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
Fluid overload - Tx
Stop intravenous fluids (prevent further deterioration)
Furosemide – can be given as a bolus or infusion.
=> Causes a diuresis and venodilation.
Senior review
ABX Prescribing - “Start Smart”
Do not start ABX in the absence of clinical evidence of bacterial infection.
Take thorough drug allergy history
Comply with local antimicrobial prescribing guidance
Document clinical indication, dose, and route
Include review/stop date or duration
Obtain cultures prior to commencing therapy where possible (but don’t delay therapy)
ABX Prescribing - “Then Focus”
clinical review and decision at 48-72 hours
- STOP
- IV to oral switch
- Change ABX
- Continue
- OPAT
What is OPAT?
= outpatient antibiotic therapy
i.e. IV ABX at home or as an outpatient
What may you consider when selecting an antibiotic?
- Identify nature and location of infection
- Identify types of bacteria that empirically colonise
- Severity of infection
- Consider patient factors
- ABX Resistance (local guidelines)
How common is penicillin allergy?
Occurs in 1-10% of exposed patients
( anaphylaxis in <0.05% treated patients).
Nature of penicillin allergy
Patients allergic to one penicillin will be allergic to all (the hypersensitivity is related to the basic penicillin structure).
It is important to clarify the nature of the reported allergy (may be an intolerance rather than an allergic reaction).
Patients with a penicillin allergy may also have cross-over allergy to other beta-lactam ABX (e.g. cephalosporins, carbapenems)
What is gentamicin?
What are the risks?
Aminoglycoside antibiotic
Risk of nephrotoxicity and ototoxicity
RFs:
• Other nephrotoxic/ototoxic drugs
• Increasing dose, increasing age
• Duration >3 days
Gentamicin dosing
Follow local guidance for dosing and administration (dose adjustment required in obesity/renal impairment)
Check trough levels (pre-dose) are within target range
What is vancomycin?
What are the risks?
Glycopeptide antibiotic
Risk of nephrotoxicity and ototoxicity at high doses
Also risks associated with rapid administration
What are the risks associated with rapid administration of vancomycin?
• Anaphylactic reactions
• Flushing of upper body (“red man syndrome”)
• Pain in chest/back
therefore MAX administration rate = 10mg/min
What is the max administration rate of vancomycin?
Why?
Max administration rate = 10mg/min
Risks of anaphylaxis and red man syndrome with rapid administration
Vancomycin dosing
Check pre-dose trough levels (usual target 10-15mg/L)
Gram +ve bacteria
Staphylococci
Streptococci
Enterococci
Bacilli
=> Aerobic – Listeria
=> Anaerobic – Clostridium
Gram -ve Bacteria
Neisseria
Enterobacterales – e.g. E. coli
Pseudomonas
Anaerobic – e.g. Bacteroides
Atypical bacteria
(These don’t have a proper cell wall and therefore do not stain properly and can’t be termed gram +ve or -ve)
Legionella,
Mycoplasma,
Chlamydia.
Which ABX target the cell wall?
• Beta-lactams - e.g., Penicillins, cephalosporins, carbapenems, monobactams.
• Glycopeptides - e.g. Vancomycin, Teicoplanin
Cephalosporins - generations
• First generation – Cefalexin
=> have the most gram +ve cover
• Second generation – Cefuroxime
• Third generation – Ceftriaxone, ceftazidime (Only has gram -ve cover, active against Pseudomonas)
• Fourth generation – e.g. Cefepime.
=> Broad spectrum G+ and G- activity and Pseudomonas activity
What are the carbapenems?
= ABX of last resort!
• Ertapenem
• Meropenem
• Imipenem
How do beta-lactam ABX work?
Bind to and inhibit penicillin binding proteins (PBPs).
PBPs play a role in cross linking the peptidoglycan layer of the cell wall
Inhibition of this process leads to weakening and rupture of the cell wall
beta-lactamase inhibitors
These have weak antibacterial activity on their own.
Given in combination with β-lactam antibiotics
Bind to bacterial β-lactamase enzyme and protect β-lactam from destruction.
e.g. Clavulanic Acid (co-amox) , Tazobactam (Tazocin)
What is important to remember when prescribing tetracyclines?
Avoid in pregnancy and children!
What are problems associated with use of Quinolone ABX?
Can prolong QT interval,
Can cause tendinopathy,
Increased risk of C. diff,
Lower seizure threshold.
What is important to remember when prescribing trimethoprim?
Avoid in first trimester of pregnancy due to anti-folate action
Unfractionated Heparin - MOA
- Accelerates the action of antithrombin III
- Inactivates factor XIIa, IXa, Xa, IIa
- Prevents production of fibrin
When is unfractionated heparin used and why?
- Used in patients with higher risk of bleeding, where rapid reversal of therapy may be required.
=> Short half-life – effects terminated rapidly by stopping infusion
=> Specific antidote available (protamine sulphate) - Used in patients with significant renal impairment (CrCl <15 mL/min)
=> Increased elimination by non-renal routes - Treatment of choice in MASSIVE PE
What is the antidote for unfractionated heparin?
protamine sulphate
How is unfractionated heparin normally given?
Usually given by IV infusion due to short half-life.
One-off loading dose followed by continuous infusion
What monitoring is required with unfractionated heparin?
Requires monitoring of activated partial thromboplastin time (APTT)
Rate of heparin infusion adjusted to maintain therapeutic APTT
=> APTT is checked 4-6 hours after initiation
=> Also checked 4-6 hours after any adjustment to dose.
LMWH - MOA
How does it compare to Unfractionated heparin?
Inhibits Factor Xa but NOT thrombin
=> equivalent anticoagulant effect to unfractionated heparin, but less action on platelet function and easier to administer
LMWH - indications
Standard 1st line choice for immediate anticoagulation in VTE
Thromboprophylaxis
LMWH in pregnancy
CAN be used in pregnancy
Different doses used for Tx and prophylaxis of VTE in pregnancy
LMWH - administration and monitoring
Usually administered by s.c. injection, once or twice daily.
Routine monitoring of anticoagulation effect not required
What is the antidote for LMWH?
Protamine can be used to treat overdose, BUT it only partially neutralises effect.
What is the standard Tx dose of enoxaparin?
= 1.5 mg/kg once daily
different doses in renal impairment, pregnancy and obesity
Where is a heparin infusion prescribed (on NUH drug charts)?
Needs to be prescribed on heparin chart and IV infusions chart (with a cross-reference to the main prescription chart).
Management of Over-heparinisation
- Stop the infusion
- If there is life-threatening bleeding or rapid reversal is required, give IV protamine sulphate (dose depends on when the pump was turned off).
Why do you not give more than 50mg protamine sulphate to neutralise heparin?
at higher doses it has an anticoagulant effect
VTE Risk assessment process
- Assess VTE risk and bleeding risk
- Balance risks and decide whether pharmacological VTE prophylaxis is appropriate
- If using pharmacological, initiate ASAP (and within 14 hours of admission)
REASSESS risk of VTE and bleeding at point of consultant review / or whenever clinical condition changes
What do you need to consider when dosing enoxparin for thromboprophylaxis?
Medical / Surgical patient
Low risk (1 risk factor for VTE) / high risk (>1 risk factor)
Renal function
Weight
What is Mechanical thromboprophylaxis?
What are the advantages/disadvantages?
Works by reducing the pooling of blood in the deep venous system, to increase venous blood flow and venous return to the heart.
- Anti-embolism stockings
- Intermittent pneumatic compression sleeves (used post-stroke)
- Foot impulse device
Advantage – absence of effect on coagulation, so no increased risk of bleeding.
Disadvantages – will be contraindicated in some patients (see reverse side of VTE risk assessment).
Dosing of DOACs
Differs for different indications – e.g. VTE, stroke prophylaxis in AF, extended thromboprophylaxis.
Doses may need to be reduced due to weight, serum Cr, age or drug interactions
Which NSAIDs are highest risk for GI toxicity?
Highest risk = piroxicam, ketoprofen
Intermediate risk = naproxen, high dose ibuprofen
Lowest risk = low-dose ibuprofen (up to 1.2 g/day)
Selective COX-2 inhibitors have a lower GI risk, BUT caution due to increased risk of thrombotic events.
How do PPIs work?
PPIs inhibit gastric acid secretion by blocking the hydrogen-potassium ATPase enzyme system (the “proton pump”) of the gastric parietal cell.
Omeprazole and clopidogrel
Omeprazole may reduce effectiveness of clopidogrel
Avoid omeprazole where possible (review need for PPI or consider lansoprazole/H2-RA as alternatives)
PPIs and warfarin
May cause raised INR
Monitor INR closely, particularly when starting/stopping and adjust warfarin dose accordingly
How can PPIs affect absorption of some medications?
PPIs reduce stomach acidity
=> May increase/decrease absorption of medicines with pH-dependent absorption.
H. pylori eradication
= triple therapy
- PPI - typically omeprazole (20 – 40mg) or lansoprazole (30mg)
- 2x ABX – amoxicillin plus clarithromycin OR metronidazole
What is considered the peri-operative period ?
= the time between admission to hospital for surgery and discharge.
Includes admission, anaesthesia, surgery, and recovery.
How long does the patient need to be NBM for fluids before surgery?
Clear fluids can usually be safely consumed with no limit on volume until 2 hours before planned surgery.
Medicines can be given within the 2 hour period, with up to a small cupful of water (especially important for Parkinson’s/diabetes/epilepsy meds).
What is important to consider for patients on long-term steroids undergoing surgery?
During surgery/stress, endogenous cortisol is released. This is impaired in those who are on long term steroid treatment (or have been within the last 12 months)
=> RISK of hypoadrenal crisis, hypotension, circulatory collapse & shock
At-risk patients require cover with corticosteroids – IV hydrocortisone (until the patient can take the usual oral dose).
Minor & dental surgery - do you need to stop warfarin?
No dose modification of warfarin usually necessary if INR <3.0.
Check INR 72 hours prior to surgery, adjust dose if necessary.
Major surgery - do you need to stop warfarin?
Aim for INR <1.5
Stop warfarin 5 days pre-op
Check INR 24 hours before surgery
Start enoxaparin as per trust guidelines for reason for anticoagulation (e.g. AF/DVT/PE)
For prosthetic heart valves and recurrent thromboembolic disease, always discuss pre- & post-op heparin regime with consultant haematologist.
Emergency surgery - patients on warfarin
Administer Vitamin K 0.5 – 1mg IV (in 50 – 100 mL glucose 5% over 30 mins).
Recheck INR after 8-12 hours
If more rapid reversal required, or surgery is within 8 hours of admission and INR >2, discuss with consultant haematologist.
Restarting warfarin post-op
Restart warfarin when able to take oral medicines & risk of bleeding reduced.
Usually restart at usual maintenance dose
=> Sometimes use a modified loading dose
Does low-dose aspirin need to be stopped for surgery?
Not normally
Does clopidogrel need to be stopped for surgery?
Consider stopping 7 days pre-op (needs to be a whole week stopped to have any effect)
=> If possible, swap to aspirin for this period.
Do beta-blockers need to be stopped for surgery?
Continue – reduce peri-operative CV morbidity & mortality & complications (incl. HTN, AF, TIA, stroke)
Can be withdrawal effects on stopping
Do ACEis need to be stopped for surgery?
Usually omit on morning of surgery.
Can cause profound hypotension on induction of anaesthesia & reduced tolerance of hypovolaemia.
Do diuretics need to be stopped for surgery?
Consider omitting diuretics on morning of surgery to avoid volume depletion & patient discomfort.
However inappropriate withdrawal may worsen symptoms of cardiac failure.
What considerations are there for diabetic patients undergoing surgery?
Ideally put first/early in the theatre list, to PREVENT PROLONGED STARVATION
If the patient has a short fasting period, the patient can be managed by MODIFICATION of their usual diabetes medication (antidiabetic meds or insulin)
Otherwise, patient may need variable rate IV insulin infusion
What is considered a short fasting period for diabetic patients undergoing surgery?
= no more than one missed meal
What does a Variable Rate IV Insulin Infusion consist of?
- IV infusion of insulin
=> Rate set and altered with capillary blood glucose (CBG)
=> Aim for CBG 6-10 mmol/L - Continuous IV infusion of fluid containing glucose & potassium
What should happen to the patient’s normal insulin when they are on VRIII?
If the patient is already on long-acting insulin (e.g. Lantus), this should be continued
Short acting is stopped while on VRIII
How long is VRIII continued for?
VRIII & substrate (fluid) should be continued until the patient is eating and drinking normally and back on usual glucose lowering medication.
The 1st injection of s.c. insulin should be given with a meal and the VRIII and fluids discontinued 30-60 minutes later.
Should HRT be stopped for surgery?
Increased VTE risk with oral HRT preparations (not seen with topical preparations).
Consider stopping HRT 4 weeks pre-op if patient has other risk factors for VTE.
Restart after full mobilisation.
If HRT continued, prescribe VTE prophylaxis & compression stockings.
Should COCP be stopped for surgery?
COCP = Increased VTE risk
Consider stopping 4 weeks pre-op (for major elective & leg surgery or prolonged immobility)
=> Restart at first menses occurring at least 2 weeks after full mobilisation.
If COCP continued, prescribe VTE prophylaxis
Should progesterone-only pill be stopped for surgery?
POP can be continued.
Should Tamoxifen be stopped for surgery?
Increased VTE risk
Evidence that benefits > risks, so should be continued.
40% of VTEs occur within 3 months of surgery – educate on how to recognise symptoms
Discuss with oncology team if considering stopping.
Should Lithium be stopped for surgery?
Sometimes stopped 24 hours pre-op & resumed when renal function & fluid & electrolyte balance normal
Check therapeutic level if toxicity is suspected.
Risk of withdrawal syndrome if stopped abruptly – discuss with mental health team.
Check for drug interactions
What are important drugs to continue during the peri-operative period?
Anti-epileptics
=> abrupt withdrawal may precipitate seizures; may need to administer via alternative routes if NBM for prolonged periods.
Madopar (Co-beneldopa)
=> swap to patch if prolonged NBM, or place first on list to minimise NBM period.
Ciclosporin / immunosuppressants
=> continue, risk of transplant rejection if omitted.
What anticipatory meds might be prescripted in End of Life care?
Pain
- Opioid Analgesia – morphine / diamorphine / oxycodone / fentanyl / afentanil
- Remember to provide REGULAR and BREAKTHROUGH doses
Respiratory Secretions
- Hyoscine Butylbromide
Anxiety
- Midazolam
Agitation
- Haloperidol, levomepromazine, midazolam
Nausea & vomiting
- Cyclizine, metoclopramide, haloperidol or levomepromazine
Breathlessness
- Midazolam or an opioid
What pain medication is typically used in anticipatory medications
Opioid analgesia - morphine / diamorphine / oxycodone / fentanyl / alfentanil
In End-stage renal failure => AVOID morphine, diamorphine and oxycodone.
Morphine tends to be 1st line if <72 and intact renal function.
Prescribing anticipatory meds
should be prescribed in advance of the start of the symptoms.
PRN and hourly
Breakthrough PRN dose for pain
=> 6-10% of the 24 hour opioid dose
Preferred route = subcutaneous.
There should be a LOW THRESHOLD for moving to syringe driver (>2 PRN meds in 24 hours)
What is a Syringe Driver?
What is typically the opiate of choice?
= Continuous 24 hour s.c. infusion of multiple medications
Diamorphine tends to be the opiate of choice as it is very soluble and potent.
=> Add the total regular opiates and PRN doses in the last 24 hours and convert to s.c. diamorphine
How does warfarin work?
Inhibits the enzyme responsible for regenerating “active” vitamin K
=> Thus, producing an anti-coagulative state similar to vitamin K deficiency
Takes up to 5 days to have an effect on clotting factor levels, and has an initial prothrombotic effect so should always be combined with a heparin agent until INR is within therapeutic range.
Warfarin - CIs
peptic ulcer disease,
bleeding disorders,
severe HTN,
pregnancy
Target INRs with warfarin
Depends on indication for anticoagulation and local guidelines
Generally:
- Single DVT / PE: 2 – 3
- AF: 2 – 3
- Recurrent DVT / PE: 3 – 4
- Prosthetic Metal Heart Valves: 3 – 4
Starting warfarin
When starting warfarin:
- Loading dose is given
- INR measured on alternate days
- Dose titrated according to INR
- Counselling for patient
Over anticoagulation in warfarin
If 4.5 – 6 => reduce dose of warfarin or omit dose, restart when INR <5
If 6 – 8 => stop warfarin and restart (at a lower dose) when INR <5
If >8 with no bleed / minor bleed => stop warfarin
=> Also give 0.5-2mg oral vitamin K if risk factors for bleeding
If major bleed => stop warfarin; give 5-10mg vitamin K IV, plus octaplex or FFP (according to local guidelines).
Vitamin K can take several hours to work, so is not sufficient in an acute bleed.
Octaplex
= combination of vitamin K dependent clotting factors
MOA of DOACs
Dabigatran = direct thrombin inhibitor.
Apixaban, rivaroxaban, Edoxaban = factor Xa inhibitors
Advantages of DOACs
- Rapid onset of anticoagulant effect
- More predictable pharmacokinetics
- Lower potential for clinically important interactions with food, lifestyle and other drugs.
- There is no need for routine coagulation monitoring
DOACs - disadvantages
With the exception of dabigatran, there is currently no licensed reversal agent for DOACs.
Tend to be partially cleared by the kidney (need dose reduction in CKD).
Should be avoided in pregnancy and breastfeeding
LMWH
- how is it given?
- how long is its action?
- what is the mechanism of action?
- what lab monitoring is required?
- what is the impact of renal failure on dosage?
Given s.c. (e.g. Enoxaparin)
Long-acting
Works to inactivate factor Xa (but not thrombin)
No lab monitoring is usually required
=> But if required (e.g. severe renal impairment) then anti-factor Xa levels are used
Can accumulate in renal failure, so a lower dose is used prophylactically and UFH used therapeutically
Unfractionated Heparin (UFH)
- indications?
- mechanism of action?
- monitoring?
Given IV or SC
Short-acting
Indications:
- Used if high risk of bleeding (anticoagulation can be terminated rapidly).
- Also useful in severe CKD where LMWH is contraindicated
Potentiates anti-thrombin III
=> Increasing its ability to inhibit thrombin, factor Xa and IXa
APTT is used to monitor therapy and adjust dosage:
- Should be checked at 6 hours
- Aiming for APTT of 1.5 – 2.5
SEs of heparins
Common to both LMWH and UFH (but less common in LMWH)
- Bleeding – e.g. GI, operative site, intracranial
- Heparin-induced thrombocytopaenia (HIT)
- Osteoporosis with long-term use
- Hyperkalaemia
Over-anticoagulation with Heparins
Stop infusion (UFH)
Give protamine sulphate to counteract effects
=> Only partially effective in LWMH
Streptokinase
Purified fraction of filtrate obtained from haemolytic streptococci
Activates plasminogen to form plasmin
ANTIGENIC
=> patient develops streptococcal antibodies
=> Cannot be used repeatedly
Alteplase
Recombinant tissue type plasminogen activator (t-PA)
Leads to increased plasminogen activation and fibrinolysis
Not antigenic, but has a slightly higher risk of intracerebral haemorrhage.
What are the indications for thrombolysis?
What drugs are used
STEMI,
Stroke,
Cases of severe VTE (massive pulmonary embolism or extensive deep vein thrombosis)
Drugs = streptokinase, Alteplase
Thrombolysis - CIs
Active bleeding:
=> Any sign of cerebral haemorrhage in stroke
=> Suspected aortic dissection in ACS
Severe HTN (>200/120)
Recent head trauma
Recent surgery (2 months)
Pregnancy or recent delivery (10 days)
Severe liver disease / oesophageal varices
Prolonged / traumatic CPR
Drugs to hold in AKI
(OSADMAN)
O - opiates
S - Sulphonyureas/SGLT-2 inhibitors
A - ACEis
D - diuretics
M - metformin
A - ARBs
N - NSAIDs
What should be done if a statin is suspected to be causing myopathy?
If CK is markedly elevated (>5 times upper limit of normal) and muscular symptoms are severe
STOP statin
if symptoms resolve and CK reduces, the statin should be re-introduced at a lower dose
Common CYP450 Enzyme inhibitors
Macrolides – e.g. clarithromycin, erythromycin
Quinolones – e.g. ciprofloxacin, levofloxacin
Azoles – e.g. fluconazole, miconazole
SSRIs
Acute alcohol intake
Grapefruit juice
…and more
Common CYP450 Enzyme inducers
= PC BRASS
Phenytoin
Carbamazepine
Barbiturates
Rifampicin
Alcohol (chronic)
Smoking
St John’s Wort
Common “victims” of CYP450 enzyme inhibitors/inducers
Warfarin
Statins
COCP
Theophylline
Steroids
100% solution
= 1g per ml
10% solution
= 100mg per ml
1% solution
= 10mg per ml
0.1% solution
= 1mg per ml
1:1000 solution
= 1 mg/ml
1:10,000 solution
= 100 mcg/mL
1:250,000 solution
= 5 mcg/ml
What is the standard adult dose of adrenaline for anaphylaxis ?
500 micrograms IM - i.e. 0.5 mL of 1:1000 adrenaline
What are some drugs that are contraindicated while breastfeeding?
Opiates
Anticancer drugs
Amiodarone
Lithium
Iodine
Gold salts
