Flashcards in Pharmo Deck (442)
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What are the different sorts of active failure in prescribing?
Violation - Directly contravening known guidelines
Slips - e.g. Copying one dose for multiple drugs
Lapses - e.g. Missing a contraindication
Mistakes - e.g. Not knowing to reduce a drug in renal failure
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What is reasons model of accident causation?
A number of factors that come together, all required but non sufficient to cause the error alone. Includes latent conditions, active failure and failure of defences.
2
Why do errors happen?
High expectations from day 1
Exhaustion on nights
Lack of senior support
Routine task boredom
Lack of familiarity with patients
New drugs
Increased uses of drugs
Older patients with co morbidities and poly pharmacy
3
What is the individual vs systems base for medical drug errors?
Individuals fault - fear, retrain, litigation, naming and shaming
System fault - safeguards, barriers, acceptance and improvement
4
What is pharmacovigilance?
What are the aims?
The process of id and responding to safety issues about marketed drugs.
- id previously unrecognised safety hazards
- what causes the toxicity
- obtain evidence of safety to allow widening of drugs use
- identify false positive adrs
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What are type a and type b drug reactions?
A - predictable, exaggerated pharmocological response, dose dependant, common, high morbidity low mortality
B - unpredictable, not expected, in dependant of dose, rare, high mortality
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What are the dissadvantages of a clinical trial vs clinical prescription?
Small number of patients vs millions
Restricted age, pmh and dhx vs anyone indicated
Limited duration vs lifelong
Specialists prescribers vs generalists
High level of clinical monitoring vs low
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How are adrs identified?
Spontanious reporting
Cohort studies
Case control studies
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What is the yellow card scheme?
What drugs should be especially reported?
A report of potential adrs to mhra
Mhra then consider the cohort or case control studies
Black triangle drugs (1st year out of trials)
Unusual or serious reactions from established drugs
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Problems with yellow card scheme?
Significant undereporting
Delays in reporting
Poor data - filled in too fast
Misleading reports
No control group (how many recieve with no issues)
Difficulty recognising previously unknown adrs
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Why is reporting of adrs low?
Failure of pt to report
Adr is trivial
Not knowing report
Lack of time
Uncertainty of causal relationship
Experience with process
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What is bioavailability? How is it calculated?
Fraction of administered drug that reaches systemic circulation
F = AUC (oral) / AUC (iv)
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What factors effect bioavailability?
Active - gi membrane pumps, enzymatic destruction, first pass metabolism
Passive - lipid solubility, molecular size of drug, pKa of drug
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What factors determine drug distribution?
Lipophilicity
Plasma protein binding
Tissue protein binding
Variation in compartment size etc. (E.g. Obese with more fat)
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How do we work out volume of distribution of a drug?
Calculate concentration (C0) in plasma at time zero by extrapolating backwards from successive concentration measurements.
Vd = initial dose / C0
Assumes immediate distribution of the drug
Alternatively plot Vd using initial dose over current concentration against time then extrapolate back to get Vd at time 0
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What does Vd show?
What would a reading of 5L, 10L, 200L suggest?
Equivalent volume of plasma a drug is distributed within - indicitive of compartments
5 - in plasma
10 - in ECF
200 - in muscle or fat too
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How can Vd be expressed?
Total (e.g. 8L) or as a propotion of weight (e.g. 0.2 L/kg)
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What reactions occur in phase 1 metabolism?
Redox reactions, hydroxylation
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What enzymes are most commonly involved in phase 1 metabolism? Which subset?
CYP450
CYP459 3A4
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How does phase 1 metabolism contribute to differing half lives of drugs?
CYP enzymes very generalist and therefore have variable rates with different drugs
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What non modifiable factors can influence drug metabolism?
Ethnicity
Sex
Age
Genetics
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What does pharmacogentetics allow?
An understanding how different genotypes will relate to different drugs to determine which drugs are effective and which are safe
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Give an example of pharmacogenetics applied to antihypertensive drugs
Why? What is given instead?
Ace inhibitors is less effective in black people
Afro caribbeans patients have lower RAS activity so medication would not be so effective.
Thiazide or calcium channel blocker.
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What adr are afrocaribbean pts more likely to suffer from lisinopril?
Angioedema
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What is the formula for half life?
T1/2 = 0.7 Vd/CL
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What is the definition of half life?
The constant fraction of a drug eliminated over a certain time period
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What are routes for drug elimination?
Urinary
Bile
Exhaled air
Breast milk
Sweat
Tears
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How is steady state concentration calculated in an infusion?
CpSS = dose rate / clearence
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How long does it take for a drug given at a constant rate to reach steady state?
Five. Half lives
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