Drugs affecting the cardiovascular system

They can be divided into the following groups:
1.Agents increasing intracellular

content of Ca ions
Na+,K+-ATPase inhibitors (cardiac glycosides): digoxin, strophanthin, corglyconum
Agents increasing cAMP content (non-glycosides structure):
Drugs increasing cAMP content by activating adenylyl cyclase (agents stimulating β1-adrenoreceptors): dopamine, dobutamine
Drugs increasing cAMP content by inhibiting phosphodiesterase 3: milrinone
2. Agents increasing the sensitivity of myofibrils to Ca ions - levosimendan

cardiotonic effect, but they do not increase the heart rate.

They can be used for the treatment of acute and chronic heart failure.
The other drugs increase contractile force and heart rate. They are used for the treatment of acute heart failure only.

which unsaturated lactone ring is attached) and glycone (one or

more sugar -glucose or digitoxose).
Cardiotonic effect is the property of aglycone. The saccharine part determines the solubility of glycosides and their fixation in the tissues.

→ Na+,K+ flow disturbance → ↑ intracellular Na+, but ↓

K+ → ↑ intracellular Ca (Ca enters the cardiomyocites from outside via the Ca L-channels and releases from the sarcoplasmatic reticulum) → Ca interacts with the troponine complex and eliminates its suppressive effect on the contractile proteins.
Actin interacts with myosin→ rapid and intensive myocardial contraction.
There is more complete emptying of failing and dilated ventricles—cardiac output is increased and end-diastolic volume is reduced.

and create the most economical regimen of cardiac work (restoring

the energetic resources of the myocardium).
Mechanism: ↑ vagal stimulation, cardio-cardiac reflex.

systole

diastole

Before treatment

After treatment

effect).
Myocardial excitability is increased (positive batmotropic effect).
CGs increase arterial

blood pressure, but decrease venous pressure. Peripheral vascular resistance decreases, blood supply and tissue oxygenation are improved. The dysfunction of organs ( the CNS, kidneys, lungs, liver, GI) gradually resolve. Edema gradually disappear.

Increased P-Q interval (due to slowing of A-V conduction), A-V

block at toxic doses.
Shortening of Q-T interval (reflecting shortening of systole).
Decreased amplitude or inversion of T wave.
Depression of ST segment.

Before treatment

After treatment

vision (colour) disturbances, fatigue, muscle weakness, dyspepsia (nausea, vomiting, diarrhea),

mental disorders (agitation, hallucinations), headache, skin rash.
Treatment: potassium agents (“Asparcam”, “Pananginum”), phenytoin, lidocaine, atropine; digoxin Fab (digibind), unithiol (contains sulfhydryl groups).

kidneys and mesenteric vessels (dopamine receptors and β2 R).
D.

is used for the treatment of cardiogenic shock, is administered intravenously drip.
D. can cause tachycardia, arrhythmia, excessive increases in peripheral vascular resistance and cardiac work.

to calcium ions.
Increases intensity of heart contractions without increased myocardial

oxygen consumption.
Dilates coronary vessels, increases oxygen delivery to the myocardium.
Dilates blood vessels, reduces peripheral vascular resistance, decreases pre- and afterload.
L. is used IV for the treatment of acute cardiac failure.
Side effects: arrhythmias, hypotension, headache, dizziness.

(↓ the preload).
It is used intravenously drip in case of

acute cardiac decompensation.
Side effects: ↑heart rate, arrhythmia, thrombocytopenia, hypotension.

cardiac arrhythmias.
Classification
D. mainly blocking ion channels of the cardiomyocytes

(of the cardiac conduction system and contractile myocardium)
A) D. blocking sodium channels (membrane stabilizing D.)
Subgroup 1A: Quinidine, Procainamide
Subgroup 1B: Lidocaine, Phenytoin
Subgroup 1C: Propaphenone

repolarization and duration of action potential; class III): Amiodaron
C)

D. blocking L-type calcium channels (class IV): Verapamil, Diltiazem
D) D. blocking sodium/potassium channels of sinoatrial node (block of If inward current; group V; bradycardic drugs): Ivabradine

heart:
D. that suppress adrenergic effects: β-adrenoblockers – Propranolol, Metoprolol
D. that

intensify adrenergic effects: Dobutamine, Ephedrine
D. suppressing cholinergic effects: M-cholinoblockers (Atropin)
3. Other drugs possessing antiarrhythmic activity:
Cardiac glycosides, Magnesium and potassium agents

↓automatism
Inhibit the conductance of fast Na channels (0 phase) →

↓AV conduction
Inhibit K channels (phase 3)→ ↑ action potential duration (APD),
↑effective refractory period (ERP), ↓ excitability

and AV conduction.
Procainamide has less M block than quinidine

and no alpha block.

Use: paroxysmal supraventricular and ventricular tachycardia, fibrillation and atrial flutter, extrasystoles

neurological effects (ringing in ears, vertigo, deafness, visual disturbances and

mental changes)
Procainamide: nausea and vomiting, weakness, mental confusion and hallucinations, hypotension hypersensitivity reactions (rashes, fever, angioedema), agranulocytosis and aplastic anaemia.

in ectopic foci of Purkinje fibers
L. slightly inhibits fast Na

channels→ decreases APD in PF and ventricular muscle
Drugs slightly affect conduction, increase repolarization (activate K+ channels)
Use: ventricular tachyarrhythmias (extrasystoles)

paresthesias, vision changes, tremor, seizures.
Phenytoin is used orally. Side effects:

nystagmus, ataxia, tremor, gingival hyperplasia, dyspepsia.

is used for the treatment of ventricular arrhythmias orally or

IV.
Side effects: nausea, vomiting, constipation, bronchospasm, weakness, fatigue, arrhythmogenic effect.

↑ APD;
↓ automaticity, excitability and conduction in the SA and

AV, ectopic foci;
blocks of β – and α-AR.
Use: supraventricular and ventricular tachycardia, fibrillation and atrial flutter, extrasystoles.

the skin and the cornea, phototoxicity, thyroid dysfunction.

nodes, ↓spontaneous diastolic depolarization (4-phase) →↓automaticity pacemaker - ↓heart rate;
Lengthens

the 0-phase of action potential - ↓conduction;
Increases ERP, ↓ excitability.
They are used: sinus tachycardia, supraventricular tachyarrhythmia.
Side effects: bradycardia, decreased heart contractility, ↓BP; dizziness, swelling of the ankles, nausea, constipation.