PRACTICAL APPLICATIONS OF THE ANTIANGINAL DRUGS

I. THEORETICAL PART
Antianginal drugs reestablish the balance between the oxygen demand and supply in
the ischemic myocardium, with decreasing the frequency of angina crisis. They act through:
 Decreasing the cardiac activity (lower intotropism, chronotropism)
 Decreasing the peripheral resistance (vasodilation)
 The association of both
Antianginal substances increase the oxygen supply and decrease the myocardial
oxygen consumption, modifying the factors that have an influence upon this consumption:
 The stress in the myocardial wall (dependent to the intraventricular pressure,
ventricular radius, wall thickness)
 Heart rate
 Contractility

CLASSIFICATION
Organic nitrates
• GLYCERYL TRINITRATE (GTN) – NITROGLYCERINE
• ISOSORBIDE DINITRATE (ISDN)
• ISOSORBIDE 5 MONONITRATE (ISMN)
• PENTAERYTHRITYL TETRANITRATE
Other antianginal drugs
• MOLSIDOMIN
• BETA BLOCKERS
• CALCIUM CHANNEL BLOCKERS
• IVABRADIN (inhibitor of the SN)
• RANOLAZINE (inhibitor of the sodium influx)

GENERAL PRINCIPLES OF ADMINISTRATION

1. Nitrates are indicated in coronary diseases (ischemic cardiopathy, AMI) and in heart
failure (only in association with other drugs).
2. In angina pectoris crisis, short acting, sublingual nitrates are administered:
Nitroglycerine 1 tablet or 1 puff. The dose may be repeated after a few minutes. If
there is no relief after the third administration, the patient should see a doctor,
suspecting an AMI.
3. The patient should always have Nitroglycerin available, which can be used also in
prophylaxis, if the patient knows the determing circumstances of an angina crisis
(physical effort, stress).
4. Nitroglycerine for sublingual use expires quickly, after 6 months (do not prescribe
several packages).
5. Nitrates with a long duration of action (oral or transdermic) are prescribed for the
prophylaxis of angina crisis together with beta blockers or calcium channel blockers,
in the daily treatment of ischemic cardiopathy.
6. The transdermic patch with Nitroglycerine should be applied on healthy, dry, hairless
and clean skin. For a better adhesion to the skin, it should be kept pressed with the
palm for several seconds. A patch that has been used, should be never reapplied.
Nitroderm TTS 5 (5 mg/24 hours) releases a dose of 0.2 mg/hour for a contact surface
of 10 cm2.
7. Nitrates can be responsible of hypotension (especially after the first dose or in case of
increasing the dose) and reflex tachycardia, with dizziness and fatigue. Another
 adverse effect of nitrates is the tolerance, which appears after a prolonged treatment.
For the prevention, nitrates should be discontinued during the therapy and replaced by
another antianginal drug.
8. Molsidomin is a vasodilator with an antiplatelet effect. It is used as an alternative in
patients with severe headache after nitrates, 2 tab./day.
9. In patients with ischemic cardiopathy, the antianginal treatment should be associated
with an antiplatelet agent (Aspirin 75-100 mg/day, Ticlopidin 2 tab/day) and
sometimes with an antilipemic drug.
10. The administration of Ivabradine or Ranolazine require EKG monitoring.

THE TREATMENT IN AMI

1. Oxygen 4-8 l/min

2. Antianginal treatment
• GTN
• 1 tab/puff sublingual every 5 min, max. 3x
• IV infusion 1-3 mg/h (in left heart failure up to 6 mg/h)
• Beta blockers, in case of GTN failure or tachycardia, but without left heart
failure
• Calcium channel blockers (not dihydropyridines), in case of GTN and beta
blockers failure
3. Antiplatelet agents
• Aspirin
• 150-300 mg p.o. (250 mg IV), continue with 75-100 mg/day, plus
• ADP antagonist (asap, plus 12 months)
• 60 mg Prasugrel or 180 mg Ticagrelor
• 600 mg Clopidogrel in absence of Prasugrel or Ticagrelor
4. Anticoagulants
• In NSTEMI: Fondaparinux or Enoxaparin or UFH
• In STEMI:
• First choice: PCI, plus Enoxaparin or UFH
• Second choice: Streptokynase 1.5 mil. IU in 30-60 min or Alteplase
(expensive) 15 mg bolus IV => 0.75 mg/kg in 30 min => 0.5 mg/kg in
60 min.
5. Analgesics
• 3-5 mg IV Morphin, possibly repeat in min.

Preparations

Generic drug Brand name Route of Pharmaceutical

administration dosage form
Glyceryl trinitrate Nitroglicerina sublingual Tab. 0,5 mg
 
Nitromint sublingual Spray 0,4 mg/puff
Nitroderm(R) transdermic Patch 5mg/24h
TTS 5
Trinitrosan IV Conc. for infusion
5mg/ml
Nitroglicerina apply on skin Ointment 2%,
precordial
 Isosorbide dinitrate Isodinit p.o. Tab. 10 mg
Isosorbide mononitrate Olicard p.o. Tab. 40 mg, 60 mg
   
Pentaerythrityl Pentalong p.o. Tab. 20 mg, 50 mg
tetranitrate
Molsidomin Corvasal p.o. Tab. 2 mg
IV Vials 2 mg/l ml
Ivabradin Bixebra p.o. Tab. 5 mg, 7,5 mg
 
Ranolazine Ranexa p.o. Tab. 375 mg, 500 mg,
750 mg

PRACTICAL APPLICATIONS OF THE ANTIARRHYTHMIC DRUGS

Antiarrhythmics are drugs which depress the myocardial automatism, conductance and
excitability, administered in the prophylaxis and treatment of cardiac arrhythmias.

CLASSIFICATION
I. Sodium channel blockers
 I.A prolong repolarization: QUINIDINE, PROCAINAMIDE, DISOPYRAMIDE
 I.B shorten repolarization: LIDOCAINE, TOCAINIDE, MEXILETINE,
PHENYTOIN
 I.C little effect on repolarization: FLECAINIDE, PROPAFENONE, MORICIZINE
II. Beta blockers: PROPRANOLOL, ESMOLOL, METOPROLOL, ATENOLOL
III. Potassium channel blockers : AMIODARONE, SOTALOL, BRETYLIUM
IV. Calcium channel blockers: VERAPAMIL, DILTIAZEM
V. Antiarrhythmics that work by other or unknown mechanism: ADENOSINE, DIGOXIN

GENERAL PRINCIPLES OF ADMINISTRATION

1. The antiarrhtythmic should be prescribed only after the arrhythmia was proven on the
EKG/Holter and the risk is superior compared to the side effects of the drug. All
antiarrhythmics have the paradoxal proarrhythmic effect.
2. Before starting the treatment, the patient’s heart function should be evaluated, the
favouring factors for arrhythmias treated (hypokalemia, hypomagnesemia) and
arrhythmogenic drugs administration should be stopped (sympathomimetics, Miofilin,
tricyclic antidepressants).
3. The dose should be individualised, according to the EKG and the response to the
treatment.
4. Most of the antiarrhythmics have a negative inotropic effect and should not be given
in heart failure. Exceptions: Amiodarone, Lidocaine, beta blockers.
5. The pharmacological conversion to sinus rhythm in recurrent atrial fibrillation can be
made outside the hospital by administering a single dose of Propafenone or Flecainide
(„pill-in-the-pocket”).
6. In atrial fibrillation, besides the antiarrhythmic, an anticoagulant treatment should be
administered to prevent a stroke or AMI.

THE EMERGENCY TREATMENT IN ATRIAL FIBRILLATION

• WITH HEART FAILURE

 • Amiodarone IV 150-300 mg. If no response:
• Digoxin IV 0.25 mg every 2 hours until reaching the dose of 1.5 mg
• WITHOUT HEART FAILURE
• Beta blocker IV: Esmolol 0.5 mg/kg in one min. => 0.05-0.2 mg/kg/min or
Metoprolol 2.5-5 mg in 2 min. or Propranolol 0.15 mg/kg or
• Verapamil IV 0.075-0.15 mg/kg in 2 min or Diltiazem IV 0.25 mg/kg in 2 min
=> 5-15 mg/h

THE EMERGENCY TREATMENT IN VENTRICULAR TACHYCARDIA

• IN HEMODYNAMICALLY STABLE PATIENT

• First line: Amiodarone
• Second line: Lidocaine IV 1-2 mg/kg or infusion 2-4 mg/min
• Potassium and magnesium
• IN HEMODYNAMICALLY UNSTABLE PATIENT
• Short IV anesthesia and cardioversion
• In cardiorespiratory arrest: cardiopulmonary resuscitation

II. PRACTICAL PART

1. Write a medical prescription to a patient with ischemic cardiopathy. Effort induced
angina pectoris.