CLINICAL PHARMACY IN CARDIOLOGY

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• CLINICAL PHARMACY IN CARDIOLOGY

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FREQUENCY of arterial hypertension (AH)AP gt
140/90 mm Hg

• 20-30 in population
• At elderly people - 45-50

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Principles of treatment of arterial hypertension
1. Treatment should be started as soon as
possible and should be hold till the end of life.
Canceling antihypertensive drugs administration
causes relapse of AH. 2. All the individuals with
increased arterial pressure should obtain
drugless treatment (modifying lifestyle)
-rejection from smoking and alcohol -in
creasing of physical activity -restriction
of salt consumption (less than 6 g per
day) -decreasing of body weight in a case
of obesity. 3. Scheme of drug treatment should
be the most availably simple 1 tablet per day
if possible it is better to use drugs with long
duration of action (prophylaxis of considerable
fluctuation of blood pressure during the day). 4.
Rapid decreasing of blood pressure to low figures
is dangerous, especially for elderly patients. 5.
Main aim of the treatment is to decrease blood
pressure to 140/90 mm Hg. To improve life
prognosis is the aim that has a more significant
meaning than character of drugs used to reach
this aim. It is better to prescribe cheap and
non modern drugs than dont treat the patient
at all.
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Treatment of arterial hypertension Drugs of
first row -diuretics (furosemid, dichlothiazide,
spironolacton) -inhibitors of ACE
(captopril, enalapril, ramipril) -antagonists of
angiotesine II receptors (?R? ??)
(losartan) -ß-adrenoblockers (anaprilin,
atenolol, thymolol) -a-adrenoblockers
(prasosine, terasosine) -a-, ß-adrenoblockers
(labetolol, carvedilol) -Ca ions antagonists
(niphedipine, amlodipine, verapamil) Drugs of
second row -agonists of a2 adrenoreceptors of
central action (clopheline, methyldopa) -sympathol
ytics (reserpin, octadin) -direct vasodilators
(molsidomin, hydralasin) New drugs -imidasolines
(moxonidine, rilmenidine) -serotonin receptors
blockers (ketanserin) -monateril (calcium
antagonist, a2 -adrenoblocker)
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Mechanism of action of thiaside diuretics in case
of arterial hypertension
Dychlothiaside (hypothiaside)
Oxodolin (chlortalidon, hygroton)
Thiaside diuretics
Holding sodium and water
Volume of circulating blood
Peripheral vascular resistance
Cardiac output
Decreasing of arterial pressure
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FUROSEMIDE

• High ceiling (loop) diuretic
• Properties
• 1. diuretic action
• 2. dilation of peripheral venous
• 3. decrease left ventricular filling pressure
• 4. potent anti-inflammatory effect (similar to
  indometacine and other NSAID)
• Administration hypertensive emergencies,
  long-term treatment of arterial hypertension
• Adverse reactions dehydration, hypokalemia,
  hearing loss - deafness, hypocalcaemia

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THIAZIDES and RELATED DIURETICS

• Medium efficacy diuretics
• Benzothiadiazines (chlorothiazide,
  hydrochlorothiazide, clopamide), related thiazide
  like (chlorthalidone, indapamide)
• for long-term treatment of arterial hypertesion
  (oral administration)
• Duration of action (6-12 hours for
  hydrochlorothiazide, 12-18 hours for clopamide,
  48-50 hours for chlorthalidone)
• Adverse reactions dehydration, hypokalemia,
  hyperuricaemia (rise of blood urate level)

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Furosemid (diuretic)
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Furosemid (diuretic)
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TORASEMID
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Mechanism of action of beta-adrenoblockers (anapri
lin, atenolol, methoprolol etc.) in case of
arterial hypertension
ß- adrenoblockers
activation of
ß1-adrenoreceptors of
heart
Cardiac output
Decreasing of blood pressure
Peripheral resist- ance of vessels
Angiotensine ??
Renin
Aldosterone
Holding sodium and water
Volume of
blood circulation
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ß-adrenoblockers

• Used for mostly mild to moderate cases of AH
  (frequently in combinations with other drugs)
• Stable hypotensive response develops over
  1-3 weeks
• Titration the effective dose
• Antihypertensive action is maintained over
  24 hr after single daily dose
• Withdrawal syndrome if discontinue quickly
• Contraindications bronchial asthma, peripheral
  vascular disease, diabetes

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Atenolol ß - adrenoblocker
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Anaprilin ß1- ß 2 adrenoblocker
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Vasocardin 100 mgMethoprolol tartrate
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Nadolol( ß1, ß 2 - adrenoblocker )
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Tenoretic(atenolol chlortalidon)
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a1-adrenergic blockers(prazosin, terazosin,
doxazosin)

• Do not block presynaptic a2-adreno-receptors, so
  do not cause reflex cardiac stimulation (as
  compared to nonselective a-adrenoblockers)
• Dilate resistance and capacitance vessels
• Adverse effects postural hypotension (effect of
  first dose), tolerance gradually develops with
  monotherapy

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Prasosine (a1 adrenoblocker)
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a, ß adrenoreceptors blockers(labetalol,
carvedilol)

• Labetalol is used for long-term treatment of AH
  and for emergencies (i. v. - hypertensive
  crisis, clonidine withdrawal, cheese reaction)
• Carvedilol produces vasodilatation,
  antioxidant/free radical scavenging properties,
  it is used for HD and for CHF

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MECHANISM OF ACTION OF IACE
ANGIOTENSINOGEN
sympathetic tone
Renin (kidneys)
ANGIOTENSIN (inactive)
Decrease of arterial pressure
peripheral vessels tone
Decrease angiotensine II production
retention of Na and H2O
ACE
Decrease aldosterone production
-
bradicinine
IACE
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IACE (ANGIOTENSIN CONVERTING ENZYME INHIBITORS)

• Captopril, enalapril, ramipril, perindopril etc.
• Decrease the levels of mortality and morbidity
• When used for monotherapy control AP in 50 of
  patients
• Frequently combined with diuretics (not with
  potassium-sparing diuretics !) and
  ß-adrenoblockers - the effectiveness of therapy
  grows to 90
• Adverse effects cause the retention of potassium
  ions, dry persistent cough (requires
  discontinuation of IACE or treatment with NSAID)
• Contraindicated for the patients with bilateral
  renal artery stenosis)

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PERINDOPRIL (IACE)
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KOZAAR (Losartan) ?R? ??
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CALCIUM CHANNEL BLOCKERS (dihydropyridines
DHPs)

• Short acting DHPs (nifedipine) can increase
  mortality as a result of reinfarction (long term
  controlled trials)
• Retard forms of DHPs (Amlodipine) are used widely
  for AH
• Do not contraindicated in asthma, do not impair
  renal perfusion, do not affect male sexual
  function
• Can be used during pregnancy
• Can be given to diabetics
• Adverse reactions ankle edema, slight negative
  inotropic / dromotropic action, nifedipine
  decreases insulin release (diabetes accentuating)
  

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NIFEDIPINE(calcium channels blocker)
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NIFEDIPINE(calcium channels blocker)
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NIFEDIPINE(calcium channels blocker)
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NIFEDIPINE(calcium channels blocker)
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NORVASC (AMLODIPINE) (calcium channels blocker)
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Calcium channels blockers administration
diseases
DRUGS
Arterial hypertension
Verapamil
Dilthiasem
Niphedipin
Felodipin
Amlodipin
Ischemic heart disease
Dilthiasem
Niphedipin
Amlodipin
Verapamil
Supraventricule tachicardia
Verapamil
Dilthiasem
Possibility to combine with beta-blockers
Dilthiasem ?????????
Niphedipin
Amlodipin
Felodipin
recommended drug
to use carefully


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CLOPHELINE

• a2 - adrenergic receptors agonist (in brainstem
  stimulates a2 - adrenergic receptors and
  imidazoline receptors)
• decreases vasomotor centers tone - reduces
  sympathetic tone - fall in AP
• Increases vagal tone - bradycardia
• Has analgesic activity
• For hypertensive emergencies (i. v. dropply or
  very slowly)
• Side effects and complications postural
  hypotension, sedation, mental depression, sleep
  disturbance, dry mouth, constipation, withdrawal
  syndrome

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CLOPHELINE(decreases vasomotor centers tone)
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SINEPRESS(dihydroergotoxine reserpine
hydrochlorthiaside)
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TRIRESIDE(reserpine hydralasine
hydrochlorothiaside)
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CRISTEPIN(clopamide dihydroergocristine
reserpine)
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MANAGEMENT OF HYPERTENSIVE EMERGENCY
(intravenously)
Drug Dose Onset Side effects
Sodium nitroprussid 0,5-10 mcg/kg/min (dropply) immediately nausea, vomiting, fibrillation of muscles, sweating
Nitroglyceri-num 5-10 mcg/kg (dropply) 2-5 min tachicardia, flushing, headache, vomiting,
Diazoxidum 50-100 mg (quickly) 300 mg (during 10 min) 2-4 min nausea, vomiting,, hypotension, tachicardia, flushing, redness of skin, chest pain
Apressinum 10-20 mg 10 min flushing, redness of skin, headache, vomiting
Furosemidum 20-60-100 mg during 10-15 sec 2-3 min hypotension, fatigue
Clophelinum 0,5-1 ml 0,01 solution (in 15-20 ml 0,9 solution NaCI slowly) 15-20 min somnolence
Anaprilinum 5 ml 0,1 solution (in 20 ml 0,9 NaCI solution slowly) 20-30 min bradicardia
Magnesium sulfas 5-10-20 ml 25 solution (i. v. very slowly or dropply) 15-20 min redness of skin
Labetololum 20-80 mg (slowly 10 min) or 2 mg/kg (dropply) the whole dose 50-300 mg 5-10 min nausea, vomiting,, hypotension, dizzeness
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Factors which promote development ofINTOXICATION
WITH HEART GLYCOZIDES

• DECREASING OF TOLERANCE TOWARDS HG in case of
  considerable damage of myocardium with
  pathological process
• (acute MI, myocarditis, chronic lung heart)
• Patients which need HG the most are the most
  sensitive of diuretics (furosemis,
  dychlothiazide), GCS, glucose with to them
• HYPOPOTASSIUMEMIA, HYPOPOTASSIUMHISTIA OF
  MYOCARDIUM, HYPOMAGNESIUMEMIA
• - administration insuline, amphotericine B
• secondary hyperaldosteronism, vomiting, diarrhea
• HYPERCALCIUMEMIA, KIDNEY, LIVER INSUFFICIENCY

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Factors which promote developmentINTOXICATION
WITH HEART GLYCOZIDES

• Digitoxin is a choice drug when HI is combined
  with kidney insufficiency, but contraindicated
  if liver is damaged (it is metabolized by liver)
• Digoxin is not contraindicated even in case of
  liver cirrhosis (it is not metabolized in liver),
  but contraindicated in case of kidney
  insufficiency (it is excreted by kidneys)

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(No Transcript)
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Intoxication with heart glycosides
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Treatment of intoxication with heart glycosides

• Immediate quitting of HG introduction
• Correction of hypopotassiumemia (KCl, panangin)
• Introduction of unitiol (1 ml of 5 solution /
  kg of weight i.m. 2-3-5 times per day)
• Clearing of GI tract (vaseline oil,
  cholestyramin, magnesium sulfate)
• Treatment of arrhythmias (anaprilin, verapamil,
  difenin, lidokain, atropine)
• Na ?DTA (trilon B), Na citrate
• Calcitrin
• Antibodies towards digoxin (Digibind)
• Oxygen therapy

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NONGLYCOSIDE CARDITONIC DRUGS

• Xantins, derivatives of isoquinoline
  (ethophiline)
• Pyridines, and bipyridines (amrinon, milrinon)
• Derivatives of imidazole (vardax)
• Derivatives of piperidine (buquineran,
  carbazeran)
• Polypeptides (glucagon)
• Carboxyl antibiotics (lasolacid, calcimycin)
• Derivatives of other chemical groups
  L-carnitin, heptaminol, creatinol-o-phosphate,
  trapidil, etc.

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NONGLYCOSIDE CARDIOTONIC DRUGS

• Dobutamin beta1-adrenomimetic - in case of
  acute and chronic heart insufficiency
  intravenously dropping 2,5-5-10 mcg/(kg.min)
  in case of constant infusion tolerance develops
  after 3-4 days in case of increasing of dose
  heart arrhythmias
• Amrinon, milrinon inhibitors of
  phosphodiesterase for temporary improvement of
  patients condition in terminal stage of HI

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INHIBITORS OF ANGIOTENSINE TRASFORMING ENZYME
(IATE)

• Captopril, enalapril, ramipril, lysinorpil
• In case of HI they brake pathological
  consequences of activation of renin-angiotesine
  system by inhibiting ATE
• production of angiotensine II decreases
  (vasoconstrictor, inductor of aldosterone,
  norepinephrine, endothelin secretion, myocardium
  hypertrophy)
• Accumulation of bradikin (inductor of
  prostacycline and nitrogen oxide synthesis)

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INHIBITORS OF ANGIOTESINE TRANSFORMING ENZYME
(IATE)

• Increase duration and improve quality of life of
  patients with HI
• Increase tolerance towards physical loads
• Decrease risk of recurring MI
• Brake development of miocardium hypertrophy

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CAPTOPRIL (CAPOTEN)

• Dose titration from 6,25-12,5 mg per day to
  12,5-50 mg 3 times a day until appearance of
  effect
• Side effects dry cough (can be decreased by
  nonsteroid antiinflammatory), considerable
  decreasing of AP, worsening of kidneys
  function, hyperpotassiumemia, tachycardia,
  neutropenia, aphtose stomatitis
• Contraindicated in case of bilateral stenosis of
  kidney arteries, should not be combined with
  potassium drugs

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ANTAGONISTS OF ANGIOTESINE II RECEPTOS
(?R? II)

• LOSARTAN (cosaar)
• Blocks receptors of angiotensine II
• Decreases mortality of patients with HI
• on 50
• Breaks development of myocardium hypertrophy
• It is approved to combine IATE with ?R? II

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DIURETICS

• Dichlotiazide, hyhrotone (oxodoline), clopamide
  (brinaldix)
• Furosemid, etacrine acid
• Spironolacton
• improve currency of the disease, increase
  tolerance of patients towards physical loads,
• spironolacton decreases quantity of relapses
  and mortality

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PERIPHERAL VASODILATORS

• Arterial hydralasin, calcium ions antagonists,
  minoxydil
• Venous nitrates, molsidomin
• Of mixed action (influence on tone of arterioles
  and venules) sodium nitropruside, prasosine,
  inhibitors of ATE, ARA II
• Isosorbide dinitrate (30-160 mg/day)
• hydralasin (50-300 mg/day) for patients
  which have contraindications towards
  administration of IATE

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PERIPHERAL VASODILATORS

• Unfavorable action in case of HI
• They activate sympatic-adrenalsystem and
  intermediately renin-aldosterone system

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BETA-ADRENOBLOCKERS

• Carvedilol, methoprolol, bisoprolol
• They decrease mortality, improve disease
  currency and quality of patients lives in case
  of stagnant HI
• Mechanism of treatment action in case of HI
• Renewing of quantity and sensitivity of
  beta-adrenoreceptors in heart, which leads to
  increasing of systolic volume after 8-10 weeks of
  regular administration (paradox of
  beta-adrenoblockade)
• Prevent calcium overload of myocardium, improve
  coronary blood circulation
• Decrease production of renin
• Prevent arrhythmias
• Carvedilol alpha1-adrenoblocking and
  antioxidant action

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BETA-ADRENOBLOCKERS

• Scheme of administration of beta-adrenoblockers
  in case of HI
• The treatment is started from a small dose
• (3,175-6,25 carvedilol), every 2-4 weeks it
  is doubled until obtaining the effect (usually
  develops after 2-3 months).
• Average effective doses
• carvedilol 50 mg
• metoprolol 100 mg
• bisoprolol 5 mg
• Administration of beta-blockers is possible
  only in case of constant condition of the
  patient, before development of stabile
  improvement of condition temporary worsening may
  develop

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DRUGS OF METABOLIC ACTION

• Vitamins ?, ?, ? group
• Ryboxin
• Mildronate
• Phosphaden, ATP
• Creatinphosphate
• Potassium orotate, anabolic steroids
• Drugs manifest cardiocytoprotective action,
  improve energetic metabolism in myocardium

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PECULIARITIES OF TREATMENT OF DIASTOLIC
DISFUNCTION OF MYOCARDIUM

• Indicated
• IATE, ?R? II,
• Beta-adrenoblockers, calcium ions antagonists
• Contraindicated
• Nitrates, diuretics, heart glycosides

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Diuretics
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Classifiction of diuretics accordingly to power
of action ? Strong (slowing down of Na
reabsorbtion for 10-20) furosemide,
etacrynic acid, clopamide, bufenox ?? Medial
power of action (slowing down of Na
reabsorbtion for 5-8) dichlothiaside,
oxodoline ??? Light (slowing down of Na
reabsorbtion not more than for 3)
diacarb, spironolactone, amiloride, triamteren,
xanthines (theophylline)
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Mannitol
15 solution
rapid intravenous introduction
intravenous dropping introduction
diuretic action
dehydrating action
diuretic action
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• 
  Mannitol
• Indicatoins
• Brain oedema (in case of maintaining ofHEB
  permeability)
• Toxic lung oedema (poisoning with gasoline, gass,
  formaline, skipidar etc.)
• 3. Larynx oedema of allergic or inflammatory
  genesis
• 4. Holding of forced diuresis (poisoning with
  barbiturates, salycylates, sulphonamides, PASA,
  metanole, boric acid, haemolytic poisons,
  antifreezers in case of trasfusing of
  incompatible blood, massive hemoglobinuria etc.
• In oliguric phase of acute nephral insufficiency
• Burns, osteomielitis, peritonitis, sepsys
• Contrainidications
• Acute cardiac insufficiency, skull trauma,
  intracranial hemorrhages, arterial hypertension

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FUROSEMIDE

• High ceiling (loop) diuretic
• Properties
• 1. diuretic action
• 2. dilation of peripheral venous
• 3. decrease left ventricular filling pressure
• 4. potent anti-inflammatory effect (similar to
  indometacine and other NSAID)
• Administration hypertensive emergencies,
  long-term treatment of arterial hypertension
• Adverse reactions dehydration, hypokalemia,
  hearing loss - deafness, hypocalcaemia

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• Furosemide (lazix)
• Effective even in case of decreased
  glomerular filtration less than 10 ml/min. (norm
  127ml/min)
• Indications
• Acute left ventricular insufficiency, lung oedema
• Chronic cardiac insufficiency
• Arterial hypertension, including hypertensive
  crisis
• Brain oedema of any etiology
• Acute nephral insufficiency
• Performing of forced diuresis
• For excretion of Calcium ions (hypervitaminosis
  D)

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• 
  Side effects of furosemide
  
• Hypopotassiumaemia, hypopotassiumhystia
• Hypovolemia, vascular collapse, hyposodiumaemia,
  hypocalciumaemia, hypochloraemia, metabolic
  alkalosis
• Ototoxic action
• Contrinsular action (manifestation of latent
  diabetes mellitus)
• Formation of oxalate and phosphate stones in
  urinary tracts
• Decreasing of secretion of uric acid (acute
  attack of gout)
• It should not be combined with antibiotics,
  aminoglycosides and cephalosporines!

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Furosemide (diuretic)
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THIAZIDES and RELATED DIURETICS

• Medium efficacy diuretics
• Benzothiadiazines (chlorothiazide,
  hydrochlorothiazide, clopamide), related thiazide
  like (chlorthalidone, indapamide)
• for long-term treatment of arterial hypertesion
  (oral administration)
• Duration of action (6-12 hours for
  hydrochlorothiazide, 12-18 hours for clopamide,
  48-50 hours for chlorthalidone)
• Adverse reactions dehydration, hypokalemia,
  hyperuricaemia (rise of blood urate level)

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• 
  Dichlotiaside (hypothiaside)
• Indications
• Oedema in case of chronic cardiac insufficiency
• Oedema in case of chronic pathology of liver and
  kidneys
• Treatment of arterial hypertension
• Diabetes insipidus
• Side effects
• Hypopotassiumaemia, hypopotassiumhystia
• Hypochloraemic alkalosis
• Retention of uric acid - artralgy, acute attack
  of gout, chronic nephropathy
• Hyposodiumaemia of dilution nausea, vomitting,
  diarrhea, weakness
• Pancreatitis

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Indapamide (ariphone sulphamoil benzamide)
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Pharmacokinetics of some diuretic drugs
Drug Way of administration Latent period Duration of action
Sulfonyl derivates Sulfonyl derivates Sulfonyl derivates Sulfonyl derivates
Oxololin (chlortalidon, hyhroton) peroral 2-4 hours Till 3 days
Clopamide peroral 1-3 hours 8-18 (till 24) hours
Bufenox (bumetanide) intravenous 20-40 min. 2-5 min. 4-6 hours 1-3 hours
Potassium-, magnesium-sparing Potassium-, magnesium-sparing Potassium-, magnesium-sparing Potassium-, magnesium-sparing
Spironolactone peroral 2-5 days 2-3 days
Triamteren (pterophen) peroral 20-30 min. 6-8 hours
Amiloride peroral 2 hours till 24 hour
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Spironolactone
(aldactone)
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• Combined administration of diuretics
• Mannitol furosemide (etacrynic acid)
• Dichlotiaside triamteren (spironolactone)
• Furosemide spironolactone
• Furosemide (excretes Calcium ions)
  dichlotiaside
• (retains Calcium ions)

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Triampur (triamteren
hydrochlorthiaside)
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Blue corn-flowers (Flores Centaureae cyani)
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Juniper berries (Fructus Juniperi)