To be able to describe: Hypertension: its prevalence, cardiovascular mortality risks & complications. Anti hypertensive drugs: classification, mechanism of action & side effects D) In collecting duct, sodium enters through sodium channels & transferred into interstitial fluid by sodium pump, while potassium is pumped in opposite direction and moves through potassium channels into tubular fluid. Aldosterone stimulates these processes by increasing synthesis of messenger RNA that encodes for sodium channel and sodium pump proteins. The potassium-sparing diuretics exert their effects via two mechanisms: amiloride and triamterene inhibit the entrance of sodium into the principal cells, whereas spironolactone blocks the mineralocorticoid receptor and thereby inhibits sodium reabsorption and potassium secretion. 

1. PHARMACOTHERAPY
OF
HYPERTENSION
YEAR 3 CARDIOVASCULAR & RESPIRATION
MODULE
DR AWAIS IRSHAD
Department of Pharmacology FAZAIA RUTH PFAU MEDICAL COLLEGE 1

2. OBJECTIVES
To be able to describe:
Hypertension: its prevalence, cardiovascular mortality risks &
complications.
Anti hypertensive drugs: classification, mechanism of action &
side effects
Department of Pharmacology FAZAIA RUTH PFAU MEDICAL COLLEGE 2

3. 3
http://www.who.int/chp/chronic_disease_report/saudi_arabia
HYPERTENSION – CHRONIC
problem
Department of Pharmacology FAZAIA RUTH PFAU MEDICAL COLLEGE

4. RISK FACTORS ( NON – MEDICINAL
TREATMENT )
Multifactorial.
Predisposing Factors:
Age, Sex, Gender, Race.
Genetic Factors
Fetal Factors
Lifestyle / Environmental
Factors
Humoral Mechanisms
4
Department of Pharmacology FAZAIA RUTH PFAU MEDICAL COLLEGE

5. A) In proximal tubule, carbonic anhydrase catalyzes reversible conversion of hydrogen ion &
bicarbonate to carbon dioxide and water, thereby enabling the reabsorption of sodium
bicarbonate.
This process is inhibited by carbonic anhydrase inhibitors such as
acetazolamide.
B) In thick ascending limb of the loop of Henle, Na + ,K + ,2Cl − symporter transports sodium,
potassium, and chloride ions into tubular cells, and then sodium is transferred to interstitial fluid by
sodium pump. Potassium back-diffuses into lumen and contributes to positive transepithelial potential
that drives paracellular calcium and magnesium reabsorption.
By inhibiting symporter, loop diuretics reduce back-diffusion of
potassium and increases excretion of calcium and magnesium.
Sites and Mechanisms of Action of Diuretics
Department of Pharmacology FAZAIA RUTH PFAU MEDICAL COLLEGE 5

6. C) In distal tubule , sodium is transported into tubular epithelial cells
by Na + ,Cl −symporter and then is transferred to interstitial fluid by
sodium pump. Na + ,Cl −symporter is inhibited
by thiazide diuretics.
D) In collecting duct, sodium enters through sodium channels & transferred into interstitial fluid by sodium
pump, while potassium is pumped in opposite direction and moves through potassium channels into tubular
fluid. Aldosterone stimulates these processes by increasing synthesis of messenger RNA that encodes for
sodium channel and sodium pump proteins. The potassium-sparing diuretics exert their effects
via two mechanisms: amiloride and triamterene inhibit the entrance of sodium into the
principal cells, whereas spironolactone blocks the mineralocorticoid receptor and thereby
inhibits sodium reabsorption and potassium secretion.
Sites and Mechanisms of Action of Diuretics
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7. LOOP DIURETICS: FUROSEMIDE
Potent diuretic, to treat
hypertension when thiazide diuretics is
not effective or contraindicated.
In severe hypertension.
In renal insufficiency.
In cardiac failure.
In cirrhosis where sodium retention is
marked.
Spironolactone
Aldosterone receptor antagonists.
The potassium sparing diuretics have a
relatively low natriuretic effect and are
primarily employed in combination with a
thiazide or loop diuretic to reduce
potassium excretion and prevent
hypokalemia.
7
POTASSIUM SPARING DIURETICS
Department of Pharmacology FAZAIA RUTH PFAU MEDICAL COLLEGE

8. ß blockers
Lipid
soluble
Propanolol
Timolol
Metoprolol
Water
Soluble
Nadolol
Atenolol
Acebutolol
Department of Pharmacology FAZAIA RUTH PFAU MEDICAL COLLEGE 8

9. ß
blocke
rs
Non-selective (ß1, ß2)
blockers:
Pure
Blockers
Sotalol,
Timolol,
Nadolol
With MSA
Propanolol
with ISA*,
MSA**, PA*** can
activate beta
receptors
Pindolol (MSA** ±)
Carteolol
Cardio selective ß1
blockers
Pure
blocker
s
Atenolol,
Bisoprolol (most
selective) Esmolol
(shortest action)
With
MSA
Metaprol
ol
With ISA*
and
MSA**
Acebutol
ol
Drugs that
block both α
and ß
receptors
Labetalol
,
Carvedil
ol
Department of Pharmacology FAZAIA RUTH PFAU MEDICAL COLLEGE
9
* ISA – Intrinsic sympathetic activity. ** MSA – Membrane stabilizing activity. *** PA – Partial
agonist

10. Used frequently because they are relatively safe and effective in patients
who suffer from angina or with a history of myocardial infarction.
These drug are cardio protective and rarely causes orthostatic
hypotension.
Relatively safe in hepatic, renal insufficiency or hematopoietic toxicity
10
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11. BETA BLOCKERS
Relative contraindications
Asthma/COPD
Decompensated CHF
Raynaud’s phenomenon
Peripheral vascular disease
Depression
Side effects
Tiredness
Cold hands and feet
Impotence and sexual
dysfunction
May mask the effect of
hypoglycemia in DM
11
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12. Angiotensinogen
Angiotensin I
Angiotensin II
Vasoconstriction
Aldosterone
secretion
↑ TPR
↑ Na & water
retention
↑ blood pressure
Angiotensin converting enzyme
Bradykinin
Inactive
metabolites
Vasodilation
↓ TPR
↓ Blood pressure
↑Prostaglandin
synthesis
ACE
Inhibitors
Renin
Aliskiren
ARBs
Spironolactone
12
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13. ACE INHIBITORS
13
Examples
Mechanism
of Action
Actions
Adverse
Effects
•Benazepril
•Captopril
•Ebalapril
•Fosinopril
•Lisinopril
•Moexipril
•Quinapril
•Ramipril
•↓Blood
pressure &
↓peripheral
Vascular
resistance
•Vasodilation
•↓secretion of
aldosterone
•↓Na & water
retention
•Blocks ACE that
cleaves
angiotensin 1 to
form potent
vasoconstrictor
angiotensin II
•↑ Bradykinin
•Dry cough
•Rash
•Fever
•Alter taste
•Hypotension
•Hyperkalemia
•Angioedema
Contra
indications
Pregnanc
y
Bilateral
renal
artery
stenosis
Department of Pharmacology FAZAIA RUTH PFAU MEDICAL COLLEGE

14. ANGIOTENSIN RECEPTOR ANTAGONISTS
14
•Candesartan
•Eprosartan
•Irbesartan
•Losartan
•Olmesartan
•Telmisartan
•Valsartan
Examples
Mechanism
of Action
Actions
Adverse
Effects
•Arteriolar &
Venous dilation
•Block
aldosterone
secretion
•↓Blood
pressure
•↓salt & water
retention
•Do not ↑
bradykinin
•Hypotension
•Hyperkalemia
•Fever
•Rash
•Fetotoxic
•Block AT1
angiotensin
receptors
Department of Pharmacology FAZAIA RUTH PFAU MEDICAL COLLEGE

15. RENIN INHIBITORS
15
Examples
Mechanism
of Action
Actions
Adverse
Effects
•Directly
inhibits renin
•Acts on renin -
angiotensin -
aldosterone
system
•Diarrhea
•Cough
•Angioedema
•Aliskiren
•↓Angiotensin I &
II
•↓Aldosterone
•Vasodilation
•↓ salt & water
retention
Department of Pharmacology FAZAIA RUTH PFAU MEDICAL COLLEGE

16. ACE INHIBITORS & RECEPTOR BLOCKERS
≈ ACE inhibitors ↓BP by ↓ peripheral vascular resistance without reflex increase of cardiac
output, rate or contractility.
≈ ACE inhibitors ↓ both arterial & venous pressure by ↓ cardiac after & pre load.
≈ Used inpatients with coexisting heart failure, myocardial infarction, diabetes mellitus
≈ By reducing circulating Angiotensin II levels, ACE inhibitors also ↓ the secretion of
Aldosterone, resulting in ↓ sodium and water retention.
The receptor blockers, Blocks the receptors for Angiotensin1
16
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17. VASODILATORS
17
Examples
Mechanism
of Action
Actions
Adverse
Effects
•Non-selective
block of L-type
calcium channels
•Block vascular
calcium channels
& cardiac calcium
channels
•Causes nitric
oxide release
•Metabolite opens
K channels in
vascular smooth
muscles
•Verapamil
•Diltiazem
•Nifedipine
•Amlodipine
•Felodipine
•Hydralazine
•Minoxidil
•↓cardiac rate &
↓cardiac output
•↓vascular
resistance
•Vasodilation
•↓vascular
resistance
•Reflex
tachycardia
•Constipation
•Dizziness
•Headache
•fatigue
Department of Pharmacology FAZAIA RUTH PFAU MEDICAL COLLEGE

18. 18
Department of Pharmacology FAZAIA RUTH PFAU MEDICAL COLLEGE

19. CALCIUM CHANNEL BLOCKERS: MECHANISM OF ACTION:-
Three types Ca+ channels in smooth
muscles – voltage sensitive, receptor
operated and leak channel
Voltage sensitive are again 3 types – L-
type, T-type and N-type
Normally, L-type of channels admit
Ca+ and causes depolarization
(excitation-contraction) coupling
through phosphorylation of myosin
light chain – contraction of vascular
smooth muscle – elevation of BP
Calcium channel blockers
BLOCK L-type channel
 Smooth muscle relaxation
 Negative Chrono- tropic effects in heart
19
• ↓ myocardial contraction force, which reduces
myocardial oxygen requirements.
• Causes peripheral vasodilatation.
• ↓ Left ventricular stress & oxygen
requirements of myocardium.
• ↓ heart rate by decreasing activity in Sinoatrial
& Atrioventricular nodal tissues. This gives
additional benefit in controlling
supraventricular tachycardia.
Department of Pharmacology FAZAIA RUTH PFAU MEDICAL COLLEGE

20. CALCIUM CHANNEL BLOCKERS:
Nifedipine.
Causes arteriolar vasodilation. Minimal effects
on cardiac conduction or heart rate.
They can cause flushing , headache, hypotension
and peripheral edema.
Verapamil.
Slows cardiac conduction directly and thus
decrease heart rate and oxygen demand but
they are weaker vasodilator.
Causes constipation. Contraindicated in patient
with preexisting depressed cardiac function or AV
conduction abnormalities.
20
Department of Pharmacology FAZAIA RUTH PFAU MEDICAL COLLEGE

21. CALCIUM CHANNEL BLOCKERS. SIDE EFFECTS
The calcium channel blockers are generally safe and are as effective as
beta-adrenergic blockers or diuretics in the treatment of mild to moderate
hypertension
Channel blockers are well-tolerated; minor side-effects include dizziness,
headache, flushing, and edema and are most usually associated with the
dihydropyridines
Department of Pharmacology FAZAIA RUTH PFAU MEDICAL COLLEGE 21
• Efficacy can be enhanced by combination with other types of antihypertensive.
• Diltiazem or verapamil with beta-adrenergic blockers can lead to
AV block, cardiac depression, bradycardia
Verapamil with digoxin (can increase levels of digoxin, and can cause AV block)

22. CALCIUM CHANNEL BLOCKERS –
CURRENT STATUS
As per JNC 7 CCBs are not 1st line of antihypertensive unless indicated –
ACEI/diuretics/beta blockers
However its been used as 1st line by many because of excellent tolerability and
high efficacy
Preferred in elderly and prevents stroke
They are next to ACE inhibitors in inhibition of albuminuria and prevention of
diabetic nephropathy
Department of Pharmacology FAZAIA RUTH PFAU MEDICAL COLLEGE 22

23. VASODILATORS. HYDRALAZINE.
 Acts on arteries and arterioles, this results in a decreased peripheral resistance,
which in turn prompts reflex tachycardia and cardiac output.
 Indicated for moderately severe hypertension.
 Adverse effects include nausea, vomiting, sweating, arrhythmia.
 A lupus like syndrome can occur with high dosage, but it is reversible on
discontinuation of drug
Department of Pharmacology FAZAIA RUTH PFAU MEDICAL COLLEGE 23

24. VASODILATORS. MINOXIDIL.
 Acts by hyperpolarization of smooth muscles and thereby relaxation of Smooth Muscles by acting on potassium
channels
 Reflex tachycardia may be severe and may require the concomitant use of a diuretic or β-blocker.
Orally not used any more reserved for severe to malignant hypertension that is refractory to other drugs.
It also causes hypertrichosis (the growth of body hair). This drug is in use topically to treat male pattern baldness.
Topically as 2-5% lotion/gel and takes months to get effects
MOA of hair growth:
 Enhanced microcirculation around hair follicles and also by direct stimulation of follicles
 Alteration of androgen effect of hair follicles
Department of Pharmacology FAZAIA RUTH PFAU MEDICAL COLLEGE 24

25. Αlpha ¹-blockers
are second line of therapy when others agents are
ineffective or contraindicated
25
Examples
Mechanism
of Action
Actions
Adverse
Effects
•Doxazosin
•Prazosin
•Terazosin
•Selectively
blocks a-1
adrenoceptors in
arterioles &
Venules
•Prevents
sympathetic
vasoconstrictio
n
•↓peripheral
vascular
resistance
•↓arterial
pressure
•Reflex
Tachycardia
•↑risks of
congestive
heart failure
Department of Pharmacology FAZAIA RUTH PFAU MEDICAL COLLEGE

26. SYMPATHETIC NERVE TERMINAL
BLOCKERS
26
Examples
Mechanism
of Action
Actions
Adverse
Effects
•Reserpine
•Guanethidine
•Blocks vesicular
amine transporter
in noradrenergic
nerves
•Depletes
transmitter stores
•Interferes with
amine release &
replaces
nonepinephrine
in vesicles
•↓All
sympathetic
effects
epically
cardiovascular
•↓Blood
pressure
•Psychiatric
depressions
•GIT
disturbances
•Severe
hypotension
•Sexual
dysfunction
Department of Pharmacology FAZAIA RUTH PFAU MEDICAL COLLEGE

27. CENTRALLY ACTING ADRENERGIC DRUGS.
METHYLDOPA.
It diminishes the adrenergic
outflow from central α-2a
receptors to decrease
sympathetic outflow from the
CNS, leading to reduced
peripheral resistance.
Cardiac output is not
decreased and flow to vital
organs is not diminished by
its use.
Department of Pharmacology FAZAIA RUTH PFAU MEDICAL COLLEGE 27
Especially valuable in the treatment
of hypertensive patients with renal
insufficiency & in pregnancy
induced hypertension.
Common side effects include
sedation and drowsiness. Postural
hypotension sometime occurs,
particularly in volume depleted
patients.

28. 28
Hypertension Canada’s 2016 CHEP Guidelines for Blood Pressure Measurement, Diagnosis, Assessment of Risk,
Prevention and Treatment of Hypertension
Department of Pharmacology FAZAIA RUTH PFAU MEDICAL COLLEGE

29. REFERENCE
S:
2014 Hypertension Guideline Stands to Simplify Treatment
https://www.google.com.sa/url?sa=t&rct=j&q=&esrc=s&source=web&cd=4&cad=rja&uact=8&ved=0CEMQFjAD&url
=http%3A%2F%2Fwww.aafp.org%2Fnews%2Fhealth-of-the-public%2F20131218hypertensiongdln.html&ei=O3hoU-
dPIXfOKqmgRA&usg=AFQjCNG0EHrm_MpsPteAvvtZd6Xz49oyPw
2014 Evidence based guidelines for Management of hypertension. American Society of Hypertension
https://www.google.com.sa/url?sa=t&rct=j&q=&esrc=s&source=web&cd=1&cad=rja&uact=8&ved=0CC4QzwIwAA&url=https%3A%2F%2
Fscholar.google.com%2Fscholar%3Fes_sm%3D122%26um%3D1%26ie%3DUTF-8%26lr%26q%3Drelated%3AMwILUs-
KtklAkM%3Ascholar.google.com%2F&ei=O3hoU-PdPIXfOKqmgRA&usg=AFQjCNHqIcse2AhWWafoOr0s7pdhrEaiyQ.
(ACCEPTED MANUSCRIPT) Hypertension Canada’s 2016 CHEP GUIDELINES FOR BLOOD PRESSURE MEASUREMENT,
DIAGNOSIS, ASSESSMENT OF RISK, PREVENTION & TREATMENT OF HYPERTENSION. CANADIAN JOURNAL OF
CARDIOLOGY, REF CJCA 2053
Basic & Clinical Pharmacology : 15th edition by Katzung
Rang & Dale Pharmacology; 8TH EDITION
Lippincott's Pharmacology: 6TH EDITION
For queries: a.mehdi@frpmc.edu.pk
29
THANK
YOU
Department of Pharmacology FAZAIA RUTH PFAU MEDICAL COLLEGE