Download MINISTRY OF HEALTH OF UZBEKISTAN

MINISTRY OF HEALTH OF UZBEKISTAN
CENTRE FOR MEDICAL EDUCATION
Tashkent Medical Academy
Department of Clinical Pharmacology
Subject CLINICAL PHARMACOLOGY
Topic: "Pharmacological Approaches to rational prescribing of drugs for the treatment of
coronary
FAILURE "
Educational-methodical development
(For a teacher, students)
6. The content of lessons.
6.1. The theoretical part.
- Main objectives and main directions in the treatment of coronary artery disease.
- Modern classification liter. Wed for the treatment of coronary artery disease.
- Select the most effective and safe drug or combination of drugs depending on the form
of angina (stable, depending on the FC, first emerged, unstable, spontaneous)
- Select the most effective and safe drug, depending on the goals of treatment (acute
edema, prolonged therapy)
- Side effects of antianginal liter. Wed, and their correction.
- Select the most efficient and secure l.. Wed in the treatment of myocardial infarction.
- Indications, routes of administration and dosages of drugs commonly used to treat
complications of acute myocardial infarction.
Coronary heart disease (CHD) remains one of the leading causes of death, in addition,
a substantial portion of the population CHD causes left ventricular dysfunction and
arrhythmia, and is a frequent cause of hospitalization
The main goal of treatment of CHD patients:
1. Removal, reduction of symptoms of myocardial ischemia, its main clinical
manifestations - angina.
2. Improving the quality of life.
3. Improved prediction of coronary heart disease patients.
The major directions in the treatment of ischemic heart disease:
1. The main principle of treatment - it's a lifestyle change the patient, his habits and risk
factors.
2. Antithrombotic treatment, ie preventing thrombotic occlusion that is the most serious
and threatening complication.
3. Antiatherosclerotic therapy.
4. Antianginal and anti-ischemic therapy. It accordingly includes non-pharmacological
treatment - different methods of myocardial revascularization and medical treatment of
CHD.
Angina
General Provisions
Patients with angina pectoris due to coronary artery atherosclerosis should be screened
to identify risk factors for coronary heart disease. Where possible, the identified risk
factors should be addressed. Smoking should be prohibited in all its manifestations, as
hypertension and diabetes should be subjected to adequate treatment. We must strive
to achieve the ideal for the patient's body weight. Need to transfer a patient to a diet low
in fat and to determine the concentration of lipid fractions.
In patients with angina pectoris on the basis of coronary artery disease cholesterol
concentration of low density lipoprotein (LDL) cholesterol should be lowered to 100 mg /
dL (2.6 mmol / L) or below. Necessary is the identification and elimination of
precipitating factors (gastro-intestinal bleeding, infection, thyrotoxicosis, hypoxemia,
anemia, etc.).
Participation of patients in rehabilitation or wellness programs often contributes to the
ideal body weight and elimination of risk factors.
Aspirin is the absence of contraindications, patients with angina should receive aspirin
in the shell dissolves in the intestine, a dose of 160-325g.
Nitrates Nitrates are a major group in the treatment of stenokardii.Standartnoy first-line
therapy for angina is nitroglycerin sublingually appointed, which usually relieves
symptoms for about 1-5 minutes. It is recommended to take nitroglycerin at the first sign
of angina, as well as prophylactically before the expected attack. In an emergency can
be used sublingual nitroglycerin in the form of tablets (0.3-0.6 mg) or orally in the form
of a spray, a single dose is 0.4 mg. If the attack fails, nitroglycerin administered
repeatedly every 5 min. Patients should be warned about possible side effects of
nitroglycerin (headache, hypotension), the appropriateness of the drug in the sitting
position. Monotherapy with nitroglycerin sublingually or orally in the form of a spray may
be sufficient if the seizures do not develop more frequently than once a week. If after
taking the third pill seizure persists or increases the intensity of pain, need urgent
medical care.
Drugs used longer-acting nitrates as a prophylactic measure in patients with more
frequent attacks
The most common side effects of nitrates include headache, dizziness, and pressure
drop when standing up. The main drawback of long-term therapy with nitrates is the
development of tolerance.
Preventing the development of tolerance to nitrates:
1. Increasing the dose of the drug.
2. Cancel nitrate
3. Intermittent reception
4. The alternation of admission or substitution of nitrate molsidomin.
5. Appointment of "correctors" These include:
donator of SH-groups: N-acetylcysteine and methionine;
ACE inhibitors, angiotensin receptor blockers II - decrease in vascular superoxide
production, hydralazine - reduce the production of superoxide, diuretics, anti-oxidants:
ascorbic acid and vitamin E (particularly in patients with diabetes mellitus,
atherosclerosis).
Molsidomin and its metabolites have vazodilyatiruyuschim effect. At 2 mg sublingually
molsidomina antianginal effect after 2-10 minutes and lasts 5-7 hours. After taking the
pill inside molsidomina (2 mg) of the peak observed after 1 hour and lasts for 5-7 hours
also. Prolonged molsidomin valid for 12 hours. Molsidomin (korvaton) is assigned to a
dose of 8 mg / day (korvaton forte 4 mg 2 times a day) to 12 mg / day (korvaton forte 4
mg 3 times daily) and 16 mg / day (korvaton retard 8 mg 2 times a day). The drug can
be combined with calcium antagonists and beta-blockers. Of the side effects most
frequently encountered headache (27%), significantly less hypotension, dizziness,
hypertension, impotence.
Beta-blockers. Beta-blockers not only have high anianginalnoy activity, but also provide
a number of other beneficial effects, especially an antiarrhythmic and antihypertensive.
In addition, beta-blockers are effective for secondary prevention of myocardial
infarction, while nitrates do not affect the prognosis of patients with myocardial
infarction. Still popular non-selective beta-blockers (propranolol), but the future of beta1selective drugs (atenolol, metoprolol), especially long-acting (betaxolol) and
vazodilyatiruyuschimi properties (bisoprolol).
Assignment of beta-blockers are usually intended to slow the heart rate to 50-60 per
minute at rest. Cessation of therapy with beta-blockers should be a gradual reduction in
dose as possible for 3-10 days in order to avoid the phenomenon of "rebound" in the
form of the worsening of angina and possible myocardial infarction.
Calcium channel blockers
. Calcium channel blockers should be considered as second-line treatment stenokadii
which is useful for a lack of efficacy or poor tolerance to nitrates and beta-blockers, or if
there are contraindications to their destination. Preference should be given verapamil
and diltiazem, nifedipine sustained release forms (nifedipine GITS and Justice-SL), a
derivative of the second generation dihydropyridines (amlodipine, felodipine, isradipine).
Short-acting nifedipine can be given a form at a dose of no more than 30-40 mg / day
because higher doses they cause unwanted activation of the sympathetic and possibly
combining them with beta-blockers.
During pregnancy: diltiazem, nifedipine is not recommended during pregnancy and
lactation. In the elderly and cirrhotic ubolnyh T ½ increased calcium antagonists that
require dose reduction.
Lipid-lowering drugs.
Diet therapy and the use of lipotropic drugs has traditionally been the main approaches
to the prevention of coronary heart disease. The most powerful action have
gipoholesterolemicheskim statins - simvastatin, pravastatin, atorvastatin, flyuvastatin.
Statins are effective means of primary and secondary prevention in patients with
coronary artery disease. In the metabolic syndrome showed more than fibrates.
Statins are not recommended during pregnancy and lactation and children under 18.
To prevent strokes, depending on the functional class classification of the Canadian
Society of Cardiology to the following recommendations:
When I want to avoid constant FC medication and prescribe nitrates (isosorbide
dinitrate) for 1 hour prior to the proposed exercise. If it is impossible to assign nitrates
can recommend dihydropyridine calcium antagonists or molsidomin.
In the II-III shows the FC monotherapy with nitrates, beta-blockers or calcium
antagonists. Combination therapy is prescribed only after failure of monotherapy, and is
chosen individually in each case. Do not combine drugs rekomendutsya one group with
each other and want to avoid a combination of beta-blocker therapy with verapamil and
nifedipine with nitrates.
To improve effektivnsti antianginal therapy using a combination of the three drugs with
captopril, which allows you to partially overcome the development of tolerance to
nitrates, thereby greatly exponentiating their antianginal action.
When FC IV always use a combination of drugs, carefully selected in each case.
Differentiated therapy angina according to comorbidity
disease
Nitrates
Beta-blockers
Tachycardia
Use with caution
bradycardia
Medication Choices
AV blockade, II-III
century
Atrial fibrillation
advised
in the choice of
drugs
advisable not to
prescribe
not to prescribe
recommend
the most effective
atrial fibrillation
Only in severe
angina
is recommended
Medication Choices
Ventricular
tachycardia
Bronchial
obstruction
pregnancy
Hypertension
The transferred
Myocardia
infarktion
Heart failure
may be
recommended
Caution
Recommended
l Recommended
is only in severe
angina drug
to select the drugs
to use low-dose
cardioselective
drugs
is recommended
Medication Choices
of choicemetoprolol
Calcium channel
blockers
only verapamil and
diltiazem
only
dihydropyridines
only
dihydropyridines
verapamil and
diltiazem
verapamil and
diltiazem
may be cautious of
verapamil
recommended
is not recommended
choice Drugs
Recommended
individual approach
Hyperlipidemia
drugs choice
cardioselective
drugs choice
Unstable angina
Etiologic therapy aimed at combating rapidly developing thrombosis. For this purpose,
all patients except for patients with contraindications or if in the near future will bypass
grafting surgery, aspirin. The initial dose of 180 to 325 mg, followed by 80-180 mg daily
or 325 mg of aspirin daily in the shell dissolves in the intestine.
Heparin intravenously in the appointment has a stronger protective effect in the acute
phase and entered patients at high risk before the start of radical treatment. Heparin / in
(5,000-10,000 IU per / jet followed by continuous infusion of 10 - 15 IU / kg / h,
maintaining APTT at 1.5-2.5 times higher than the original). In no event should not stop
heparin before prescribing aspirin to prevent a possible phenomenon of return.
Thrombolytic therapy is not indicated, except in cases where the pain is accompanied
by ST-segment elevation or left bundle branch block.
Symptomatic treatment includes the appointment of a beta-blocker (reduces the
incidence of fatal and non-fatal myocardial infarction), a drug from the group of nitrates
or calcium antagonist and often - a combination therapy with the inclusion of
representatives of two or sometimes three classes of drugs. Widely used method of
intravenous nitrates. Nitrates / O: the infusion rate was increased to a level at which
ischemia is not renewed. The addiction can develop within 24-36 hours from the start of
administration.
Dihydropyridine derivatives without the use of beta-blocker is not recommended. Shortnifedipine is contraindicated.
The best means of permanent and emergency treatment of Prinzmetal's variant angina
are calcium channel blockers and nitrates.
If the background of drug treatment condition stabilized (no seizures within 48-72
hours), you can cancel the heparin and bed rest.
Painless myocardial ischemia
Patients underwent exercise testing to confirm diagnosis and determine the degree of
risk, and aspirin. Necessary to eliminate precipitating factors, correction of risk factors
for CHD. Mode motion activity is the same as in angina.
Shown in combination with nitrates, calcium antagonists and / or beta-blockers. Of the
three major groups of antianginal drugs may be the most reliable of beta-blockers. The
effectiveness of therapy assessed by exercise testing or Holter ECG monitoring.
The emergence of ischemia (including pain-free) during therapy or after myocardial
infarction - a poor prognostic sign.
MYOCARDIAL INFARCTION
Treatment
The main goals of treating a patient having a heart attack include:
1) symptom relief, preservation of the viability of possible large area of myocardium;
2) prevention and treatment of complications.
The fight against pain
Symptomatic therapy aimed at combating pain, it is important not only to improve the
subjective condition of the patient, but also as a means to suppress the activity of the
autonomic nervous system and reduce myocardial oxygen demand.
A. Admission of 0.4 mg of nitroglycerin under the tongue three times at intervals of 5
minutes if necessary. Hypotension, which can occur with hypovolemia or myocardial
infarction, lower, extending to the right ventricle, can be corrected by lifting his legs and
the patient is introduced into / in saline. If sublingual nitroglycerin is ineffective and pain
persists shows the introduction of morphine.
B. Morphine - tool of choice for pain management after myocardial infarction. This
provides sufficiently high degree of pain relief with minimal suppression of cardiac
activity. However, morphine can cause respiratory depression and hypotension due to
peripheral vasodilation, therefore, it is best to appoint a small multiple doses - 2-4 mg
intravenously every 15-30 min with careful monitoring of blood pressure and respiratory
rate. To correct for side effects using anti-emetics, vagotonic effects to eliminate /
maintenance of atropine (0.3-0.5 mg), hypotension prevented by the infusion fluid, a
split w / naloxone 0.4-2 mg eliminates the effects of morphine.
Restoration of coronary blood flow.
1. Thrombolysis is highly effective, but its capabilities are limited, the probability of
recovery of perfusion does not exceed 80% of early postinfarction angina frequency
compared with placebo increases, the possibility of severe bleeding, the indication for
thrombolysis is limited.
Thrombolytic therapy is most successful in the first 90 min after the onset of clinical
signs of heart attack, but continues to yield significant benefits for 6 hours, and possibly
some benefit - up to 12 hours
The main contraindication to thrombolytic therapy is a recent cerebrovascular accident
(NMC). Hemorrhagic SMC - absolute contraindication; negemorragicheskoe DCC
serves as a contraindication for 6 months. A recent (2-4 weeks), a large surgical
intervention, active internal bleeding, recent head trauma or intracranial neoplasm also
are contraindications. If in the past 10 days was carried puncture incompressible vessel,
performing thrombolysis is not recommended. Therapeutic control of systemic arterial
hypertension should be made prior to the use of thrombolytic therapy. In the therapy of
patients treated with streptokinase in the past, it is necessary to use recombinant tPA.
Currently approved for use three thrombolytic drug: alteplase (recombinant tPA),
streptokinase (SK) and antistreplaza (APSAC). In the early application of each of them
marked narrowing of the infarct, the preservation of ventricular function and improved
survival rates.
Streptokinase administered in a dose of 1.5 million units intravenously over 1 hour
APSAC can be administered in a dose of 30 IU intravenously over 5-10 minutes.
Approved dosage rekombinantnoo TAP - 100 mg, with the introduction of a 10 mg
bolus, then 50 mg over the next hour and 20 mg in the remaining 2 hours. Also
rekamendovana Fast Track: 15 mg bolus, then an intravenous drip of 50 mg or 0.75 mg
/ kg of body weight during the subsequent 1 h. The maximum dose was 100 mg.
2. Other ways to reduce the size of myocardial infarction
Beta-blockers. All patients after myocardial infarction, including receiving thrombolytic
therapy should receive therapy with beta-blockers
Treatment with beta-blockers can be started immediately on admission or a patient at 57 days after myocardial infarction.
Emergency Treatment: Metoprolol 5 mg / 3 times at intervals of 2 minutes, 15 minutes
to begin intake of 50 mg 2 times a day the first two days, then if tolerated to 100 mg 2
times a day Atenolol 5.10 mg / in, followed by 100 mg once, other beta-blockers without
sympathomimetic activity in its own / v.Beta-blockers are indicated for myocardial
infarction in all patients without hypotension, bradycardia, severe heart failure and
anamnestic indications of bronchospasm. The use of beta blockers in the acute phase
reduces infarct size and reduces mortality by 13%, significantly reduces the incidence of
ventricular fibrillation and left ventricular rupture and recurrent myocardial infarction and
intracranial hemorrhage after thrombolysis.
Calcium antagonists. In general, in acute myocardial infarction is better to use betablockers than calcium channel blockers. In unstable angina after myocardial infarction,
calcium antagonists have a positive effect when used in combination with beta-blockers.
When transmural myocardial infarction, heart attack without the formation of a
pathological Q wave or unstable angina with left ventricular ejection fraction less than
40% calcium channel blockers should not be appointed. Myocardial infarction without
pathological Q waves and an ejection fraction of 40% or unstable angina can be
assigned to diltiazem or verapamil.
Diltiazem - 90 mg 4 times daily or verapamil 120 mg 3 times a day during the first begin
treatment 2-5 days and is carried out for 1 year. Those not prescribed calcium channel
blockers, which slow the heart rate did not (nifedipine, nicardipine).
Diltiazem is effective in preventing early re-infarction without pathological tooth Q, but
increased mortality in patients with heart failure or severe violation of the contractility of
the left ventricle.
Verapamil significantly reduces the incidence of recurrent myocardial infarction,
mortality reduction is uncertain.
Nifedipine is contraindicated in myocardial infarction (increased frequency of recurrent
myocardial infarction, and mortality). Except in cases where it is used together with
beta-blocker.
Nitrates. Nitroglycerin is administered as an i / v infusion of 10-20 micrograms / min with
an increase by 5-10 mcg / min every 5 min to reduce blood pressure by 10% (of
hypertension by 30%). Nitroglycerin / can reduce the size of lesions and mortality in
anterior myocardial infarction if treatment is started within the first 4 hours. The drug is
not assigned to I / O with hypotension and right ventricular infarction. The addiction may
develop after days of continuous infusion.
Antiplatelet agents and anticoagulants.
Acute period.
1. Heparin n / a 5000 - 12 500 units every 12 hours, heparin / jet 100 U / kg followed by
infusion at 1000 - 1300 units / hour (keep aPTT at 2 - 2.5 times higher than the original).
Indication: Heparin / in - with the introduction of alteplase, the front myocardial
infarction, low cardiac output, atrial fibrillation and thrombosis of the left ventricle.
Heparin in low doses n / a - in all other cases at the time of bed rest.
Contraindications: active bleeding.
2. Aspirin 160-325 mg orally at admission (chew), then 1 per day. Shown in all cases of
myocardial infarction, begin treatment immediately, hold indefinitely.
Contraindications: active bleeding.
Emergency treatment increases the frequency of recovery of perfusion and reduces the
frequency of re-occlusion after thrombolysis reduces the incidence of recurrent
myocardial infarction, stroke, and mortality.
ACE inhibitors.
In patients with signs of left ventricular dysfunction (heart failure symptoms or
decreased ejection fraction at EhoKS), appears at any time after the development of
acute myocardial infarction, you should immediately appoint a long-term (lifetime)
treatment with ACE inhibitors in the absence of absolute contraindications.
Treatment with ACE inhibitors can begin on the first day of acute myocardial infarction
after clinical assessment of hemodynamics (systolic BP less than 100 mm Hg is a
contraindication to therapy) and other general-purpose funds received (thrombolytics,
aspirin, beta-blockers). There are no criteria for selecting patients for treatment with
ACE inhibitors in the early phase of infarction are not available. Treatment with ACE
inhibitors should not be used without considering the high mortality in the acute phase
of illness. The abolition of the ACE inhibitors, designated in the acute phase of
myocardial infarction, can be discussed in the absence of left ventricular dysfunction
after 4-6 weeks. Re left ventricular function should be examined 4-6 months after
myocardial infarction.
CONTINUING CARE MEDIKAMENTONAYA
Nitrates
There is no evidence whether long-term use of nitrates after uncomplicated myocardial
infarction. If angina recurs, these drugs can be used for urgent relief of symptoms.
Aspirin
Aspirin as an antiplatelet agent reduces the incidence of myocardial infarction in
patients with coronary artery disease. In the absence of absolute contraindications (eg,
exacerbation of peptic ulcer disease or allergies), all patients after myocardial infarction
should receive aspirin therapy. For patients with intolerance to aspirin tablets (325 mg),
dissolved in the medium of the intestine, are made soluble in the intestines of tablets, 80
mg and 160 mg.
Beta-blockers
Long-term studies show that beta-blockers without sympathomimetic activity reduces
mortality after myocardial infarction, and reduces the incidence of reinfarction.
Differences between cardioselective and nonselective agents does not.
Calcium channel blockers
In patients with intolerance to beta-blockers due to the presence of asthma, chronic lung
disease or diabetes and those who have no signs of pulmonary congestion or impaired
left ventricular function, receiving diltiazem may reduce the risk of immediate cardiac
EVELOPMENT states after myocardial infarction. Diltiazem may also be effective in
penetrating a myocardial infarction in patients without manifestations of left ventricular
dysfunction.
Anticoagulation
Warfarin is indicated for thrombosis of the left ventricle or a constant risk of
thromboembolic complications (atrial fibrillation, low cardiac output, prolonged
immobility).
Contraindications: active bleeding.
Long-term anticoagulant therapy (non-aspirin) reduces the incidence of recurrent
myocardial infarction and mortality. However, compared warfarin with aspirin alone did
not reduce the frequency of re-occlusion and mortality, but increases the risk of
bleeding complications.
Continuous therapy with digoxin digoxin (0,125-0,5 mg daily) is effective in patients with
ventricular gallop rhythm (with an abnormal tone III), the presence of stagnant wheezing
in the lungs, left ventricular ejection fraction less than 35%, or atrial fibrillation after
myocardial infarction.
Diuretics
Thiazide diuretics, loop and are able to counteract the excess sodium and water
retention characteristic of ventricular dysfunction. Necessary to carry out prevention of
hypokalemia, since it can provoke the development of arrhythmias in these patients.
ACE inhibitors
Appointment of captopril (Capoten - from 6.25 to 50 mg 3 times daily) reduces the size
of the chamber of the left ventricle after anterior myocardial infarction. Patients,
survivors of acute myocardial infarction with left ventricular ejection fraction (LVEF) 40%
or less should begin therapy with ACE inhibitors before hospital discharge. It must be
continuous (if tolerated) with the expectation of increased life expectancy. Side effects
of ACE inhibitors include persistent coughing, and renal failure, hyperkalemia, and
hypotension.
Antiarrhythmics
Long-term therapy antiaritmikam shown in cases of sustained ventricular tachycardia
occurring later than 48 hours of myocardial infarction. Amiodarone can be useful in
cases where beta-blockers are contraindicated, as in complex ectopic arrhythmias,
amiodarone is able to reduce mortality among patients with myocardial infarction.