Module 10 Flashcards
Unintended and undesired responses from drugs
Adverse drug reactions - ADRs
Canadian research suggests that ___% of hospital admissions in Canada are attributed to ADRs
7.5%
ADRs include these 7 types.
Side effects Drug toxicity Allergic reactions Idiosyncratic reactions Carcinogenic effects Mutagenic effects Teratogenic effects
Secondary to the main therapeutic effect of the drug, and are expected.
Side effects
Side effects of a drug are often due to this.
Poor specificity or selectivity of a drug
What are side effects of antihistamines? How do they come about?
Sides include drowsiness, dry mouth and urinary retention - sides occur when histamines bind to receptors in the brain
Considered any severe adverse drug event
Drug toxicity
Drug toxicity is often mediated by this.
Overdose
Drug toxicity reactions are often extensions of the _________ effect.
therapeutic
Allergy requires prior ___________.
Sensitization - patient exposed to the allergen
What cells release histamine in allergies?
Mast cells
Allergic reactions can vary from ______ and ______, to life threatening ________.
itching, rash
anaphylaxis
What are the symptoms of anaphylaxis?
hypotension, bronchospasm, edema
the intensity of allergic reactions are __________ of dosage size.
independent - therefore small doses can produce severe allergy
What percentage of ADRs are due to allergy?
10%
What is the most common drug class to cause drug allergy? What are some others?
Penicillins
Sulfonamides and NSAIDs also cause allergy
Reactions that occur rarely and unpredictably in the population
idiosyncratic reactions
What accounts for the majority of idiosyncratic reactions?
Genetic polymorphisms
Warfarin is metabolized by what enzyme?
CYP2C9
6-mercaptopurine is metabolized by what enzyme?
TMPT - thiopurine methyltransferase
Describe the CYP2C9 genetic polymorphism
Approx 15% of caucasians have a polymorphism that decreases metabolism (of warfarin).
Describe the CYP2D6 genetic polymorphism.
10% of Caucasians and African Americans are poor metabolizers - these patients do not experience pain relief when they take codeine (converted to morphine)
Describe the genetic polymorphism of thiourine methyltransferase.
Approximately 10% of patients have decreased activity, and 0.3% have none. - treatment with thiopurine drugs in these patients may result in life threatening bone marrow suppression
Describe the genetic polymorphism in OATP1B1.
OATP1B1 is an uptrake transporter in the liver
15% of Caucasian and Asian patients have a polymorphism decreasing function
has been implicated in myopathy in patients taking statin drugs
Describe the effect of G6PDH deficiency.
Important in RBC metabolism - may have RBChemolysis following analgesic or anti-malarial treatment in certain people of African or Middle-Eastern descent
Why is it difficult to determine whether a drug is carcinogenic or not?
Takes years after the initial dose to appear
Describe a drug that was pulled of the shelves for being carcinogenic.
Diethylstibestrol (DES) - used to be prescribed to prevent spontaneous abortions in high-risk pregnancies - female offspring often developed vaginal or uterine cancer
Often drugs that are mutagenic are also carcinogenic or teratogenic. When would they be approved?
If there is sufficient evidence of safety from preclinical studies
How are drugs tested for mutagenic potential?
Through the Ames test (ability of compound to induce mutations in bacteria)
Drugs causing birth defects or impair fertility
Teratogens
When do gross malformations occur when exposed to teratogens?
When is function disrupted primarily?
1st trimester - gross malformations
2nd and third trimester - affect function more than gross anatomy
Transfer of drugs across the placenta is greatest in the ______ trimester. Why?
third
b/c as the placenta develops, the surface area for transfer between maternal and fetal circulation increases and the barrier becomes thinner
Describe how the pregnancy category of a drug works.
A - no evidence
B - issues in animal studies; none in women
C - benefits outweight harm - harm in animals studies but no well controlled studies for preggo women
D - Clear evidence of risk to fetus but benefits outweight possible risks
X - clear risk, should never be used in pregnant women - risks outweigh benefits
The most common and important organ specific toxicity is observed in the ____ and the _____.
liver, heart
Most common reason for an approved drug to be removed from the market.
Hepatotoxicity
What are signs of hepatotoxicity?
jaundice, dark urine, light-coloured stool, nausea and vomitting
Describe a blood test that can determine if liver function is impaired.
Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) are liver enzymes that are usually low in the blood, unless the liver is damaged. In that case, they are higher
Hepatotoxic drugs are often contraindicated for these patients.
Alcoholics
Pts with liver disease
Patients already taking hepatotoxic drugs
Name each of the following ECG waves.
Normal atrial depolarization
rapid depolarization of the left and right ventricles
Repolarization of the ventricles
Wave that is not always seen
Time required for the ventricles to repolarize
P-wave QRS complex T-wave U-wave QT interval
A prolongation of the QT interval is a major risk factor for the development of this.
Torsades de pointes
Life-threatening form of ventricular arythmia
Torsades de pointes
Which gender is at higher risk for torsades de pointes?
Females since their QT interval is longer
Drugs that prolong the QT interval should be used with caution in these patients.
Elderly
pts with bradychardia, heart failure, low potassium or congenital QT prolongation
Most common cause of ADRs.
medication errors
Medication error caused by a HCP.
iatrogenic error
What are the 5 main types of medication errors.
Prescribing Dispensing Administration Patient education Patient
HCP prescribes the wrong drug, wrong dose or wrong route
Prescribing medication error
The prescription is correct but the pharmacist dispenses the wrong drug.
Dispensing medication error
The HCP administers the incorrect dose and/or drug.
administration medication error (can also be made by a patient)
Illiteracy or language barriers may cuase the patient to not comprehend the instruction and have a medication error.
Patient education medication error
The patient understands the instructions but doesn’t follow them
Patient medication error
Confusion over drug names represents __ of all medication errors.
What types of factors can increase drug naming errors?
15%
poor handwriting, illiteracy, strong accents
Name what each of the following may be mistaken as. Plendil Nicoderm Flomax Dioval
Pletal
Nitroderm
Volmax
Diovan
The institute for Safe Medication Practices has put together a list of error prone abbreviations.
Describe how each of the following may be mistaken and what the preferred way to write it is.
IU q.d. q.o.d. 1.0mg .5mg MgSO4 MS, MSO4
IU - misread as IV or 10 - write units
q.d. - misread as qid - write every day
q.o.d. - misread as q.d. or q.i.d. - write every other day
1.0mg - misread as 10mg - do not use trailing zeros
.5mg - misread as 5mg - use a leading zero
MgSO4 - misread as morphine sulfate - write magnesium sulfate
MS, MS04 - misread as magnesium sulfate - write morphine sulfate
