Cardiovascular Drugs Flashcards
Loop diuretics name
Furosemide, bumetanide
Loop diuretics indications
- Relief of breathlessness in acute pulmonary oedema in conjunction with oxygen and nitrates
- Symptomatic treatment of fluid overload in chronic heart failure
- Symptomatic treatment of fluid overload in other oedematous states: renal / hepatic disease - given in combination with other diuretics
Loop diuretics MOA
- Act on ascending limb of Henlé
- Inhibit Na+/K+/2Cl- co-transporter.
- This normally transports sodium potassium and chloride ions from tubular lumen into epithelial cell, allowing water to follow by osmosis
- Inhibiting this process leaves water in the lumen
- Water then excreted in urine
- Also cause dilation of capacitance veins - in HF this reduces preload and improves contractile function of overstretched cardiac muscle
Loop diuretics administration
IV: for acute pulmonary oedema - administered slowly
Oral: BD
Loop diuretics contraindications
- Severe dehydration or hypovolemia
- Caution in hepatic encephalopathy, hypokalaemia and hyponatraemia
- Gout: inhibit uric acid excretion so can worsen
Loop diuretics side effects
- Diuresis can lead to dehydration and hypotension
- Inhibiting Na+/K+/Cl- transporter increases urinary losses of sodium / potassium / chloride.
- This also increases excretion of magnesium, calcium and hydrogen, so overall can cause low electrolyte state and metabolic alkalosis
- Hearing loss / tinnitus: same co-transporter found in inner ear
Loop diuretics interactions
- Increase concentration of drugs metabolised by kidney especially lithium
- Digoxin: increased toxicity due to diuretic associated hypokalaemia
- Aminoglycosides: increase ototoxicity and nephrotoxicity
Loop diuretics patient info:
Avoid taking oral doses at night due to increased urinary output
Thiazide diuretics examples
Bendroflumethiazide, indapamide, chlorthalidone
Thiazide diuretics indications
- Hypertension: alternative where CCB would otherwise be used, but is unsuitable due to oedema or heart failure
- Hypertension additional treatment where BP is not controlled by CCB + ACEi / ARB
Thiazide diuretics MOA
- Inhibit the Na+/Cl- co-transporter in the distal convoluted tubule
- Prevents reabsorption of sodium and associated water
- Resulting diuresis causes initial fall in extracellular fluid volume
- Long-term, compensatory mechanisms such as RAAS tend to reverse this
- Longer term mechanism may be due to vasodilation
Thiazide diuretics administration
Oral
Thiazide diuretics contraindications
- CI in hypokalaemia
- Avoid in hyponatraemia
- Reduce uric acid excretion so caution in gout
Thiazide diuretics side effects
- Prevention of sodium ion reabsorption can cause hyponatraemia
- Increased delivery of sodium to distal tubule, where it can be exchanged for potassium, leads to hypokalaemia - cardiac arrhythmias
- May increase plasma glucose, LDL and triglycerides
- Impotence in men
Thiazide diuretics interactions
- NSAIDs: may reduce effectiveness - low dose aspirin fine
- Other drugs that lower serum potassium concentration best avoided
Potassium-sparing diuretics name
Amiloride (co-amilofruse, amilozide)
Potassium-sparing diuretics indication
- Part of combination therapy for treatment of hypokalaemia during other diuretic treatment
- Aldosterone antagonists e.g. spironolactone can be used as alternative
Potassium-sparing diuretics MOA
- Weak diuretics alone but in combination can enhance diuresis while preventing hypokalaemia
- Acts on distal convoluted tubule
- Inhibits reabsorption of sodium (and therefore water) by epithelial sodium channels
- Causes excretion of sodium and water and retention of potassium
Co-amilofruse: amiloride + furosemide
Co-amilozide: amiloride + hydrochlorothiazide
Potassium-sparing diuretics contraindications
- Severe renal impairment and hyperkalaemia
- Do not start in context of hypokalaemia as effect can be unpredictable
- Avoid in states of volume depletion
Potassium-sparing diuretics side effects
- Uncommon at low doses
- GI upset may occur
- In combination with other diuretics may cause dizziness, hypotension and urinary symptoms
- Low electrolyte disturbance
Potassium-sparing diuretics interactions
- Do not use in combination with other K+ sparing drugs due to risk of hyperkalaemia e.g. potassium supplements and aldosterone antagonists
- Digoxin and lithium: alters renal clearance - adjust dose
Beta-blockers examples
Bisoprolol, propranolol, metoprolol, atenolol
Beta-blockers indications
- Ischaemic heart disease: first-line, to improve symptoms and prognosis associated with angina and ACS
- Chronic heart failure: first-line to improve prognosis
- AF: first line to reduce ventricular and maintain sinus rhythm in paroxysmal
- Supraventricular tachycardia: first-line option in patients without circulatory compromise to restore sinus rhythm
- Hypertension: when CCB / ACEi / thiazides are insufficient
Beta-blockers MOA
- Block beta-1 receptor located in heart
- Reduces force of contraction and speed of conduction
- This reduces cardiac work + o2 demand and increases myocardial perfusion
- Protect heart from effects of chronic sympathetic stimulation
- Slow ventricular rate in AF by prolonged refractory period of AV node
- Break self-perpetuating circuit of SVT and restore sinus rhythm
- Hypertension: reduce renin secretion from kidney as this is mediated by beta-1
Beta-blockers administration
- Oral, take at equal intervals throughout day
- IV preparations when rapid effect necessary
Beta-blockers contra-indications
- Asthma: can cause life-threatening bronchospasm due to beta-2 antagonism in airway smooth muscle
- COPD: usually safe but should chose cardioselective (not propranolol)
- Heart failure: start at low dose as may initially impair cardiac function
- Haemodynamic instability: avoid
- Heart block: contra-indication
- Hepatic failure: dose reduction
Beta-blockers side effects
- fatigue
- cold extremities
- headache
- GI disturbance
- sleep disturbance and nightmares
- impotence in men
Beta-blockers interactions
- DO NOT PRESCRIBE with non-dihydropine CCB - verapamil, diltiazem. Can cause heart failure, bradycardia and asystole/
Calcium channel blockers examples
Dihydropine: Amlodipine, nifedipine - vascular selective
Non-dihydrpine: diltiazem, verapamil - cardioselective
Calcium channel blockers indications
- Hypertension: Dihydropines 1st line in >55 or Afro-Caribbean
- Dihydropines reduce risk of stroke, MI or death from CVD
- All used to control symptoms of stable angina - beta-blockers main alternative
- Non-dihydropines control cardiac rate in those with SV arrhythmias (SVT, atrial flutter, AF)
Calcium channel blockers MOA
- Decrease calcium entry in vascular and cardiac cells
- Causes relaxation and vasodilation in arterial smooth muscle, lowering arterial pressure
- Reduce myocardial contractility
- Suppress cardiac conduction, particularly across AV node, slowing ventricular contraction
- Reduced cardiac rate + contractility + afterload = reduced myocardial oxygen demand - prevents angina
Calcium channel blockers administration
Oral
Verapamil available IV for acute arrhythmias
Calcium channel blockers contra-indactions
- Poor LV function: non-dihydropines can precipitate HF
- AV nodal conduction delay: can provoke complete heart block
- Dihydropines contraindicated in patients with unstable angina: vasodilation causes increase in contractility and tachycardia, increasing myocardial oxygen demand
- Dihydropines contra-indicated in patients with severe aortic stenosis - can provoke collapse
Calcium channel blockers side effects
- Dihydropines: ankle swelling, flushing, headache and palpitations due to vasodilation and compensatory tachycardia.
- Verapamil: constipation, less often bradycardia, heart block and cardiac failure
Calcium channel blockers interactions
- DO NOT PRESCRIBE with non-dihydropine CCB - verapamil, diltiazem. Can cause heart failure, bradycardia and asystole as both negative chronotropes and inotropes
ACE Inhibitors examples
Ramipril, Lisinopril, Perindopril
ACE Inhibitors indications
- Hypertension: 1st / 2nd line treatment to reduce risk of cardiovascular events
- Chronic heart failure: 1st line treatment of all grades to improve symptoms and prognosis
- Ischaemic heart disease: reduce risk of subsequent cardio/cerebrovascular events
- Diabetic nephropathy and CKD with proteinuria: reduces proteinuria and progression
ACE Inhibitors MOA
- Block ACE, preventing conversion of angiotensin I to angiotensin II
- Angiotensin II causes vasoconstriction and stimulates aldosterone secretion
- Blocking reduces afterload (PVR) which lowers blood pressure
- Dilates efferent glomerular arteriole which reduces intraglomerular pressure and slows CKD progression
- Reducing aldosterone promotes sodium and water excretion - this helps reduce preload which is beneficial in heart failure
ACE Inhibitors contra-indication
- Renal artery stenosis
- AKI
- Pregnancy / breast-feeding
- CKD: use lower doses and monitor effect on renal function closely
ACE Inhibitors side effects
- Hypotension
- Chronic dry cough due to increased bradykinin
- Hyperkalaemia due to reduced aldosterone
- Cause or worsen renal failure (dilation of arteriole needed to maintain renal perfusion)
- Idiosyncratic angioedema, anaphylaxis
ACE Inhibitors interactions
-Avoid other drugs that increase potassium e.g. supplements, K+-sparing diuretics
Angiotensin receptor blockers examples
Losartan, Candesartan, Irbesartan
Angiotensin receptor blockers indications
Used 2nd line when ACEi not tolerated due to dry cough. Indications are the same:
- Hypertension: 1st / 2nd line treatment to reduce risk of cardiovascular events
- Chronic heart failure: 1st line treatment of all grades to improve symptoms and prognosis
- Ischaemic heart disease: reduce risk of subsequent cardio/cerebrovascular events
- Diabetic nephropathy and CKD with proteinuria: reduces proteinuria and progression
Angiotensin receptor blockers MOA
- Block action of angiotensin II on AT1 receptor
- Angiotensin II causes vasoconstriction and stimulates aldosterone secretion
- Blocking reduces afterload (PVR) which lowers blood pressure
- Dilates efferent glomerular arteriole which reduces intraglomerular pressure and slows CKD progression
- Reducing aldosterone promotes sodium and water excretion - this helps reduce preload which is beneficial in heart failure
Angiotensin receptor blockers contra-indications
- Renal artery stenosis
- AKI
- Pregnancy / breast-feeding
- CKD: use lower doses and monitor effect on renal function closely
Angiotensin receptor blockers side effects
- Hypotension
- Hyperkalaemia
- Cause or worsen renal failure
Angiotensin receptor blockers interactions
- Potassium raising drugs
- Diuretics: profound 1st dose hypotension
- NSAIDs: increased risk renal failure
Nitrates examples
Isosorbide mononitrate, GTN
Nitrates indications
- Short-acting (GTN) used in treatment of acute angina / ACS associated chest pain
- Long-acting (ISMN) used for angina prophylaxis where beta-blocker or CCB are insufficient / not tolerated
- IV nitrates used for pulmonary oedema, in combination with furosemide and oxygen
Nitrates MOA
- Converted to NO
- NO increases cGMP synthesis and reduces Ca in vascular smooth muscle cells causing them to relax
- This causes vasodilation
- This reduces cardiac preload and left ventricular filling, which reduces cardiac work and myocardial oxygen demand
- They also relieve coronary artery vasospasm and dilate collateral vessels, improving coronary perfusion
- Also relax systemic arteries to reduce afterload (but most effects due to reduced preload)
Nitrates administration
- Stable angina: GTN sublingual as tablets or spray as immediate relief
- ACS / HF: GTN continuous IV infusion
- ISMN: oral, patches
Nitrates contraindications
- Severe aortic stenosis: may cause collapse as heart unable to increase CO through narrow valve to maintain pressure
- Haemodynamic instability, especially hypotension
Nitrates side effects
Vasodilators: common = flushing, headaches, dizziness, vasodilation
Sustained use leads to tolerance - reduced symptom relief. Don’t take doses overnight to prevent this.
Nitrates interactions
- Phosphodiesterase inhibitors (sildenafil): enhance and prolong hypotensive effect
- Antihypertensives: cause hypotension
Nitrates patient info
GTN spray should work after 5 mins - if no effect after 2 sprays ring ambulance
Digoxin class
Cardiac glycoside
Digoxin indication
- AF / Atrial flutter: reduces ventricular rate. Beta-blocker / NDCCB usually more effective.
- Severe heart failure: 3rd line when already taking ACEi, beta-blocker and aldosterone antagonist / ARB. (Used earlier if co-existing AF).
Digoxin MOA
- Negatively chronotropic (reduces heart rate)
- Positively inotropic (increases force of contraction)
- AF: increased parasympathetic tone reduces conduction at AV node, reducing ventricular rate
- HF: directly effects myocytes through inhibition of Na+/K+ pumps, causing Na+ to accumulate in cell.
- This causes Ca to accumulate in cell, which increases contractile force
Digoxin administration
Oral: works within 2 hours
IV: works within 30 mins
Usually given loading dose
Digoxin contra-indications
- Heart block: may worsen conduction abnormalities
- Ventricular arrhythmias
- Renal failure: dose reduction
- Electrolyte disturbance: hypokalaemia, hypomagnesia, hypercalcaemia: increased risk of toxicity - hypokalaemia is the worst as it competes to bind Na+/K+ pump, so when levels are low, digoxin is increased
Digoxin side effects
- Bradycardia
- GI disturbance
- Rash
- Dizziness
- Visual disturbance: blurred or yellow vision
- Pro-arrhythmic and has a low therapeutic index - can cause a wide range of arrhythmias which can be fatal
Digoxin interactions
- Loop and thiazide diuretics: cause hypokalaemia and increase risk of toxicity
- Amiodarone, CCB, spironolactone and quinine all increase plasma concentration and risk toxicity
Amiodarone class
Anti-dysrhythmics
Amiodarone indications
- Management of tachyarrhythmias: AF, atrial flutter, SVT, VT, ventricular fibrillation. Used when other therapeutic options - drugs are cardioversion - are ineffective or inappropriate
Amiodarone MOA
- Effects on myocardial cells: blockade of sodium, calcium and potassium channels, and antagonism of alpha + beta adrenergic receptors
- This reduces spontaneous depolarisation, slows conduction velocity and increases resistance to depolarisation, including in AV node, which reduces ventricular rate
- Increases chance of conversion to / maintenance of sinus rhythm
- SVT: breaks self-perpetuating circuit to restore sinus rhythm
- VT: suppresses spontaneous depolarisation
Amiodarone administration
IV
Cardiac arrest: bolus
Other cases, given through central line
Amiodarone contraindications
- Dangerous drug, only give when benefits outweigh risks
- severe hypotension
- heart block
- thyroid abnormalities
Amiodarone side effects
-Hypotension during IV infusion
Taken chronically:
-pneumonitis
-bradycardia
-AV block
-hepatitis
-skin photosensitivity and discolouration
-hypo/hyperthyroid due to iodine content and structural similarities to thyroid hormone
-long half-life, takes months to be eliminated
Amiodarone interactions
Increases concentration of: digoxin, diltiazem, verapamil - increases risk of bradycardia / AV block / HF. Doses of these should be halved.
Aspirin class
Anti-platelet
Aspirin indications
- ACS / acute ischaemic stroke where rapid platelet aggregation inhibition can limit thrombosis
- Long-term secondary prevention of thrombotic events in pts with CV / cerebrovascular / peripheral vascular disease
- Reduce risk of intra-cardiac thrombus and embolic stroke in AF where warfarin / DOACs are contraindicated
- Mild-moderate pain / fever
Aspirin MOA
- Inhibits COX to reduce production of thromboxane, a pro-coagulatory factor derived from arachidonic acid
- Thromboxane inhibition reduces platelet aggregation
- Effect occurs at low doses and lasts whole platelet lifetime as have no nuclei to produce new COX, so only wears off as new platelets formed
Aspirin administration
Oral: 300mg loading dose, 75mg daily. Gastro-protection for daily dose.
Rectal at higher doses
Aspirin contra-indications
- Children < 16: Reye’s syndrome
- Aspirin / NSAID hypersensitivity
- 3rd trimester of pregnancy where prostaglandin inhibition leads to premature closure of ductus arteriosus
- Caution in peptic ulcer or gout as can precipitate acute attack
Aspirin side effects
- GI irritation
- Gastric ulceration
- Haemorrhage
- Hypersensitivity including bronchospasm
- Tinnitus in regular high dose
- OD: life-threatening. Hyperventilation, hearing changes, metabolic acidosis and confusion followed by convulsions, cardiovascular collapse and respiratory arrest
Aspirin interactions
Synergistic with other anti-platelets - increased risk of hemorrhage. Caution when given with heparin / warfarin / clopidogrel.
Clopidogrel class
Anti-platelet
Clopidogrel indications
Generally prescribed with aspirin - may be prescribed alone where aspirin contraindicated
1. ACS / acute ischaemic stroke where rapid platelet aggregation inhibition can limit thrombosis
- Long-term secondary prevention of thrombotic events in pts with CV / cerebrovascular / peripheral vascular disease
- Reduce risk of intra-cardiac thrombus and embolic stroke in AF where warfarin / DOACs are contraindicated
- Mild-moderate pain / fever
- Prevent occlusion of coronary artery stents
Clopidogrel MOA
- Binds to ADP PY12 receptors on surface of platelets
- This is independent of COX pathway so action is synergistic with aspirin
Clopidogrel contraindications
- Active bleeding
- Stop 7 days prior to surgery
- CAution in hepatic and renal impairment
Clopidogrel side effects
- Bleeding
- GI upset
- Thrombocytopenia
Clopidogrel interactions
- Pro-drug that requires metabolism by cP450 enzymes
- Gastric protection with PPI: use lansoprazole pantoprazole so efficacy not reduced
- Anti-coagulants / NSAIDs: increases bleeding risk
Alteplase name and class
Tissue plasminogen activator
Thrombolytics (fibrinolytics)
Alteplase indications
- Acute MI
- PE
- Acute ischaemic stroke
- Thrombolytic treatment of occluded central venous access devices
Alteplase MOA
- Activates plasminogen to form plasmin
- Plasmin works to degrade fibrin, the main constituent of venous thrombi
- Increased plasmin = degradation of thrombi
Alteplase administration
IV, injection or infusion
Alteplase contraindications
- Pulmonary disease with cavitation
- Acute pancreatitis
- Aortic dissection
- Endocarditis
- Coagulation defects
- Coma
- Cerebrovascular disease history
- Recent surgery / trauma
- Hepatic impairment
- 1st 18 weeks pregnancy due to risk of separation of placenta / foetal haemorrhage
Alteplase side effects
- Anaphylaxis
- Haemorrhage
- Cerebral oedema
- Flushing + hypotension
- Reperfusion arrhythmias
Alteplase interactions
Increased risk of haemorrhage when used with other anti-coagulants
Heparins and Fondaparinux examples
Enoxaparin, Dalteparin, Fondaparinux, Unfractionated heparin
Heparins and Fondaparinux indaictions
- VTE: LMWH 1st line prophylaxis in inpatients and treatment of PE / DVT
- ACS: LMWH / fondaparinux part of 1st line to improve revascularisation and prevent intracoronary thrombus progression
Heparins and Fondaparinux MOA
Thrombin + FXa part of coagulation pathway that leads to formation of fibrin clot.
- Unfractionated heparin: activates anti-thrombin which inactivates FXa and thrombin
- LMWH: dalteparin + enoxaparin. Preferentially inhibit FXa - more predictable and do not require monitoring.
- Fondaparinux: synthetic compound similar to heparin, inhibits FXa only. 1st line anti-coagulant for ACS.
Heparins and Fondaparinux administration
LMWH + fondaparinux: SC injection.
UFH: IV infusion
Heparins and Fondaparinux contraindications
- Patients at increased risk of bleeding
- Avoid around time of invasive procedures
- LMWH + fondaparinux dose reduction in renal impairment
Heparins and Fondaparinux side effects
- Bleeding
- Injection site reactions
- Rare: heparin induced thrombocytopenia - most likely with UFH
Heparins and Fondaparinux interactions
Anti-thrombotic drugs: increased bleeding risk. In bleeding associated with UFH, protamine can be given.
Warfarin class
Oral anti-coagulant
Warfarin indications
- To prevent clot extension and recurrence in VTE
- To prevent stroke in AF
- To prevent stroke after heart valve replacement - short-term after tissue replacement, life-long after mechanical replacement
**Not used to prevent arterial thrombosis as this is driven by platelet aggregation, so antiplatelet agents needed instead
Warfarin MOA
- Vitamin K must be reduced for synthesis of coagulation factors, and is then oxidised during synthesis.
- Vitamin K epoxide reductase enzyme reduces vitamin K to reactivate it
- Warfarin inhibits vitamin K epoxide reductase enzyme
- This Inhibits hepatic production of vitamin-K coagulation factors and co-factors
Warfarin administration
Oral, OD. 5-10mg initially, subsequent doses guided by INR
Initiate with heparin until full anti-coagulation achieved
Warfarin contraindications
- Patients at risk of immediate bleeding
- Hepatic impairment - risk of bleeding
- 1st trimester pregnancy and towards term
Warfarin side effects
- Bleeding, slight excess increases risk from existing abnormalities e.g. peptic ulcer. Large excess can cause spontaneous hemorrhage.
Warfarin interactions
-Metabolised by cP450
Low therapeutic index so inducers / inhibitors have significant effect.
-Antibiotics: kill gut flora which synthesise vitamin K so increase anti-coagulation
Warfarin patient info
Take at 18:00 to allow consistent INR readings.
Rivaroxaban class
DOAC
Rivaroxaban indications
- Initial treatment of VTE
- Prophylaxis of VTE following surgery / recurrent VTE
- Prophylaxis of stroke and systemic embolism in patients with AF
- Prophylaxis of atherothrombotic events following ACS with elevated cardiac biomarkers, in combination with aspirin ± clopidogrel
Rivaroxaban MOA
Direct inhibitor of FXa (other DOACs inhibit thrombin directly)
Rivaroxaban administration
Oral, 2.5-20mg OD
Rivaroxaban contraindications
- Active / risk of bleeding
- Previous stroke
- TIA
Rivaroxaban side effects
- GI upset
- Dizziness, headache, hypotension
- Pruritis, rash
Rare: jaundice, oedema
Rivaroxaban interactions
- Anti-coagulants: bleeding risk
- Metabolised by cP450 enzymes
Statins examples
Simvastatin, Atorvastatin, Pravastatin, Rosuvastatin
Statins indications
- Primary prevention of cardiovascular events in people > 40 with 10 year history of >20% CVS risk
Statins MOA
- Inhibit HMG CoA reductase enzyme which is involved in cholesterol production
- Decrease hepatic cholesterol synthesis
- Increase clearance of LDL
- Indirectly they reduce triglycerides and increase HDL
- These effects slow / reverse atheroscloertic process
Statins administration
Oral, OD. Simvastatin 40mg, Atorvastatin 10mg for primary prevention. 80mg for secondary prevention.
Statins contraindications
- Caution in hepatic and renal failure
2. Avoid in pregnancy / breastfeeding as cholesterol essential for development
Statins side effects
- Generally safe and well tolerated
- Muscle and headaches most common
- GI upset
- Rarer: myopathy / rhabdomyolysis
- Increase liver enzymes - drug induced hepatitis
Statins interactions
Metabolised by cP450 enzymes
Amlodipine also causes statin to accumulate
Statins patient info
Take in evening as evidence shows effects greatest when dietary intake low
