CARDIOVASCULAR DRUGS Flashcards
give an example of a loop diuretic
furosemide
bumetanide
which organ do loop diuretics act on?
kidneys
which part of the kidneys do loop diuretics work on?
ascending limb of loop of henle
how do loop diuretics act to inhibit reabsorption?
compete for chlorine binding sites by acting on sodium/potassium/chlorine co-transporters
how do loop diuretics cause more urine to be produced?
inhibits reabsorption of electrolytes, less osmosis, more urine produced
give 2 instances that loop diuretics are used
pulmonary oedema (LVF) heart failure
what is the difference between IV and oral administration of loop diuretics?
IV fast acting
oral slow acting, lasts six hours, so twice daily
name 2 circulatory instances that contraindicate use of loop diuretics
hypovolaemia
hypotension
loop diuretics can cause hyperglycaemia. name 2 conditions that can be exacerbated by this
diabetes
gout
what electrolyte imbalances can be caused by use of loop diuretics?
hypokalaemia/hyponatraemia
lead to hepatic encephalopathy/coma
what is the risk of taking loop diuretics whilst pregnant?
maternal hypovolaemia
name 2 serious GI side effects of loop diuretics
pancreatitis
hepatic encephalopathy
name 3 other side effects of loop diuretics
hypersensitivity visual disturbances tinnitus deafness BM suppression Urinary retention Metabolic alkalosis
how can loop & thiazide diuretics potentiate digoxin toxicity?
hypokalaemia
how do NSAIDs interact with loop and thiazide diuretics?
reduce efficacy (COX inhibitors)
why shouldn’t loop and thiazide diuretics be taken with corticosteroids?
enhance hypokalaemia
give an example of a thiazide diuretic
bendroflumethiazide
metolazone
Chlortalidone
where in the kidneys do thiazide diuretics act?
distal convoluted tubule
how do thiazide diuretics inhibit reabsorption?
inhibiting Na reabsorption from DCT by inhibiting Na/Cl co-transporter
how does reabsorption inhibition cause more urine to be produced in thiazide diuretics?
less osmotic force so less water reabsorbed
name 2 conditions that thiazide diuretics are used in
Chronic heart failure
First line treatment or additional treatment for hypertension
at what time in the day should thiazide diuretics be administered?
morning so don’t interfere w sleep
name 2 conditions that can be exacerbated by thiazide diuretics
diabetes
gout= reduce uric acid secretion
SLE
why are thiazide diuretics a risk in pregnancy?
neonatal thrombocytopenia, BM suppression, jaundice , hypoglycemia
what electrolyte imbalances can be caused by thiazide diuretics/
hypo-disorders
name 3 other side effects of thiazide diuretics
bone marrow depression visual disturbances tinnitus deafness hypersensitivity Impotency in men
name 2 potassium sparing diuretics
spironolactone
amiloride
how does spironolactone work?
aldosterone antagonist= binds to aldosterone receptor
It blocks the effects of aldosterone which is promotes sodium and water retention and excretion of pottasium
how does amiloride work?
interferes with sodium and potassium exchange at the DCT. Promotes excretion of sodium and water and retnation of pottasium
Relatively week diuretic
name 4 conditions where potassium sparing diuretics are used
Chronic heart failure Ascited and oedema in liver cirrhosis Nephrotic syndrome primary hyperaldosteronism Hypokalaemia= amiloride
what is an electrolyte imbalance that contraindicates use of potassium sparing diuretics?
hyperkalaemia
what is a hormone imbalance syndrome that contraindicates use of potassium sparing diuretics?
addison’s
why shouldn’t potassium sparing diuretics be used in pregnancy?
feminisation of the male foetus
why shouldn’t potassium sparing diuretics be used in conjunction with ACE inhibitors?
potentiate hyperkalaemia
why should NSAIDs be used in conjunction with potassium sparing diuretics?
COX inhibitors- reduce efficacy
give an example of a beta blocker
atenolol
how do beta blockers work?
block beta-adrenoreceptors in the heart, peripheral vasculature, bronchi, pancreas and liver
block action of sympathetic nervous system
slows the heart rate (can be vasodilatory)
give 4 when beta blockers used?
angina/MI heart failure hypertension arrhythmia= AF and SVT thyrotoxicosis migraines
why are beta blockers contraindicated with asthma?
triggers exacerbation of attacks
why are beta blockers contraindicated in pregnancy?
can cause intrauterine growth
can cause neonatal hypoglycaemia
why should beta blockers be used in caution with patients with diabetes?
can dull signs of a hypo
name 2 circulatory side effects of beta blockers
syncope
bradycardia
cold peripheries
why shouldn’t beta blockers be used with anti-arrhythmias?
slow heart rate
why shouldn’t beta blockers be used with anti-hypertensives?
lower blood pressure
why shouldn’t antipsychotics be used with beta blockers?
can increase risk of arrhythmias
why shouldn’t beta blockers or calcium antagonists be used with clonidine alpha blocker?
can cause rebound hypertension
give 2 examples of a calcium antagonist
amlodipine
verapamil
diltiazem
how do calcium antagonists work?
reduce calcium ion movement through cell membranes into vascular and cardiac cells
how do calcium antagonists affect myocardial contractility, oxygen demand and electrical impulse formation? what is the outcome of this?
In the hear reduce myocardial contractility.
They suppress cardiac conduction,= reduce ventricular rate
Reduced cardiac rate, contractility and afterload reduce myocardial oxygen demand, preventing angina
how do calcium antagonists affect coronary vascular tone?
Relaxation and vasodilation in arterial smooth muscle, lowering arterial pressure
when are calcium antagonists used?
Stable angina
hypertension
Diltiazem and verpamil are used in SVT, atiral flutter and AF
in which type of angina are calcium antagonists not effective against and can worsen the symptoms?
unstable
What are the side effects of verapamil?
Commonly= constipation Rare= bradycardia, heart block and cardiac failure
name common side effects of amlodipine?
Ankle swelling
Palpitations
Flushing
Headache
What heart condition should verapmil and diltiazem be used with caution?
Patient with left ventricle hypertrophy as it can preciptate or worse the cardiac failure
Patient with what conduction problem should avoid diltiazem and verapmil?
With increase AV node conduction delay as it can lead to heart block
What condition predisposes the patient do collapse if taking amlodopine?
Severe aortic stenosis
give an example of ACE inihibitors
ramipril
lisinopril
give 2 conditions where ACE inhibitors are used
Hypertension
chronic heart failure
IHD to prevent MI and stroke
Diabetic nephropathy and CKD with proteinuria
which organ insufficiency is contraindicated in administration of ACE inhibitors or AT1 blockers?
Renal artery stenosis or acute kidney injury
what heart abnormality is contraindicated in administration of ACE inhibitors?
aortic stenosis
name a circulatory insufficiency contraindicated in administration of ACE inhibitors
hypovolaemia
Should ACE inhibitors or AT1 blockers be used in pregnancy and breast feeding?
no
What are the common side effects of ACE inhibitor?
Hypotension espeially after first dose
Dry cough due elevated levels of bradykinin
Hyperkalaemia due to reduced levels of aldosterone so pottasium retention
how do ACE inhibitors results in vasodilation and reduce BP.
Inhibits the renin-angiotensin systemless
Inhibition of the angiotensin-converting enzyme, less angiotensin II.
Angiotensin 2 causes vasoconstriction and aldosterone production= reduced PV resistance and afterload.
Also promotes sodium and water excretion due to reduction in aldosterone and helps with HF
What is the severe interaction of NSAIDS and ACE inihibitors or AT1 blockers?
Potentiate the risk of renal failure
what serious allergic reaction can occur with ACE inhibitors?
angioedema due to bradykinin release
what electrolyte imbalance can be caused by ACE inhibitors?
hyperkalaemia
why shouldn’t ACE inhibitors or AT1 blockers be used with potassium supplements or pottasium sparing diuretics?
can cause hyperkalaemia
give an example of an angiotensin-1 blocker and why is it used?
losartan and alternative to ACE inhibitor due to dry cough
how do AT1 blockers work?
competitive inhibition of angiotensin 2 and bocks the AT1 receptor
Slow renin angiotensin system
which of these processes is not mediated by AT1 blockers?
a) vasoconstriction
b) aldosterone release
c) thermoregulation
d) renal sodium reabsorbtion
e) vasopressin secretion
c) thermoregulation
give 3 conditions where AT1 blockers are used
Hypertension
chronic heart failure
IHD to prevent MI and stroke
Diabetic nephropathy and CKD with proteinuria:
which one of these is not a contraindication for AT1 blockers?
a) pregnancy
b) renal artery stenosis
c) hyperkalaemia
d) depression
d) depression
what serious muscle condition is a side effect of AT1 blockers?
rhabdomyolysis
What are the possible side effects of AT1 blocker?
Hyerkalamia
Renal failure
Hypotension = particularly after first dose
what effect do rifampicin & fluconazole have on AT1 blockers?r
reduce effect
Give example of a short and long acting nitrate?
a) short nitrate= glyceryl trinitrate
b) long nirate = isosorbide mononitrate
how do nitrates work?
Nitrates converted to NO which prevents Ca from moving in vascular smooth muscles
Direct relaxant of smooth vascular muscle in mainly veins and arteries.
Causes reduction in venous return and left ventricle filling
What affect does nitrates have on preload?
Reduces caridac preload therefore reduce cardiac work and myocardial oxygen demand relieving the symptoms of angina and caridac failure
What 3 conditions are nitrates are used for
Short nirate for acute agina and ACS
Long nitrate for prophylaxis of angina
IV for pulmonary oedema with furosemide and oxygen
give 2 contraindications of nitrates
pregnancy
hypotension
Severe aortic stenosis = cause collapse
What are the common side effects of nitrates?
hypotension
Flushing
Headache
Light headedeness
why should nitrates not be used with alcohol or viagra?
also vasodilators - increase risk of serious hypotension
Interaction of nitrate with phospodiesterase inhibitor (sildenafil) will cause what?
It will increaes and prolong the hypotensive effects of nitrates
give an example of a cardiac glycoside
digoxin
how does digoxin cause intracellular calcium to rise and therefore treat heart failure?
Inhibits Na/K- ATPase pumps causing rise in intracellular Na, which inhibits Ca ion pump out of cell, so Ca retained which increases contractile forces
What affect does digoxin have on parasympathetic tone and therefore use for AF?
Increase in vagal (parasympathetic tone) which causes a reduction in conduction of AV node which means a reduction in ventricle rate
what does greater intracellular calcium mean in terms of myocytes in digoxin?
increased uptake - more powerful/automatic contraction
how does digoxin affect heart rate and force of heart contraction?
Decreases heart rate ( negative chronotropic)
Increases force of contraction ( positive inotropic)
give 2 conditions where cardiac glycosides are used
arrhythmia= AF and atrial flutter ( reduce ventricle rate)
congestive heart failure (severe)= 3rd line treatment
give a 3 heart conditions which contraindicates use of digoxin
2nd degreee Heart block
Intermittent heart block
Ventricle arrhythmias
What is the risk of giving digoxin when patient has electrolyte abnormalitiy? give examples
Can lead to digoxin toxicity
hypokalaemia = greatest risk as it competes with pottassium for binding to the pump
Hypomagnesaemia
Hypercalcaemia
what is digoxin a substrate of?
p-glycoprotein
a) Name two drugs that cause hypokalaemia and therefore digoxin toxicity?
b) Name 7 drugs that can increase the plasma concentration of digoxin and therefore risk of toxicity?
a) Loop diuretic and thiazide diuretic
b) amiodarone, quinine, spirolactone, verapamil, CA channel blocker, gentimicin and Itraconazole
Give an example of class 1 sodium channel blocker anti-dysrhythmics
quinidine
lidocaine
what are class 2 anti-dysrhythmics?
beta blockers
give an example of potassium channel blocker class 3 anti-dysrhythmics?
amiodarone
what are class 4 anti-dysrhythmics?
calcium channel blockers
give an example of class 5 anti-dysrthmics (unknown mechanism)
digoxin
adenosine
give 3 examples of when amiodarone is used for?
Ventricular arrhythmias AF Atrial flutter SVT ventricular tachycardia Wolfs-parkinson-white syndrome
what is wolfs-parkinson-white syndrome?
abnormal electrical conduction pathway between atria and ventricles causing ventricles to contract prematurely
why are pregnancy and breastfeeding contraindicated in amiodarone?
similar structure to thyroxine can cause foetal thyroid issues
What are the potential side effects of chronic use of amiodarone?
Lung= pneumonitis Heart= AV block and bradycardia Skin= Photosensitivtiy and great colourisation Liver= Hepatitis and jaundice
Amiodarone has similar strucutre to thyroid hormone what effect does this have on the patient potentially?
Lead to hypo or hyperthyroidism
why shouldn’t amiodarone be used with benzyl-alcohol formulations in neonates?
cause gasping syndrome
Which patients should use of amiodarone be avoided in?
Severe hypotension
Heart block
Active thyroid disease
Interaction of amiodarone with what drugs can cause bradycardia, heart failure and Av block. Therefore have there dose halved?
Verapamil
Diltiazem
Digoxin
What is the interaction of amiodarone and cytochrome p450?
Metabolised and inhibits cytochrome p450
how does amiodarone affect serum digoxin?
increases
give 2 examples of anti-platelet agents
aspirin
clopidogrel
how do anti-platelets inhibit thrombus formation?
inhibit platelet aggregation
in which circulation system are anti-platelets most effective?
arterial
how does aspirin block thromboxane formation? Leading to reduction in platelet aggregation and arterial occlusion
COX inhibitor= blocks cox 1 formation
how does clopidogrel work as an anti-platelet?
competitive inhibition of ADP receptors on surface of platelet cell membrane= prevent platalet aggregation
What are the most common adverse effect of aspirin and clopidogrel?
GI irritation leading to ulceration and bleeding.
Give the use of anti-platelet agents
ACS
Thromoblytic therapy for, Pe, cerebral infarctiona nd MI
Af to prevent stroke
Mild to moderate pain and fever = aspirin
Prevent occlusion of coronary artery stents= clopidogrel
why are anti-platelets contraindicated in haemophilia and dengue fever, peptic ulcers and hypertension?
high risk of bleeding
which anti platelet is contraindicated in the case of salicylate allergy? Causing potential bronchospasm
aspirin
why is aspirin contraindicated in hyperuricaemia and gout?
inhibits kidney excretion of uric acid
what is Reye’s syndrome and which anti-platelet is it associated with?
Liver encephalopathy after acute viral illness (influenza, varicella) in under 16 and associated with aspirin
Large doses of apsirin can cause what and why?
Tinnitus due to large doses of salicylate
how does alcohol interact with aspirin?
enhances activity
how is clopidogrel metabolised?
It is a pro drug and is metabolised by cytochrome p450 to its active form
which GI drug reduces the effect of clopidogrel?
omeprazole therefore use other PPI for GI protection
how might SSRIs and anti-platelets interact?
increase risk of bleeding
how might NSAIDs and warfarin interact with anti-platelets?
increase risk of bleeding
what is streptokinase (alteplase) and tissue plasminogen activator an example of?
thrombolytics
how is streptokinase produced?
Produced by strep bacilli
how do thrombolytics work?
Catalyse the conversion of plasminogen to plasmin which breaks down clots=
give 3 examples when thrombolytics are used
MI with ST elevation = in the first 12 hours with antiplatelet and anticoagulants.
Acute ischaemic stroke
Large PE
arterial occlusion
what type of stroke are thrombolytics contraindicated in?
haemorrhagic= CT scan before administration for acute stroke
What are the main contradications to use of thromblytics?
Factors that increase risk of bleeding such as
Recent trauma and surgery, severe hypertension, peptic ulcers and recent haemorrhage and bleeding disorders
what aortic abnormality contraindicates use of thrombolytics?
aortic dissection
What is the time framce for alteplase after a acute ischaemic stroke?
Be given within 4.5 hours of the stroke to have maximal effect
What is the risk of reperfusion of infarcted brain or heart tissue?
Causes cerebral oedema or arrhythmia respectively
what is common side effect of thrombolytics?
Nausea, vomiting and brusing around the Iv sight
With hypotension
give an example of a heparin
enoxaparin
where are heparins producedf?
basophils
mast cells
What is the mechanism of a)UF b)LMWH? c)Fondaparinux to prevent clot formation?
a) bind to and activate antithrombin III which inactivates thrombin and factor Xa
b) Direct inhibition of thrombin and factor Xa
c) inhibits factor Xa
What is the main adverse affects of heparin?
Bleeding and injection sight reaction
give 4 examples of when heparin is used
ACS
AF
DVT/PE
indwelling venous cannulas
why are IM injections of heparins avoided?
high risk of haematoma= disabling bruisingof the arm
What is a rare but serious side effect of heparin?
Heparin induced thrombocytopenia= leading to low levels of platetlet and thrombosis (blood clot formation)
Complications are DVT and PE formation
what 2 products in heparin formulations are allergens?
pork
benzyl alcohol
What contra indications are there for heparin?
Heparin should be used with caution for patients with increased risk of bleeding:
Severe uncontrolled hypertension, clotting disorders, recent trauma and surgery
What is the risk of giving heparin to a patient that has renal impairment?
Reduced excertion and causes accumulation of LMWH and fondaparinux= reduce the dose or use UF
give 2 examples of oral anticoagulants
warfarin
rivaroxaban
how does warfarin work? which clotting factors and proteins does it inhibit production of
Inhibits vitamin K epoxide reductase which inhibits vitamin K activation which stimulates synthesis of clotting factors 2, 7, 9, 10 and proteins C, S, Z
how dies rivaroxaban work?
which pathways does it interrupt
inhibits factor 10a
intrinsic and extrinsic pathways
What is the use of oral anticoagulant?
Treatment of PE and DVT
Prophylaxis of VTE ( recurrent DVT and PE)
Prevent stroke (embolic event) from AF
Short term use for prevention of embolic event from tissue valve replacement
Long term use for prevention of embolic event from metal valve replacement
give 2 conditions which would contraindicate use of oral anticoagulants
Risk of bleeding:
thrombocytopenia
ulcerative disease
active haemorrhage
what is the major side effect of anti-coagulants?
haemorrhage
what is purple toe syndrome?
what can it be a side effect of?
emboli and bruises in feet due to cholesterol deposits
side effect of oral anticoagulants
what is warfarin necrosis?
sudden drop in protein C causing rebound coagulation &massive thrombosis. Causing skin and limb necrosis (gangrene)
Why is it contradictive to giving oral anticoagulant to patient with liver impairment?
Reduced metabolism and therefore greater chance of bleeding
Why should you not give warfarin
a) 1st trimester of pregnancy
b) just before delivery?
a) neonatal malformations such as cardiac and cranial malformatuons
b) Materal haemorrhage during delivering
how are warfarin and rivaroxaban metabolised?
cytochrome p450
give an example of a statin
sinvastatin
atorvostatin
how do statins work?
HMG-CoA reductase inhibitors so interrupts cholesterol production chain.
Liver produces less cholesterol and more LDL clearance from the blood
Increase in HDL levels
give an example of primary statin therapy
prevent cardiovascular disease in those with high cholesterol and risk of cardiovascular event
give an example of secondary statin therapy
decrease mortality and further events in those who have evidence cardiovascular disease
give a hereditary condition where statins are used
familial hypercholesterolaemia (primary hyperlipidaemia)
are statins contraindicated in pregnancy and breast feeding?
Explain
yes as cholesterol is essential for the growth of neonate
Caution should be used with statin when the patient has impairment of what organs?
Liver (metabolism)
Renal (excretion)
What is are the rare MSK side effectes of statin?
Can cause muscle ache to myopathy and even rhabdomylsis
how are statins metabolised?
cytochrome p450
How does Thiazide increase renal blood flow?
By increasing the renal synthesis of prostagladins
What is the fatal outcome of using thiazide diuretic with a patient with severe liver disease?
Hypokalamia can lead to coma
What circulatory side effects are there of Thiazide Diuretics?
Postural HT
Cardiac Arrhythmias
What is the interaction between B blockers and Thiazide Diruetcs?
Potentiate hyperglycemia/ lipidaemia
What is the process of elimination of all 3 types of diuretics?
Renal with small contribution from liver
Should you give potassium sparing diuretics to someone with renal dysfunction?
no
What are the blood S/E of spirolactone?
Leucopenia, agranulocytosis and thrombocytopenia
Which of the diuretics have a possible side effect of gynaecomastia, impotence and sexual dysfunction and Steven Johnson syndrome?
PSD
Where are B1- adrenoreceptors and B2 adrenoreceptors found?
B1 found in the heart
B2 found mainly in the smooth muscles of blood vessels and airways
Which adrenoreceptors does beta blockers affect and what affect does that have?
β1-receptor,–> reduce force of contraction and speed of conduction in the heart.
How does beta blockers relieve MI symptoms?
Reduce cardiac work and oxygen demand and increase myocardial perfusion
How do beta blockers help to improve prognosis of heart failure?
By protecting the heart from chronic sympathetic stimulation
What affect does beta blockers have on the kidney to low BP?
Act on the kidney and cause a reduction in renin secretion
How does beta blockers treat Af?
By increasing the refractory period of AV node so reduction in venctricle contraction
Which two calcium channel blockers are used to treat supraventricular arrhythmias ?
Diltiazem and verapamil control cardiac rate
Give examples of supraventricular arrhythmias ?
Supraventricular tachycardia, Af and atrial flutter
Why is LMWH prefered over UF?
Low molecular weight heparins have a more
predictable effect and, unlike UFH, do not usually require laboratory
monitoring.
What is the interaction of B blocker and Verapamil/ diltiazem?
Can cause severe reduction in the force of contraction (inotrophic) and rate of the heart (chronotropic)
Causing potential bradycardia, heart block and even asystole
What affect does nitrates have on afterload and coronary perfusion?
Reduce afterload
Improve coronary perfusion by reducing coronary vasospasm and dilation of collateral vessels
What are the side effects of digoxin?
bradycardia GI disturbances Rash Dizziness Visual disturbances
What is the dose changes requirement for clopidogrel and aspirin before surgery?
Aspirin can be carried on taken throughout surgery
Have to stop clopidogrel 7 days before hand
What is the possible risk of giving thromboylsis with anticoagulants and antiplatelets for treatment of stroke?
Increase risk of haemorrahage
Is the risk of heparin induced thrombocytopenia greater with LMWH?
No reduced risk
Greater risk with Uf
For bleeding assoicated with heparin what is the antidote?
protamine = reverses the anticoagulation
What is the limitation of protamine?
Effective for UF
Reduced effectiveness to stop bleeding for LMWH
Not effective against fondaparinux
What is the interacation of aspirin and heparin?
Increase anticoagulation effects of heparin
What is a antidote for bleeding due to warfarin use?
Iv vitamin K= direct antidote
Or
Prothrombin complex concentrate
What is the pro and con of rivaroxaban?
Pro= no need to measure INR Con= no antidote for bleeding
Why is warfarin not used for arterial thrombosis (MI)?
This is due to platelet formation which is affected by antiplatetels agents such as aspirin and clopidogrel
