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 ```

Question 44

Erythromycin example Increases effect of? Mechanism?

Answer 44

Warfarin, carbamazepine, theophylline, cyclosporin | Inhibit CYP450

Question 45

Midazolam example | Increased plasma conc by

Answer 45

Erythromycin, grapefruit juice, omeprazole | Inhibits CYP3A --> sedation

Question 46

St John's Wort

Answer 46

``` Herbal drug for anxiety Enhances metabolism and reduces plasma levels therefore efficacy Affects oral contraceptive Immunosuppressant Midazolam ```

Question 47

Lidocaine and liver

Answer 47

Lidocaine is CYP3A4 substrate Clearance limited by hepatic blood flow HBF reduced by propranolol Hepatic enzyme metabolism inhibited by cimetidine

Question 48

LA Safety Mechanism XS

Answer 48

Safe is used within dosage Inhibits neuronal activity Initially stimulates CNS then depresses (in XS) XS leads to addictive effect

Question 49

Mortality due to LA - max dose

Answer 49

MD more rapidly reached with 3% mepivacaine than 2% lidocaine

Question 50

Adrenaline a/beta agonists a1 b2

Answer 50

vasoconstriction - skin and mucous membrane | vasodilation - skeletal muscles

Question 51

Benzodiazepines (examples)

Answer 51

Diazepam/Temazepam

Question 52

Benzodiazepines | Mechanism

Answer 52

``` Inhibit CYP3A4 Increased plasma or Induction decreased plasma ```