B.8

Question 1

Drugs influencing the oxygen demand and oxygen supply of the heart. Drugs improving microcirculation

Answer 1

1. Drugs influencing the oxygen demand and oxygen supply of the heart: Nitroglycerin, Isosorbid-mononitrate, Trimetazidine, Ivabradine, BBLs and CCBs
2. Drugs improving microcirculation: Vinpocetin, Nicergoline, Cilostasol, Pentoxyfylline, Ca-dobesilate, Cinnarizine

Question 2

Nitroglycerin, Isosorbid-mononitrate

Answer 2

MOA: Nitrates are NO donors→ NO activates guanylyl cyclase→ cGMP↑ in SMC→ dephosphorylation of MLC→ SMC relaxation (nitrates ↓preload→ tension in the ventricles↓ and O2 demand of the heart↓→↑coronary perfusion);
IND: Hypertensive crisis (i.v), chronic stable angina (sublingual), angina pectoris (t.d patch→12h on-12h off), CHF;
Kinetics:
-acute angina attack/acute use- i.v adm., for angina prophylaxis/chronic use- sublingual/T.D adm. (→absorbed from oral mucosa→goes to vena cava and ↓preload),
-Isosorbid-mononitrate: usually p.o adm (extended release) ;
Contra-IND: preload dependent patients (e.g. RV-failure, hypovolemia);
SEs: Tachycardia, paradoxical bradycardia (Bezold-Jarish effect→usually leads to syncope, preload drops quickly and ventricles try to compensate by ↑contractility→ mechanical tension causes a vago-vagal effect), syncope, headache, blushing, TOLERANCE, orthostatic hypotension, erection, methemoglobinemia (rare);
Drug-interactions: often used with BBL in synergy, not to use with Sildenafil (PDE-I→will lead to extreme hypotension+syncope+loss of conciousness)

Question 3

Trimetazidine

Answer 3

MOA: inhibition of 3-ketoacyl-CoA-thiolase (→ inhibition of fatty acid oxidation pathway→ the heart will make acetyl-CoA only from glucose and no lactate will be formed), optimizes the O2 consumption of the heart; IND: Adjunctive therapy in chronic stable angina and other ischemic heart diseases;
Kinetics: p.o adm.;
SEs: parkinsonian symptoms (in elderly patients); Contra-IND: parkinson’s disease

Question 4

Ivabradine

Answer 4

MOA: Inhibit If current (→HR↓→diastole ↑→coronary perfusion↑);
IND: Angina, CHF,Ischemic heart diseas with HFrEF and resting HR>70bpm;
SEs: bradycardia, AV-block, SA-block;
Contra-IND: sick sinus syndrome, AV-block, SA-block, bradyarrhythmias;
Kinetics: p.o adm., Hepatic metabolism (CYP3A4)

Question 5

β-blockers and Ca2+ channel blockers

Answer 5

-BBL: ↓the demand and ↑the supply, can cause vasospasm in prinzmetal angina
(IND angina: Bisoprolol, metoprolol, propranolol, carvedilol);
-CCB: Verapamil (given 3-5X/day can lead to hypotension), Nifedipine (retard pill) generally CCBs decrease TPR, Decrease CO

Question 6

Vinpocetin

Answer 6

MOA: Vinca alkaloid derivative.
Inhibits Na+ channel, Ca2+ channel, NMDA-R and AMPA-R (increases cerebral perfusion by improving microcirculation of cerebral tissue → platelet aggregation inhibitor, increases deformability of RBCs); IND: cerebral circulation disturbances, memory loss, vascular and medication-induced hearing loss, tinnitus; SEs: Tachycardia, Hypotension

Question 7

Nicergoline

Answer 7

MOA: Ergot alkaloid.
α-R blocker (vasodilator, platelet aggregation inhibitor, increases cerebral DA metabolism;
IND: Impaired cerebral blood supply, dementia, rehabilitation of ischemic stroke, peripheral circulation disorders, metabolic vascular diseases of the eye and inner ear;
Kinetics: p.o adm, hepatic metabolism, renal excretion; Contra-IND: MI (→coronary steal syndrome), arrhythmia, hemorrhage, lactation, combination with other ergot alkaloid

Question 8

Cilostazol

Answer 8

MOA: PDE3-inhibitor, platelet aggregation inhibitor, arterial vasodilator, ↓TAG level and ↑HDL level;
IND: symptomatic treatment of intermittent claudication, secondary prevention after ischemic stroke, PCI (if other agents cannot be administered); Kinetics: p.o adm., T1/2- 11-13h, ↑plasma protein binding, Hepatic metabolism (CYP3A4), excreted by urine/feces;
SEs: Headache, diarrhea, dizziness, tachycardia, cough, dyspepsia;
Contra-IND: chronic HF, active bleeding ulcer

Question 9

Pentoxifylline

Answer 9

MOA: Methylxanthine derivative. Improves rheological features of blood (→inhibits pathological deformation of RBCs, inhibit platelets aggregarion and decreases viscosity);
IND: Arteriosclerotic, diabetic and inflammatory peripheral circulation disturbances. Impaired circulation (of the eye, ear and brain→ vertigo, tinnitus, trouble concentrating),
Postapoplectic symptoms (severe headache, paralysis of eye muscles, loss of peripheral vision etc);
Kinetics: p.o adm., T1/2- 4-6h, in acute cases i.v injection/infusion, 2-3x/day;
SEs: GI symptoms, Tachycardia, Angina, flushes, allergy

Question 10

Ca2+-dobesilate

Answer 10

MOA: decreases blood vessels permeability, decreases blood viscosity;
IND: diabetic retinopathy, microangiopathies, hemorroids;
SEs: fever, skin reactions, arthralgia, GI disorders;
ROA: P.O adm

Question 11

Cinnarizine

Answer 11

MOA: Ca2+-channel blocker in SMC and other cells (BUT NOT IN THE myocardium and cardiac conduction system), it causes vasodilation, inhibits platelet aggregation, decreases RBCs rigidity (reversible deformation), also strong H-R antagonist;
IND: Peripheral narrowing of vessels, Meniere disease, Trophic disorders, cerebral vasoconstriction, migraine prophylaxis, kinetoses (travel sickness);
ROA: P.O adm.;
SEs: depression, somnolence, insomnia, abdominal pain, weight gain;
Contra-IND: depression, lactation

Question 12

Claudication

Answer 12

pain in the legs/arms that occurs while using the arms or walking. It is usually a symptom of peripheral arterial disease, in which the arteries supplying blood to the area are narrowed.

Question 13

Meniere diease

Answer 13

inner ear problem that can cause dizzy spells, also called vertigo, and hearing loss