EXAM PREP Flashcards
Discuss the key aspects of individualised drug therapy
Is the diagnosis correct?
Is the drug therapy necessary?
What is the right drug based on good evidence for this condition?
Is the drug appropriate for this patient?
Is this patient susceptible to certain Adverse Drug Reactions?
Is a loading dose or low initial dose necessary?
Does the maintenance dose rate need to be adjusted for this patient?
What are the therapeutic objectives?
How are efficacy and toxicity going to be monitored?
Is adherence likely to be a problem?
What is the duration of therapy/when should therapy stop?
What is the best way to deprescribe?
Explain how the renal and hepatic system contribute to drug clearance.
Most drugs are cleared by the liver or kidneys (or both). The renal system filters, reabsorbs, secretes and ultimately excretes drugs into the urine, clearing it from the body.
The hepatic system metabolises drugs into metabolites and then clears them from the body in stools via the biliary system.
These processes are hindered when renal or hepatic dysfunction is present, often necessitating an adjusted dose to account for less efficient renal or hepatic clearance.
Explain the influence of renal and hepatic dysfunction on dosing
Renal and hepatic dysfunction hinders the processes by which drugs are cleared from the plasma and the body, meaning that if doses are not adjusted, then there is a risk of toxicity resulting from plasma concentrations that are too high. Doses must be reduced or spaced out further to account for the dysfunctional clearance of the drug.
Explain the key principles of prescribing during pregnancy and lactation
Pregnancy:
Drugs should be prescribed in pregnancy ONLY if the expected benefit to the mother outweighs the risk to the foetus.
All drugs should be avoided if possible during the first trimester.
Drugs which have been extensively used in pregnancy and appear to be safe should be prescribed in preference to new or untried drugs.
The smallest possible dose should be used.
Lactation:
Consider non-drug measures first.
Avoid all drug therapy if possible, as the infant does not usually benefit from the drug exposure via breastmilk.
Monitor the infant for adverse effects of the drug.
Dose after feeding where possible to minimise drug exposure.
Consider the term of the baby at birth.
Explain the key principles of prescribing in the context of renal impairment (severe)
The level of renal function below which the dose of a drug must be reduced depends on the proportion of the drug eliminated by renal excretion and its toxicity.
For more toxic drugs with a small safety margin or in patients at extremes of weight, dose regimens based on creatinine clearance (Cockcroft & Gault equation) should be used. When both efficacy and toxicity are closely related to plasma-drug concentration, recommended regimens should be regarded only as a guide to initial treatment; subsequent doses must be adjusted according to clinical response and plasma-drug concentration.
Nephrotoxic drugs should, if possible, be avoided in patients with renal disease because the consequences of nephrotoxicity are likely to be
more serious when renal reserve is already reduced.
Explain the key principles of prescribing in the context of hepatic impairment
For drugs metabolised by the liver (fe < 0.5) dose reductions should be considered in relation to
the estimation of the degree of liver impairment
Consider non-drug measures first; When prescribing ‘start low & go slow’.
Consider dose tapering after desired effects are achieved; Discontinue unnecessary drugs
Consider using drugs cleared renally rather than metabolically
Consider drug interactions, especially enzyme induction or inhibition
Consider reducing doses of drugs that are predominantly metabolised (fe<0.5) in relation to
impairment of liver metabolic function. If albumin is <30g/L &/or INR is>1.2 (severe), reduce the
dose by 50%. For non-severe chronic liver disease, reduce dose by 25%
State the tests used to estimate hepatic function
There is no single marker for the degree of liver dysfunction, standard liver function tests (e.g.
ALT, ALP) do not accurately reflect liver dysfunction, however severe liver dysfunction is
indicated by an albumin of <30g/L & or INR of >1.2
State the tests used to estimate renal dysfunction
Renal function in adults is routinely reported on the basis of estimated glomerular filtration rate (eGFR) normalised to a body surface area
of 1.73 m2 using the CKD- EPI formula
Discuss beneficial and harmful polypharmacy
Beneficial polypharmacy has been described as ‘prescribing for an individual for complex conditions or for multiple conditions in circumstances where medicines use has been optimised and where the medicines are prescribed according to best evidence’
Harmful polypharmacy is the prescribing of many medicines inappropriately or
adding an inappropriate medicine to an existing regime
Polypharmacy is associated with:
reduced adherence to therapies
significant costs to patients and health services
poor health outcomes, such as adverse drug events, drug interactions, admissions to hospital and death
Describe geriatric syndrome associated with polypharmacy
Polypharmacy is associated with negative health outcomes including adverse drug reactions, poor adherence and clusters of health problems described as “geriatric
syndromes”, for example, urinary incontinence, cognitive impairment and impaired balance leading to falls. Geriatric syndromes make elderly people even more vulnerable to poor health and situational outcomes, and death.
Detail the effects of advancing age on PK & PD
PK:
Impaired renal & hepatic drug clearance.
Both renal function & drug metabolism decline by approximately 1% per year after the age of 40.
PD:
Altered sensitivity [mostly increased] to most drugs, particularly anticholinergic, benzodiazepines,
NSAIDs, diuretics, proton pump inhibitors, & tricyclic antidepressants.
Increased adverse affects [even at usual therapeutic concentrations] which can be cumulative.
Impaired ability to compensate for the effects because of impaired homeostasis & multiple
disease states.
Increased susceptibility to nephrotoxic drugs, particularly if renal clearance is reduced due to
acute illness & dehydration.
Explain the principles of prescribing in the elderly
Consider non-drug measures first; start low & go slow; adjust dose in relation to renal & metabolic function
Reduce harmful polypharmacy
Review total therapy frequently; use minimum dose required for effect, & discontinue unnecessary drugs
Consider adherence & utilise appropriate dosage formulations & compliance aids
Provide clear instructions & ensure shared goals & understanding
Explain the practice & purpose of drug concentration monitoring
Drug concentration monitoring involves measurement of the drug concentration in body fluids (usually plasma, serum or blood) AND clinical interpretation of the result with the aim of individualising the dosing regimen to produce the desired plasma concentration for optimal patient benefit and reduce risk of toxicity or inefficacy.
Criteria for drug concentration monitoring:
1. Narrow therapeutic range
2. Difficult to predict concentration from dose [Significant pharmacokinetic
variability]
3. Relationship between concentration and effect
4. Therapeutic endpoint is not easy to quantify
5. Appropriate drug assay available
Exclusion for drug concentration monitoring:
1. Pharmacological effects can be measured e.g. BP, HR,
blood glucose, serum cholesterol, pain relief
2. Clinical outcome is not related to concentration
3. Dosage need not be individualised
4. Drugs have a wide therapeutic range
State several drugs monitored using plasma drug concentrations
Lithium
Theophylline
Phenytoin
Azathioprine
Aminoglycosides
Vancomycin
Clozapine
Explain the pharmacology of poisoning and management, including antidotes for clinically important drugs associated with overdose (opioids, paracetamol, benzodiazepines)
Pharmacological poisoning occurs when the drug taken has a toxic effect on the body. This may be dose-dependent (overdose) or occur at a reasonable dose.
Priorities of management of poisoning:
Maintain vital physiological functions.
Reduce or prevent absorption and enhance elimination to minimise the tissue concentration of the poison.
Combat the toxicological effects of the poison at the effector sites.
Some drugs that commonly cause toxic effects have antidotes. For example, for opioid overdose the antidote is naloxone, which stops opioids from binding to opioid receptors, lessening the effect of opioids. Acetylcysteine is a paracetamol antidote and works by increasing glutathione which is a powerful antioxidant that helps protect cells from oxidative stress. Flumazenil is a benzodiazepine antidote, which works by stopping benzodiazepines from binding to the GABA receptors, therefore reducing its effect.
