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Antihypertensive Drugs

Azza Baraka
Prof of Clinical Pharmacology
Faculty of Medicine
Alexandria University

Definition
Elevation of ABP > 140/90 mm Hg. Can be caused by:
primary or essential hypertension
Primary Hypertension cannot be cured, but it can be
controlled

Secondary hypertension, e.g. hyperthyroidism cured by


treating cause

Classification of blood pressure


levels
Category

Systolic (mmHg)

<120
High Normal
120139
Hypertension Stage1 140159
9099
Hypertension Stage 2
>160
>100
Normal

Diastolic
(mmHg)

<80
8089

Major Risk Factors That Increase Mortality


in Hypertension

Smoking
Dyslipidemias
Diabetes Mellitus
Age >60
Gender: men, postmenopausal
women
Family history

Treatment Thresholds for Essential Hypertension


Stages

Risk group A

Risk Group B

Risk Group C

(no major risk


factors, no target
organ damage)

One or more major


risk factors
(except diabetes),
no target organ
damage

Target organ
damage and/or
diabetes

High
Normal

Lifestyle
Modification

Lifestyle
Modification

Lifestyle
Modification and
Drug Therapy

Stage 1

Lifestyle
Modification (up
to 12 months)

Lifestyle
Modification and
Drug Therapy

Lifestyle
Modification and
Drug Therapy

Stage 2

Lifestyle
Modification and
Drug Therapy

Lifestyle
Modification and
Drug Therapy

Lifestyle
Modification and
Drug Therapy

Treatment Goals
Short-term goal of antihypertensive therapy:
Reduce blood pressure
Long-term goal of antihypertensive therapy:
Reduce mortality due to hypertension-induced end
organ damage:
Encephalopathy (Stroke)
Left ventricular hypertrophy(LVH)
-Congestive heart failure
Nephropathy

ABP=COPX PVR
=SV X HR X PVR
To BP:

1. LV systolic
performance: negative
Modulators of COP
inotropes and
SV( blood volume, venous
chronotropes
return,
Contractility).
2. blood volume
Heart Rate .
3. venous tone and thus
venous return.
Modulators of PVR
4. PVR

- Diameter of peripheral arterioles

Blood pressure treatment goals

Systolic BP be reduced to less than 140 mmHg


and diastolic BP to less than 90 mmHg in the
general population of patients.

Lower systolic BP goal (<130 &<80 mmHg) in


diabetics and in patients at a very high
cardiovascular risk .

Management of
hypertension

Non pharmacological therapy


Sodium Restriction
DASH high fruit , vegetable, whole grains
& low fat dairy foods

1.
2.

Pharmacological therapy

ABCDEs

ACE inhibitors and AT-II antagonists


-adrenoceptor blockers
Ca2+ channel blockers
Diuretics
Extras: Vasodilators, centrally acting symptholytics,..

Considerations for choice of initial


antihypertensive monotherapy
Target end organ damage (A or B)
Coexisting : IHD(B or C), or
diabetes (A or C).
Renin status (Age). High renin (A
or B), low renin (C or D).
Presence or absence of side effects
to the selected drug.

Ideal antihypertensive drug


(1) decrease
(2) couple

BP

the
antihypertensive
effectiveness with no harmful side effects
(3) provide greater protection against the
organ
damage
associated
with
hypertension.
(4) provide
inhibition of the counterregulatory mechanisms (SNS & Na
retention). i.e. does not cause reflex
tachycardia nor fluid retention

First line antihypertensive drugs (A B C


D ) for simple HTN not associated wih
IHD or diabetes
Hypertension (HTN) can be classified as:
High renin hypertension (younger<55)
Low renin hypertension (elderly>55)
Therefore HTN treated initially with one of two
categories of AHDs:
1-those that inhibit RAS, namely ACE inhibitors
(A) and beta-blockers (B)
2- those that do not, namely calcium channel
blockers (C) and diuretics (D)

I- Diuretics

Indications
Drug of choice for uncomplicated
mild-moderate
HTN
in
elderly
patients (low renin)
Synergistic with other AHDs in
severe HTN

I-a Low dose Thiazide


diuretics

AT start of their use, they lower BP by


causing diuresis leading to a fall in plasma
volume & COP.
After chronic use they cause a reduction in
BP by VD PVR, likely related to shift of
sodium from vascular smooth muscle wall to
ECF.
In low doses, their side effects seem to be
minimized.

Advantages
Well tolerated with few side effects.
Have synergistic effect when added
to other AHDs .
Relatively inexpensive.
Disadvantages
Metabolic adverse effects
(hypokalemia,hypercalcemia etc);
are dose- related.
Lose their effectiveness in renal insufficiency.

I-b Loop diuretics (Furosemide-Lasix)

Loop diuretics are used for hypertension associated


with renal insufficiency.

II- -Adrenoceptor blockers, e.g.


atenolol

Complicated HTN
Drugs of 1st choice for uncomplicated HTN in
high renin patients (<60).
HTN associated with IHD

-Adrenoceptor blockers

Mechanism of blood pressure reduction


Reduction of HR and myocardial contractility
Inhibition of renin release

Types of -blockers
Non cardioselective ,e.g. propranolol
Cardioselective, e.g. atenolol.
Side effects: bronchoconstriction especially by noncardioselective beta blockers.
Contraindications: diabetes mellitus patients treated
with insulin. Because they mask symptoms of
hypoglycemia.

III-Drugs Interacting With the


RAS
Angiotensin converting enzyme
inhibitors(ACEis)

Angiotensin
receptor
blockers(ARBs)

Physiology of ReninAngiotensin System

Physiological Effects of AII:


1. VC of arteries & veins
2. + aldosterone secretion
3. + renal sodium resorption & RBF,
glomerular capillary pressure
4. + LVH
5. Facilitate adrenergic transmission

Mechanism of action of ACEIs


Inhibition of ACE

Angiotensin II
BradykininVD

Angiotensin
I
Inactive
product

Angiotensin
II
CE
Bradykinin

Mechanism of BP by ACEIs
11 aldosterone release salt & water
retention
2. VD of both arterioles & veins
3. Decrease adrenergic activity

Therapeutic Uses in Hypertension


Drug of choice in high renin hypertension (<55)

Drug of choice in hypertension with end organ damage


(nephropathy, LVH)

Drug of choice in hypertension with concomitant:


diabetes mellitus.
Why drug of choice in HTN with diabetes?

Intraglomerular pressure thus reduce proteinuria.

No adverse metabolic effects on blood glucose or lipid


profile

Types of ACE Inhibitors


Active molecules: Captopril,
lisinopril
Prodrugs: Enalapril

All metabolized by liver except


lisinopril by kidney.

Adverse effects of ACEIs


Hypotension esp in volume depleted individuals
2. Cough : dt accumulation of BK in the lung
It is a dry cough. Occur in 30% of patients
3. Angioedema: dt BK
4. Teratogenicity
5. Hyperkalemia
1.

1.
2.
3.
4.

Contra-indication for
ACEIs
Pregnancy
Bilateral renal artery stenosis
Low blood pressure: SBP< 90mmHg
Hyperkalemia

ARBs
Block angiotensin II receptors
Differences vs ACEIs: ARBs do not affect BK
system, No cough and No angioedema

IV-Ca2+ Channel Blockers


Indications in hypertension:
Low renin hypertension when diuretics are
contraindicated.
Hypertension with diabetes in presence of
contraindication to ACEIs & ARBs

CCBs Mechanism of antihypertensive


action
Block calcium channels in the arterial
smooth muscles VDPVR
Block calcium channels in the cardiac
muscles HR & force of contraction
Types;
Dihydropyridines, e.g. nifedipine, amlodipine
Non dihydropyridines, e.g. verapamil &
diltiazem

Dihydropyridines
Nifedipine

Non dihydropyridines
Diltiazem Verapamil

>> selective action on vascular CC

= action on vascular and cardiac CC

Arterial vasodilation++++
Reflex tachycardia

Arterial vasodilation ++
Heart rate
Therefore VD with no reflex tachycardia

Uses :
Essential hypertension
Angina pectoris

Uses :
Essential hypertension
Angina pectoris
Supraventricular arrhythmia

Side effects:
1.Hypotension
2.Reflex tachycardia
3.Flushing

Side effects:
1.Hypotension
2.Bradycardia

Contra-indication: tachyarrhythmia
Can be safely combine with BB

Contra-indication: HF & heart block, severe


bradycardia
Combination with BB is not safe

Vasodilators to A&V: Sodium nitroprusside Acts

by releasing NO that increase


cGMP that dilate A & V.
Clinical use:
Emergency treatment of severe
hypertension
Given by IV infusion( it has a very short t )
Adverse effects
Hypotension,Reflex tachycardia
Prolonged infusion ( more than 72 hrs)
Cyanide

& Thiocyanate accumulation

Preferred antihypertensive drugs


for hypertension in pregnancy
Agent
Methyldopa

labetalol

CCB(nifedipine )

Drug Interactions of AHDs

Prolonged use of NSAIDs e.g. aspirin (>1 week) may


decrease the efficacy of beta-blockers, ACE inhibitors, and
diuretics. (Other pain relievers such as paracetamol can be
used to avoid this side effect.
Caution should be taken when using local anesthesia
(containing adrenaline) with non cardio-selective betablockers (propanolol, nadolol, pindolol & esmolol) as
hypertension may result due to unopposed alpha -1
stimulation.

Dental Management
Guidelines

Defer elective care and provide only urgent


care for patients with Stage 2 HTN or those
experiencing
hypertensive
signs
and
symptoms.
Avoid
long,
stressful
appointments.
Minimize the use of local anesthesia with
vasoconstrictor ( NO more than 2
cartridges per setting).
Raise the chair slowly to avoid orthostatic
hypotension.

Drug Class
Diuretics

Side Effects
Xerostomia, postural
hypotension,

ACE inhibitors

Xerostomia, teeth
discoloration, taste
disturbances
Gingival enlargement,
postural hypotension

Calcium channel
blockers
Alpha-methyl dopa

Salivary gland pain or


swelling

Please be acquainted
:with

other diseases treated with antihypertensive drugs (such as


atenolol, amlodipine,) as headaches, regional pain, renal
failure, glaucoma, and congestive heart failure.
measuring BP will be done in the dental office
to every new patient, for each visit.