Therapeutics / Prescribing Flashcards
Important things to enquire about during a drug history
Current medication (regular and occasional)
=> Drug, dose, frequency and timing, date/time of last dose.
=> Compliance
=> ADRs / side effects
=> Recently started/stopped/changed
=> OTC, herbal remedies, OCP/HRT, weekly/monthly medicines
=> Inhalers, eye drops, creams, insulins
Steroid use within the last 12 months / steroid emergency card
Allergies and reaction
When are “generic” drugs used and when are brand names used?
Typically always use “generic” drug name unless there is a specific exception (inhalers, anti-epileptics, insulin, immunosuppressants, etc.)
Where are infusions prescribed?
STAT infusion = document on STAT chart (with no dosing information) and on infusion section.
Regular antibiotic infusion = antibiotic section only.
Regular medication infusion = regular section only.
Continuous infusion = infusion section and cross reference on regular section (with no dosing information, and all times circled).
What are the potential problems encountered with medication and reduced renal function?
Altered pharmacokinetics
Toxicity due to failure to excrete medicines and metabolites
Reduced tolerance of side effects / increased sensitivity to drug
Drug no longer effective (e.g. nitrofurantoin)
Options for compensating for renal impairment when prescribing
- Reduce the dose (consider if loading dose required)
- Extend the dosing interval (e.g. BD instead of TDS)
- Use an alternative
eGFR - advantages and disadvantages
Advantages:
- Reported on U&E results
- commonly used to report kidney function
Disadvantages:
- not useful if the patient is not an adult or is above/below “average” body surface area
When should CrCL be used over eGFR?
Toxic drugs
Drugs with narrow therapeutic window that are mainly renally excreted – e.g. digoxin, gentamicin, vancomycin
DOACs
Elderly patients (age 75 and over)
Patients at extremes of weight (BMI <18 or >40)
Medication review in AKI
- Stop high-risk medications (“nephrotoxins”):
- NSAIDs, ACEIs, ARBs, spironolactone - Avoid nephrotoxic antibiotics (e.g. gentamicin, vancomycin) unless essential
- Hold diuretics
- Hold anti-hypertensives
=> although CCBs are normally fine to continue in AKI - Stop Metformin
- Avoid contrast, if possible
(Generally hold medications for 48-72 hours and then review renal function and see if they can be restarted)
Is aspirin considered a high-risk medication in AKI?
Although aspirin is an NSAID, low-dose aspirin is not considered the same risk!
Why is metformin stopped in AKI
If Cr >150 or eGFR <30
due to risk of lactic acidosis
Why are NSAIDs contraindicated in renal impairment?
Patients with renal impairment / CCF / liver cirrhosis, are often reliant on PGs for normal renal function.
=> NSAIDs inhibit renal PG synthesis, which thereby reduces renal blood flow and GFR
=> This leads to impaired renal function and increased sodium & water retention
Even short NSAID courses can induce AKI
ACEIs and renal function
ACEIs are reno-protective in microalbuminuria / proteinuria, irrespective of whether BP is raised or not.
No absolute contraindication to use in renal impairment (except in patients with aortic / bilateral renal artery stenosis)
Renal function may deteriorate following initiation / dose increase of ACEI or ARB
Contrast-induced AKI
Iodinated contrast agents are potentially nephrotoxic.
Contrast-induced AKI (CI-AKI) most likely to occur 2-3 days after administration of contrast.
Prevention:
- Check renal function and assess for risk factors of CI-AKI
- Encourage oral hydration before and after procedure
- Consider IV volume expansion if at particularly high risk
Steps of WHO pain ladder
Step 1 = Paracetamol or NSAID
Step 2 = Add codeine
Step 3 = Strong opioid (e.g. morphine) in place of codeine
Remember to check DOSE of analgesia and COMPLIANCE before stepping up.
What is important to remember when using codeine?
There can be variable efficacy between individuals due to differing metabolism.
Breakthrough Pain
= pain occurring between regular doses of pain relief.
An additional dose of immediate release medication should be given.
What is the standard dose of a strong opioid for breakthrough pain medication?
The standard dose of a strong opioid for breakthrough pain is usually 1/10th to 1/6th of the regular 24-hour dose, repeated every 2-4 hours as required.
Paracetamol - advantages
Well tolerated
Can give PR or IV if NBM
Analgesic of choice in hepatic/renal failure
Opioid sparing
Paracetamol - disadvantages
Highly toxic in overdose
Shorter analgesic effect after given IV than PO
Often not sufficient alone
When does paracetamol dose need to be reduced?
if weight <50kg
if Pt has risk factors for hepatotoxicity.
NSAIDs - advantages
Very effective for pain caused by injury/inflammation (e.g. post-op) and bone pain
Generally well tolerated
NSAIDs - disadvantages
Many cautions and contraindications
Risk of significant (fatal) SEs, esp. in the elderly
Cardiovascular safety variable
NSAIDs and renal impairment
All NSAIDs diminish renal function, avoid NSAIDs in patients at risk of severe renal failure (eGFR <50)
If using them, monitor renal function closely.
NSAIDs and asthma
Not contraindicated in asthma, unless asthma previously worsened by aspirin or NSAIDs.
If Pt has not taken NSAIDs/aspirin before, monitor closely during first few doses.
NSAIDs and heart failure
Depends on the NSAID – diclofenac is contraindicated in all stages of heart failure
Other NSAIDs are cautioned in heart failure, but contraindicated in severe CCF.
What is an absolute contraindication for NSAID use?
Active peptic ulcer / GI bleed
History of NSAID-induced GI bleed
Severe heart failure
When should prophylactic gastroprotection be prescribed with regular NSAID use?
should be considered in patients at high risk of GI complications:
- Age >65
- Hx of peptic ulcer/bleeding
- DHx of medicines that would increase complications
- Serious co-morbidities
- Heavy smoking
- Excessive alcohol consumption
- Prolonged requirement for NSAIDs
What is the typical NSAID + gastroprotection regimen used?
Ibuprofen 1.2 g/day + Omeprazole 20mg o.d. prophylaxis
NSAID drug interactions
Warfarin => NSAIDs reduce platelet activity, so can prolong bleeding time
Heparin/LMWH => Potential increased risk of bleeding
Methotrexate => NSAIDs reduce excretion of methotrexate leading to increased toxicity.
Lithium => Regular NSAID use increases lithium levels
Quinolones => Increased risk of seizures
Selective COX-2 inhibitors - advantages and disadvantages
ADVANTAGES
As effective as NSAIDs
Lower GI risk than non-selective NSAIDs
DISADVANTAGES
Cardiovascular safety concerns (increased risk of thrombotic events)
Codeine - Advantages
Place in therapy well-established
Use in addition to non-opioids
Cost-effective
Codeine - disadvantages
Variability in patient response
Share full-strength opioid side effects (e.g. constipation, N&V, drowsiness).
Tramadol - advantages
More effective in neuropathic pain
May be effective if codeine is ineffective due to having opioid and non-opioid actions
Tramadol - disadvantages
Less well-tolerated than other mild opiates (esp. elderly)
Wide variability in patient response
Significant drug-drug interactions
Significant drug-disease interactions
Schedule 3 CD
What side effects are there typically with tramadol?
Minor side effects = N&V, dizziness, constipation, tiredness, headache
Major side effects = hallucinations, confusion, convulsions
Morphine - advantages
Effective for severe pain
Can be administered by most routes
Morphine - disadvantages
Serious side effects
Toxicity may be seen at therapeutic doses
Why is post-op analgesia important?
Pain is predictable post-op
Poor post-op pain management reduces lung function, increases HR and BP and magnifies the stress response to surgery.
Factors affecting post-op analgesic requirements
• Site and nature of operation
• Psychological factors
• Management of anaesthesia
• Age
• Hepatic & renal function
• Current opioid usage
What is the general principle of post-op analgesia?
start HIGH then step DOWN
What is PCA?
PCA utilises a programmable syringe pump to allow patients to self-administer their own IV opioid medication.
Typically 1mg/mL morphine in the bag
=> button releases a 1mg bolus, with a lockout interval of 5 minutes
Equipment allows you to view doses received and number of times the button was pressed during the lockout period.
PCA - advantages
Maintains therapeutic blood levels
Patient in control of their pain
Avoids delays in dosing
Reduces staff workload
Allows early mobilisation
PCA - disadvantages
Highly trained staff required
Patients must understand how to use the equipment
Caution in patients with a history of drug abuse
Changes in renal/liver function may cause significant variability in drug availability.
What is important to remember for a patient with a PCA?
Important to continue with supportive medication (regular paracetamol/NSAIDs/weak/strong opioids as appropriate; anti-emetics; laxatives).
Close observation is vital – BP, HR, RR, sedation, oxygen sats, pain scores, itching, N&V, temperature
How is opioid-induced respiratory depression managed?
Naloxone immediately reverses opioid-induced respiratory depression (RR < 8/minute).
(May need to repeat dose due to short duration of action)
Naloxone also antagonises the analgesic effect, so may precipitate severe pain.
Naloxone doses
Dose = 400 micrograms by IV injection
then 800 micrograms for up to 2 doses at 1 minute intervals if no response to preceding dose,
then increased to 2 mg for 1 dose if still no response (4 mg dose may be required in seriously poisoned patients)
If still no response then review diagnosis
What are the two main fluid compartments?
- intracellular (ICF) = ~2/3
- extracellular (ECF) = ~1/3
=> interstitial
=> intravascular
Composition of the intracellular fluid
• A high potassium concentration.
• A low sodium concentration.
• Intracellular solute concentrations remain more or less constant.
Composition of the extracellular fluid
• A high sodium concentration.
• A low potassium concentration.
What are a patient’s sources of fluid intake?
Any oral fluids
Any parenteral fluids
(Water released from metabolism) - it is standard clinical practice not to include this in calculations
What are a patient’s sources of fluid loss?
Urine
GI losses
Insensible losses
=> i.e. via the skin, breathing and other immeasurable routes.
Others
=> Surgical drains – electrolyte rich fluid loss.
=> Third space loss (body cavities where fluid does not normally accumulate)
=> Bleeding
=> Burns – excessive fluid loss through the skin
Fluid loss - urine
Generally ~1.5 – 2.5 Litres per day; aim for a minimum urine output of 0.5mL/kg/hour
Fluid loss - GI losses
Normally minor (approximately 100 ml/day lost via the faeces)
Can be substantial in someone with diarrhoea, vomiting, biliary drains and high stoma output.
Fluid loss - insensible losses
via the skin, breathing and other immeasurable routes.
~500 – 800 ml per day
Insensible losses can increase (e.g. if patient is sweating, febrile, tachypnoeic, or undergoing open cavity surgery).
What is the fluid requirement of an average healthy adult with no extra losses?
Maintenance requirements are about 2 to 2.5 litres of fluid per day (urine plus insensible losses).
What is the ideal combination of maintenance fluids?
25-30 mL/kg/day of water
Approximately 1 mmol/kg/day each of sodium, chloride and potassium
50 - 100 g/day of glucose to limit starvation ketosis
When would you consider prescribing LESS maintenance fluids?
Pts who are older adults and/or frail,
Pts with renal/cardiac failure,
Pts who are malnourished and at risk of refeeding syndrome
What are the typical electrolyte requirements for an average healthy adult requiring IV maintenance fluids?
Sodium 1 mmol/kg/day
Chloride 1 mmol/kg/day
Potassium 1 mmol/kg/day
What electrolytes are typically lost in sweat?
Sodium
What electrolytes are typically lost in Diarrhoea or increased stoma output ?
sodium, potassium and bicarbonate
What electrolytes are typically lost in vomiting ?
potassium, chloride and hydrogen ions
(and thus leads to a picture of hypochloraemic metabolic alkalosis)
What electrolytes are typically lost in breathing ?
NONE
(essentially pure water loss)
What is the electrolyte composition of sodium chloride 0.9%?
Na+ = 154 mmol/L
Cl- = 154 mmol/L
No other electrolytes
What is the electrolyte composition of Hartmann’s?
Sodium = 131 mmol/L
Chloride = 111 mmol/L
Potassium = 5 mmol/L
Lactate = 29 mmol/L
Calcium = 2mmol/L
Glucose = 0
Crystalloids
= Solutions of mineral salts.
Depending on their solute concentration, they are classified as hypo-, hyper- or isotonic solutions.
Will eventually redistribute between the interstitial and intravascular
Can be used as maintenance and replacement fluid.
Colloids
Contain larger water-insoluble molecules
e.g. - Blood, Dextrans, Gelatin (e.g. gelofusine), Human albumin solution, Hydroxyethyl starch (HES)
Remain in the intravascular compartment and draw in fluid from the interstitial to the intravascular compartment.
Small, but well-established risk of anaphylaxis.
What factors should help you choose the fluid and rate of infusion ?
- Type of fluid loss.
- Renal function.
- Cardiac function.
- Concomitant electrolyte abnormalities.
Fluid resuscitation
NICE recommends 500 ml of a crystalloid containing sodium in the range 130-154 mmol/litre (e.g. sodium chloride 0.9%) administered over less than 15 minutes.
You should refer the patient to critical care if they have hypotension refractory to fluid resuscitation.
Fluid - passive leg raise
The passive leg raise manoeuvre is thought to mimic the administration of a fluid bolus by redirecting blood from the lower limbs to the heart (i.e. increased pre-load).
Has been shown to increase cardiac output in patients’ who are fluid depleted.
Used to predict which patients are most likely to respond to administration of a fluid bolus.
The PLR manoeuvre is only validated in patients on the intensive care unit with invasive monitoring and ventilation.
What are the possible complications of fluid overload?
- Dilutional hyponatraemia
- Pulmonary oedema