Heart Drugs Flashcards
What is the mode of action of Lidocaine?
Inactivates Na gated channels in both nerves AND cardiac muscle
Therefore decreases conduction.
What are the side effects of lidocaine?
CNS activation / depression
Hypotension
How is lidocaine administered?
Is not orally active so has to be given by injection
Metabolised by liver
1/2 life = 90-120 mins
Describe the 4 phases of the cardiac cycle
Phase 0 – rapid depolarisation due to voltage-gated Na+ channels opening – Na+ flows into myocyte.
Phase 1 – initial repolarisation – Na+ channels close, DRKC open – K+ leaves myocyte
Phase 2 – plateau – Ca2+ channels opened (time and voltage dependent) – Ca2+ in = K+ leaving. Ca channels stay open until end of plateau phase when they start to close.
Phase 3 – rapid repolarisation – Ca2+ channels closed, DRKC open, K+ leaves – myocyte repolarises.
Phase 4 – resting potential – K+ leaves myocyte through IRKC
K+ channels – are 2 types = inward rectifier K+ channels and delayed rectifier K+ channels.
- Inward rectifier K+ channels (IRKC) = maintain resting Vm until AP. Open when Vm <-60mV. Function – to clamp the Vm at rest by letting K+ out of cell, repolarising it.
- Delayed rectifier K+ channels (DRKC) = part of AP – open when membrane depolarises and closes after time delay = is both voltage and time dependent.
How do β blockers affect the nodes?
They slow spontaneous depolarisation of cardiac tissue
Which drugs are considered Class I in the VW classification?
Class I = Fast channel blockers
Disopyramide
Lidocaine
Flecanide
Which drugs are considered Class II in the VW classification?
Class II = Β blockers
Bisoprolol
Atenolol
Which drugs are considered Class III in the VW classification?
K+ channel blockers
Amiodarone
Which drugs are considered Class IV in the VW classification?
Ca Channel Blockers
Verapamil
Diltiazem
How do Class 1 agents selectively inhibit tachycardias?
They bind strongly when the channel is open or inactive (not resting).
Therefore the more frequently the channel is open (e.g. in tachycardia) - the greater the block.
Thus they inhibit tachycardia but allow normal HR
What is the difference between class 1 drugs?
What is flecanide used for?
Paroxysmal AF
AVRT
WPW
Slows condition in accessory pathways
Stabilises atria
DONT USE FOR VENTRICULAR ARRHYTHMIAS
What are the SEs of flecanide?
Can be pro-arrhythmic - do Echo prior to starting to check for abnormalities
Increases pacing thresholds - do pacemaker check before prescribing
Dizziness
Blurred vision
(Because it acts on neurological tissue as well as heart tissue)
Do ECG before starting and changing dose
Is amiodarone lipo-phillic or lipo-phobic?
Lipiophillic - highly - concentrates in the fat in the body
Means it has a LONG half life!
What is the loading dose of amiodarone?
200mg TDS - 1 week
200 mg BD - 1 week
200mg OD
Which molecule does amiodarone contain?
Iodine
How does amiodarone work?
Blocks ion channels inc delayed rectifier K+ channels = prolonged action potential (delays Phase III depolarisation)
Stabilises atrial and ventricular myocytes
Slows AV node conduction
Blocks accessory pathways
What are the side effects of amiodarone?
Lots!
Inc blue grey skin
Initially it causes pneumonitis which can progress to fibrosis
Iodine - important in thyroid hormone - can cause hyper and hypo thyroid
Secreted in tears - can become deposited on the cornea and cause keratitis. Can cause visual problems at night
How often should Ps on amiodarone be monitored?
What can amiodarone be used for?
AF - when other medication has failed to control
Malignant ventricular arrhythmias
Apart from amiodarone, which other Class III agent can be used for arrhythmias?
Dronedarone
Not used very often - used as an alternative to amiodarone when they can’t tolerate it - much less effective than amiodarone
What are the following receptors in the adrenergic system responsible for?
- α 1
- α 2
- β 1
- β 2
Which drug is first line for most tachyarrhythmias?
β blockers
What can β blockers be used for?
Tachyarrhythmias
Ectopic beats
VF
VT
SVT
AF
How do calcium channel blockers work?
They block calcium channels = less intracellular calcium
=>
Smooth muscle relaxation
Decreased force of cardiac contraction
Decreased AV node conduction
When are calcium channel blockers contraindicated?
Severe left ventricular dysfunction = dont want to reduce the force of contraction that you have?
Their use is limited to structurally and functionally normal hearts
When are Verapamil and Diltiazem used?
Not effective for ventricular arrhythmias
Only used for supraventricular arrhythmias
Mainly - AF - slows ventricular rate by blocking the AVN.
Also used for SVT - IV Verapamil is 2nd line (not if on β blocker or has HF). Oral V or D used to prevent SVT.
How does Adenosine work?
Blocks the AV node conduction via the A1 receptor
Used IV to terminate SVT
What is adenosine used to treat?
SVTs - given rapid IV
Will terminate - AVNRT, atrioventricular tachycardia
Will temporarily slow & reveal - atrial tachycardia & atrial flutter
Will reveal occult accessory pathways
What are the side effects of adenosine?
Nasty drug - slows the heart aggressively and causes marked vasodilation and poss bronchoconstriction, Ps feel like they are dying for about 20 seconds
- chest tightness, breathlessness, dizziness, nausea, hypotension (from vasodilation)
When is adenosine contra indicated?
In asthmatic patients - because it causes bronchoconstriction
How does atropine work?
Is a competitive antagonist of ACh muscarinic receptors (M1 - M5)
Cardiac action - blocks M2 receptors - increases SAN rate and AV conduction - increases HR.
Does the opposite of adenosine
What is atropine used for?
Sinus bradycardia
2nd or 3rd degree HB at the AVN (i.e. narrow complex).
Does not work for HB below the AVN - only works on conduction tissue at the AVN level or above.
If broad complex - atropine will not work.
Why do Ps who have an inferior MI often become bradycardia?
Because the RCA that causes inferior infarcts supplies the SAN and AVN
How does isoprenaline work?
Is a non-selective β agonist
- inc HR, force of contraction and vasodilator
What is isoprenaline used for?
2nd / 3rd degree HB below the AVN
I.e. HB with broad complexes
Only ever given as a bridge to a pacemaker
Which channel is the one responsible for cardiac auto-tonicity?
If channel (funny channel)
Uses a large Na+ current inward and tiny K+ current outward
Which drug is used as a specific blocker of the If current - therefore acts solely on the SAN to reduce HR?
Ivabradine
Why can Ivabradine not be used in AF?
The SAN doesn’t work in AF - therefore will have no effect
What is Ivabradine used for?
Inappropriate sinus tachycardia - e.g. post-covid, POTS
How does Digoxin work?
Inhibits Na+/K+ ATPase pump
- inc Na+, inc intracellular Ca
- thus increases contractility of the heart.
Not known why - but slows AVN conduction as a result
What is digoxin used for?
AF - but often 2nd or 3rd line
Due to the fact it has a narrow therapeutic window and can cause almost every arrhythmia possible
How can digoxin present on ECG?
With a reverse tick
What is the antidote to digoxin?
Digibind
Do drugs help improve prognosis in arrhythmias?
No - they reduce frequency and help Sx but do not improve prognosis
(Except β blockers in congenital long QT syndromes)
Which class of the VW classification drugs may be pro-arrhythmic?
Class I and III
May prolongate QT and QRS intervals
What do we want to do when treating angina?
Reduce O2 demand
Increase O2 supply
Can you improve the O2 supply if there is fixed stenosis?
Not without stenting or bypassing the stenosis
Which are the most effective anti anginal drugs?
β blockers
They reduce HR and force of contraction => reduction of myocardial O2 demand
What forms of nitrate are there?
GTN Spray
Slow release tablets - Isosorbide mononitrate & Isosorbide denigrate
IV GTN & ISMN - for use in unstable angina
What are the side effects of nitrates?
Vasodilation can cause headache, hypotension, dizziness, syncope (GTN)
Can also get tolerance with continuous use
- need to take nitrate holidays or slow-release preparations.
How do Ca channel blockers work?
Dec intracellular Ca by blocking Ca channels
=>
Dilation of arterioles
Dec ionotropy
Dec HR via SAN and AVN
Which Ca channel blocker only works by vasodilation?
Amlodipine - has no effect on the heart itself
Which drugs (1st and 2nd line) are used as anti platelets for chronic stable angina?
Why are anti platelets used for chronic stable angina?
1st L = aspirin
2nd L = DOACs (Clopidogrel, then Prasugrel or Ticagrelor)
Antiplatelets are used because patient has atherosclerotic obstructive artery disease underlying their angina. You therefore want to prevent thrombosis which might occlude an artery = anti-platelets.
Which anti-anginal drugs (1st and 2nd line) are used for chronic stable angina?
1st line = Bisoprolol (+ GTN prn)
2nd line = Diltiazem, Amlodipine, Isosorbine Mononitrate
Which anti-hypertensive drugs are first and second line for chronic stable angina?
1st line = Ramipril
2nd line = Losartan, Candesartan & Amlodipine
Which lipid-lowering agent is first and second line for chronic stable angina?
1st line = Atorvastatin
2nd line = Simvastatin or Rosuvastatin
What are the two aims when treating angina?
Want to reduce O2 demand
Want to increase O2 supply
Which are the most effective anti anginal drugs?
β blockers - they reduce HR and ionotropy - thus reducing myocardial O2 demand
Why are nitrates used in the treatment of angina?
They reduce preload and afterload (by dilating veins and arterioles) - thus reducing cardiac workload
Which nitrates are given as
- spray
- slow release tablets
- IV
Spray = GTN
Slow release = isosorbide mononitrate
IV = GTN/Isosorbide mononitrate
What are the side effects of nitrates?
Headache (can be severe and put Ps off using)
Hypotension/dizziness
Syncope (GTN)
Why do Ps have to have nitrate holidays? What can they use instead?
You can get tolerance with continuous use of nitrates = loss of effect
Can use slow-release preparations instead
Why are calcium channel blockers used for angina?
They reduce afterload (by vasodilation) - amlodipine only works in this manner.
They can also reduce contractility and HR = reduced demand on the heart
When choosing between a β blocker and Ca channel blocker for angina - what helps you choose which drug to go with?
β blocker good if Ps have HF, migraine or arrhythmias.
Can cause ankle swelling.
Ca channel blocker good if P has Raynaud’s or hypertension, asthma, COPD, PVD or resting bradycardia.
When would you not use Ca channel blockers for angina?
If a P has an underlying diagnosis of HF.
Calcium channel blockers, with the exception of amlodipine, should be avoided in heart failure as they can further depress cardiac function and exacerbate symptoms. Have a negative inotropic effect and may cause hemodynamic decompensation in patients with reduced ejection fraction.
First step for angina is to choose between β blocker and Ca channel blocker. What is the next step in Rx?
To add in the other drug - i.e. β blocker or Ca channel blocker depending on what was chosen first of all.
Why should you never use Diltiazem with a β blocker?
Together there is a combined propensity to block the AVN = this can cause profound bradycardia.
After starting a P on β blocker AND ca channel blocker, what is the next line Rx for angina?
Addition or substitution of:
- Slow release nitrate (isosorbide mononitrate)
- Ivabradine
- Nicorandil
- Ranolazine
Which anti-platelet drug is used for unstable angina?
Aspirin
Some Drs also prescribe DOACs at this stage but not NICE guidance.
Which anti-anginal drug is used for unstable angina?
Bisoprolol
GTN PRN
Which anti-coagulant drug is used for unstable angina?
Fondaparinux (or other LMWH)
Fondaparinux often used because it is OD and cheap
Which investigations are done for unstable angina and why?
Serial ECGs - checking for ischaemia
Repeat troponin - ?progressing to MI
Echo - check LV function and see if there is a regional wall motion abnormality
Coronary angiogram - ?whether P needs revascularisation
How do platelets aggregate to form a clot?
Plaque rupture exposures collagen
VWF binds to this - allows platelets to adhere (uses GP1b receptor).
Platelets nearby are then activated using GP2b3a receptors (binds with fibrinogen), P2Y12 receptors (needs ADP) and Tx Receptors (needs COX1)
Which anti-platelet drugs are used in IHD?
Aspirin
DOACs
What is the downside of using clopidogrel?
There can be patient resistance to the drug - up to 40% of Ps dont get the full benefit. This means there is a huge variation in how Ps respond.
Prasugrel and Ticagrelor are more reliable and potent that clopidogrel
What anti platelet Rx is given for stable IHD?
Aspirin
PCI
6m of clopidogrel following PCI
What antiplatelet Rx is given for NSTE-ACS (i.e. unstable angina or NSTEMI)?
Aspirin - 300mg admission then long term
12m Prasugrel or Ticagrelor (sometimes Clopidogrel)
However dont start 2nd agent straight away - often these Ps have something else going on - start 2nd agents when sure of the diagnosis (e.g. following coronary angiogram)
What anti platelet Rx is given for STEMI?
Aspirin + Praugrel or Ticagrelor at time of diagnosis
LT = aspirin + 12m Prasugrel or Ticagrelor
When is LMWH contraindicated?
In Ps with severe renal impairment (<30 GFR) - because they are renally excreted. If severe renal impairment - the drug won’t be excreted and therefore the P will be over anti-coagulated.
If LMWH is contraindicated due to renal impairment - what can be given instead?
Unfractionated heparin
4mm ST elevation in leads II, III and aVF would indicate what?
Inferior STEMI - Right coronary artery occlusion
What timeframe do you have for PCI to be undertaken?
Within 2 hours
Why is PCI preferred to thrombolysis?
Thrombolysis = less reliable than PCI - only open up about 50%, often only achieves partial flow, and has major bleeding risks.
Which two drugs are used for thrombolysis?
Alteplase
Tenecteplase
What is the difference between secondary prevention and primary prevention in IHD?
Which drugs should be given to patients post-MI?
Which anti-platelet drugs are given to Ps post MI? Why?
Aspirin
Prasugrel or Ticagrelor
Both prevent plaque and stent thrombosis
What community care is given to Ps after suffering an MI?
What lifestyle advice should be given to Ps with IHD for primary and secondary prevention?
What are the commonest causes of exertional syncope?
Hypertrophic cardiomyopathy
Dilated cardiomyopathy
Arrhythmogenic cardiomyopathy
What is a cardiomyopathy?
Disease of the cardiac muscle
What causes dilated cardiomyopathy?
Ischaemic causes = IHD - 70% (e.g. chronic ischaemia due to multi vessel disease)
Non-ischaemic causes =
- HT (2nd commonest cause)
- Congenital
- ETOH
- Viral
- Toxins (chemo drugs)
- Metabolic - hypothyroid, iron overload, thiamine deficiency
- Idiopathic
What is the standard Rx for HFrEF?
ACEI
β blocker
Aldosterone antagonist
SGLT2 inhibitor
What conditions require anti-thrombotic medication?
CAD - angina, STEMI, NSTE-ACS, post-PCI and post-CABG
AF
Mechanical heart valves
LV aneurysm with thrombus
What is the MOA of aspirin?
Irreversible inhibitor of COX1
COX1 - involved in both promoting and inhibiting platelet aggregation
Stimulates both Thromboxane - promotes and prostacyclin - inhibits
Under normal circumstances - these two molecules cancel each out - however when you give high dose aspirin - you inhibit both
But at LOW dose - you only inhibit Thromboxane & platelet aggregation - which means prostacyclin and its inhibition of platelet aggregation dominates
When is aspirin given?
MI
ACS
Angina
Post PCI / Post CABG
What are the SE of aspirin?
Peptic ulceration - give PPI
Rash
Ototoxic at high dose
Reyes syndrome in children - fatal brain and liver damage
What is the name of the syndrome that aspirin can cause in children?
Reye’s syndrome
How does clopidogrel work?
Inhibits P2Y12 receptors - stops platelet adhesion, aggregation and activation
What are the SEs of clopidogrel?
Bleeding - effects can last for 7 days after cessation - can be CI for surgery
Rash
40% have clopidogrel resistance - do not get full platelet inhibition
How do ticagrelor and prasugrel work?
Both inhibitor P2Y12 - more potent and reliably than clopidogrel
What are the SEs of ticagrelor and prasugrel?
Bleeding risk = more than clopidogrel. Prasugrel has the highest risk.
Ticagrelor can cause breathlessness
Which drugs target the GP2b3a receptor?
Abciximab
Tirofiban
What is the risk of Abciximab and Tirofiban?
They are very powerful anti-thrombotic drugs
Therefore carry high bleeding risk
When are abciximab and tirofiban used?
Only during high risk coronary stent procedures
What drugs are given for CAD?
Aspirin (or clopidogrel if intolerant)
DAPT given for 12m following ACS - Prasugrel or Ticagrelor
DAPT given for 6m following elective PCI - Clopidogrel
2b3a only given during high risk PCI
When do we start DAPT?
If definitely a STEMI - start both drugs immediately
Elective PCI - prior to procedure
Non-STE ACS - give aspirin at diagnosis and 2nd agent after angiogram has confirmed diagnosis
What drug needs to be given with a mechanical heart valve?
Warfarin
What are usual target INR levels when on warfarin?
2-3
Can go as high as 3.5-4.5
What is the mode of action of warfarin?
1972 was diSCo
Inhibits - 2, 7, 9 and 10, protein C and protein S
When is warfarin used?
Mechanical heart valves
Mitral stenosis w AF
Intra-cardiac thrombus
When are DOACs preferred to warfarin/
AF Stroke prophylaxis
DVT
PE
How can warfarin be reversed?
Slowly with Vit K
Rapidly with IV blood factors
What are the SEs of warfarin?
Teratogenic
Warfarin induced skin necrosis (if you start warfarin with out heparin anticoagulation - the first thing that gets inhibited are Protein C & S - short 1/2 L.
Means that without heparin the P is transiently hypercoaguable = skin necrosis)
Which factors does heparin inhibit
2+7 =9,10,11,12
Which pathway is used to monitor heparin?
APTTr (intrinsic pathway)
What are the side effects of heparin?
Bleeding
What is the antidote for heparin?
Protamine - potent vasdilator
When is heparin used?
CKD
Dialysis
ECMO / Bypass
Elective PCI
Which are the LMWH?
Dalteparin
Enoxaparin
Tinzaparin
What are LMWHs used for?
NSTE-ACS
AF
In pregnancy in place of warfarin
When are LMWHs contra-indicated?
When there is poor renal function - they are renally cleared
What is the serious side effect of heparin?
HIT - Heparin Induced Thrombocytopenia
More common with UFH than LMWH - caused by ABs (previous exposure) - activate platelets causing a prothrombotic state
What are the S&S of heparin induced thrombocytopenia?
Falling platelet count
Blood clot - either growing or new
Can get skin necrosis
When is anticoagulation recommended using CHADVASC?
1 = should be considered
2 = anticoagulation is recommended
How do DOACs work?
Inhibit FactorX
What is the mode of action of Dabigatran?
Thrombin inhibitor (2a)
When should you consider fibrinolysis in acute thrombotic stroke?
If a P cannot (or has not) transferred to PCI within 2 hours
Which drugs are used for fibrinolysis?
Alteplase
Tenecteplase
How do alteplase and tenecteplase work?
Activate plasminogen into plasmin - this breaks cross-links between fibrin molecules = breaks down clots
What are the SEs of alteplase and tenecteplase?
High bleeding risk - 5%
How can you differentiate between acute and chronic HF?
Acute = causes pulmonary oedema
Chronic = peripheral oedema
At what BP can Ps said to be in cardiogenic shock?
<90mmHg
What do we want to stop in order to treat HF?
Stop RAAS
Stop SS activation
Give diuretics
How do loop diuretics work?
Block NaK2Cl transporter in LOH = loss of Na = loss of water
V powerful
Also cause vasodilation of pulmonary arteries
What are loop diuretics used for?
Peripheral oedema
IV for acute pul oedema
Which drugs are loop diuretics?
Furosemide
Bumetanide
What are the SEs of loop diuretics
Ototoxicity
Low K
Low Na, Ca & Mg
Inc uric acid
Dehydration
Renal impairment
Why do you get hypokalaemia with loop diuretics?
Get Na loss in the LOH
= means more Na travels to the DCT - where more Na/K is activated - causing Na reabsorption and loss of K+ = hypokalaemia
Which are the ACEIs?
Ramipril
Lisinopril
Enalapril
What are the SEs of ACEIs?
Which SEs of ACEIs are caused by excess bradykinin?
Dry cough
Angioedema
How do AR2Bs work?
Block ATII effect - similar effect to ACEIs without the cough
Which drugs are AR2Bs?
Losartan
Candesartan
How do aldosterone antagonists work?
Block upregulation of Na channels in the DCT by aldosterone
= less Na reabsorbed
= more water excreted
= less pressure in the vessels
What are aldosterone antagonists also known as?
Potassium-sparing diuretics
What are the side effects of spironalactone?
Impaired renal function
Hyperkalaemia
Gynaecomastia
Why does the SS nervous system get activated in HF?
Low CO
= SS activation = inc ADR
this increases contractility -> inc CO
also - activates RAAS = vasoconstriction = inc afterload
Why is SS activation in HF a bad thing?
Causes cardiotoxicity from the catecholamines
-> structural changes inc LV dilation and adverse remodelling
-> in LV systolic dysfunction
What does activation of β 1 receptors cause?
inc HR
inc contractility
inc renin release
Which β blockers are used in HF?
Bisoprolol
Carvedilol
Why are β blockers used in HF?
Slow HR = inc diastolic filling time
Reduce afterload (BP)
Reduce renin release by reducing RAAS activation
Do not affect contractility (unlike calcium blockers)
What are the SEs of β blockers?
Fatigue
Bradycardia
Breathlessness
Inc asthma
Claudication, cold hands / feet, Erectile dysfunction
Which drug works by blocking in the If current in the SAN?
Ivabradine
Which SGLT2 inhibitor has the strongest evidence base for CHF?
Dapagliflozin
What are the 4 pillars of HFrEF management?
ACEi / ARB / ARNI
BB
MRA (Spironalactone)
SGLT2i
If Sx persist in HFrEF - what can ACE/ARB by replaced with?
Valsartan - if EF <35%
If Sx persist in HFrEF - what meds can be added?
Ivabradine
Hydralazine and nitrate
Digoxin (if sinus rhythm)
How does Valsartan work?
What is the main SE?
Neprilysin inhibitor
SE = angio-oedema - high incidence
What can cause acute HF?
MI
Valve dysfunction
What is the most serious potential complication of acute HF?
Cardiogenic shock - as heart is unable to maintain CO
Ps will be cold, clammy, thready pulse, SBP <90
At what pulmonary capillary pressure will pulmonary oedema occur?
> 25mmHg
What management do we do for acute HF?
PODMAN
Position - sit upright
Oxygen
Diuretics - IV furosemide
Morphine
Anti-emetic
Nitrate - GTN spray, IV isosorbide mononitrate
What drug must you not give in acute HF?
Β blockers
Decreased Cardiac Output: In acute heart failure, the heart’s pumping ability is severely impaired. Beta-blockers can further reduce cardiac output due to their negative inotropic and chronotropic effects, worsening the condition.
Worsening Symptoms: By lowering the heart rate and contractility, beta-blockers can exacerbate symptoms such as shortness of breath and fatigue due to insufficient blood flow and oxygen delivery to tissues.
Inadequate Perfusion: Reduced cardiac output and blood pressure can lead to inadequate perfusion of vital organs, which is especially dangerous in acute settings where the body’s demand for oxygen and nutrients is high.
What are the steps of managing acute HF according to NICE?
Pul oedema? Give IV furosemide
If not effective - start NIV ventilation
If still not good - Intubate and ventilate
Only give nitrates if HT, MI or MR/AR
Opiates - use for severe distress
If Ps have cardiogenic shock and acute HF - what type of drug can be given?
Inotropes & Pressors
What types of NIV can be given in acute HF?
CPAP
BiPAP
How is cardiogenic shock managed?
TREAT MAIN CAUSE
IV saline (not if pul oedema!)
Ionotropes - dobutamine, adrenaline
Pressors - noradrenaline
Intubate, ventilation, ECMO, intra-aortic ballo pump
What is cardiogenic shock most commonly due to?
Acute MI (STEMI more than NSTEMI - more myocardium damaged in STEMI)
Acute valve dysfunction - endocarditis
Arrhythmias
Myocarditis
Drug toxicity
What is ECMO?
Extra corporeal membrane oxygenation
What is CRT?
Cardiac resynchronisation therapy
When should Ps be considered for device therapy in CHF?
Ps with poor LV function - with EF <35% and BBB should be considered - especially LBBB.
