Safe Prescribing & ADME Flashcards
What are the different codes for prescribing according to method of delivery?
IM = intramuscular IV = intravenous PO = oral PR = per rectum SC = subcutaneous SL = sublingual IT = intrathecal SR = slow release
What is the first step of the checklist for avoiding medication error?
Consider the patient
i.e. young or elderly, pregnant, etc.
What is the second step of the checklist for avoiding medication error?
Correct chart & correct patient?
Check patient name, D.O.B., & hospital no.
What is the third step of the checklist for avoiding medication error?
Diagnosis/therapeutic aim
Correctly identified underlying disorder?
What is the fourth step of the checklist for avoiding medication error?
Right drug for patient
- avoid therapeutic duplication e.g. paracetamol + co-codamol
- any serious drug-drug interactions (cause treatment failure or ADRs)
- any allergy to agent/group of agents (note antibiotics that contain penicillin but do not end in -illin)
- drug name spelt correctly/not open to misinterpretation
- no drug abbreviations
- form of drug is correct (e.g. liquid for children/dysphagia) AND change the dose & freq. to reflect this
What is the fifth step of the checklist for avoiding medication error?
Illness effect on distribution/elimination?
HRH, obesity
What is the sixth step of the checklist for avoiding medication error?
Alternatives to choice of drug?
- efficacy & safety
- cost
- non-drug options
- alternatives in BNF
What is the seventh step of the checklist for avoiding medication error?
Non-prescription medication interactions
e.g. St. John’s Wort (antidepressant)
What is the eighth step of the checklist for avoiding medication errors?
Route of administration
e.g. oral antibiotics preferred to IV, insulin absorption differs depending on route of administration
What is the ninth step of the checklist for avoiding medication error?
Correct dose
- doses can vary between GP & hospital
- doses can vary according to indication
- risk of ADRs increases with dose
- ?modify in HRH impairment & body weight extremes
- DECIMAL POINT ERRORS!!!!
- CONFUSION BETWEEN UNITS!!!! (use g & mg but write out micrograms & nanograms)
What is the tenth step of the checklist for avoiding medication error?
Correct frequency/timing
- timing relevant to meals can be important (esp. for lipid-soluble drugs)
- appropriate timings e.g. diuretics in the morning to avoid nocturia
- some drugs are prescribed weekly (ensure not prescribed daily)
What is the eleventh step of the checklist for avoiding medication error?
Duration of therapy
- how long will it be required?
- when will the treatment be stopped and what will determine this?
What is the twelfth step of the checklist for avoiding medication error?
ADRs
Most frequent & most serious
What is the thirteenth step of the checklist for avoiding medication error?
Drug/therapeutic monitoring required?
If so, what observations will indicate that the therapeutic aim has been achieved (by when and by whom)
What is the fourteenth step of the checklist for avoiding medication error?
Information/explanation to patient
How much info does the patient require for the therapy to be successful? Compliance?
What is the fifteenth step of the checklist for avoiding medication error?
Special prescribing requirements
e.g. controlled drug prescriptions require total quantity in words and figures on TTO
What are some rules to follow when writing prescriptions to avoid misunderstandings?
Use generic names of drugs (unless instructed by BNF)
Avoid abbreviations
Some doses depend on body weight (g/kg) but only up to a point (max. dose allowed)
TTO (to take out) - write total quantity of controlled drugs in words and figures
Amend electronic record if incorrect to prevent repeat prescription prescribing errors
What are some patient factors which cause prescribing errors?
- rapid throughput of patients
- new drug developments
- increasing complexity & specialisation
- sicker & older patients = more vulnerable to ADRs due to co-morbidities (e.g. HRH impairment), multiple drugs, etc.
What are some pharmaceutical factors causing prescribing errors?
- clinical evidence for drug efficacy & safety based on relatively healthy patients & volunteers
- some ADRs only discovered during post-marketing surveillance
What are some doctor factors causing prescribing errors?
- expected to be perfect on first day of practice
- medical education on prescribing differs
- fatigue/hypoglycaemia/hypovolaemia
- shift work/reduced hours (lower exposure to teaching, working alone, less ward teaching & feedback, poorer morale, lack of continuity of care)
- on call (rarely know patients, routine jobs e.g. re-writing drug charts, prescribing fluids, prescribing unfamiliar drugs, prescribing old drugs in absence of results)
Define an error. What are the different types of error in Reason’s framework of accident causation?
ERROR = failure of a planned sequence of actions to achieve desired goal because an adequate plan was incorrectly executed (skill-based slips or memory-based lapses) OR because an inadequate plan was made (rule-based or knowledge-based mistakes)
- slips = actions in which there are recognition or selection failures (“whoops”)
- lapses = failure of memory or attention
- mistakes = incorrect choice of objective, or choice of an incorrect path to achieve it (rule-based or knowledge-based)
What is a violation in Reason’s framework of accident causation?
VIOLATION = instances in which rules of correct behaviour are consciously ignored
What are the different codes for prescribing according to time of day?
mane = morning nocte = night
What are the factors at the level of individual responsibility for failure?
LATENT CONDITIONS = organisational process and management decisions
e.g. staffing levels, culture, poor education/training, handwritten prescriptions
ERROR-PRODUCING CONDITIONS = environment, team, individual, or task factors that affect performance
- environment = busy ward, interruptions
- team = lack of supervision
- individual = limited knowledge
- task = repetitive, poor chart design
Defences e.g. pharmacists checking prescriptions
What are the legal requirements of prescriptions?
- indelible ink
- name, D.O.B., & address of patient
- signed
- dated
- name & address of prescriber
- controlled drugs: total quantity in words and figures and specify preparation
What is the purpose of the Yellow Card Scheme?
ADR reporting
- black triangle drugs AND unlicensed herbal preparations —> report all suspected reactions, regardless of severity
- all paediatric reactions should be reported
Black triangle drugs = being intensively monitored, includes:
- newly released
- changed indications
- changed formulations
- combination products
Define a serious drug reaction.
Any reaction which results in or prolongs hospitalisation
inc. fatal, life-threatening, disabling, incapacitating
Give some examples of factors affecting pharmacokinetics.
- smoking (tobacco or marijuana)
- age
- sex
- pregnancy
- lactation
- exercise
- sunlight exposure
- barometric pressure
- disease
- infection
- immunisation
- occupational exposures
- drugs
- circadian/seasonal variations
- diet
- CVS function
- GI function
- immunological function
- liver function
- renal function
- [albumin]
- stress
- fever
- starvation
- [alcohol]
What does the area under the curve of a concentration-drug graph indicate?
Total drug exposure
Define bioavailability.
Fraction of a dose which finds its way into a body compartment
note: IV bolus = bioavailability is 100%
Bioavailability = Area under curve (oral)/Area under curve (IV)
What factors affect bioavailability?
Absorption:
- drug formulation (e.g. maintenance doses, immediate release v.s. modified release)
- age
- food (lipid-soluble drugs affected by food intake)
- vomiting/malabsorption (esp. oral drugs)
First-pass metabolism
Define first-pass metabolism. What are the different components of first-pass metabolism?
FIRST-PASS METABOLISM = any metabolism occurring before the drug enters the systemic circulation
- gut lumen (gastric acid, proteolytic enzymes, grapefruit juice)
- gut wall (P-glycoprotein efflux pumps = pump drugs out of intestinal enterocytes back into the lumen)
- liver (Phase 1 & 2)
note: enterohepatic recirculation = metabolites re-enter gut before being further metabolised by the liver (oestrogens, warfarin)
What factors affect drug-protein binding? When are the changes in drug-protein binding especially important?
Factors affecting protein binding:
- hypoalbuminaemia
- pregnancy
- renal failure
- displaced by other drugs (may need to increase dose, precipitant drugs)
Changes in protein binding important when:
- high protein binding drug
- low volume distribution
- narrow therapeutic window
What is the hypothetical volume of distribution directly proportional to? What is the volume of distribution affected by?
Dose/[Drug]at t=0s
Affected by:
- specific receptor sites in tissue
- regional blood flow
- lipid solubility
- active transport
- disease states
- drug interactions
What are the approximate values for the volumes of distribution in a 70kg male?
23l intracellular space
14l interstitial space
5l intravascular space
(42l total)
What is the purpose of metabolism of drugs?
Enhances ionic charge to enable renal excretion (essential for lipophilic drugs)
What is the rate of elimination of drugs determined by? How do the kidneys eliminate drugs?
- plasma protein binding
- tubular urinary pH (proportion of weak acids & bases diffusing back into bloodstream)
Kidneys: organic anion transporters & organic cation transporters
Why do zero order drugs need to be monitored? Give some examples.
More likely to result in toxicity (half life not calculable) esp. with polypharmacy (same CYP/renal transporter affected)
e. g. high dose aspirin, phenytoin, verapamil, fluoxetine, alcohol, ecstasy
note: most drugs exhibit zero order kinetics at high doses (receptors & enzymes become saturated)
What factors affect drug clearance?
HEART = factors affecting blood flow to main organs of elimination (GFR)
RENAL = factors affecting renal elimination (active secretion, passive reabsorption inc. pH & urine flow rate)
HEPATIC = factors affecting hepatic elimination
What are the different codes for prescribing according to the dosing frequency?
od = once daily bd = twice daily tds = three times daily qds = four times daily stat = single one off dose
Define pharmacovigilance. What are the methods and aims of pharmacovigilance?
Process of identifying and then responding to safety issues about marketed drugs
- survey the safety of drugs
- develop strategies to minimise risks & optimise benefits
Aims:
- identify previously unrecognised drug safety hazards (i.e. not known about during development and testing) and seek to quantify their frequencies
- elucidate those factors predisposing for toxicity (i.e. why drug hazards occur)
- attempt to obtain evidence of safety so that a new drug’s use can be widened (i.e. alternative applications e.g. thalidomide in leprosy)
- “false positive” adverse drug reactions (hazards NOT due to drug but falsely identified as being an ADR)
Define and contrast pharmacogenetics and pharmacogenomics.
Pharmacogenetics = understanding how different individual genotypes relate to different drugs
Pharmacogenomics = pharmacogenetics applied to the entire genome
Has effect on treatment efficacy and likelihood of ADRs
How does pharmacogenetics affect the drug regimen for hypertension?
White individuals (increased RAAS activity) generally respond better to ACE inhibitors than black individuals (decreased RAAS activity)
Vice versa for Ca2+ channel blockers
Black individuals are also more likely to have angioedema as an ADR to ACE inhibitors
Therefore the first-line treatment for hypertension in white individuals = ACE inhibitors + angiotensin receptor blockers
Therefore the first-line treatment for hypertension in black individuals (and old people - reduced RAAS activity) = thiazide diuretics & Ca2+ channel blockers
How do genetic polymorphisms affect the efficacy and toxicity of drugs?
Pharmacokinetics (ADME) & pharmacodynamics (e.g. receptors, ion channels, enzymes, immune system)
e.g. if A = normal metabolism, a = impaired metabolism (increased area under [drug] v.s. time curve), B = normal receptor, b = abnormal receptor (reduced efficacy of drug but same toxicity curve)
AB = high efficacy, low toxicity Ab = low efficacy, low toxicity aB = high efficacy, high toxicity ab = low efficacy, low toxicity
Give some examples of common genetic polymorphisms affecting drug metabolism.
6% of white individuals have two null alleles for CYP2D6 (responsible for metabolism of 25% of drugs e.g. anti-depressants, anti-psychotics, beta-blockers, opioid analgesics) ——–> increased [drug] ——> have increased efficacy but increased toxicity
High rate of G6PD deficiency in black individuals —> primaquine, dapsone, and nitrofurantoin cause haemolytic anaemia
Individuals with intermittent porphyria —> OCP, alcohol, anti-convulsants, and barbituates cause acute porphyria
Give some examples of conditions frequently resulting in negligence cases.
- subarachnoid haemorrhage (ask about onset of headache, beware ache at back of the neck)
- pulmonary embolism (always consider with unexplained breathlessness)
- cauda equina syndrome (ask about urinary symptoms and altered saddle sensation)
- acute appendicitis (less classical presentation = urinary symptoms, diarrhoea, no right iliac fossa tenderness)
- ischaemic foot (check pulses, reconsider gout and cellulitis in red painful foot)
- malignant melanoma
- breast cancer (examination can miss small cancers)
- colorectal cancer (review borderline symptoms = anaemia, rectal bleeding, looser stools)
- cervical cancer (breakthrough bleeding that persists e.g. after changing contraceptive pill)
- diabetic ketoacidosis (always check urine for ketones in unwell Type 1 diabetics)
- achilles tendon rupture (ask about “snaps”, check standing on tiptoe, do calf squeeze test)
- septicaemia (measure and record temperature, pulse, and BP in febrile patient; beware rapid progression of UTIs)
- unexpectedly abnormal result (repeat if not overly deranged)
Give some examples of prescribing error red flags.
Mistakes twice as likely in children and elderly (weight, metabolism)
50% of error caused by prescribing errors of:
- methotrexate
- digoxin
- warfarin
- aspirin
- beta-blockers
- NSAIDs
- opioids
Give some examples of checklists used to prevent prescribing errors.
WARD:
- consent
- allergies
- baseline obs.
- intended procedure
THEATRE:
- before induction of anaesthesia
- before start of surgical intervention
- before leaving OR
Blood transfusion checklist
What are the types of clinical incident?
Patient Safety Incident
Near Miss
Serious Untoward Incident
- unexpected or avoidable death (patients, staff, public) or serious harm (requiring intervention, prolonged pain, psychological harm)
- serious breach in confidentiality
- allegations of abuse
- Never Event = seriously largely preventable patient safety incident that should not occur
How can you report a clinical incident?
Serious incidents require urgent Datix reporting and inform key line managers immediately
Define the duty of candour.
Volunteering of all relevant information to persons who have or may have been harmed by provision of services, whether or not the information has been requested and whether or not a complaint or report about that provision has been made.
LAW
i.e. if an error has occurred, the patient should be informed and an apology made, and attempts should be made to alleviate harm caused and to prevent the same errors occurring in the future
What happens to the relative concentration of a moderately lipophobic drug ionised at physiological pH and not bound to plasma proteins?
Low Vd
High [drug]blood
What happens to the relative concentration of a drug which is moderately lipophilic, slightly charged, and not bound by plasma proteins?
High Vd
Low [drug]blood
What happens to the relative concentration of a drug which is lipophilic and also binds to muscle protein?
Higher Vd
Lower [drug]blood
What happens to the relative concentration of a drug which is slightly lipophilic, charged, and heavily bound to plasma proteins?
High Vd
High [drug]blood (but low [free drug]blood)
Give examples of drugs which have different apparent volumes of distribution. Which compartments might each drug enter?
LOW Vd (e.g. 0.12l/kg = 0.12 x 70 = 8.4l in 70kg man)
e. g. warfarin, insulin, penicillins
- blood
- extracellular spaces
MEDIUM Vd (e.g. 0.26lkg = 0.26 x 70 = 18.2l in 70kg man)
e. g. atropine
- muscle
- intracellular spaces
HIGH Vd (e.g. 3.4l/kg = 3.4 x 70 = 238l in 70kg man)
e. g. amiloride, morphine
- fat
- intracellular spaces
How does weight affect the apparent volume of distribution of drugs? How might this effect the dose of drug required?
Increased weight increases the volume of distribution
Increased dose might be required
What are the primary enteral and parenteral routes for drug administration?
ENTERAL:
- oral
- sublingual
- topical
- transdermal
- ophthalmic
- otic
- nasal
- rectal
- inhalation
- vaginal
PARENTERAL:
- intravenous
- intramuscular
- subcutaneous
- intrathecal
- epidural
- intradermal
What are the pros and cons of administering drug via enteral routes?
PROS:
- can exert a local and systemic effect (oral, rectal, vaginal)
- continuous effect (transdermal)
- safe (noninasive)
- convenient
- less expensive
CONS:
- inappropriate if patient is nauseated/vomiting
- inappropriate if patient has reduced intestinal motility
- inappropriate if patient have restricted oral intake
- inappropriate if patient cannot swallow
- not useful in emergency (slow onset)
- first pass effect can reduce efficacy
What are the pros and cons of administering drugs via parenteral routes?
PROS:
- can be used for drugs which are poorly absorbed/ineffective/inactive when given orally
- avoids first pass effect (100% bioavailability)
- IV has immediate onset
- control circulating levels of drug (titration)
CONS:
- additional training required
- aseptic technique required
- expensive
- painful
- additional equipment
How are topical drugs applied? Give examples of sites of administration.
Applied directly onto surface of skin/mucous membrane
- eyes
- nose
- ears
- lungs
- vagina
- urethra
- colon
What are the pros and cons of administering drugs topically?
PROS:
- local therapeutic effects
- not well absorbed into the deeper layers of the skin/mucous membrane (reduced risk of side-effects)
- easy
- non-invasive
- good patient adherence
CONS:
- most drugs have a high Mw and are poorly lipid soluble; therefore are not appropriate to use topically, as they will not be absorbed by the skin and mucous membrane)
- very slow absorption
