Cardiovascular System Flashcards
Name two thiazide/thiazide-like diuretics
Bendroflumethiazide
Indapamide
What is the mechanism of action of thiazide diuretics?
Inhibit Na+/Cl- cotransporter in DCT
What are some ADRs of thiazides?
- Loss of Na+ and water
- Hypokalaemic metabolic alkalosis (loss of H+ via Na+- H+ transporter (Na+ reabsorbed later on due to high conc ) and more K+ loss later in tubule due to more Na+)
- Increased Ca2+ reabsorption (hypercalcaemia)
- Gout
- Erectile dysfunction
HyperGLUC
Name two loop diuretics.
Bumetanide and Furosemide
What is the mechanism of action of loop diuretics?
Inhibit Na+/K+/2Cl- cotransporter in loop of Henle
What are some ADRs of loop diuretics?
- Loss of Na+ and water - hyponatraemia
- Hypokalaemic metabolic alkalosis (increased loss of H+ and increased loss of K+ later on, due to more Na+ in tubule)
- Increased Ca2+ loss (loss of positive luminal membrane as less K+ transported back into tubule via ROMK, so no driving force for divalent cation reabsorption)
What is an example of a potassium sparing diuretic?
Amiloride
What is the mechanism of action of amiloride?
Block ENaC at luminal surface of renal tubule
What are some ADRs specific to furosemide?
- Ototoxicity
- Gout
- Alkalosis
- Raised LDL and TG
What is an ADR specific to bumetanide?
Myalgia
What is an example of an aldosterone antagonist?
Spironolactone
What is the mechanism of spironolactone?
Competes with aldosterone at mineralocorticoid receptor in DCT/CD
(normally aldosterone upregulates ENaC channels)
What are common indications for diuretics and which classes are used?
- Hypertension - thiazides, spironolactone
- HF - loop, spironolactone
- Decompensated liver disease - spironolactone, loop
- Nephrotic syndrome - Loop, thiazides, amiloride
- CKD - loop
What are the concerns of using ACEi and K+ sparing diuretics together?
Increased hyperkalaemia risk - cardiac problems
What are the concerns of using aminoglycosides and loop diuretics together?
- ototoxicity
* nephrotoxicity
What are the concerns of using digoxin and thiazide/loop diuretics together?
- Hypokalaemia
What are the concerns of using beta blockers and thiazides together?
- Hyperglycaemia
- Hyperlipidaemia
- Hyperuricaemia
What are the concerns of using steroids and thiazide/loop diuretics together?
Hypokalaemia risk increased
What are the concerns of using lithium and thiazide/loop diuretics together?
- Lithium toxicity (thiazides)
* Reduced lithium levels (loop)
What are the concerns of using carbamezepine and thiazides together?
Increased risk of hyponatraemia
What is an example of a class IB anti-arrhythmic?
Lidocaine
What is an example of a class IC anti-arrhythmic?
Flecainide
When is flecainide indicated?
- Supraventricular tachycardia
- Ventricular arrhythmia
- WPW syndrome
What are the ADRs of flecainide?
- Pro-arryhthmic
- Flecainide flutter - increased ventricular response
- GI and CNS effects
What is the effect of flecainide?
Decreased phase 0
Give two examples of beta-blockers used as anti-arrhythmics.
Bisoprolol and metoprolol
What are the effects of bisoprolol and metoprolol on the heart? and on the ECG?
Increased APD and refractory period in the AVN
Decreased phase 4 depolarisation
Increased PR and decreased HR
What are the uses for bisoprolol and metoprolol?
Treat sinus and catecholamine dependent tachycardias
Cardioconvert reentrant arrhythmias at AVN
Protect ventricles in atrial flutter/fibrillation or flecainide flutter
What are some ADRs of bisoprolol and metoprolol?
- Bronchospasm
* Hypotension
What are two examples of class III anti-arrhythmics?
Amiodarone and sotalol
What are some ADRs of amiodarone?
- pulmonary fibrosis
- hepatic injury
- increased LDL cholesterol
- thyroid disease
- photosensitivity
- optic neuritis
What are the cardiac effects of amiodarone?
Increased ADP and refractory period Decreased phase 0 and conduction Increased threshold Decreased phase 4 Decreased AVN conduction
varying class effects
What are the effects of amiodarone on an ECG?
Increased PR, QT and QRS
Decreased HR
What are the uses for sotalol?
Wide spectrum: supraventricular tachycardias and ventricular tachycardias
What are the cardiac effects of sotalol?
Increased ADP and refractory period in atrial and ventricular tissue
Slowed phase 4 (beta blocker part of it)
Slowed AVN conduction
Which drugs are good for AF?
Rate and rhythm control
Rate: Bisoprolol/verapamil/diltiazem +/- digoxin
Rhythm: Sotalol/Flecainide + bisoprolol/amiodarone
Which drug do you give via IV for VT?
Metoprolol/lidocaine/amiodarone
Should flecainide be used alone in atrial flutter?
No - give with a AVN blocking drug to reduce ventricular rates in atrial flutter e.g. bisoprolol
Whats the best treatment for WPW? Which type of drugs should you avoid?
Flecainide
avoid AVN blocking drugs due to risk of exacerbating the symptoms
Which drugs can you use for ectopic beats?
First line: bisoprolol
then calcium channel blockers
Which drugs can you use to treat sinus tachycardia?
Ivabradine - no drop in BP
Bisoprolol/verapamil - more tolerated? can use in pregnancy
Which drugs can you use in re-entrant NCT acutely and chronically?
Acutely (IV) - adenosine, verapamil if asthmatic or fleciainide if above fails
Chronically (oral) - Bisoprolol/verapamil, if not then… sotalol, flecainide, amiodarone
What are some ADRs of sotalol?
- pro-arrhythmic
- fatigue
- insomnia
What are two examples of non-dihydropyridine CCBs/class IV anti-arrhythmics?
Verapamil and diltiazem
What are the ADRs of class IV anti-arrhythmics?
- Asystole if use with beta-blocker
- Hypotension
- Decreased CO/sick sinus
- Constipation
What are the cardiac effects of class IV anti-arrhythmics?
Slow conduction through AVN (preventing Ca2+ influx)
Increased refractory period at AVN
Increase slope of phase 4 in SA - slows HR
What effect does adenosine have on the heart?
Binds to A1 receptors and blocks adenylyl cyclase - reduced cAMP - activated K+ currents in the AVN and SAN - hyperpolarisation - reduced HR
What is the mechanism of action of ivabradine?
Blocks If ion current at SAN - slows the SAN but doesn’t effect BP
What are some ADRs of ivabradine?
- flashing lights
* unknown if teratogenic
When is ivabradine used?
Reduce HR in heart failure (no effect on BP)
What is the mechanism of action of digoxin as an anti-arrhythmic?
Increases vagal activity (Increased K+ currents, decreased Ca2+ currents, increased refractory period)
Slows AV conduction and hence HR
What is atropine?
a selective muscarinic antagonist
What is the mechanism of action of atropine?
blocks vagal activity so speeds AV conduction increased HR
When is atropine used?
In vagal bradycardia
When is digoxin used?
In Afib and flutter and to reduce ventricular rates
What are two examples of alpha adrenoreceptor blockers?
Doxazosin and tamsulosin
What are 3 examples of beta-blockers used for hypertension?
Atenolol
Labetalol
Propanolol
What are two ACEi’s?
Ramipril
Lisinopril
What are two ARBs?
Losartan
Candesartan
How do nitrates like glyceryl trinitrate and isorbide mononitrate work?
Activate guanylyl cyclase - increase in cGMP - leads to vasodilation
Name the two dihydropyridine CCBs
Amlodipine
Nimodipine
Name the two non-dihydropyridine CCBs
Verapamil
Diltiazem
Which calcium channels do the CCBs block?
L-type calcium channels
What is the mechanism of action of warfarin?
Vitamin K antagonist - inhibits vitamin K epoxide reductase
What are the vitamin K dependent clotting factors?
10, 9, 7 and 2
Why is warfarin’s onset of action delayed?
Due to the circulation of already produced clotting factors
Which drugs potentiate warfarin?
Antibiotics that reduce vitamin synthesis by bacteria in the gut e.g. cephalosporins
CYP2C9 inhibitors - amiodarone, clopidogrel
NSAIDs displace warfarin from plasma albumin
How do you monitor warfarin?
Measuring the INR - lower means thicker blood (less anti coagulated), higher means thinner blood (more anti-coagulated) - aiming for around 2.5-3
What does unfractionated heparin do?
Inhibit Xa and IIa (thrombin)
For Xa needs to bind to only ATIII
For IIa needs to bind to ATIII and IIa
Give two examples of LMWHs
Dalteparin
Enoxaparin
What is LMWH’s mechanism of action?
Inhibit factor Xa by enhancing ATIII activity
What is fondaparinux?
Synthetic heparin pentasaccharide - inhibits Xa by binding to ATIII
What drug can be used for heparin reversal?
Protamine sulphate - binds to heparin forming an inactive compound
What can be used for warfarin reversal?
Vitamin K1 or prothrombin complex concentrate - they promote the production of clothing factors
Which DOACs work on inhibiting Xa?
Apixaban
Edoxaban
Rivaroxaban
Which DOAC work on inhibiting IIa?
Dabagitran
How does aspirin work as an antiplatelet drug?
Reduced TXA2 synthesis by COX-1 inhibition
What is an example of a phosphodiesterase inhibitor?
Dipyridamole
What is the mechanism of action of a phosphodiesterase inhibitor?
Inhibits phosphodiesterase so prevents cAMP degradation so inhibits the expression of GPIIb/IIa
Also Inhibits cellular reuptake of adenosine, so increased adenosine plasma conc - so inhibits platelet aggregation via A2 receptors
What are three ADRs of dipyridamole?
Vomiting
Diarrhoea
Dizziness
When is dipyridamole used?
- Secondary prevention of ischaemic stroke and TIA
* Adjunct for thromboembolism prophylaxis
What are three examples of ADP receptors antagonists?
Clopidogrel
Prasugrel
Ticagrelor
Which of the ADP receptor antagonists bind irreversibly and are prodrugs?
Which have a faster onset of action?
Clopidogrel and Prasugrel
Prasugrel and Ticagrelor
When are Prasugrel/Ticagrelor used?
With aspirin in ACS patients undergoing PCI for up to 12 months
What class of drug is Abciximab?
Glycoprotein IIb/IIIa inhibitor (GPIIb/IIIa)
What are the two fibrinolytic drugs?
Alteplase
Streptokinase
What is the antifibrinolytic drug and when is it used?
Tranexamic acid
Nose bleeds
Heavy painful periods
Name two statins
Atorvastatin
Simvastatin
Name a fibrate
Fenofibrate
What is the mechanism of action of fenofibrate?
Activates nuclear transcription factor PPAR-alpha - factor that regulates expression of genes that control lipoprotein metabolism - increased LPL production
What are some ADRs of fenofibrate?
- Cholelithiasis
- GI upset
- Myositis
What is a DDI of fenofibrate?
Warfarin - increased anticoagualtion when taking with fenofibrate
What is an example of a cholesterol absorption inhibitor?
Ezetimibe
What is the mechanism of action of ezetimibe?
Inhibits the NPC1L1 transporter in the brush border of the gut - so reduced cholesterol absorption
It’s a prodrug and has enterohepatic circulation
What are the ADRs of ezetimibe?
- Abdo pain
* GI upset
DDIs of ezetimibe?
Caution with statins - increased risk of rhabdomyolysis
Ciclosporin increased levels of ezetimibe
What drug class is Alirocumab? And hence mechanism of action?
PCSK9 inhibitor
Monoclonal antibody that inhibits the PCSK9 enzyme, so prevents degradation and internalisation of LDL-R