Cardio Flashcards
Mode of action of furosemide
Short acting, within an hour, diuresis takes 6 hrs
- acts on the ascending loop of henle to inhibit Na/K/2Cl pump causing inhibition of Na K and water reabsorption, leading to an increased loss of salt, water K
- blood becomes hypovolaemic, reducing BP
Drug class of furosemide
Loop diuretic
Indications for furosemide
- pulmonary oedema (secondary to left ventricular failure)
- chronic HF - oedema
- oliguria secondary to renal failure
- resistant hypertension
Contraindications of furosemide
Hypovolaemia
Dehydration
Hyponatraemia (severe)
Comatose States (associated with liver cirrhosis)
Side effects of furosemide
Mild GI disturbances
Hypotension
Hyperglycaemia
Electrolyte disturbance
Which type of diuretic, loop or thiazide, is more likely to cause hyperglycaemia as a side effect ?
Thiazide
When May a particularly high dose of furosemide be required ?
In renal impairment - may cause deafness as a side effect
What are the possible interactions of furosemide ?
Antibacterials: increased risk of ototoxicity with amino glycosides, colistin, vancomycin
Digoxin: furosemide-induced hypokalaemia with digoxin causes arrhythmias
What class of drug is bendoflumethiazide
Thiazide diuretic
How do thiazide diuretics work ?
Inhibit sodium reabsorption at the beginning of the distal convoluted tubule
- act within 1to 2 hrs
- diuresis usually takes 12 to 24 hrs, usually given early in day so doesn’t interfere with sleep
Indications for bendoflumethiazide
Oedema
Hypertension (alone in mild or combo in severe)
Mild to moderate HF
Contraindications of bendoflumethiazide
- (Refractory) hypokalaemia, hyponatraemia, hypercalcaemia
- (symptomatic) hyperuricaemia
- Addison’s disease (primary adrenal insufficiency)
- caution with: gout, diabetes, SLE
Side effects of bendroflumethiazide
GI disturbances Postural hypotension Altered plasma/lipid concentrations Metabolic/electrolyte disturbances Gout
Possible interactions of bendroflumethiazide
Digoxin: hypokalaemia caused by diuretic with digoxin can cause dysthymia
Lithium: increases excretion further causing inc plasma conc and inc risk of toxicity
What drug class is spironalactone
Potassium sparing diuretic
How does spironalactone work ?
Acts on receptors in distal Tubule: competitive inhibition if aldosterone
Inhibits Na retention; increased Na excretion
(Often given in combo with another diuretic instead of potassium supplements)
Indications for spironalactone
Oedema Ascites (cirrhosis of liver, malignant) Nephrotic syndrome Congestive heart failure Primary hyperaldosteronism (conn syndrome)
Contraindications of spironalactone
Hyperkalaemia
Hyponatraemia
Anuria
Addison’s disease (primary adrenal insufficiency)
Side effects of Spironolactone ?
GI disturbances Impotence Gynaecomastia Menstrual irregularities Lethargy/headache/confusion
Possible. Interactions of Spironolactone
Can increase blood levels of other drugs due to hypovolaemia, therefore increasing their potency
Why a class of drug is atenolol?
Beta blocker
How do beta blockers work ?
For hypertension, anti-arrhythmic, angina
Acts on beta 1 receptors in the heart (peripheral vasculature, bronchi, pancreas and liver)
- Decreases HR and force of contraction therefore decreasing workload of the heart
- reduced renin production from kidneys = anti-hypertensive
- reduced conduction/AP initiation of heart = anti-arrhythmic
Indications for atenolol
Hypertension Angina Supra ventricular dysrhymias MI prophylaxis Migraine prophylaxis
Contraindications for atenolol
Asthma HF 2nd/3rd degree heart block Bradycardia COPD
Side effects of atenolol?
Lethargy Bradycardia Cold extremities AV block Sleep disturbance/nightmares
Which beta blockers are less likely to cause nightmares as a side effect ?
Those that are water soluble e.g. Atenolol, celiprolol, nadolol, sotalol
- less likely to to enter brain
Possible interactions of atenolol
Verapamil: increased risk of HF/bradycardia/AV block
Insulin: masks symptoms of hypoglycaemia
Diltiazem: (ca channel blocker) increased risk of bradycardia/AV block
What drug class is diltiazem ?
Calcium channel blocker
How do calcium channel blockers work ?
Inhibit Ca influx into vascular smooth muscle and myocardium by inhibiting L-type Ca channel
Causing relaxation of vascular smooth muscle which results in:
- decreased myocardial contractility
- decreased conduction at AV node (inc refractory period)
- decreased after load and HR meaning decreased oxygen consumption
Which calcium channel blockers should usually be avoided in heart failure and why ?
They may further depress cardiac function and cause significant clinical deterioration
Can use dihydropyridine ca channel blockers instead e.g. Amlodipine etc which have more effect on the vessels and less on the myocardium
Indications for diltiazem
Angina (prophylaxis and treatment)
Hypertension (longer acting formulation used)
* may be used in patients who are contraindicated to beta blockers or ineffective*
Contraindications of diltiazem
Severe bradycardia
Heart failure
2nd/3rd degree heart block
Pregnancy/breastfeeding
Side effects of diltiazem
Headache, nausea, dizziness, hypotension, bradycardia, ankle swelling
Possible interactions of diltiazem
Antiarrythmics: cause increased myocardial depression
Beta blockers: increased risk of AV block/bradycardia
Causes increased plasma conc of cyclosporins and digoxin
What class of drug is ramipril ?
Ace inhibitor
How do ace inhibitors work ?
Inhibits angiotensin converting enzyme, causing:
- decreased angiotensin 2 synthesis = decreased peripheral resistance/fluid overload
- increased bradykinin = peripheral vasodilation
Indications for ramipril ?
Hypertension
Heart failure
Post-MI
Diabetic neuropathy
Which medications should be stopped before starting an ACE inhibitor for treatment of HF in order to avoid hyperkalaemia?
Potassium supplements and potassium sparing diuretics
*note: low dose Spironolactone in severe HF may be beneficial if serum potassium levels monitored carefully *
An ACE Inhibitor may be most appropriate initial drug for hypertension in which patients ?
Younger Caucasian
Respond less well:
Afro Caribbean
Aged over 55
Primary aldosteronism
Why are ACE inhibitors particularly indicated for hypertension in patients with type 1 diabetes with nephropathy ?
ACE inhibitors potentate the hypoglycaemic effect of insulin and oral antidiabetic drugs
Contraindications of ramipril
Renovascular disease Aortic stenosis Pregnancy Acute porphyria Angioedema
Common side effects of ramipril ?
Postural hypertension
Dry cough
Renal impairment
GI & other upper resp
Possible interactions of ramipril ?
Diuretics = pronounced hypotension
K- sparing diuretic = inc risk hyperkalaemia
Lithium & NSAIDs = inc plasma conc
NSAID also risk of renal damage
What class of drug is losartan ?
Angiotensin 2 receptor antagonist
In what way are AT2 blockers different to ACE inhibitors ?
Do not inhibit the breakdown of bradykinin- therefore unlike,y to cause persistent dry cough
Indications for losartan ?
Hypertension Chronic HF (when ACEi unsuitable) Diabetic nephropathy in type 2 diabetes
Contraindications of losartan
Pregnancy/breastfeeding Caution with: Renal artery stenosis Aortic or mitral valve stenosis Hepatic or renal impairment
Possible interactions of losartan
Antibacterials: plasma conc of losartan its active metabolite reduced by rifampicin
Side effects of losartan
Hypotension/ dizziness
Hyperkalaemia occasionally
usually very MILD
How do cardiac glycoside drugs work ?
Reduce conductivity within AV Node
- increased AV refractory period -> decreased HR
Increase force of contraction of myocardium
- inhibits Na/K pump causing increased intracellular conc of Na which in inhibits Na/Ca pump -> less Ca pumped out, increased intracellular Ca -> increased force of contraction
What is the most commonly used cardiac glycoside ?
Digoxin
Why is digoxin rarely used for rapid control of heart rate ?
Even with IV admin response may take hours
For what are cardiac glycosides most useful for ?
Controlling ventricular response in atrial fibrillation and flutter
What electrolyte disturbance predisposes to digitalis toxicity in patient taking digoxin ?
Hypokalaemia
Indications for digoxin
Supraventricular arrhythmias - Atrial fibrillation and flutter
HF (sinus rhythm, unresponsive to ACE inhibitors, b blocker and diuretic)
What is the effect of digoxin on heart failure ?
- how affects symptoms, exacerbation, mortality
Improves symptoms and exercise tolerance
Reduces hospitalisation due to acute exacerbations
Does not reduce mortality
Contraindications of digoxin
Complete heart block
Wolff-Parkinson-white syndrome
Ventricular tachycardia or fibrillation
Hypertrophic cardiomyopathy
Possible interactions of digoxin
Increased risk of digoxin toxicity with:
Antiarrythmics: Amiodarone, propafenone, quinidine
Ca channel blockers
Diuretics
Side effects of digoxin
Nausea, vomiting, anorexia, diarrhoea
Visual disturbances
What class of drug is isosorbide mononitrate ?
Nitrate
How do nitrates work?
Metabolised to NO in smooth muscle cells causing activation of guanylyl cyclise, which causes vascular smooth muscle relaxation resulting in vasodilation of coronary arteries and systemic veins = decreased preload and increased oxygen supply to myocardium
+ reduction in venous return reducing left ventricular work
Indications for isosorbide mononitrate
Angina prophylaxis
Congestive heart failure
Contraindications of isosorbide mononitrate
Hypotension/hypovolaemia
Hypertrophic cardiomyopathy
Aortic/mitral stenosis
Side effects of isosorbide mononitrate ?
Headache, dizziness, postural hypertension, flushing, tachycardia
Interactions of isosorbide mononitrate
Sildenafil (Viagra): increased hypotensive effects
How can nitrate tolerance be avoided when taking isosorbide mononitrate ?
Drug free periods of 8 hours
How do beta blockers act as anti arrhythmics?
By attenuating the effects of sympathetic nervous system on automaticity and conductivity within the heart
What class of drug is amiodarone ?
(Class III) anti arrhythmic
What is the mechanism of action of amiodarone ?
Block K+ channels, slowing cell depolarisation and increasing refractory period; also blocks Na, Ca channels and beta receptors
Indications for amiodarone
Ventricular fibrillation
Haemodynamically unstable ventricular tachycardia
Wolff-Parkinson-White tachyarrhythmias
Contraindications of amiodarone ?
Severe sinus node dysfunction causing bradycardia
2nd/3rd degree heart block
Hepatitis
Thyroid dysfunction
What function tests should be monitored before treatment with amiodarone and then every 6 months ?
Liver and thyroid function
Side effects of amiodarone
Arrhythmia Nausea/vomiting Skin discolouration Vision disturbances Photo sensitivity Thyroid disorders Hepatotoxicity
Possible Interactions of amiodarone
B blockers and diltiazem /verapamil: increased risk of bradycardia, AV block and myocardial depression
Digoxin and phenytoin: increased risk of toxicity
Warfarin: inhibits warfarin metabolism, increased risk of bleeding
What drug class is aspirin ?
Anti platelet/salicylate
Mechanism of action of aspirin ?
Inhibits cyclooxygenase (COX) enzymes; Anti platelet actions due to irreversible acetylation of COX1 in platelet preventing their activation
Indications of aspirin
Acute MI & primary/secondary prophylaxis
Secondary prophylaxis of cerebrovascular events
Analgesic, antipyretic, anti inflammatory
Contraindications of aspirin
Active peptic ulcer
Bleeding disorders
NSAID/aspirin hypersensitivity
Breast feeding (Reyes syndrome)
Caution with:asthma, third trimester of pregnancy
not to be given <16yrs unless for anti-platelet
Elimination of aspirin hepatic or renal ?
Renal
Side effects of aspirin ?
Dyspepsia
Urticaria
Bronchospasm
GI bleeding/ulceration
What drug class is clopidogrel ?
Anti platelet: adenosine diphosphate (ADP) receptor blocker
Mechanism of action of clopidogrel ?
Inhibits platelet activation by blocking the actions of ADP on P2Y12 (subtype of ADP receptor) which inhibits eventual cross linking by fibrin (aggregation)
Indications for clopidogrel
Prevention of atherosclerotic events in PAD + STEMI
Post MI/Ischaemic stroke
Contraindications of clopidogrel
Active bleeding
Severe hepatic impairment (bleeding risk)
Pregnancy and breastfeeding
Side effects of clopidogrel ?
Diarrhoea, dyspepsia, abdo pain
Rash
Haemorrhage
Possible interactions of clopidogrel ?
NSAIDS and aspirin increase risk of bleeding
What class of drug is streptokinase ?
Thrombolytic
How do Thrombolytic drugs work ?
Promote conversion of plasminogen to plasmin. Plasmin is a proteolytic enzyme which dissolves the clots
Indications for streptokinase ?
- Acute MI (within 12hrs, preferably within 1) - biggest benefit in this with STEMI (anterior infarct) and bundle branch block
- DVT
- PE
- acute arterial thromboembolism
- central retinal venous or arterial thrombosis
Contraindications of streptokinase
Recent haemorrhage, trauma, surgery
Coagulation defects, bleeding conditions, aortic dissection, aneurysm
anything that will increase risk of bleeding
Side effects of streptokinase
Nausea/vomiting Bleeding Reperfusion arrhythmias, recurrent Ischaemia, angina (MI), cerebral oedema Hypotension Fever
Interactions of streptokinase
Activated by liver enzyme cytochrome p450:
Decreased warfarin metabolism, more in blood, increased risk of bleeding
What drug class is enoxaparin
Heparin (LMWH)
Why are low molecular weight heparins usual,y preferred over unfractionated heparin in the prevention of venous thromboembolism ?
As LMWHs are equally as effective with less risk if heparin induced thrombocytopenia
Also don’t require monitoring and have longer duration if action so can use once daily for convenience
Indications for enoxaparin
PE DVT Prophylaxis of thromboembolic disorders Unstable angina STEMI and non-Q-wave MI
Contraindications of enoxaparin
Active bleeding Neonates Severe liver disease Peptic ulcer Bacterial endocarditis
Side effects of enoxaparin ?
Haemorrhage
Thrombocytopenia
Elevated liver aminotransferases
Possible interactions of enoxaparin
Aspirin increased risk of bleeding
What is the main route of elimination of enoxaparin ?
Renal
What drug class is warfarin ?
Vitamin k antagonist (anticoagulant)
Mechanism of action of warfarin ?
Prevents activation of vitamin k, a key cofactors in the coagulation cascade, therefore inhibiting coagulation
Clotting factors 2,7,9&10 dependent on vit k
Indications of warfarin ?
Prophylaxis of embolisation in rheumatic heart disease and AF
Prophylaxis after prosthetic heart valves
Prophylaxis after treatment of PE and venous thrombosis
TIA
Contraindications of warfarin
Peptic ulcer
Severe hypotension
Pregnancy (1st and 3rd trimester) & avoid breastfeeding
Severe Renal or kidney disease
Main route of elimination for warfarin ?
Liver
Side effects of warfarin
Haemorrhage
Headache
Nausea/vomiting/diarrhoea
Purple toe syndrome
Possible interactions of warfarin
Amiodarone : increases effect of warfarin by inhibiting metabolism (cyt P450)
Cranberry juice: increased anticoagulant effect
How do statins work ?
Competitively inhibit HMG CoA-Reductase, the key enzyme in cholesterol synthesis, therefore reducing cholesterol production
Indications for simvastatin
Hypercholesterolaemia/hyperlipidaemia
Prophylaxis of CV events in those with atherosclerotic disease/diabetes
Contraindications of simvastatin
Active liver disease
Pregnancy/breast feeding
Side effects of simvastatin
Myositis -> rhabdomyolysis (rare but significant)
GI disturbances
Rarely pancreatitis, anaemia
Possible interactions of warfarin
Cyclosporins and fibrates: increased risk of myositis
Warfarin: increased effects of warfarin
Elimination of warfarin
Liver
