MISTRY SHIVANGI N, M.PH IN PHARMACOLOGY, ASSISTANT PROFFESSOR IN BHAGWAN MAHAVIR COLLEGE OF PHARMACY, PATHOPHYSIOLOGY AND TREATMENT

1. MS. SHIVANGI MISTRY
M.PHARM (PHARMACOLOGY)
ASSISTANT PROFESSOR
BHAGWAN MAHAVIR COLLEGE OF PHARMACY

2. CONTENT
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PATHOPHYSIOLOGY
 TREATMENT

3. PATHOPHYSIOLOGY
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1. GENETIC FACTOR :
• It is estimated that up to 30% to 50% of variability in blood
pressure may have a genetic basis.
• The majority of these polymorphisms appear to be involved
directly or indirectly in renal sodium re-absorption, which
may represent future therapeutic drug targets.

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2. CARDIAC OUTPUT :
• Factors which elevate cardiac output may, in theory,
contribute to the development of primary hypertension.
• Increases in cardiac output and subsequent blood pressure
may arise from factors that increase preload (fluid volume)
or contractility of the heart.

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3. SODIUM REGULATION :
• The contribution of sodium to the development of primary
hypertension is related to excess sodium intake and/or
abnormal sodium excretion by the kidneys.
• There appears to be a threshold effect of sodium intake in
the range of 50 to 100 mmol/day [1.2 to 2.4 grams of
sodium per day is equivalent to 3 to 6 grams of sodium
chloride per day (50 to 100 mmol/day)] and its impact on
blood pressure.

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 The proposed mechanisms behind high sodium intake and
blood pressure include increases in intracellular calcium,
insulin resistance, paradoxical rise in atrial natriuretic
peptide, and other pressor effects.
 Other theories supporting abnormal renal sodium retention
suggest a congenital reduction in the number of nephrons,
enhanced renin secretion from nephrons that are ischemic, or
an acquired compensatory mechanism for renal sodium
retention.

7. 4. RENIN-ANGIOTENSIN-ALDOSTERONE SYSTEM
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 The role of the RAAS in primary hypertension is supported
by the presence of high levels of renin, suggesting that the
system is inappropriately activated.
 Proposed mechanisms behind this inappropriate activation
include increased sympathetic drive, defective regulation of
the RAAS (nonmodulation), and the existence of a sub-
population of ischemic nephrons which release excess renin.

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5. SYMPATHETIC OVERACTIVITY :
• direct activation of the SNS may lead to enhanced sodium
retention, insulin resistance, and baro-receptor dysfunction.
6. PERIPHERAL RESISTANCE :
 The increase in peripheral resistance typically observed may
be due to a reduction in the arterial lumen size as a result of
vascular remodeling.
 This remodeling, or change in vascular tone, may be
modulated by various endothelium derived vasoactive
substances, growth factors, and cytokines.

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 This increase in arterial stiffness or reduced compliance
results in the observed increase in systolic blood pressure.
7. OTHER CONTRIBUTING PROCESSES AND
FACTORS :
• Many other processes are proposed to contribute to the
development of hypertension, including physical inactivity,
insulin resistance, potassium and magnesium depletion,
chronic moderate alcohol consumption, and transient
effects of cigarette smoking and caffeine intake.

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 Some people develop excessive and unrepresentative blood
pressure when attending the Doctor’s surgery, so called
“White Coat Hypertension”.

12. TREATMENT
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A. NONPHARMACOLOGIC THERAPY:

13. B. PHARMACOLOGICAL THERAPY
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16. 1. DIURETICS
• first line of drug for the treatment of mild hypertension.
 M. O. A :-
• Urine Volume
cation conc. In blood, extracellular fluid volume, plasma
volume
decrease in peripheral resistance and lower blood pressure.
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17. i. Thiazide :
 They are well absorb orally.
 Renal actions depends on excretion of drug into tubule.
Thus, thiazides may be ineffective, if there is renal
impairment.
ii. Loop diuretics :
 In hypertensive patient loop diuretics are indicated only
a) In chronic renal failure when thiazides are inactive
b) In hypertension resistant to std triple therapy including
thiazide
c) In combination with vasodilators or angiotensin
converting enzyme inhibitor in server resistence
hypertension
d) In co existing refractory congestive cardiac failure.
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20. iii. Potassium sparing diuretics :
 Used in combination with other diuretics and ACE
inhibitor to avoid or which produce hyperkalemia.
 ADRs :
 Hypokalemia,
 Hyperuraemia,
 Hyperglycemia,
 Hypercalcemia,
 Skin rashes and
 Thrombocytopenia.
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22. 2. DRUGS ACTING ON SYMPATHETIC SYSTEM
i. Centrally acting: (clonidine)
 M. O. A:
 Stimulates α2 adrenoceptors
α2 adrenoceptors in peripheral are situated on presynaptic
membrane
regulates release of adrenaline
Stimulation of these presynaptic α2 adrenoceptors
inhibits release of noradrenaline
other mechanism is in plasma in plasma renin levels.22

23. Pharmacological action :
 Decrease cardiac output
 Produce sodium retension. Hence, diuretics given with it.
ADRS:
 Drowsiness
 Dryness of mouth
 Constipation
 Vertigo
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24. ii. Catecholamine depleters: (Reserpine)
 Obtained from root of rouwolfia serpentina
 M. O. A : depletion of catecholamines (adrenaline and
noradrenaline)
decrease sympathetic tone
 Pharmacological action:
 sympathetic activity
 produce bradycardia (slower heart rate) and cardiac output
and peripheral resistance.
 Produce postural hypotension (drop in BP due to change in
body position).
 Antipsychotic activity & sedation.
 gastic acid secretion & peristalsis.24

25.  ADRs:
 Excessive salivation
 Nasal cogestion
 Increase gut motility
 Bardycardia
 Increase gastic acid secretion
 Drowsiness
 Water retension
 Mental depression
 Parkinsonism
Dose : 0.25 -1 mg daily.
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26. iii. Adrenergic receptor blocker :
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29. 29 Pheochromocytoma – development of adrenal gland

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