Drugss

1. Hypo- and
hypertensive drugs
Lection №10

2. Hypertension is defined as a systolic blood
pressure (sBP) of 140 mm Hg or more, or a diastolic
blood pressure (dBP) of 90 mm Hg or more
Hypertension may be PRIMARY, which may develop as
a result of environmental or genetic causes, or
SECONDARY, which has multiple etiologies,
including renal, vascular, and endocrine causes.
Primary or essential hypertension accounts for 90-95%
of adult cases, and secondary hypertension
accounts for 2-10% of cases.

3. Arterial hypertension
Primary (essential) hypertension: in 20-40%
patients with boundary arterial hypertension
(neurocirculatory dystonia of hypertensive type,
diagnosed on the basis of three times fixed within a
week SBP up to 159 mmHg, DBP up to 94 mmHg
without the signs of target organs damage the nervous
system, the heart, the eye, the kidneys)
Secondary – symptomatic (vascular: dilatation of
the renal artery as a result of renal diseases, etc.;
initially humoral: pheochromocytoma, Cushing’s
disease, etc.)
The correct choice of hypotensive therapy
depends on knowledge of etiology, basic links of
arterial hypertension pathogenesis being an
object of medicinal influence!

4. Hypertension is a major health problem, especially be
cause it has no symptoms.
Many people have hypertension without knowing it.
Hypertension is more common in men than woman
and in people over the age of 65 than in younger
persons.
Hypertension is serious because people with the
condition have a higner risk for heart disease and other
medical problems than people with normal blood
pressure:
arteriosclerosis, also called atherosclerosis
heart attack, stroke, kidney damage.
Serious complications can be avoided
by getting regular blood
pressure checks and treating hyper-
tension as soon as it is diagnosed.

6. Changing our lifestyle can go a long way toward
controlling high blood pressure.
Doctor may recommends eat a healthy diet with less
salt, exercise regularly, quit smoking and maintain a
healthy weight. But sometimes lifestyle changes aren't
enough.
In addition to diet and exercise, doctor may recommend
to the patients medication to lower blood pressure.

7. Our blood pressure treatment goal depends
on how healthy we are.
Blood pressure treatment goals*
*Although 120/80 mm Hg or lower is the ideal blood
pressure goal, doctors are unsure if you need treatment
(medications) to reach that level.
Less than150/90 mm Hg If you're a healthy adult age 60 or
older
Less than140/90 mm Hg If you're a healthy adult younger
than age 60
Less than140/90 mm Hg If you have chronic kidney
disease, diabetes or coronary artery disease or are at
high risk of coronary artery disease

8. Antihypertensive (hypotensive)
drugs
The action of these drugs is directed upon
decrease of the peripheral artery tone,
reduction of the cardiac output and
diminution of the circulating blood
volume,
which are the main links of the arterial
hypertension pathogenesis.

9. Clinical classification of antihypertensive
drugs
І. Drugs of main group (First-Line
Treatment for Hypertension):
Diuretics
Adrenoblockers
ACE-inhibitors
Angiotensin ІІ receptor blockers
Calcium channels blockers
II. Drugs of supplemental group
Agonists of central α2-аdrenoreceptors
Sympatolytics
Myotropic antispasmodics
Agonists of imidasoline (І1) receptors
Ganglion blockers

10. Transition Page
 Neurotropic drugs;
 Myotropic drugs
 Сa++ channel blockers
 K+ channel activators
 Agents which influence upon the renin-
angiotensin system
 Agents who influence upon the sodium
and water balance (diuretics)
Classification of
hypotensive drugs according to
the mechanism of action

11. 1. Drugs with central action (decrease the tone of
vasomotor center)
а) Sedatives (Natrii bromidum, extr. Valerianae,
b) Hypnotics (Phenobarbitalum)
c) Neuroleptics (Aminazinum)
d) Tranquilizers (Sibasonum, Gidazepamum)
e) Central α2-adrenoreceptor activators (Clophelinum,
Methyldopa)
i) Activators of central imidazoline receptors
(Moxonidinum)
I. Neurotropic drugs(acts on the different
parts of nervous system)

13. Clophelinum
 Causes central action on the vasomotor
center of medulla oblongata
 Stimulates α2-adrenoreceptors
 Decreases sympathetic vasoconstrictor
impulsation to the peripheral vessels
 Decreases rennin secretion
The beginning of the effect - after 30-60 min (per os),
maximal effect – after 2-4 hours, duration of the effect
– 8 hours.
After i.v. introduction the beginning of the effect will
be after 3-5 min.

14. Indications for usage:
orally - for the systematic treatment of arterial
hypertension.
i.v. - to arrest hypertensive crisis.
Side effects:
«Withdrawal syndrome» - rapid increasing of
BP after sudden cessation of the drug
dry mouth, drowsiness, lethargy
Ortostatic collapse
Dyspeptic disorders
N.B! This drug potentiates effects of different
drugs with depressive effect on the CNS (alcohol)

16. Mechanism of action:
• Central agonist of imidazoline receptors, localized in vasomotor
center. Can decrease their influence on blood vessels and
myocardium. Inhibits sympathetic nervous system activity and blood
pressure
• Doesn’t influence on α2-adrenoreceptors (doesn’t cause dry mouth
and sedative effect).
• Doesn’t influence cardiac output, doesn’t cause bradycardia
Indications for use:
Arterial hypertension (in case of effectiveless of ACE-inhibitors, β-
adrenoblockers and Са++ -channel blockers
Side effects
Dry mouth, dizziness, asthenia, somnolence
Contraindications
Bradycardia (< 50 /min), AV-blockade
Acute and chronic heart failure
Childrens, breast feedings
Hypersensitivity
Moxonidinum

17. Neurotropic drugs with peripheral
neurotropic action
1) ganglion blockers (Benzohexonium,
Pentaminum, Hygronium)
2) sympatholytics (Octadinum, Reserpinum)
3) adrenoblockers
a) α-adrenoblockers - (Prazosinum,
Doxazosinum)
b) β-adrenoblockers – (Propranololum,
Atenolol, Metoprolol, Nebivolol)
c) α-β–adrenoblockers – (Labetalol,
Celiprolol, Carvedilol)

18. Antiadrenergic drugs
Systemic
Propranololum
Oxprenololum
Pindololum
Cardiselective
Talinololum
Nebivololum
Bisoprololum
Labetalolum
Carvedilolum
β -adrenoblockers
α-adrenoblockers
α, β-
adrenoblockers
Prazozinum
Doxazosinum
Terazosinum

19. Beta-adrenoblockers
Mechanism of action – blockade of β1-
adrenoreceptors of myocardium, decreasing of cardiac
output, reduction of renin secretion, lowering of the
vasornotor centre tone, that leads to the dilation of vessels
They ere used most commonly for the
systematic treatment of the arterial
hypertension.
Alfa-adrenoblockers
Mechanism of action – blockade of α-
adrenoreceptors of peripheral vessels,
decreasing of the BP owing to the dilation of
peripheral arteries.

20. Beta-adrenoblockers
Systemic
Propranololum,
Oxprenololum
Pindololum
Cardioselective
Bisoprololum
Talinololum
Nebivololum

21. Beta-adrenoblockers
Block of β-
receptors of the
juxta-glomerular
apparatus of the
kidney
Block of β-
receptors of
the vessels
 Central
links of
sympathetic
Block of β-
receptors of
the heart
 renin
secretion
 tone of
peripheral
vessels
Hypotension
 force and
heart rate
 stroke and
cardiac output
 myocardial
demands in O2
Antianginal
 automaticity,
conductivity
and excitability
of myocardium
Antiarrythmic

22. Beta-adrenoblockers
 Arterial hypertension
 Ischemic heart disease
 Tachyarrhythmia
 Glaucoma – timolol
 Hyperthyreoidism – propranolol
 Neurological disorders
(migraine) - propranolol
Indications for use

23. Beta-adrenoblockers
 CVS – arrythmogenic action (AV-conduction
abnormalities, bradycardia, etc.), heart failure,
hypotension, edemas ( renin)
 Bronchial spasm
 Hypoglycemia
 Dysfunction of the thyroid gland
 Atherogenic effect
 thrombocyte aggregation
 Contraction of pregnant uterus
 Rebound syndrome
Adverse effects

25. III.Vasodilators with myotropic action
(myotropic drugs).
1) Calcium channel blockers - Nifedipine, Felodipine,
Amlodipine
2) Potassium channels activators - Minoxidil, Diazoxlde
3) Agents which release nitric oxide (NO) - Natrium
nitroprusside
4) Miscellaneous drugs - Dibazolum, No-spa, Papaverinum,
Masnesium sulfas
IV. Agents who influence upon the
sodium and water balance
(diuretics) - Dichlothiazidum, Furosemide,
Triamterene, Spironolactone

26. • apressin (hydralasin), activators
of potassium channels, vasotropic
calcium channel blockers, etc.
Arterial:
•papaverine, drotaverine
(no-spa), α-adrenoblockers,
ganglion blockers, nitrates
(sodium nitroprusside), etc.
Arterial and
venous:
Myotropics (vasodilatators)
Majority of myotropic drugs are intended for hypertensive crisis
arrest and additional therapy in the arterial hypertonia complex
treatment!

27. Calcium channel blockers (Nifedipinum,
Felodipinum, Amlodipinum).
The mechanism of action is blockade of Ca++
channels of blood vessel myocyte membranes,
that leads their relaxation and to the dilation of
the peripheral vessels.
 are the most specific correctors of increasing
vascular resistance during arterial
hypertension
 block the Ca++ ions flow
 dilate blood vessels and decrease BP
 cause antiarrythmic effect
 cause antiischemic (antianginal) effect

28. Classification of calcium channel blockers
I type – cardiotropic (phenylalkylamine derivates)
•1 generation – verapamil,
•2 generation – hallopamil, etc.
II type - vasotropic
General action: dihydropyridine derivates –
•1 generation – nifedipine (cordafen);
•2 generation –nicardipine, etc.
•Cerebrovasotropic – diphenylpiperasine derivates
•1 generation – cinnarizine (stugerone);
•2 generation – flunarizine, as well as nimodipine
III type – mixed (benzothiazine derivates)
•1 generation – diltiazem
•2 generation – clentiazem

29. Peculiarities of hypotensive effect of
calcium channel blockers
 Systolic BP and DBP
 + Moderate diuretic action
  Blood flow to vital organs (the heart, the brain, the
kidneys),  microcirculation
  Hypertrophy of the left ventricle
 ABP proportional to the dose, in therapeutic doses
have a slight influence to normal ABP, do not cause
orthostatic phenomena
 I generation – ABP variability + reflex tachycardia
 II generation – maximal antihypertensive effect of
retarding forms of I generation of all the calcium
blockers develops after 2-4 week therapy without
pause; amlodipine – after 4-8 weeks

30. DOSAGE AND TOXICITY OF THE CALCIUM
INFLUX-BLOCKING DRUGS
Drug Onset of
action
Plasma
half-life
Dose Toxicity
Verapamil
(Isoptin)
< 1,5 min after
i.v., 30 min after
oral
administration
6 hours 75 – 150
mg/kg i.v. 80 –
160 mg every
8 hours orally
Hypotension,
myocardial
depression, heart
failure, dependent
edema
Nifedipine
(Adalat)
< 1 min after i.v.,
<3 min after
sublingual,
< 20 min after
oral
administration
4 hours 3 – 10 mg/kg
i.v.; 10 – 40
mg every 8
hours orally
Hypotension,
dizziness, flushing,
nausea,
constipation,
dependent edema
Diltiazem < 3 min after i.v.,
> 30 min after
oral
administration
3 – 4
hours
75 – 150
mg/kg i.v.; 30
– 80 mg every
6 hours orally
Hypotension,
dizziness, flushing,
bradycardia

33. Myotropic drugs
1. Potassium channels activators (Minoxidil,
Nicorandil)
2. Nitrogen oxide (NO) donators – (Natrii
nitroprussidum)
Cause potent, fast and short effect (5-15 min).
Use by transfusions in cause of severe
hypertensive crises, lung edemas, acute heart
faulure
3. Myotropic spasmolytics (Dibasolum, No-
spa, Papaverini hydrochloridum, Magnesium
sulfas)

34. Myotropic drugs (Dibazolum, No-spa,
Papaverini hydrochloridum)
The mechanism of action - inhibition of enzyme
phosphodiesterase. This leads to blocks of the
Ca++ influx into the cells. Smooth muscles of blood
vessels relax, and BP decreases.

36. Magnesii sulfas (25% - 10 ml)
After parenteral introduction:
- hypotensive,
- vasodilative
- sedative
- anticonvulsive
- tocolytic
- Myorelaxing
- hypnotic
- suppress breathing center
Mechanism of action. Magnesium is physiological antagonist of calcium,
blocks intake of Са++ throw presynaptic membrane. Relaxes
smooth musculature, decreases BP
Effects starts after i.v. introduction- immediately and after 0,5-1 hour
after i.m. introduction.
Duration of action after i.v. – 30 min, after i.m. – 3-4 hours.
After oral inrtoduction:
- bile-expelling
- laxative

37. Drugs influence the renin-
angiotensine system
Captoprilum
Enalaprilum
Lisinoprilum
Ramiprilum
Fosinoprilum
Moexiprilum
Perindoprilum
Blockators of
angiotenzine II
receptors
Angiotensin-
converting
enzyme inhibitors
Losartanum
Valsartanum
Irbesartanum
Candesartanum

38. Mechanism of action
Inhibition of "angiotensin-converting enzyme”, decrease of
angoitensin II creation, that leads to vasodilation,
reduction of aldosterone release and, as a result of
this, decrease of BP.
Promote the accumulation of bradykinin, prostaglandins E2,
I2, which cause significant vasodilating action.
Do not change the cardiac output and the heart rate.
They are used
systematic treatment of arterial hypertension (renal origin)
chronic heart failure (as they decrease the cardiac afterload).
ACE-inhibitors (Captoprilum, Enalaprilum)
 Dry cough
Hypotension (after first dose)
 Gustatory disorders
Allergic reaction
Tachycardia
Side-effects:

40. systematic treatment of the arterial
hypertension.
Angiotensin receptor blockers (Losartan,
Valsartan, Candesartan)
Mechanism of action
blockade of the AT1-angiotensin receptors, that
leads to elimination of all angiotensin effects
(including vasoconstriction and increase of the
aldosterone release).
Usage
Side-effects
headache, vertigo, allergic reactions.

42. Mechanism of the antihypertensive action :
1) increased excretion of water causes decrease of
the circulating blood volume;
2) amplification of Na+ ion excretion leads to
decrease of vascular tone as a result of reduction
of excitability of the vessel smooth muscles;
3) decrease of the perivascular fluid amount leads to
the reduction of the peripheral blood vessel tone;
4) diuretics potentiate the action of other
antihypertensive drugs
Diuretics – Dichlothiazidum,
Furosemidum, Triamteren, Spironolacton

43. Diuretics - these are the drugs which promote the
excretion of sodium, chlorine ions and water with the urine
out from the organism.
 The most effective in elderly patients;
 Use in patients with edemas;
 Use in patients with concomitant cardiac pathology;
 Use in patients with concomitant renal failure
Thiaside diuretics
Loop diuretics
К+-sparing diuretics
Hydrochlorothiazidum
Indapamidum
Furosemidum
Torasemidum
Acidum etacrуnicum
Spironolactonum
Triamterenum

45. Improvement the effectiveness
of treatment due to:
 Influence on different
pathogenic links of drugs
with different mechanisms
of action
 Potentiation the effects
  duration of action
  freacvency of side
effects due to usage of
lower doses of each
component
Rational combine pharmacotherapy
of arterial hypertension

46. Transition Page
Central-acting drug + diuretic
Rational combinations of hypotensive drugs
ACE-inhibitor (АРАІІ) + Diuretic
Са++ channel blocker + ACE-inhibitor
β -adrenoblocker + Са++ channel blocker
(nifedipine)
β -adrenoblocker + ACE-inhibitor
β -adrenoblocker + diuretic
β -adrenoblocker + α-adrenoblocker

47. Classification of the hypotension
drugs according to the clinical
usage:
І. Drugs for arrest the hypertensive
crisis:
Magnesii sulfas
Clophellinum
Dibasolum
Furosemidum
II. Drugs for treatment of hypertonic
disease
adrenoblockers, ACE-inhibitors,
Ca++ antagonists, diuretics
i.m., i.v.
orally

48.  Adrenomimetics:
Drugs increasing the cardiac stroke volume
and the vascular tone: Adrenaline, Ephedrine
Drugs that increase chiefly the vascular
tone:
Noradrenaline, Mesatone;
 Dopaminotropics: Dopamine
 Glucocorticoids – Hydrocortisone, Prednisolone
 Mineralocorticoids - DOXA
 Peripheral vasoconstrictors - Angioteninamide
 Analeptics: Caffeine, Cordiamine
 Аdaptogens – drugs of Eleuterococcus, Ginseng,
etc.