Antianginal drugs Flashcards
What is angina pectoris? (ischemic heart disease)
Stable (atherosclerotic,
classic) – associated with
coronary atherosclerosis
Unstable – progressive, episodes at rest, caused by episodes of increased epicardial coronary artery tone or small platelet clots in the vicinity of the atherosclerotic plaque
Angiospastic – Prinzmetal
angina, variant angina
What are the factors determining the oxygen demands for the myocardium?
Contractility
Heart rate
Left ventricular wall tension
- -Intraventricular pressure (after-load)
- -Ventricular volume (pre-load)
Saturation of blood with oxygen
Coronary blood flow
- Duration of diastole
- Aortic (perfusion) pressure
- Coronary vascular resistance
How are anti-anginal drugs classified?
І. BAB Non-selective – Propranolol, etc. Selective – Metoprolol, Atenolol, etc. Vasodilating – Carvedilol, etc.
ІІ. Calcium channel blockers 1. Dihydropyridines Second generation Felodipine, etc. Third generation Amlodipine, etc. 2. Phenylalkylamines Verapamil 3. Benzothiazepines Diltiazem
ІІІ. Nitrates 1. Glyceryl trinitrate (Nitroglycerin) Rapid and short acting forms – subling. tabl., subling. spray Form with prolonged action – TTS 2. Long-acting nitrates Isosorbidе dinitrate Isosorbide mononitrate Pentaerithrityl tetranitrate
IV. Inhibitors of If current
Ivabradine
V. Metabolic modulators
Trimethazidine
What are the pharmacokinetics of nitrates?
Nitroglycerin
subling. tabl. , subling. spray
TTS
- onset of effect: 1-3 min, duration of effect: 15-30 min/ 24h
Isosorbide dinitrate tabl. (p.o.) prolonged-release tabl. - onset of action: 30 min Duration of effect: 4-6h / 6-10h
What is the hemodynamic mechanism of action of nitrates?
- Dilation of venous blood vessels
decrease of pre-load
decrease О2 demands - Dilation of arterial blood vessels
decreased after-load
decreased О2 demands
Dilation of coronary vessels, better filling of coronaries
during the diastole
↑ О2
supply
What is the molecular mechanism of action of nitrates?
Organic nitrate ↓ Nitrate ion ↓ Н+ NO ↓- SH-thiols Nitrosothiols ↓ Cytosolic GC
GTP ↓ GC cGMP ↓ Dephosphorylation of myosin light cnains ↓ Prevention of the actinmyosin interaction ↓ Relaxation of the vascular smooth muscle
What are the clinical uses of nitrates?
- Angina pectoris
Prevention of attack (Isosorbidе dinitrate,
Isosorbide mononitrate, Pentaerithrityl
tetranitrate)
Treatment of attack (s.l. Nitroglycerin) - Acute myocardial infarction (i.v.
Nitroglycerin)
What are the adverse reactions of nitrates?
І. Caused by the vasodilation
Headache – dilation of meningeal vessels
- pulsating in nature
- not affected by analgesics
- resolves spontaneously
- tolerance develops to it
Dizziness
Flushing (face and upper thorax)
Decrease of BP to postural collapse (elderly!)
Reflex tachycardia and enhanced contractility
Edema of lower limbs
ІІ. Tolerance
What is the tolerance to nitrates?
Decrease of SH-groups
Compensatory reactions due to activation
of the sympathetic nervous system and
RAAS (retention of NaCl and water)
How do calcium channel blockers play a role in antianginal action?
- Decrease of О2 demands of the myocardium
decreased after-load (DHP)
decreased heart rate (non-DHP)
decreased contractility of the myocardium (non-DHP)
Increase of О2
supply for the myocardium
decreased coronary vascular resistance (DHP)
What are the clinical uses of calcium channel blockers?
Angina pectoris
- Prevention of attack
- DHP – drugs of choice for the angiospastic
(variant) angina (Prinzmetal angina)
First-genertation CCB (nifedipine in short-acting
forms) are not used as antianginal drugs because
they cause reflex tachycardia and may induce
ischemic pain
How do BABs play a role in anti-anginal action?
Decrease of heart rate
Decrease of contractility
–decreased О2 demands of the myocardium
Increase of peripheral vascular resistance
(after-load)
↑ О2 demands of the myocardium
The resultant effect
decreased О2 demands
What are the clinical uses of BABs?
As antianginal drugs they are used for the
prevention of attack
They are not used for the angiospastic
(variant) angina (Prinzmetal angina)
They can be combined with calcium
channel blockers (DHP) and nitrates
Their early application after AMI reduces
the risk of re-infarction and sudden death
What are the PK, PD, clinical use, adverse reactions, and contraindications of Ivabradine?
PK: Rapid and almost complete oral absorption; 2 times daily Bioavailability ~40% (first-pass metabolism) Меtabolism: CYP3A4 (interactions with inducers and inhibitors)
PD:
Blockade of the If current
Clinical use: Chronic stable angina In patients with normal sinus rhythm In patients who can not take BABs In combination with BABs in patients whose symptoms are not adequately controlled with a BAB alone and whose heart rate is more than 60 beats per min.
Adverse reactions: The most common (over 10%) – phosphenes (temporary brightness in the visual field)
Contraindications: Heart rate under 60 beats/min Cardiogenic shock AMI, unstable angina Heavy renal failure Heart failure class III-IV Pregnancy and lactation
What is the mechanism of action of Trmethazidine?
Preferential use of glucose (inhibition of
the oxidation of fatty acids in ischemic
conditions)
Correction of ion imbalance in ischemia
- Increases the synthesis of ATP and provides
energy for the К+/ Nа
+ pump
decrease intracellular accumulation of Nа+ → decrease of
intracellular edema
Preserves the intracellular levels of К+
Аntioxidant activity
decreased peroxidation of membrane lipids
decreased cytolysis induced by Н2О2 и ОН-
