Cardiovascular System Flashcards
Which NOAC has twice daily dosing?
Which has once daily dosing?
Twice daily: Apixaban (5mg BD), Dabigatran (150mg BD)
once daily: Rivaroxiban (20mg OD)
Which NOAC requires loading?
Apixaban
10mg twice daily for 7 days followed by 5mg BD maintenance
Which NOAC interacts with verapamil and subsequently requires a dose reduction? What other medication has the same interaction?
Dabigatran
Verapamil increases dabigatran levels, so patients also on verapamil need to take a reduced dose of dabigatran (110mg BD as opposed to 150mg BD)
Same with amiodarone- use max dose of 110mg dabigatran with amiodarone
Which one of the three NOACs is a DIRECT THROMBIN inhibitor?
What are the other two?
Dabigatran is a direct thrombin inhibitor
Apixaban and rivaroxaban are Direct factor Xa inhibitors (remember ban Xa)
An INR within ____ units of the target range is generally satisfactory
0.5 units
A target INR of ____ is used for most things! Eg treatment of DVT/PE, AF patients, electrical cardioversion, myocardial infarction…
2.5 used for most things
Apart from recurrent DVT/PE if patient was already on anticoagulation with a INR over 2 and they still got a clot… Aim for 3.5 here (thinner blood)
Or if they have a mechanical heart valve! Ask manufacturer for the target INR, also if a clot occurs whilst at the target INR then increase the target INR
Do the NOACS have any food interactions?
No
But remember to take Rivaroxiban with food to increase absorption
Which NOAC may be crushed an mixed with apple purée/ put through an NG tube before administration?
Rivaroxiban
Which CCBs need to be avoided in Heart failure?
Verapamil and diltiazem
When should a target INR of 3.5 be used? What is the target for most other conditions?
Only when the patient has had a DVT or PE when receiving anticoagulation with warfarin / NOACs and had an INR of 2 or more, they must be susceptible to clots so need a higher target of 3.5.
For most other conditions we set a target of 2.5
Warfarin’s time to peak effect ranges from 3-5 days, so it is not good if immediate effects are needed. NOACs have a much faster onset to action, what is this? Which is the fastest?
1 - 4 hours
Dabigatran fastest: peak action 0.5-2 hours after oral admin
(Apixaban and rivaroxaban take around 2-4 hours to peak)
What is the difference between Phytomenadione and Phenindinone?
Phytomenadione is the reversal agent for warfarin overdose
Phenindinone is another oral anticoagulant (coumarin) like warfarin!
What baseline tests do patients need before commencing on a NOAC?
Which NOAC is least likely to be chosen with renal impairment ?
Baseline renal function - dose reduction required in renal impairment
Dabigatran has most caution with renal function: it is CI if CrCl is under 30 ml/min
Apixaban and Rivaroxiban are less dependent on renal function
Which NOACs require hepatic metabolism therefore should not be used in severe liver disease?
Apixaban
Rivaroxiban
We know that warfarin interacts with a lot of the CYP enzyme inhibitors and inducers, Which NOACs also have a similar problem? Can you think of any interactions?
Apixaban and Rivaroxiban
CYP3A4 inhibitors effect these: ketoconazole, itraconazole,
Inducers effect these: carbamazepine, rifampicin, phenytoin, St. John’s wort
Which NOAC cannot be put in a compliance aid?
Dabigatran
It is moisture sensitive
Shouldn’t put warfarin in too
Can put Apixaban and rivaroxaban in
Which NOAC needs the warning label “swallow whole, do not chew or crush”
Dabigatran
Opening capsules increase risk of bleeding
Which is more problematic if a dose is missed, warfarin or the NOACs?
NOACs - shorter half life so if dose is missed there is more time without coagulation
If miss a dose of a NOAC- usually take it ASAP (if within 6 hours with dabigatran) but with warfarin usually just skip it and move on to next
What is the reversal agent for LMWHs?
Protamine sulfate
Name me three LMWHs
Dalteparin
Enoxaparin
Tinzaparin
When in pregnancy should warfarin be avoided?
First trimester for sure
Crosses the placenta especially in first and third trimester
Safe in breast feeding
Which NOAC is commonly used following Total hip replacement/ knee replacement ?
Rivaroxiban
Which NOAC caused the most GI side effects?
What other random SEs does this cause?
Rivaroxaban: constipation, diarrhoea, abdo pain, nausea, vomiting
Also causes:
pain in extremities
Pruritis (itchy)
Rash
What is heparin induced thrombocytopenia and which heparins is it more common with?
Development of very low platelet count
It is an immune mediated reaction that can develop after 5-10 days
More common with UFH than LMWHs
Management: stop the heparin, use something else like the Heparinoid Danaparoid
What anticoagulant is indicated in patients with a history of heparin-induced thrombocytopenia?
Danaparoid
This is a Heparinoid so won’t cause the Same reaction
What heparin should we choose in patients with renal impairment?
UFH (un fractionated heparins). Still may require dose reduction
This is because the LMWHs Dalteparin, enoxaparin and tinzaparin have their risk of causing bleeds increased in renal impairment
Dalteparin vs dabigatran?
Dalteparin is LMWH
Dabigatran is a NOAC
What is the treatment for a VTE (DVT or PE)?
LMWH or UFH
Continue the heparin for at least 5 days or until the INR has been over 2 for 24 hours
LMWH usually preferred as they have a longer duration of action, however if the patient has a high risk of bleeding or has renal impairment choose UFH (as effects can be more rapidly reversed)
Warfarin usually started at same time (but takes around 3 days to start working)
Heparins are used because they give most rapid effects
What can be used for VTE treatment in pregnant women?
Heparins are Safe in pregnancy as they do not cross the placenta.
LMWHs usually preferred as they carry a lower risk of osteoporosis and heparin induced thrombocytopenia
Dose alteration will be needed as LMWHs eliminated more rapidly in pregnancy
NB: BNF states not licensed for treatment of VTE in pregnancy for Dalteparin, enoxaparin, tinzaparin
What do we need to monitor with heparins?
Weight- dose based on weight Renal function- espesh with LMWH Platelet count (must be over 50) K+ (can cause hyperkalemia) LFTs
What is Bivalirudin and when is it used?
Remember this is the “rude boi drug”
It’s a thrombin inhibitor, and it used as an anticoagulant for those undergoing PCI and in NSTE-ACS
What is the anticoagulant used in NSTEMI/ unstable angina episode is angiography is NOT planned within the next 24 hours? What kind of drug is this?
Fondaparinux
Synthetic pentasaccharide
If angiography is planned: used LMWH as can easily reverse their effects due to shorter half life
Which beta blocker has been associated with severe liver damage?
Labetalol
Sotalol is a beta blocker commonly used in ventricular arrhythmias, different tachycardias and as Rhythm control following cardioversion in AF. There is an important safety warning that comes with Sotalol, do you know what it is?
QT prolongation! May cause life threatening ventricular arrhythmias!!
Electrolyte disturbance- especially Hypokaleamia and hypomagnesaemia- need to be sure these are corrected before starting Sotalol or there will be even more risk of arrhythmias
What are the nitrates (GTN, isosorbide dinitrate, isosorbide mononitrate) used in?
Principle role in ANGINA- they reduce venous return so reduce left ventricular work of the heart
What are some of the undesirable effects of the nitrates? (3)
Flushing
Throbbing Headache
Postural hypotension / dizziness
GTN is one of the most effective drugs at providing rapid symptom relief from angina, it’s effects only last for ______
20-30 minutes
You know GTN has a short duration of action, what about isosorbide mononitrate/ dinitrate?
Much longer- MR has duration of 12 hours, but not as rapid onset so not as effective for rapid symptomatic relief of angina
NB: isosorbide mononitrate is just the active metabolite of dinitrate
NITRATES can lead to TOLERANCE and reduced therapeutic effects if long-acting preparations used/ transdermal preps used. What can be done to overcome this?
Need to reduce blood nitrate concentration for 4-12 hours each day to avoid tolerance.
Eg. If transdermal: leave the patch off overnight
If MR isosorbide dinitrate: give the second of the two daily doses after 8 hours rather than 12 hours
What if patients on Statin therapy develop symptoms of Dysponea, cough and weight loss, what should be done?
Seek medical attention ASAP as this could indicate interstitial lung disease
Why is brand specific prescribing required with Nifedipine preparations?
Different versions of the the MR preparations may not have the same clinical effects
NB: ADALAT - LA and VALNI- XL are both not appropriate in hepatic impairment
Why should adequate urinary output be established before initiating therapy with a Loop diuretic?
Because loops can result in urinary retention if there if an enlarged prostate/ other disruption of urinary flow…
Loops usually stimulate more urine production!
If a loop diuretic (eg. Bumetanide, furosemide, co-amilofruse) is needed twice daily, when should the doses be taken?
One in the morning and one before 4pm- no later than this otherwise person will be weeing through the night
Which ACE inhibitor can cause Stomatitis (mouth ulcers, sores)?
Ramipril!
All ACEi’s may cause ulcers- ‘Apthous stomatitis/ canker sores’ is the medical term
What is sodium nitroprusside prescribed for?
Hypertensive emergencies
Rapidly reduces blood pressure
What anti-platelet drug can cause a throbbing headache as a side effect?
Dipyridamole
What does a positive D-dimer test indicate?
High level of cross-linked fibrin by-products, i.e. a clot has formed - DVT/ PE
Max dose of furosemide daily?
120mg in divided doses.
Remember furosemide is a loop and if given twice daily the second dose should be before 4pm so around 2pm
Following admission to hospital when should a VTE risk assessment be carried out?
Within 24 hours
What does mechanical prophylaxis involve with VTE prevention?
Stockings, hoisery, blow up thing etc
Can you think of any risk factors for VTE?
NB: Classed as HIGH risk if one or more of these are present! VTE risk assessment within 24 hours of admission
Active cancer/ cancer treatment Aged > 60 Dehydration History of DVT/VTE Obesity: BMI over 30 Comorbidites- Heart disease, endocrine, inflammatory condition COC's/ Tamoxifen/ HRT Varicose veins Pregnancy
Can you think of any risk factors for bleeding?
Recent surgery recent stroke Spinal intervention anticoagulants Uncontrolled HTN Acute liver failure
For patients treated for DVT, PE and prevention of their re-occurence, who want to switch from warfarin to the NOAC rivaroxiban, at what INR can they do so?
Once INR is less than or equal to 2.5
As HIT develops the platelet count typically begins to fall _____ days after starting Heparin.
5-10 days
Patients who receive any type of heparin (LMWH and UFH, remember its more common with UFH) should have a baseline platelet count, but after this platelet monitoring is not usually needed.
Colestyramine is a Bile acid sequesterant used in hypercholesteremia when a statin and ezetimibe have failed. When should patients be advised to take other medicines with this?
Take other medicines at least 1 hour before or 4 hours after Colestyramine as it can effect their absorption considering it tampers with bile acid
What medication should be added if a patient has a particularly high level of TRIGLYCERIDES?
Fenofibrate
A patient has suffered muscle pain with three different statins now, and the consultant asks you where to go next. Their Triglycerides are within range. Your options are: Fenofibrate Ezetimibe Nicotinic acid Colestyramine
Usual guidance: Statin»_space; Ezetimibe»_space; Fibrate if TGL is high/ bile aid sequesterant/ nicotinic acid.
Ezetimibe may also cause Myalgia so rule this out.
Patients TGL’s are normal so rule out Fibrates.
Best option: probably Colestyramine (bile acid sequesterant)
What is the reversal agent for Dabigatran?
Idarucizumab- a monoclonal Antibody
Which is more potent Loop: Bumetanide or Furosemide?
Bumetanide
Bumetanide dosing: 1mg BD usually, resistant oedema= 5mg
Furosemide: max dose 120mg
Why don’t Afro-carribean patients respond as well to ACE inhibitors/ ARBs?
Because these work on the renin-angiotensin system and it has been established that black people have low circulating renin
What kind of drug is Amiloride?
Potassium sparing diuretic - hyperkaleamia risk !!
