CVS Drugs Flashcards
Thiazide like diuretics examples
Bendromethiazide
Indapamide
Thiazide like diuretics mechanism of action
Inhibition of sodium chloride co-transporter in the DCT. This is decreases sodium and water reabsorption.
Thiazide like diuretics indications
Hypertension
Heart failure
Thiazide like diuretics ADRs
Hypokalaemia
Arrhythmias
Hyperglycaemia
Hypercholesterolaemia
Thiazide like diuretics drug interactions
NSAIDs
Loop diuretics
Loop diuretics examples
Furosemide
Bumetanide
Loop diuretics mechanism of action
Inhibition of sodium potassium 2chloride co-transporter in the loop of henle
Loop diuretics indications
Oedema
Hypertension
Heart failure
Loop diuretics ADRs
Dizziness
Headache
Electrolyte imbalance
Nausea
Dehydration
Loop diuretics drug interactions
Thiazide like diuretics
Diabetic medication
Potassium sparing drugs examples
Amiloride
Potassium sparing drugs mechansim of action
Blocks ENaC channels at the luminal surface of the renal tubule. This decreases sodium reabsorption without affecting the reabsorption of potassium.
Potassium sparing drugs ADRs
Hyperkalaemia
Potential arrhythmias
Potassium sparing drugs indications
Heart failure
Potassium sparing drugs drug interactions
ACEi
ARBs
Aldosterone receptor antagonist example
Spironolactone
Aldosterone receptor antagonist indications
Oedema
Heart failure
Hypertension
Aldosterone receptor antagonist mechanism of action
competitively inhibits aldosterone dependant Na+ K+ exchange channels in the DCT. This action leads to increased sodium and water excretion, but more potassium retention
Aldosterone receptor antagonist ADRs
Hyperkalaemia
Gynaecomastia
Aldosterone receptor antagonist drug interactions
Drugs that increase potassium levels
Class 1b drugs indications
Ventricular tachycardia
Class 1b ADR
CNS effects : dizziness and drowsiness
GI upset
Class 1b drugs examples
Lidocaine
Mexiletine
Class 1b agents mechanism of action
Decreased depolarisation in ischaemic tissue
Increased sodium threshold
Class 1c drugs examples
Flecainide
Class 1c drugs indications
Supraventricular arrhythmia
Wolff-Parkinson-White syndrome
Class 1c drugs ADR
Pro-arrhythmia
Flecainide flutter
CNS and GI effects
Class 1c agents mechanism of action
Increases refractory period and the action potential
Decreases automaticity
Class 2 drugs examples
Propranolol, bisoprolol and metoprolol
Class 2 drugs indications
Re-entrant arrhythmias
AFIB
Sinus tachycardia
Class 2 drugs ADR
Bronchospasm
Hypotension
Class 3 drugs examples
Amiodarone
Class 3 drugs indications
Wide spectrum - most arrhythmias
Class 3 ADR
Pulmonary fibrosis Hepatic injury Increase LDL cholesterol Thyroid disease Photosensitivity Optic neuritis
Class 3 drugs interactions
Digoxin
Warfarin
Common thromboembolic diseases
DVT PE Consequence of AF TIA MI Ischaemic stroke
How does Prostacyclin - PGI2 - prevent platelet aggregation ?
Prostacyclin is released from endothelial cells which then binds to platelet receptors. This increases the concentration of cAMP in platelets. This causes decreased calcium. This decreases platelet aggregatory events and stabilises inactive GPIIb/IIIa receptors.
What are 3 anti-platelet and fibrinolytic targets ?
The COX-1 enzyme
Fibrinogen acting at the GPIIb/IIIa receptors
ADP and thromboxane 2 upregulating receptors
What class is aspirin ?
Cyclo-oxygenase inhibitor
Indications of aspirin ?
AF post stroke
Secondary prevention of stroke or TIA
MI
Aspirin mechanism of action
Aspirin irreversibly inhibits COX-1 mediated production of thromboxane 2 and reduces platelet aggregation
Aspirin ADR
GI irritation
GI bleeding
Haemorrhage
Aspirin contra-indications
Reye’s syndrome - children having flu or chicken pox while taking aspirin
Hypersensitivity
Pregnancy in 3rd trimester
Aspirin DDI
Other anti-platelets and anti-coagulants
ADP receptor antagonist examples
Clopidogrel
Prasugrel
Ticagrelor
ADP receptor antagonists mechanism of action
Inhibit binding of ADP to P2Y12 receptor which inhibits activation of GPIIb/IIIa receptors.
Differences between Clopidogrel and prasugrel to Ticagrelor
Clopidogrel and Prasugrel are irreversible inhibitors of P2Y12 receptors
Ticagrelor acts reversibly at a different site and has active metabolites
ADP receptor antagonists indications
Ischaemic stroke
TIA
MI + aspirin
Usually used as a second agent in a dual anti platelet therapy
ADP receptor antagonist ADR
Bleeding
GI upset - dyspepsia and diarrhoea
ADP receptor antagonist cautions
High bleed risk patients
Renal and hepatic impairment
ADP receptor antagonist DDI
Clopidogrel requires CYPs for activation so CYP inhibitors such as omeprazole can affect drug efficacy
Dipyridamole drug class
Phosphodiesterase inhibitor
Dipyridamole mechanism of action
Dipyridamole inhibits cellular re-uptake of adenosine. This increases concentration of adenosine which inhibits platelet aggregation via adenosine receptors.
It also prevents cAMP degradation which inhibits expression of GPIIb/IIIa
Dipyridamole indications
Secondary prevention of ischaemic stroke and TIA
Stroke
Dipyridamole ADR
Vomiting
Diarrhoea
Dizziness
Dipyridamole DDI
Anti-platelets
Anti-coagulants
Adenosine
Abciximab drug class
Glycoprotein IIb/IIIa inhibitor
Abciximab mechanism of action
Abciximab prevents the binding of fibrinogen and von Willebrand factor at the GPIIb/IIIa receptors
Abciximab ADR
Bleeding
Abciximab DDI
Anti-platelets
Anti-coagulants
Fibrinolytic agents - clot busters examples
Streptokinase
Alteplase
Fibrinolytic agents - clot busters mechanism of action
Promotes conversion of plasminogen into plasmin. This dissolves the fibrin mesh work of the thrombus.
Fibrinolytic agents - clot busters indications
Acute ischaemic stroke
STEMI
Fibrinolytic agents - clot busters ADR
Bleeding
Fibrinolytic agents - clot busters DDI
Anti-platelets
Anti-coagulants
What is given for secondary prevention of ACS ( STEMI, NSTEMI and unstable angina ) ?
ACEi
Beta blocker
Dual anti platelet therapy - aspirin + ADP receptor antagonist
Statin
Clotting cascade - intrinsic pathway
Factor XII is converted to factor XIIa.
Factor XI is converted to factor XIa by factor XIIa.
Factor IX is converted to factor IXa by factor XIa.
Factor X is then converted into factor Xa by factor IXa.
Prothrombin is then converted into Thrombin by factor Xa.
Thrombin converts fibrinogen into fibrin.
Clotting cascade - extrinsic pathway
Factor VII is converted into factor VIIa by tissue factor.
Factor X is then converted into factor Xa by factor VIIa.
Prothrombin is then converted into thrombin by factor Xa
Thrombin then converts fibrinogen into fibrin.
Unfractionated heparin mechanism of action
Binds to antithrombin III causing a conformational change and increasing activity of ATIII.
This inhibits factor Xa.
Low molecular weight heparin examples
Dalteparin
Enoxaprain
Fondaparinux
Dalteparin and enoxaparin mechanism of action
Enhance activity of ATIII activity and inhibit factor Xa specifically
Fondaparinux mechanism of action
It is a synthetic pentasaccharide which selectively inhibits Xa by enhancing ATIII.
Heparin indications
Prevention of thromboembolism DVT PE Acute coronary syndromes Can be used in pregnancy as it doesn’t cross the placenta
Heparin ADR
Bruising Bleeding Heparin induced thrombocytopenia Hyperkalaemia due to inhibition of aldosterone secretions Can cause osteoporosis in long term use
Heparin cautions
Clotting disorders
Renal impairment
Heparin DDI
Other anti - thrombotic drugs
ACEi / ARB
Amiloride
Spironolactone
What is given for heparin reversal ?
Protamine sulphate as it forms an inactive complex with heparin. Heparin dissociates from ATIII and irreversibly binds to protamine sulphate.
Warfarin drug class
Vitamin k antagonist
Warfarin mechanism of action
Inhibits activation of vitamin k dependent clotting factors - factor II, VII, XI and X. This prevents the clotting cascade and the production of fibrin.
Warfarin indications
PE
Venous thromboembolism
DVT
AF
Warfarin ADR
Bleeding - epistaxis
What is given for warfarin reversal ?
Vitamin K
Warfarin DDI
NSAIDs displace warfarin from albumin causing higher INR
CYP Inducers - Barbiturates, phenytoin and rifampicin accelerate warfarin metabolism causing lower INR
CYP2C9 inhibitors - amiodarone, Clopidogrel and alcohol inhibit hepatic metabolism causing higher INR
Cephalosporin reduces vitamin K production by decreasing gut bacteria
DOAC examples
Apixaban
Edoxaban
Rivaroxaban
Dabigatran
Apixaban mechanism of action
It inhibits both free Xa and that bound to ATIII.
Dabigatran mechanism of action
It is a selective direct competitive thrombin inhibitor of both circulating and thrombus bound IIa
DOAC ADR
Bleeding
DOAC cautions
Dabigatran is contra-indicated in low creatinine clearance
Avoid in pregnancy due to little information known
DOAC DDI
Reduced effectiveness by CYP inducers
Increased concentration by macrolides
DOAC antidotes
Andexanet
Idarucizumab
Tranexamic acid mechanism of action
Inhibits fibrinolysis
Tranexamic acid drug class
Anti-fibrinolytic
What are the primary hypertensive agents ?
ACEi
ARB
CCB
Diuretics
ACEi mechanism of action
ACEi inhibit angiotensin converting enzyme and limit conversion of angiotensin 1 to angiotensin 2. This causes vasodilation, reduction in aldosterone release and reduced ADH release.
ACEi examples
Ramipril
Lisinopril
ACEi ADR
Hypotension
Dry cough
Hyperkalaemia
Angio-oedema - more common in Afro-Caribbean patients
ACEi cautions
Renal artery stenosis
AKD
Pregnancy
Idiopathic angioedema
ACEi DDI
Drugs that increase potassium
NSAIDs
Other anti-hypertensives
ARB examples
Losartan
Candesartan
ARB mechanism of action
Directly target and block AT1 receptors - more effective at inhibiting angiotensin 2 mediated vasoconstriction than ACEi.
ARB cautions
Renal artery stenosis
AKD
Pregnancy
ARB DDI
Drugs that increase potassium
NSAIDs
ARB ADR
Hypotension
Hyperkalaemia
ARB indications
Heart failure
Hypertension
ACEi indications
Hypertension
Heart failure
Dihydropyridine examples
Amlodipine
Nifedipine
Dihydropyridine mechanism of action
They are selective for peripheral vasculature and block L type calcium channels preventing calcium entrance into smooth muscle cells. This prevents vasoconstriction.
Chronotropic effect meaning
Changes in HR
Ionotropic effects meaning
Changes in the contractility of the heart
Dihydropyridine ADR
Ankle swelling
Flushing
Headaches
Palpitations
Dihydropyridine cautions
Unstable angina
Severe aortic stenosis
Amlodipine DDI
Amlodipine increases the effect of simvastatin
Dihydropyridine indications
Angina
Hypertension
Verapamil drug class
Phenylalkylamine
Verapamil mechanism of action
They depress the SA node and slows AV conduction
Prolongs action potential and effective refractory period
Has negative chronotropic and ionotropic effects
Verapamil indications
Arrhythmia
Angina
Hypertension
Verapamil ADR
Constipation
Bradycardia
Heart block
Cardiac failure
Verapamil cautions
Poor LV function
AV nodal delay
Verapamil DDI
Beta blockers
Other anti-hypertensive and anti-arrhythmia agents
Benzothiazapine example
Diltiazem
Spironolactone drug class
Aldosterone receptor antagonist
Spironolactone indication
Resistant hypertension
Spironolactone ADR
Hyperkalaemia
Gynaecomastia
Spironolactone cautions
Hyperkalaemia
Addison’s
Spironolactone DDI
Drugs that increase potassium
Pregnancy
What drugs should be given if potassium is high instead of Spironolactone ?
Alpha or beta blockers
What anti-hypertensive should be given in pregnancy ?
Labetolol
Beta blockers mechanism of action in hypertension
They decrease the sympathetic tone by blocking noradrenaline and reducing myocardial contraction resulting in decreased CO
Beta blocker cautions
Asthma
Hepatic failure
Beta blocker DDI
Non-Dihydropyridines can cause asystole with beta blockers
Beta agonists cancel out beta blockers
Doxazosin drug class
Alpha blocker
Doxazocin mechanism of action
Selectivel antagonism of alpha 1 receptors and reduce peripheral vascular resistance
What alpha blocker can be given for BPH ?
Tamsulosin
Doxazosin ADR
Postural hypertension Dizziness Syncope Headache Fatigue
Doxazosin cautions
Postural hypertension
Doxazosin DDI
Dihydropyridines - increase oedema
Glyceryl trinitrate drug class
Nitrate
Glyceryl trinitrate indications
Angina
Hypertension
Heart failure
Glyceryl trinitrate cautions
Aortic stenosis
Hypovolaemia
Hypotension
Glyceryl trinitrate ADR
Arrhythmia Dizziness Drowsiness Headaches Hypotension
Glyceryl trinitrate mechanism of action
It is denitrated to produce the active metabolite nitric oxide. This then causes venodilation.
Class 4 drug examples
Verapamil
Diltiazem
Class 4 drug mechanism of action
Slow conduction through AV
Increase refractory period in AV node
Class 4 drug indications
Supraventricular tachycardia
Class 4 drug ADR
Constipation
Hypotension
Class 4 drug DDI
Beta blockers can cause asystole if used together
Adenosine mechanism of action
Adenosine binds to A1 receptors and blocks adenylyl cyclase and reduces cAMP. This causes a potassium influx which results in hyperpolarisation. This decreases HR.
Adenosine indications
Re-entrant supraventricular arrhythmias
Ivabradine mechanism of action
It blocks the funny current in the SAN
Ivabradine ADR
Flashing lights
Ivabradine cautions
Avoid in pregnancy due to possible teratogenity
Ivabradine indications
Sinus tachycardia
Decreases HR in HF and angina
Digoxin indications
AF
Atrial flutter
Digoxin mechanism of action
Enhances vagal activity which slows AV conduction and HR
Atropine mechanism of action
It selectively blocks Muscarinic receptors and blocks vagal activity to increase AV conduction and increase HR
Atropine indications
Vagal bradycardia
Statin examples
Atorvastatin
Simvastatin
Statins mechanism of action
Competitively inhibit HMG-CoA reductase decreasing production of cholesterol
It also contributes to the upregulation of hepatic LDL receptors and increases clearance of circulating LDL
Statin ADR
GI disruption
Nausea
Headaches
Myalgia
Statin cautions
Renal and hepatic impairment
Pregnancy
Statins DDI
Amiodarone, diltiazem and macrolides increase statin concentration as well as Amlodipine
Fenofibrate drug class
Fibric acid derivatives ( fibrates )
Fenofibrate mechanism of action
Activation of nuclear transcription factor - PPAR alpha. This regulates expression of genes that control lipoprotein metabolism. There is also increased production of lipoprotein lipase. This results in increased triglyceride removal and increased fatty acid uptake by the liver.
Fenofibrate ADR
Cholelithiasis
GI upset
Myositis
Fenofibrate cautions
Photosensitivity
Gall bladder disease
Fenofibrate DDI
Warfarin - increased anti coagulation
Fenofibrate indication
Hyperlipidaemia
Ezetimibe drug class
Cholesterol absorption inhibitor
Ezetimibe indications
Used as an adjunct to a statin
Ezetimibe mechanism of action
It inhibits NPC1L1 transporter at brush border which reduces cholesterol absorption in the gut.
Ezetimibe ADR
Abdominal pain
GI upset
Angioedema
Ezetimibe caution
Hepatic failure
Ezetimibe DDI
Increased risk of rhabdomyolysis alongside statins
Alirocumab drug class
PCSK9 inhibitor
Alirocumab indications
Primary hypercholesterolaemia
Inclisiran mechanism of action
It is a siRNA which inhibits hepatic translation of PCSK9 blocking its action.