This document discusses hypertension (high blood pressure) including its causes, mechanisms of blood pressure control, and antihypertensive drug treatments. It describes how hypertension is defined and its prevalence. It explains the roles of the baroreceptor and renin-angiotensin-aldosterone systems in long-term and short-term blood pressure regulation. Finally, it provides details on major classes of antihypertensive drugs including diuretics, beta blockers, ACE inhibitors, angiotensin receptor blockers, calcium channel blockers, and others.

1. Syed Sulaiman
Pharmacology
Anesthesia
AMI Peshawar

2.  Introduction to hypertension
 Causes of hypertension
 Mechanism for controlling blood
pressure
◦ Baroreceptors
◦ Renin-angiotensin-aldosterone
system
 Anti-hypertensive drugs

3.  Also known as high blood pressure (HBP)
 Long-term medical condition in which the
blood pressure in the arteries is increases
 Systolic blood pressure of greater than 140 mm Hg
 Diastolic blood pressure of greater than 90 mm Hg
 Normal: 120/80
 Elevated blood pressure is an extremely
common disorder, affecting approximately 15
percent of the population of the United States
(60 million people)

4.  Family history
 Age
 Diabetics
 Obesity
 Disability states
 Environmental factors
◦ Stressful life
◦ Increase Na+
◦ smoking

5.  Hypertension is directly related to the
cardiac output
 Cardiac output and peripheral
resistance, in turn, are controlled
mainly by two overlapping control
mechanisms:
A. Baroreceptors
B. Renin-angiotensin-aldosterone system

6.  Baroreceptors are present in the aortic arch
 Baroreflexes act by changing the activity of
the sympathetic nervous system
 Therefore, they are responsible for the rapid,
moment-to-moment regulation of blood
pressure
 If blood pressure increases baroreceptors
activated and send fewer impulses to
cardiovascular centers in the spinal cord

7.  This prompts a reflex response of increased
sympathetic and decreased parasympathetic
output to the heart and vasculature,
resulting in vasoconstriction and increased
cardiac output

8.  The kidney provides for the long-term control of
blood pressure by altering the blood volume
 Baroreceptors in the kidney respond to reduced
arterial pressure by releasing the enzyme renin
 Low sodium intake and greater sodium loss also
increase renin release
 This renin converts angiotensinogen to angiotensin
I, which is converted, in turn to angiotensin II, in
the presence of angiotensin-converting enzyme
(ACE)

9.  Angiotensin II is a potent circulating
vasoconstrictor
 Constricting both arterioles and veins,
causing an
◦ Increase GFR
◦ Increase renal Na+ reabsorption
◦ Stimulate aldosterone secretion
◦ increase in blood pressure

10.  Anti-hypertensive dugs contain the following
groups
◦ Diuretics
◦ Beta blockers
◦ ACE inhibiters
◦ Angiotensin II receptors blockers
◦ Renin inhibiters
◦ Alpha receptors blockers
◦ Calcium Chanel blockers
◦ Centrally acting adrenergic drugs
◦ Vasodilators

11. A. Thiazide diuretics
 “Hydrochlorothiazide and chlorothalidone”
 lower blood pressure initially by increasing
sodium and water excretion
 This causes a decrease in extracellular
volume, resulting in a decrease in cardiac
output and renal blood flow
 Thus decrease in B.P.
 Thiazide diuretics induce hypokalemia and
hyperuricemia in 70 percent of patients and
hyperglycemia in 10 percent of patients

12. B. Loop diuretics
 “Furosemide, bumetanide, and
torsemide”
 These drugs inhibit the Na/K+ co-
transport in ascending loop of henle
 Thus decrease the reabsorption of
ions

13. C. Potassium-sparing diuretics
 “Amiloride, spironolactone,
triamterene”
 These drugs decrease k+
reabsorption

14.  “propranolol, metoprolol, atenolol etc”
 The β-blockers reduce blood pressure
primarily by decreasing cardiac output
 They may also decrease sympathetic outflow
from the central nervous system (CNS) and
inhibit the release of renin from the kidneys,
 Thus decreasing the formation of angiotensin
II and the secretion of aldosterone

15.  Hypotension
 Bradycardia
 Fatigue
 Insomnia
 Sexual dysfunction

16.  “Enalapril, lisinopril”
 The ACE inhibitors lower blood pressure by
reducing peripheral vascular resistance
without reflexively increasing cardiac output,
rate, or contractility
 These drugs block the ACE that cleaves
angiotensin I to form the potent
vasoconstrictor angiotensin II

17.  Dry cough
 Skin rash
 Fever
 altered taste
 hypotension (in hypovolemic states),
and
 hyperkalemia

18.  “Losartan, irbesartan”
 The ARBs are alternatives to the ACE
inhibitors
 These drugs block the AT1 receptors
 Their pharmacologic eff ects are similar to
those of ACE inhibitors in that they produce
arteriolar and venous dilation and block
aldosterone secretion, thus lowering blood
pressure and decreasing salt and water
retention

19.  “aliskiren”
 Aliskiren directly inhibits renin and, thus, acts
earlier in the renin-angiotensin-aldosterone
system than do ACE inhibitors or ARBs
 It lowers blood pressure about as effectively
as ARBs, ACE inhibitors, and thiazides
 Aliskiren can cause diarrhea, especially at
higher doses
 Aliskiren can also cause cough and
angioedema but probably less often than ACE
inhibitors

20.  They are effective in treating
hypertension in patients with angina
or diabetes
 The calcium-channel blockers are
divided into three chemical classes
1. Diphenylalkylamines
2. Benzodiazepines
3. Dihydropyridines

21.  Verapamil is the only member of this class
that is currently approved in the United States
 Verapamil is the least selective of any
calcium-channel blocker and has significant
effects on both cardiac and vascular smooth
muscle cells
 It is also used to treat angina,
supraventricular tachyarrhythmia's, and to
prevent migraine and cluster headaches

22.  Diltiazem is the only member of this
class that is currently approved in the
United States
 Like verapamil, diltiazem affects both
cardiac and vascular smooth muscle
cells, but it has a less pronounced
negative inotropic effect on the heart
compared to that of verapamil

23.  This group includes the first-generation
“Nifedipine” and
 five second-generation agents
◦ Amlodipine, felodipine, isradipine, nicardipine, and
nisoldipine
 All dihydropyridines have a much greater
affinity for vascular calcium channels than for
calcium channels in the heart

24.  Calcium enters muscle cells through special
voltage-sensitive calcium channels
 Calcium-channel antagonists block the
inward movement of calcium by binding to
L-type calcium channels in the heart and in
smooth muscle of the coronary and
peripheral arteriolar vasculature
 This causes vascular smooth muscle to
relax, dilating mainly arterioles

25.  Clonidine
◦ Inhibit sympathetic vasomotor center
◦ Reduce total peripheral resistance
◦ Decrease BP
 α-Methyldopa
◦ Diminished adrenergic outflow from the
CNS
◦ This leads to reduced total peripheral
resistance and decreased blood pressure

26.  “Hydralazine , minoxidil”
 These are not used primary drugs to treat
hypertension
 These vasodilators act by producing
relaxation of vascular smooth muscles artery
and arterioles
 Thus result in decrease peripheral resistance
and therefore BP