Cardiovascular drugs Flashcards
Loop Diuretics - how do they work?
Used for..?
Loop diuretics act on the Na+-K+-2Cl− symporter (NKCC2) in the thick ascending limb of the loop of Henle to inhibit sodium, chloride and potassium reabsorption. Loop diuretics also inhibits NKCC2 at macula densa, reducing sodium transported into macula densa cells. This stimulates the release of renin, which through renin–angiotensin system, increases fluid retention in the body, increases the perfusion of glomerulus, thus increasing glomerular filtration rate (GFR - they not trigger a response that reduces the GFR)
Loop diuretics also inhibits magnesium and calcium reabsorption in the thick ascending limb. By inhibiting the potassium recycling, the voltage gradient is abolished and magnesium and calcium reabsorption are inhibited.[3] By disrupting the reabsorption of these ions, loop diuretics prevent the generation of a hypertonic renal medulla. Without such a concentrated medulla, water has less of an osmotic driving force to leave the collecting duct system, ultimately resulting in increased urine production. This diuresis leaves less water to be reabsorbed into the blood, resulting in a decrease in blood volume.
Used for relief of breathlessness in acute pulmonary oedema (+ O2 and nitrates)
* For symptomatic treatment of fluid overload – HF, renal/liver failure
Loop diuretics SE?
Drug interactions?
SEs: HTN, dehydration (avoid in hypovolaemic/dehydrated patients). Direct loss of sodium, potassium and chloride (and indirectly other minerals) = low electrolyte state (check U&Es). Can also effect endolymph concentration leading to tinnitus/hearing loss
Will increase urine flow & frequency– take dose earlier in the day, avoid at night.
Interactions: Increased toxicity of drugs excreted via kidneys e.g. lithium, digoxin (due to hypokalaemia) andaminoglycosides
Indapamide = ?
When used?
(thiazide-like diuretic)
Antihypertensive: Alternative first line treatment for HTN when Ca-channel blocker would have been used but is unsuitable due to oedema/HF (helps w/ fluid overload). Can also be used as a hypertension add-on treatment (step D)
Thiazide diuretics – Bendroflumethiazide - how do they work?
They control hypertension in part by inhibiting reabsorption of sodium (Na+) and chloride (Cl−) ions from the distal convoluted tubules in the kidneys by blocking the thiazide-sensitive Na+-Cl− symporter. This in turn causes a lowering of the osmotic concentration of the medulla of the kidney meaning less water diffuses out of the distal tubal.
Thiazide diuretics also increase calcium reabsorption at the distal tubule. This can help avoid further formation of kidney stones and can increase bone resorption of Ca lessening the effects of osteoporosis.
Potassium sparing diuretics name?
How do they work?
Used first line in which conditions? and also used in which?
SE?
Spironolactone, Amiloride
Aldosterone antagonist –competitively inhibit aldosterone Receptor, increasing sodium and water excretion and potassium retention
Used first-line in ascites and oedema due to liver cirrhosis. Used in chronic HF and primary hyperaldosteronism (when patients waiting/unable to have surgery)
SEs: Hyperkalaemia (check they don’t have it) - muscle weakness, arrhythmia, cardiac arrest. Causes gynecomastia, can cause liver impairment, jaundice and Stevens-Johnsome syndrome (T cell hypersensitivity -bullous skin eruption)
Avoid potassium sparing diuretics in which pts?
Dangerous interactions?
Avoid in severe renal impairment, Addison’s (aldosterone deficient) and in pregnant/ lactating women.
Interactions: Potassium elevating drugs e.g. ACEi, ARBs increases risk of hyperkalaemia
Beta blockers - name some (2)
Used (first line) in ..?
How do they work ?
Atenolol, bisoprolol (usually PO)
Used (first line) in ischaemic heart disease: angina and acute coronary syndrome, heart failure (start at low dose), atrial fibrillation, supraventricular tachycardia (restores sinus rhythm) and add on to HTN
B-blockers work on B1 Receptor to reduce the force of contraction and speed conduction in the heart (relieves ischaemia by reducing cardiac work & O2 demand). Slows ventricular rate by prolonging the refractory period of the atrioventricular node, In HTN they also reduce renin secretion from the kidney which is mediated by B1 Receptor
SE of B blockers?
Avoid in which PTs?
SEs: Fatigue, cold extremeties, headache & GI disturbance. Sleep disturbance, impotence in men.
Warning: Avoid in asthma (life-threatening bronchospasm). Avoid in heart block, haemodynamic instability and decrease dose in hepatic failure.
Interactions: NEVER use in non-di-hydopyridine Ca- channel blockers Vermparil, Diltazem, LEADS to HF, Bradycardia, asystole
Calcium antagonists aka Ca-channel blockers - name one dihydropyridine (more selective for vasculature) and one non-dihydropyridine (more selective for heart)
USES?
HOW do they work?
SE’s ?
Interactions?
Amlodipine - dihydropyridine
Diltiazem - non-dihydropyridine
USES
Amlodipine – HTN (decrease risk of storke, MI, CVD death)
All Ca-channel blockers used in stable angina (B blocker = alternative)
HOW do they work? -
Decrease Ca entry into vascular and cardiac cells causing relaxation and vasodilation in the atrial smooth muscle (decrease atrial pressure). In the heart they reduce the myocardial contractility and supress cardiac conduction (esp AV node, slowing ventricular rate).
SEs: ankle swelling, flushing, headache and palpitations (caused by vasodilation and tachycardia)
Don’t use B-blockers w/ non-dihyropyridines.
ACE inhibitors examples?
use in?
How does it work?
SE’s?
Interactions?
Ramipril (PO), Captopril, Imidapril, Lisinopril, Quinapril
Use: HTN, chronic HF, ischaemic heart disease, Diabetic nephropathy and chronic kidney disease with proteinuria (reduce proteinuria and progression of nephropathy)
Angiotensin converting enzyme inhibitors prevent the conversion of angiotensin I to Angiotensin II. (Angiotensin II is a vasoconstrictor). Reduces vascular resistance and lowers BP and dilates glomerular arteriole (CKD)
SEs: hypotension (dizziness, esp first dose – take before bed), persistent dry cough and hyperkalaemia. Can casue or worsen renal failure. Avoid in pregnancy. Rarely cause severe allergic reactions: angioedema and anaphylaxis.
Interactions: avoid other potassium elevating drugs e.g. spironolactone and NSAIDs e.g. OTC ibuprofen increase risk of renal failure (check U&Es & BP)
What do ARB’s do? name some and which conditions they are indicated for
ARBs block the action of angiotensin II on the AT1 Receptor (similar to ACEi)
Losartan, candersartan
Same uses as ACEi, they are used when ACEi not tolerated e.g. cough: HTN, chronic HF, ischaemic heart disease (reduce risk of CVD), Diabetic nephropathy and chronic kidney disease
Which drugs should GTN spray be combined with in most occasions?
GTN SE?
When to prescribe long acting GTN?
How does GTN work?
Prescribe a beta-blocker or a calcium-channel blocker (CCB) as first-line regular treatment for stable angina.
SEs: Flushing, headaches, light-headedness, hypotension (may need to rest 5 mins before and after taking). Tolerance (reduced symptom relief).
Long acting (isosorbide mononitrate) used to prevent angina where B blocker/Ca-channel blocker are insufficient/not tolerated
Nitrates NO - reduces intracellular Ca: Relaxation of the venous capacitance vessels (reducing cardiac preload) reducing cardiac work and myocardial oxygen demand.
Digoxin - used when? Is a what? Mechanism? Interactions? Contraindications?
Used in atrial flutter - after B-blocker/non-dihydropyridine Ca-channel blocker, and Severe Heart Failure - 3rd line in patients taking ACEi, B blocker and ARB/aldosterone antagonist.
Is a Cardiac Glycoside
Mechanism: Negatively chronotropic (reduces HR) and positively inotropic (increases the force of contraction). Increased vagal (parasympathetic tone) - reduced AVN conduction, decreasing ventricular rate (AF, atrial flutter). Increases intracellular Ca in myocytes - increase contractile force (HF)
Interactions: Digoxin toxicity increased in: Loop & thiazide diuretics (hypokalaemia) and Amiodarone, Ca-channel blockers, spironolactone and quinine (increase conc)
* Can cause ST depression (this is normal, not worrying)
Contra-indications: 2nd and 3rd degree heart block
Amiodarone (IV) - when used?
Interactions?
Treatment of arrhythmias, particularly when other drugs are ineffective or contra-indicated (including paroxysmal supraventricular, nodal and ventricular tachycardias, atrial fibrillation and flutter, ventricular fibrillation, and tachyarrhythmias associated with Wolff-Parkinson-White syndrome)
Only use when risk-benefit balance justifies (avoid in hypotension, heart block, thyroid disease)
Reacts with many drugs to increase toxicity e.g. digoxin, diltiazem/vermapril
Acute coronary syndrome, acute ischarmic stroke and for long term secondary prevention of thrombotic arterial events in patients w/ cardiovascular, cerebrovascular and peripheral arterial disease. To reduce risk of intracardiac thrombus and embolic stroke in AF (where warfarin and novel anti-coagulants are contra-indicated) To control mild-moderate pain and fever. - which drugs (2)
How do they work?
Cautions?
Interactions?
Aspirin and Clopidogrel
Mechanism: Aspirin irreversibly inhibits COX, reducing thromboxane and reducing platelet aggregation and risk of arterial occlusion (occurs at low doses). Clopidogrel prevents platelet aggregation by binding to ADP Rs on the surface of platelets.
Caution: gout, peptic ulcer, 3rd trimester pregnancy
Interactions: caution w/ other antiplatelets and anticoagulants as acts synergistically (beneficial but also increased risk of bleeding) Clopidogrel is metabolised by hepatic P450 therefore efficacy may be reduced by CYT p450 inhibitors e.g. omeprazole, ciprofloxacin, also caution w/ other anti-platelets/anti-coagulants.
