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1.

BP is regulated by:
a. CO
b. PVR
c. Vol. of intravasc fluid (controlled at the
kidney)
2. Baroreflexes adjust moment-to- moment
blood pressure: Carotid baroreceptors

3. Reduction in renal perfusion pressure
1. CO: syst. BP
a. SV Sirc. Vol : diuretics
inotropic (-) : -blockers
b. HR : -blockers

2. PVR : Dyast. BP syst. BP
vasodilator

3. Combination : Main effect!
1. DIURETICS
2. SYMPATHOLYTIC DRUGS
3. VASODILATORS
4. ACE INHIBITORS AND
ANGIOTENSIN II RECEPTOR
ANTAGONISTS
5. CALSIUM CHANNEL BLOCKERS
Mech. of ACTION & hemodynamic EFFECT :
- Depleting Na
+
BV & CO, PR may .
(adaptation)
- 6-8 weeks : CO normal ; PR

BP
BP
Thiazide
CO
Blood Vol
Na
+
, water
retention
PR
THIAZIDE DIURETICS :
Mild or moderate essential HT (normal renal & cardiac
function)



Hypokalemia, precaution :
a. Persons taking digitalis
b. Chronic arrhythmias
c. AMI

Hypomagnesia
Metabolic effect (especially at
dose):
a.Glucose intolerance
b.Serum lipid
c.Uric acid , precipitate gout

2A. BLOCKERS
DRUGS:Prazosin, terazosin, doxazosin

Action:
A. & V Relax PR and arterial BP
CO, RBF, GFR min. (tachycardia and
increased renin release do not occur)

1
blockers:
postural hypotension
syncope after the 1
st
dose (1
st
pass effect) the 1
st

dose should be small and should be administered at
bedtime

Mild to moderate HT.

In combination with propranolol or a diuretic for
additive effect.
Activation of
1

on heart
CO
PR
Angiotensin II
Renin

Aldosteron
Sodium, water
retention
Blood volume
-Adrenoceptor
blockers
2B. Blockers
BP
Non selective: propranolol, nadolol, carteolol

1
blockers (cardioselective): atenolol, metoprolol
(relative), betaxolol, bisoprolol
Partial agonist (-blockers with ISA): acebutolol
(cardioselective), pindolol, penbutolol, bopindolol.
-blockers with -blocking effect: labetalol &
carvedilol
Propanolol:
Oral doses >> IV doses (1
st
-pass hepatic
metabolism) T 3-6 hrs.
- HT with tachyarrhythmia, previous MI, A. pectoris,
glaucoma, migraine headache.

- It more effective : young patient > elderly

A. Hidralazine & minoxidil (p.o):
long term outpatient Th/
B. Nitroprusside & diazoxide
Hypertensive Emergencies.
C. Calcium channel blockers

Dilates arteries and arteriole (not veins)


PR and reflex HR & CO.

Pharmacokinetics :
Bioavailability (25%)
Metabolism : rapid & slow acetylators
Hydralazine
Toxicity:
headache, anorexia, palpitations, Sweating and
flushing

Usage: Th/ moderately severe HT
It is almost always as combination
with a -blockers and diuretics
(see figure 5)
Diastolic BP > 150 mmHg or >130 mmHg with
complications :
- Encephalopathy
- Cerebral hemorrhage
- Left ventricular failure
- Aortic stenosis

Goal Th/ : rapidly reduce blood pressure
Direct-acting arteriolar vasodilator.
Vascular effect hydralazine.
For coronary insuff. patients : diazoxide IV


USAGE: Th/ HT emergency, esp.:
- Malignant HT
- HT encephalopathy
- Eclampsia
TOXICITY: Excessive hypotension
ACTION :
- Inhibit Ca
++
influx into vasc. smooth muscle cells
vasodilatation PR BP

- Intrinsic natriuretic effect

- Useful in HT with asthma, diabetes, angina and
peripheral vascular disease
A. Dihydropyridine family:
- Nifedipine
- Isradipine
- Nicardipine
- Nisoldipine
- Amlodipine
- Felodipine
- Nimodipine
(cerebral vasodilator)

Pharmacological effect of Dihydropyridine
family :

- Vasculoselective
- Cardiac depr. <<< verapamil/diltiazem
- Reflex sympathetic activation: slight tachycardia
and slight increases CO
It has the greatest effect on the heart:
Slows cardiac cond. HR , balanced by
reflex activation

Contraindicated in patient with preexisting
depressed cardiac function or AV conduction
abnormalities !!!

Weak vasodilator
It reduces HR (lesser than verapamil),
BP .
Excessive inhibition of Ca
++
influx serious
cardiac depression

SIDE EFFECT :
- Flushing - Headache
- Hypotention - Peripheral edema
- Constipation - Fatigue

A. ACE-INHIBITOR
- Captopril - Fesinopril
- Enalapril - Moexipril
- Lisinopril - Quinopril
- Benazepril - Ramipril (long acting)
B1. Angiotensin Type 1 (AT
1
) Receptor
Blocking Agents
- Losartan
- Valsartan

B2. Analog and competitive Inhibitor of
Angiotensin II : Saralasin
Pharmacological effect:
Captopril:
- VR BP
- Aldosteron secretion Na
+
& water retention
K
+
retention

- Bradikinin vasodilation
- Vasodilator preload CO



ARF (particularly in renal stenosis)
Hyperkalemia
Dry cough
Angioedema
Altered sense of taste
Allergic skin rashes, Drug fever
Contraindication:
2
nd
and 3
rd
trimesters of pregnancy



- Mild-moderate hypertension
- Hypertension who were refractory to
standard multidrug antihypertensive
regimens
- Hypertension with chronic congestive
heart failure
Diuretic + -blocker/centrally acting drug

Diuretic + Vasodilator (ca-channel blocker, ACE
inhibitor, analog and competitive AT II)

Diuretic + adrenergic antagonist + Vasodilator

-blocker + Vasodilator

ACE inhibitor + ca-channel blocker
2 same class drugs

-blocker + centrally acting drug

-blocker + diltiazem/verapamil (AV nodes
depression )
Not at Goal Blood Pressure (<140/90 mmHg)
(<130/80 mmHg for those with diabetes or chronic kidney disease)
Initial Drug Choices
Drug(s) for the compelling
indications
Other antihypertensive drugs
(diuretics, ACEI, ARB, BB, CCB)
as needed.
With Compelling
Indications
Lifestyle Modifications
Stage 2 Hypertension
(SBP >160 or DBP >100 mmHg)
2-drug combination for most (usually
thiazide-type diuretic and
ACEI, or ARB, or BB, or CCB)
Stage 1 Hypertension
(SBP 140159 or DBP 9099 mmHg)
Thiazide-type diuretics for most.
May consider ACEI, ARB, BB, CCB,
or combination.
Without Compelling
Indications
Not at Goal
Blood Pressure
Optimize dosages or add additional drugs
until goal blood pressure is achieved.
Consider consultation with hypertension specialist.