SESSION 2 Flashcards
In gentamicin prescribing what should you do if peak level is too high?
Lower the dose
In gentamicin prescribing what should you do if trough level is too high?
Increase the interval between the doses
How should you monitor a pt on naloxone?
RR, oxygen sats and a blood gas
What drugs most commonly cause acute interstitial nephritis?
Beta-lactam antibiotics
Fluoroquinolone antibiotics
PPIs
NSAIDs
Outline the difference in consideration of Tx of acute and chronic hyponatraemia
Acute hyponatraemia needs urgent treatment to prevent cerebra oedema. Chronic hyponatraemia is more at risk from rapid correction of hyponatraemia with the risk of osmotic demyelination syndrome. Serum sodium should not rise by more than 10mmol/L in the first 24 hours in hyponatraemia and then no more than 8mmol/L every 24 hours thereafter
When correcting hyponatraemia, serum Na+ should not rise by more than what in the first 24 hours?
10mmol/L
When do signs of osmotic demyelination tend to occur after too-rapid correction of hyponatraemia?
3-4 days after treatment
Signs of osmotic demyelination?
Confusion
Dysarthria
Mutism
Dysphagia
Lethargy
Affective changes
Seizures
Spastic quadriplegism
Coma
Death
Drug Tx of orthostatic hypotension?
Fludrocortisone
MOA of fludrocortisone for orthostatic hypotension?
Binds to mineralocorticoid receptors in the kidneys and increase sodium reabsorption which increases blood pressure
Reversal agent for warfarin?
Vitamin K
Reversal agent for dabigatran?
Idarucizumab
Reversal agent for rivaroxaban?
Andexanet Alfa
Reversal agent for apixaban?
Andexanet Alfa
What is andexanet Alfa?
a recombinant form of human factor Xa protein which binds specifically to apixaban or rivaroxaban, thereby reversing their anticoagulant effects.
Can DOACs be used if renal function <15?
Nope!
What are the 2 isomers of warfarin?
R and S stereoisomers of the drug.
S-warfarin is 3-5 times more potent an inhibitor of the vitamin K epoxide reductase complex, the target of action, than R-warfarin. S is more common. S is metabolised by CYP450 so this drug can be heavily influenced by other drugs
DOACs vs warfarin?
Comparable effectivenebrss for VTE
DOACs have lower rates of major bleeding events
Warfarin has lower rates of GI bleeding
Outline the HAS-BLED score?
It’s a score where each point is 1 point and it assesses the bleeding risk for a pt going on to anticoagulation
• hypertension that is uncontrolled or >160 systolic
• Liver disease (cirrhosis or bilirubin >2x normal with AST/ALT/AP >3x normal)
• Renal diseases (dialysis, transplant, Cr >200)
• Stroke Hx
• Bleeding RF or major bleeding event
• Labile INR (unstable or high INRs or time in therapeutic range <60%)
• Elderly >65
• Drugs (that increase risk of bleeding) or alcohol >=8 drinks a week
Half life of warfarin vs DOAC?
What does this mean for when a pt needs surgery?
Warfarin - ~36-40 hours
DOACs 7-14 hours
If a pt is on warfarin you must stop it 3-5 days before surgery and make sure INR <1.5
DOACs can be stopped 48 hours before surgery
Do you need to stop antiplatelets for surgery?
Yes 5 days before
Outline CT rules for a pt with head trauma and on an anticoagulant
If head trauma + anticoagulant = CT head within 8 hours!
If any of the following = CT head in 1 hour
◦ GCS <13 initially
◦ GCS <15 at 2 hours post-injury
◦ Suspected skull or basal skull fracture
◦ Seizure since injury
◦ Focal neurological deficit
◦ >1 episode of vomiting
What is the yellow book?
The warfarin anticoagulant record
What investigations need to be done before starting warfarin?
FBC
U&Es
LFTs
Coagulation
INR
What are the 2 ways of starting warfarin treatment?
Fast and slow induction
What is the rapid anticoagulation method of prescribing warfarin?
When you give a loading dose of warfarin at the same time as LMWH to bridge this
Daily checks of the INR and using the warfarin chart to determine the dose to give. This is continued until INR is in the therapeutic range for 2 consecutive days once at least 5 days have been reached
What are risk factors for pts with increased sensitivity to warfarin?
Body weight <50kg
Low serum albumin
Known bleeding risk
Age >65
Raised baseline INR
Interacting drugs
Hepatic failure
Cardiac failure
What should you do if your pt has risk factors for an increased sensitivity to warfarin?
Give a smaller loading dose!
Why does warfarin require bridging therapy?
Warfarin takes a few days to reach therapeutic level but also it can have prothrombotic effcts in the first few days so using bridging therapy protects against this
What is the slow induction method for warfarin treatment?
Very rarely used but can be done for pts that dont require fast anticoagulation e.g. pts with paroxysmal AF or delayed stroke etc
This is used becase it reduces the risk of bleeding
Takes place over 3-4 weeks and only requires monitoring once a week. Start on medium dose of warfarin 3mg for 7 days and check INR. Adjust dose and recheck INR in 7 days
Who is the slow induction method for warfarin not suitable for?
Pts with a baseline INR >1.3
Management of a pt on warfarin with a major bleed?
Stop warfarin
Urgent IV vitamin K 5mg
PCC
Management of a pt on warfarin with an INR >8 and minor bleeding?
Stop warfarin
IV vitamin K 1-3mg
Restart warfarin when INR <5
Management of a pt on warfarin with an INR >8 and no bleeding?
Stop warfarin
Oral vitamin K 1-5mg using the IV preparation
Restart warfarin when INR <5
Management of a pt on warfarin with an INR 5-8 and minor bleeding?
Stop warfarin
Iv vitamin K 1-3mg
Restart warfarin when INR <5
Management of a pt on warfarin with an INR 5-8 and no bleeding?
Omit 1-2 doses of warfarin and then reduce the maintenance dose
Treatment options for preventing VTE in hospital?
Stockings
LMWH
(Note even the stockings need to be prescribed!!)
When should you re-assess the VTE risk in a pt?
24 hours after first assessment
Before a pt starts on LMWH what should you check?
Platelets as the pt will need regular FBC to measure platelets for heparin-induced thrombocytopenia
Which DOACs require bridging therapy with LMWH?
Dabigatran and edoxaban
Which DOACs require bridging therapy with LMWH?
Dabigatran and edoxaban
At what HAS_BLED score should you consider stopping anticoagulants?
> =3
Anticoagulants if cr clearance is 15-50?
Apixaban or rivaroxaban or LMWH followed by warfarin/edoxaban
Anticoagulants if cr clearance is <15?
LMWH or UFH or LMWH then warfarin
What is the difference between LMWH and unfractionated heparin?
LMWH is derived from UFH by breaking it down into smaller fragments. Its effects last longer & it has a longer half life and more predictable pharmacokinetics. Lower risk of HIT.
LMWH inhibits factor Xa whilst UFH inhibits thrombin and factor Xa
Reversal agent for heparin?
Protamine sulphate
Benefits of uUFH?
Traditionally used for pts with severe renal function but now LMWH is used too. UFH is cleared by the liver predominantly.
UFH has a very quick on and offset due to its short half life so really good if you are worried about bleeding on top of poor renal function
What is heparin produced from?
Porcine intestine
Monitoring requirements for heparin?
APTT checked 4 hours after first time giving heparin and then 2 hours after a dose adjustment! Then daily.
Platelet counts should be measured just before treatment with unfractionated or low molecular weight heparin, and regular monitoring of platelet counts may be required if given for longer than 4 days. Can cause HIT
Plasma-potassium concentration should be measured in patients at risk of hyperkalaemia before starting the heparin and monitored regularly thereafter, particularly if treatment is to be continued for longer than 7 days. Can cause hyperkalaemia
Why does heparin require such frequent monitoring?
As it has a narrow therapeutic window, unpredictable pharmacokinetics, short half life and follows zero order kinetics
This means very small changes in dose can have large effects!!
What is zero-order kinetics?
When a constant amount of drug is eliminated per unit time
This means the rate of elimination is constant and is dependant of the total drug concentration in the plasma
MOA of rivaroxaban, apixaban and edoxaban?
Direct and reversible inhibitors of factor Xa (you can remember this as they all have Xa in the names)
MOA of dabigatran?
Reversible inhibitor of thrombin
MOA of warfarin?
Inhibits the vitamin K dependant clotting factors (II, VII, IX, X) ans the anticoagulant proteins C and S
MOA of warfarin?
Inhibits the vitamin K dependant clotting factors (II, VII, IX, X)
