Pharmacotherap

y in cardiology
P. Peichl, MD, PhD

Department of cardiology
IKEM,Praha
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 Main drug groups
ACEI/AT II blockers
Ca blockers
Betablockers
Diuretics
Nitrates
Antiarrhythmic drugs
Anticoagulation and antiaggregation
therapy
Hypolipidemic therapy
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Regulation of BP

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 System:
renin-angiotensin
aldosteron (RAAS)

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 System:
renin-angiotensin
aldosteron (RAAS)
Plays improtant role in several homeostatic
processes
Regulation of blood pressure, water and mineral
homeostasis
Effects on cardiovascular system
Vasoconstriction increases BP
Production of grow factors fibrosis
Renal function:
Constriction of vas efferens
reabsorption of Na+ in kidney
sympathetic tone in kidney IKE
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 ACEI/AT blockers
Effects:
Vasodilatation
Lower BP
Prevent retention of Na+ and water
By inhibition of aldosteronu
Antiproliferative effect
Prevent remodelation of the left ventricle
Prevents progression of renal
insufficiency/proteiuria
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 ACEI/AT II
ACEI
Short acting captopril, enalapril
Long acting perindopril, ramipril,
trandalopril, lisinopril

Blockers of angiotensin II receptors

Losartan, valsartan, candesartan
Similar indications and side effects except
of cough
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 ACEI
Side effects:
Dry cough (10-15%)
Due to accumulation of bradykinin
Indication for substitution with AT II blockers
Hypotension after first dose
Decrease in renal functions
Angioneurotic edema

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 System:
renin-angiotensin
aldosteron (RAAS)

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 ACEI/AT II
Contraindictions:
Stenosis of both renal arteries or
single artery in case of solitary kidney
Gravidity and lactation
Known hypersensitivity to ACE-I/AT II
High potassium
Creatinin level above 250umol/l

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 ACEI/ATII
Indications:
Arterial hypertension
Favourable metabolic effect
Congestive heart failure with systolic dysfunction
EF<40%
Prevents remodelling and improves prognosis
Acute myocardial infarction
Indicated in all, in early phase it prevents remodelling
Chronic CAD
Nephropathy with/without hypertension
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Pathophysiology of CHF

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Mann DL. Circulation 1999;100:999-1008 M

Autonomic nervous
system

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 Autonomic nervous
system
Distribution and effects of adrenoreceptors

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 Betablockers
Blocks beta receptors
Classification:
selectivity to 1 receptors
Presence of intrinsic
sympathomimetic activity ISA
Hydrophilic x lipophilic
Lipophilic better diffuse into tissue
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Betablockers

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 Betablockers
Nonselective BB without ISA
Metipranol, propranolol
Nonselective BB with ISA
Pindolol, bopindolol
Selective BB without ISA
Atenolol, metoprolol, bisoprolol, esmolol
Selective BB with ISA
Acebutolol
BB with vasodilatation effect
Carvediol, labetalol, celiprolol, nebivolol
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 Betablockers
Effects:
Decrease of pressoric response to
catecholamines during stress and efford
Decrease of central/peripheral sympathetic
activity lowering BP
Decrase in contractility
Decrease in impulse conduction and heart
rate
Inhibion of renin secretion

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 Betablockers
Side effects:
Bradycardia, AV block, fatique
Worsening of astma
Cold extremities
Depresion, erectile dysfunction (lipophilic)
Worsening of insulin sensitivity, dyslipidemia
CAVE abrupt cessation - tachyphylaxis
Contraindictaions:
Astma, chronic obstructive pulmonary disease
Acute heart failure
Vasospastic AP
Pheochromocytoma (in monotherapy)

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 Betablockers
Indications:
Congestive heart failure
Acts differently in acute and chronic therapy
heart rate and oxygen consumtion leads to better perfusion of
myocardium in diastole
nitrocelullar concentration of Ca
Improved metabolism
Protection of myocardium from toxic effects of catecholamines
of activity of renin-angiotensin system
Decrease of risk of death by 31%
Necessity of slow titration of dose in stable patient
Proven only for carvediol, metoprolol, bisoprolol
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 Betablockers
Indications:
CAD, myocardial infarction
In chronic phase lower mortality by 20-30%
In acute phase rather in hospital
Angina pectoris, silent ischemia
Arrhythmias
Sinus tachycardia, extrasystole
Slowing the ventricular response during atrial fibrillation
Ventricular tachycardia
Arterial hypertension
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 Diuretics
Loop (loop of Henley)
Furosemid
Thiazid (distal tubulus)
Hydrochlorothiazid, chlorthalidon,
indapamid
Potassium sparing (collecting tubulus)
Spironolacton, amilorid

Gradual decrease in diuretic effect

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 Diuretics
Effects:
Decrease in circulating volume drop in BP

Side effects:
Low potassium, hyponatremia, dehydratation,
metabolic alkalosis, gout
Opposite in potassium sparing diuretics
Metabolic hyperglycemia, dyslipidemia
Gynecomasty (spironolakton)
Ototoxicity (furosemid)
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 Diuretics
Indication
Arterial hypertension
Congestive heart failure
Affect only symptoms
Improvement of prognosis only after spironolactone

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 Ca channel blockers
Block L type of Ca channel
Classification according to chemical
structure:
Dihydropyridins (effect vessels)
Nifedipin (I.gen) x amlodipin, felodipin
Fenylalkylamins (effect heart)
Verapamil
Benzothiazepins (effect both)
Diltiazem IKE
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 Ca channel blockers
Effects:
Lower intracelular concentration of Ca2+
Relaxation of smooth muscle cells - vasodilatation
Decrease in myocardial contractility
Decrease in conduction of AV node and heart rate
(verapamil)
Side effects:
Hypotension
Bradycardia, AVB, obstipation (verapamil)
Perimaleolar edema (amplodipin)
Danger of reflex tachycardia in short acting Ca blockers
(nonretarded nifedipin)

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 Ca channel blockers
Indications:
Arterial hypertension
Retarded dihydropyridins Norvasc, Zorem
Angina pectoris
Spastic form
Combination therapy (+ BB, + Nitrates)
Paroxysmal supraventricular arytmias
Verapamil (slows conduction through AV node)

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 Cardiac glykosides
Described before 200years (extracted from herb foxglove)
Block Na/K ATP and increase intracellular content of Ca
Digoxin
Effects:
Positive inotropic
Slowing of AV conduction
Side effects:
Arrhythmias, nausea, CAVE narrow therapeutic window
Indications:
Heart failure, atrial fibrilaltion with rapid ventricular response

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Foxglove
Digitalis purpurea

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 Inotropic drugs
Sympatomimetics
mimetics
Dopamin, dobutamin
mimetics
Noradrenalin

Inhibitors of phosphodiesterases III

Amrinon, milrinon
Calcium sensitisers
Levosimendan
Indications: during episode of heart failure, should be
used for limited period !

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 Nitrates
Lead to release of NO that is identical to
endotelium derivated relaxing factor
(EDRF)
NO production depends on presence of
sulfhydryl groups
Nitrate tolerance depletion of SH-
groups
Should be used with
night pause
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 Nitrates
Effects:
Vasodilatation (more veins), decrease of preload,
decrease of wall stress in myocardium and decrease of
oxygen consumption
Side effects
Hypotension, headache, CAVE Viagra!
Nitrates
nitroglycerin NTG
isosorbide dinitrate ISDN
isosorbide mononitrate ISMN

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 Nitrates
Used in therapy for more than 100 years
Indications:
Therapy of anginy pectoris
Only symptomatic therapy!!!, does not
improve prognosis
Short acting spray during angina attack
Long lasting (e.g ISMN)
Decrease intesity and numbers of attacts
Pulmonary edema, left sided heart
failure

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 Antiarrhythmic drugs
Classification - Vaughan Williams
I class Na channels blockers
IA, IB, IC - propafenon
II class betablockers
III class blockers of potassium channels
Amiodarone, sotalol
IV class Ca blockers
Most drugs have act using multiple
mechanisms (blocks multiple channels)
Classification of Sicilian gambit IKE
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 Antiarrhythmic drugs
Risk of proarrythmia in heart failure (CAST
study)
Except amiodarone
Effective antiarrhytmic drug with low
proarrhythmi risk
Higher risk of noncardiac side effects:
thyreopathy, pulmonary fibrosis, fotosensitivity,
hepatopathy, accumulation in cornea

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Antiaggregation
therapy

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 Antiaggregation
therapy
Acetylsalicylic acid (ASA, Aspirin)
Irreversible blockade of cyklooxygenase
Common dose 100mg daily
Side effects: gastrointestinal bleeding, astma, hearing loss
Antagonist of ADP thienopyridiny
ticlopidin, clopidogrel
Side effects: neutropenia (ticlopidin), bleeding
Indications: Acute coronary syndromes, after PCI
IIb/IIIa antagonists
Abciximab, eptifibatid
Indications: used during catheter interventions IKE
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 Anticoagulation
therapy
Prevents activation of prothrombin to thrombin
Unfractionated heparin
Human substance, short halftime
Together with AT III blocks f. II, IX, X, XI, XII
Continuous infusion iv., necessity for monitoring aPTT
Side effect - trombocytopenia
Low weight heparins s.c.
Enoxaparin, dalteparin, nadroparin
Dosage 1-2x daily
Indication:
ACS, pulmonary embolism, deep vein hrombosis,
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 Anticoagulation
therapy
Coumadine - Warfarin p.o.
Vitamin K antagonist (f. II, VII, IX, X)
Long half time (36hod)
Dosage 1x daily
Monitoring of INR (Quick test)
Usual target value of INR is 2-3
Indications:
Atrial fibrillation, arteficial valves, pulmonary
embolism, deep vein thrombosis, pulmonary
hypertension
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 Fibrinolytic therapy
Streptokinas, tissue plasminogen activator
(t-PA)
Indications: acute myocardial infarction,
pulmonary embolism, stroke, deep venous
thrombosis
Administration: general x local
Absolute contraindications:
Hemorhagic stroke, recent surgery, GIT
bleeding, aortic dissection

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 Hypolipidemics
Statins
Inhibitors of HMG-CoA reductase (hydroxymetylglutaryl)
Effects:
LDL, less TG, less HDL
Pleiotropic effects antiinflamatory, antithrombogenic = stabilize
athero plaque
Side effects: myopathy, CI: gravidity
Atorvastatin, simvastatin, fluvastatin, rosuvastatin
Indications:
Prim. prevention - cholesterol>5mmol/l, LDL>3mmol/l
Sec. prevention cholesterol >4mmol/l, LDL>2mmol/l

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 Hypolipidemics
Fibrates
Complex mechanism
catabolism and synthesis of VLDL, HDL
Effects:
TG, HDL, small decrease in LDL
Side effects:
Elevation of liver enzymes, myopathy
Fenofibrt, clofibrt
Ezetimib
Blocks absorbtion of cholesterol in enterocytes
Used in combination with statins
Bile acid sequestrant, nikotin acid
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 Lba hypertenze
Clov hodnota
5 zkladnch skupin

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 Lba ICHS
Po infarktu myokardu
4 lky: Anopyrin, BB, ACEI,
hypolipidemikum

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