Drugs used to treat hypertension - PowerPoint

							Antihypertensive drugs
   Hypertension

   Systolic BP more than 140mmHg &/or diastolic BP
    more than 90mmHg.

                         BP = CO x PVR



Cardiac output may be          Peripheral resistance is
increased in children or       determined by the caliber and total
young adults during the        cross-sectional area of the resistance
earliest stages of essential   vessels (small arteries and arterioles)
hypertension                   in the various tissues.
                               - Influence of predisposing factors
Ways of Lowering Blood
      Pressure

                   • Reduce cardiac output (ß-
                     blockers, Ca2+ channel
                     blockers)

                   • Reduce peripheral
                     vascular resistance
                     (vasodilators)


 BP = CO X T PVR
                             Hypertension


Essential (primary)                         Secondary
- most (90-95 %) patients with              - is secondary to some
persistent arterial hypertension              distinct disease:
- genesis of hypertension unknown           -Renal artery stenosis
- predisposing factors:                     -Cushing's syndrome
                                            -phaeochromocytoma
                                            -Mechanical defect
susceptive                                   (coarctation of aorta)
(obesity, stress, salt intake, lack of      -Hypertension in pregnancy
Mg2+, K+, Ca2+, ethanol  dose,             -Drug-induced hypertension
smoking)                                     (sympathomimetics,
                                                glucocorticoids)
        non-susceptive                      -Conn`s syndrome
        (positive family history, insulin
        resistance, age, sex, defect of
        local vasomotoric regualtion)
         Classification of BP


Category              Systolic   Diastolic
• Normal              <130       <85
• High normal         <139       <89
Hypertension
• Stage 1             140-159    90-99
• Stage 2             160-179    100-109
• Stage 3             180-209    110-119
• Stage 4             >210       >120
                         Treatment
A- Non pharmacological therapy
Lifestyle modifications
B- Drug treatment of hypertension

The choice of antihypertensive drug will depend on the
relevant indications or contra-indications for the individual
patient:

 1. Drugs influencing sympathetic nerves
 2. Angiotensin-converting enzyme inhibitors (ACEI),
 blockers of AT1 receptor
 3. Calcium-channel blockers
 4. Direct vasodilators
 5. Diuretics
                        1. Drugs influencing sympathetic nerves

a) b -adrenoreceptor antagonists

 Mechanism of action:

 - Block β1 receptor.
 - decrease myocardial contractility
 -the fall in cardiac output   BP
 -they reduce renin secretion
Pharmacokinetic

Atenolol , Nadolol, Bisoprolol                 water soluble

Oxprenolol, Metoprolol                         Lipid soluble
Propranolol, pindolol


There are pharmacokinetic differences among B-blocker in first pass metabolism,
serum half lives, degree of lipophilicity, and route of elimination.
Propranolol and metoprolol undergo extensive first-pass metabolism.
Atenolol and nadolol have relatively long half lives and are excreted renally.
                    1. Drugs influencing sympathetic nerves

                        b-adrenoreceptor antagonists

  cardio-selective:
    b1 blockers                               atenolol, metoprolol
    b1 blockers with ISA                      acebutol
    b1,2 + a1 blockers                        labetalol, carvedilol


  cardio non-selective:
   b1 + b2 blockers                            nadolol, propranolol,

    b1 + b2 blockers with ISA                 pindolol, oxprenolol

Note: Partial agonist activity (intrinsic sympathomimetic activity – ISA) - may be
an advantage in treating patients with asthma because these drugs will cause
bronchodilation; they have moderate (lower) effect on lipid metabolism, cause
lesser vasospasms and negative inotropic effect.
                   1. Drugs influencing sympathetic nerves


Adverse effects

   - bradycardia
   - antrioventricular blockade
   - congestive heart failure (unstable)
   - asthmatic attacks
   -sleep alteration
Beta blocker should be avoided in

 1.Asthma
 2.DM
 3.Peripheral vascular disease
 4.Hyperlipidemia
 5.2nd &3rd degree heart block
                 1. Drugs influencing sympathetic nerves


b) a -adrenoreceptor antagonists
     Mechanism of action:
     - vasodilatation (reduce vascular resistence) and decreased blood
     pressure by antagonizing of tonic action of noradrenaline on a1
     receptors (vascular smooth muscle)
 Phentolamine and prazosin
 Doxazosin and terazosin
 Phenoxybenzamin

SE :-
    - drowsiness, weakness, orthostatic hypotension,
    reflex tachycardia.
    - Nausea, vomiting, diarrhoea
                  1. Drugs influencing sympathetic nerves

c) Centrally acting drugs (a2-agonist actions)


  Methyldopa
  Central a2 agonist ,false transmitter
  Clonidine direct a2-agonist

 - limited use in the treatment of hypertension.
 - methyldopa  hypertension during pregnancy
Adverse effects:


- drowsiness, fatigue (esp. methyldopa), depression, nightmares.
- nasal congestion, anticholinergic symptoms (constipation, bradycardia)
- dry mouth
- hepatitis, drug fever (with methyldopa)
- sexual dysfunction, salt and water retention
- hypertensive rebound associated with anxiety, sweating, tachycardia
         and extrasystoles (rarely hypertensive crisis)
2. Angiotensin-converting enzyme inhibitors (ACEI), blockers of AT1 rc.

 ANGIOTENSIN-CONVERTING ENZYME INHIBITORS (ACEI)
 Captopril, enalapril, quinapril, lisinopril, ramipril, cilazapril


Indications

 - hypertension where thiazide diuretics and beta-blockers are
  contraindicated
 - useful in hypertensive patients with heart failure (beneficial effect)
 - can limit the size of myocardial infarction
 - diabetic nephropathy
2. Angiotensin-converting enzyme inhibitors (ACEI), blockers of AT1 rc.

  Mechanism of action


                          Angiotensin I                  Bradykinin
                           (inactive)               (active vasodilator)



                                       angiotensin-
   ACE                                  converting
 inhibitors                              enzyme



                          Angiotensin II             Inactive metabolites
                     (active vasoconstrictor)
                (stimulate aldosterone secretion)
2. Angiotensin-converting enzyme inhibitors (ACEI), blockers of AT1 rc.



 Pharmacokinetics:

 - active when administered orally
 - most of ACEIs are highly polar, eliminated in the urine, without CNS
   penetration

         fosinopril - metabolized by the liver
         enalapril, quinapril - prodrugs  require metabolic conversion to
                                              active metabolites
         enalapril, quinapril and lisinopril - given once daily
         captopril - administered twice daily
2. Angiotensin-converting enzyme inhibitors (ACEI), blockers of AT1 rc.
 Adverse effects and contraindications of ACEI:

 First dose hypotension

 Dry cough

 Urticaria and angioneurotic edema

 Hyperkalemia

 Proteinuria, glumerulonephritis and acute renal failure.
 

 Contraindicated in
  bilateral renal artery stenosis
  pregnancy
2. Angiotensin-converting enzyme inhibitors (ACEI), blockers of AT1 rc.

                   B) BLOCKERS OF AT1 RECEPTOR
                   Telmisartan, Losartan, Valosartan, Irbesartan,
                   Candesartan, Eprosartan

  - The receptor blockers - competitively inhibit angiotensin II at its AT1
    receptor site

         most of the effects of angiotensin II - including vasoconstriction
          and aldosterone release - are mediated by the AT1 receptor
         AT1-blockers do not block AT2 receptor, which is exposed to
            high concentration of angiotensin II during treatment with AT1-
            blockers
         they influence RAS more effective because of selective blockade
          (angiotensin II synthesis in tissue is not completely dependent only
          on renin release, e.g. in heart, but could be promote by serin-
          protease - stronger influence on the myocardial remodelling)
                      References
-Journal of cardiovascular pharmacology
-Wikipedia, the free encyclopedia.htm :
-Drug digest –drug library
-Drugs for the heart Lionel H. Opie,bernard J. Gersh
-Clinical pharmacology D R Laurence
-The Internet Journal of Cardiology



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