Cardiovascular Drugs Flashcards
Name loop diuretics
Furosemide, bumetanide
When to use loop diuretics
1) Acute pulm. oedema
2) Chornic heart failure
3) Symptomatic fluid overload
How do loop diuretics work?
Inhibits the Na+/K+/2CL- transporter in the ascending loop of Henle
Also dilate capicatance veins –> reduces preload and improves contractile function of heart in acute heart failure
Side effects of loop diureits
Dehydration + hypotension
Increased loss of sodium and potassium –> also indirectly causes the excretion of Mg, Ca and H+
Hearing loss and tinnitus at high doses –> this is because there is a similar transporter in the ear
Contraindications of loop diuretics
Severe kypokalaeamia
Caution of loop diuretics
Hepatic encephalopathy ( as low potassium can cause/worse coma)
Hypokalaemia/natraemia
Gout (as they inhibit the excretion of uric acid)
Interactions of loop diurectics
1) Lithium increased (due to reduced excretion)
2) Increased risk of digoxin toxicity due to possible hypokalaemia
3) Increased risk of ototoxicity and nephrotoxicity with aminoglycosides!
Name potassium sparing diuretics
Amiloride
How does amiloride work
Weak dirutetic alone
Inhibits Na reabsorption via ENaC channels in the distal convoluted tubule
Causes sodium and water excretion
How is amiloride normally prescribed
As combination e.g.
Co-amilofruse or co-amilozide
Adverse effects of amiloride
GI Upset
Hypotension and urinary symptoms
Contrainidcations of amiloride
Severe renal impairment
Hyperkaelaemia
Do not start amiloride if??
Hypokalaemia as effects on potassium are unpredictable
Severe volume depretion
What drugs do most diuretics effect
Most diuretics effect the renal clearance of digoxin and lithium increasing there dose so monitor this!!
Name an aldosterone antagonist
Spirinolactone, eplerone (only for heart failure)
Indications for aldosterone antagonists
1) Ascites and oedema due to liver cirrhosis –> first line
2) Chronic heart failure: usually with ACEi and beta blocekr
3) Primary hyperaldosteronism
How does aldosterone antagonists work
Normally aldosterone produced by the adrenal cortex –> Increase ENaC activity causing Na and water reabsorption
BUT these block this
Adverse effects of aldosterone antagonists
Gynacomastia
Hyperkalaemia –> muscle weakness, arrhytmias
Liver impairment and jauncide
Steven Johnsons Syndrome
Contraindications of aldosterone antagonists
Severe renal impairment and hyperkalaemia Addisons disease (aldosterone deficient) Avoid in pregnant or lactating women
Interactions of aldosterone antagonists
1) Other potassium elevating drugs e.g. ACEi and ARB)
Don’t combine with potassium supplements
Name Beta blockers
Bisoprolol, atenolol, metoprolol (beta 1 selective)
Propanolol (non-selective)
Indications of beta blockers
1) IHD –> 1st line to improve angina & ACS
2) CHD –> 1st line to improve prognosis
3) AF –> 1st line to ventricular rate and in paroxysmal AF to maintain sinus rhythm
4) SVT –> 1st line
5) Hypertension –> not for initial therapy, use 4th line; after ACEi, ARBs, Ca2+ channel blockers, thiazide diuretics
Where are the different types of beta receptors
B1 receptors - mainly heart
B2 receptors - smooth muscle in vessels and airways
How do beta blocker work
Via B1 receptors reduce the force of contraction and speed of condution in the heart
This decreases oxygen demand to relieve ischaemia and increase myocardial perfusion
Also protects the heart from chronic sympathetic stimulation
Prolongs the refractory period of the AV node
Breaks self-perpetuating circuits of SVT
Reduce renin secretion from the kidney –> as this is mediated by B1 receptors
Adverse effects of beta blockers
Fatigue Cold extremities Headache GI disturbance Impotence Sleep distrubance
Contradindications of beta blockers
Asthma
Heart failure –> can use but start slow dose as initially decreases cardiac function
Haemodynamic instability
Hear block
Avoid with verapamil and diltiazem (non-DHP calcium channel blockers ) –> can cause HF, bradycardia and asystole!
Name thiazide diuretics
Bendroflumethiazide
Indications of thiazide diuretics
1) Alternative 1st line for hypertension (where Ca blockers otherwise unsuitable e.g. oedema or features of heart failure)
2) Add on tratment for hypertension –> in patients who bp isnt controlled by ACEi or Ca channel blockers
How do thiazide diuretics work
Inhibit the Na+/Cl- transported in the distal convoluted tubulue
Diuresis causes fall in extracellular volume –> overtime compensatory changes this (due to RAS activation)
Long term anti-hypertesnive effect is due to vascodilatation
Adverse of effects of thiazide diurtetics
Hyponatraemia
Hypokalaemia (as increase Na delivery to distal tubulae, is exchanged for K+)
Increased glucsoe –> may unmask type 2 DM
Increase LDL triglycerids
Impotence in men
Contraindications of thiazide diuretics
Hypokalaemia
Hyponatraemia
Gout (decreases uric acid excretion_
Interactions of thiazide diurietics
NSAIDS –> reduce their efffect
Avoid combo with other drugs that lower potassium
Name cardiac glycosides
Digoxin
Indications for digoxin
1) AF or atrial flutter –> 3rd line
2) Severe HF –> 3rd line after ACEi and beta blocker
Actions of digoxin
Negatively chronotropic and positively inotropic (decreaeses HR and increases force of contraction)
Increaese parasympathetic tone –> slow conduction at the AV node
Inhibits the Na/K ATPase pump –> sodium accumulates in the cell
Adverse effects of digoxin
Bradycardia GI disturbance Dizziness Visual distubance Rash Proarrhythmic --> Low therapeutic index
Contraindications of digoxin
2nd degree heart block
ventricular arrhytmias
Caution of digoxin in
Renal failure –> as eliminated by kidneys
Electrolyte disturbance –> potassim is the most important as digoxin competes with K+ at the Na/K pump, hence low potassium enhance the effects of digoxin
Interactions of digoxin
Loop and thiazide diuretics –> these decrease potassium
Amiodarone, calicum channel blockers, spirinolactone, quinine –> all increase the risk of digoxin toxicity
Name an anti-dysrhythmic
Amiadorane
How does amiodarone work?
Blockade of the Na, Ca and K channels
Antagonism of the alpha and beta adrenergic receptors –> this reduces spontaneous depoaliration, slows conduction velocity, increases refractoriness, affects the AV node
Breaks the self-perpetuating circle in SVT
Treats VT and refractoy VF by suppressing spontaneous depolaristations
Indications for amiodaroneq
Wide range of tachyarrhytmias
e.g. SVT, AF, refractory VF, ventricular tachycardia
Adverse effects of amiodarone
Hypotension if IV
Chronic side effects: pneumonitis, hepatitis, bradycardia, skin photosensitivity and grey discolouration, thyroid abnormalaties
Why does amiodarone cause thyroid abnormalities
As it has a similar structural similarties to thyroid hormones
Warnings of using amiodarone
Avoid in severe hypotension
Heart block
Active thyroid disease
Incteractions of amiodarone
Increases the plasma conc of digoxin, dilitazem and verpalmil
This may incrases the risk of bradycardia, AV block and heart fialure therefore doses of these drugs should be halved if amiodarone is started
Name calcium antagonists
Amlodipine, nifedipine
Verapamil, diltiazem
Indications of calcium antagonsis
1) Hypertension –> 1st line
2) stable angina –> use all calcium channel blockers
3) Supraventricular arrhytmias -> use diltiazem and verapamil
Action of calcium antagnosis
Decreases Ca2+ entry into vasculr and cardiac cells
Causes relaxation and dilatation of arterial smooth mucle
reduces myocardial contractility
Suppresses cardiac conduction –> particularly across the AV node
What are the 2 classes of calcium antagonists
1) Dihydropyridines: Amlodipine and nifedipine –> relatively selective for vessels
2) Non-DHP: Verampil and diltiazem. Relatively cardioselective, diltiazem some action on vessels
Side effects of calcium antagonists
Dihydropyridies: Ankle swelling, flushing, headaches, palpitations
Non- DHP: Constiption, bradycardias, hert block, F
Contraindications of calicum antagonists
Poor LV function
Avoid in AV nodal delay
Unstable angina –> as vasodilatation causes reflex increase in contractility and tachycardia increases o2 demand
Severe aortic stenosis
Interactions of calcium antagonists
Avoid non-DHP and beta blockers unless close supervision:
Both drugs are -vely chronotropic and negatively inotropic –> together might cause HF, bradycardia and even asytole
Name nitrates
GLyceryl trinatrate
Isosorbine mononitrate
Indications of nitrates
1) acute angina/ACS
2) angina prohylaxis
3) Pulm oedema –> with O2 and furosemide
How do nitrates work
Converted to NO–> increases intracellular cGMP and decreases intracellular calcium
Causes venous and arterial vasodilatation (arterial lesser)
Relaxation of cappacitance veins –> decreases preload and LVF filling –> this reduces cardiac work and myocardial demand hence relieving angina and AF
IT IS REDUCING PRELOAD THAT RPEVENT MOST ANDINA
It also relieves coronary vasospasm and dilates collateral vessels to increase coronary perfusion
Adverse effets of nitrates
Vasodilatory effects: headache, flushing, light-headedness, hypotension
Sustained use can cause tolerance
Contraindications of nitrates
Severe aortic stenosis
Haemodynamic instability
Hypotension
Interactions of nitrates
1) DO NOT USE WITH PHOSPHODIESTERASE INHIBITOS –> these enhance and prolong the effects of nitrates
2) Caution with anti0-hypertensives
Name some statins
Simvastatin, atorvastatin, rosuvastatin, pravastatin
Indications for statins
1) Primary preventin of CV Disease
2) Secondary prevention of CV disease
3) Primary hyperlipidaemia
Action of statins
Inhibit HMG CoA Reductase –> Decreases cholesterol production by the liver and also increases clearance of LDL cholesterol
Indirectly also reduces triglycerides and slightly increases HDL levels
Adverse effects of statins
Headaches and GI disturbances
Sumple aches to more serious myopathy and rhabdomyolysis
Can cause a rise in liver enzymes (ALT)
Contraindications of statins
Pregnancy
Breastfeeding
Caution of statins in
Heptic
Renal impairment
What should you avoid grapefruit juice when taking?
Statins
As grapfruit juive is a CP450 inhibitor, enzymes whcih eliminate simvastatin and atorvastatin
Interactions of statins
Metabolism reduced by CP450 inhibitos
Amlodipine –> has a similar interaction to CP450 inhibitors
Name some CP450 inhibitors
Amiodarome, diltiazem, itraconazide, macrolides, protease inhibtors, grapefruit juice
When should you take statins
at night as they have greater effect when dietary intake is at its lowest
Uses of heparins
1) VTE
2) ACS –> use LMWH and fondaparinux as first line to impve revascularisation and prevent intracoronary trombus progression
How does UFH work
Activates antithrombin –> inturn inactivates FXa and thrombin
How does LMWH work?
Similar action to UFH but preferentially inhibits FXa
How does fondaparinux work?
It is a synthetic ocmpound that only inhibits FXa
Adverse effects of heparins
Bleeding
Injection site reactions
Heparin induced thrombocytpenia –> stop drug immediately if this occurs
Caution of heparis
1) Increased bleeding risk
2) renal impairment –> as can accumulate
3) AVOID AROUND TIME OF INVASIVE PROCEDURES
Interactions of heparins
Avoid combining with other antithrombotics except
1) when initiating warfarin
2) antiplateletls with fondaparinux/LMWH in ACS
What reverses heparin
Protamine –> doesnt work for fondaparinux
How do we give heparins?
SC injection
How do we measure UFH effect
APTT
How do we measure LMWH and fondaprinux’s effect
FXa activity –> rarely requires monitoring
Name TPAs
Alteplase, Reteplase, tenetplase
Uses of TPAs
1) Acute MI
2) Fibrinolytic treatment of acute ischaemic stroke
3) Acute massive PE with haemodynamic instability
How do TPA’s work
Convert plasminogen to plasmin
Plasmin then breaks down the clots
Adverse effects of TPAs
1) Haemorrhages –> intracererbal and haeamatomas are common
2) Hypersensitivity
3) Cardiac disorders –> ischaemia/angina and hypotension and heart failure are common
Contrainidications of TPAs
1) Hypersensitivity to the drug OR gentamicin
2) High risk of haemorrhage
What shoudl we avoid the use of when taking TPAs
Rigid catheters
Interactions of TPAs
1) ACEi –> enhanced risk of anaphylactoid reactions
2) anticoagulants –> enhances risk of haemorrhage
What is the short life of TPAs
4-5 minutes hence quickly eliminated
What are the infications for warfarin?
1) VTE –> 3-6 months if single episode, life long if recurrent
2) AF
3) Heart valve replacement –> short term if tissue replacement, lifelong in mechanical
What should we not use warfarin to prevent
Do not use to prevent arterial thrombosis as they are primarily driven by platelet aggregation
How does warfarin work
VKOR Inhibitor
This prevents oxidised vitamin K being reactivated which is needed for coagulation factors
Adverse effects of warfarin
Bleedigin
Contraindicatinos fo warfarin
1) immediate risk of bleeding
Cautions of warfarin
1) Liver disease –> less able to metabolise drug and can be over-anticoagulated
2) Avoid in first trimester as teratogenic and avoid in the last trimester as associate with maternal haemorrhage
Interactions of warfarin
1) CP450 inhibitors can cause increased bleeding risk (e.g. fluconazole, macrolides and protease inhibitors
2) CP450 induces increase the clot risk (e.g. carbamzepine, rifampicin, phenytoin)
3) Antibiotics increase anticoagulation as they kill gut flora that synthesis vitamin K
What time shoudl you take warfarin?
18:00
What is the INR target in AF & VTE
2-3
Indications of NOACs
AF
VTE
DVT + PE (Apixiban only)
Mechanisms of NOACs
Riovoraxiban and Apixiban = FXa inhibitors
Dabigatran = Direct thrombin inhibitor
ADVERSE EFFECTS OF NOACS
Bleeding
GI Upset
Contraindications of NOACS
ACtive pathological bleeding
Hypersensitvity
Mechanical/prosthetic heart valves
Interactions of NOACs
Antiplatelets/NSAIDS
CP450 Inhibitors –> increases the bleeding risk
How are NOACS eliminated
Dabigatran –> primarily renally eliinitaed
Rivoroxciban –> 1/3 eliminated by the liver unchanged, the rest is by hepatic CP450 enzymes
