There Are Many Classes of Antihypertensives

8/13/2019 There Are Many Classes of Antihypertensives

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INTRODUCTION

Hypertension is the term used to describe high blood pressure. Blood pressure is a measurement

of the force against the alls of the arteries as the heart pumps blood throughout the body. It may

!ary according to age and se" of the patient. B# is measured in mm of mercury $Hg%. High B#

increases the chance of stro&e' heart attac&' heart failure' &idney disease' and early death$Brunton' ()**%.

Classification Systolic pressure Diastolic pressure

mmHg a mmHg a

Normal +),**+ *(,*-.+ ),/+ 0.),*).-

#rehypertension *(), *1+

*.),*0.-

0),0+ *)./,**.+

2tage * hypertension *3),*-+

*0./,(*.(

+),++ *(.),*1.(

2tage ( hypertension 4*) 4(*.1 4*)) 4*1.1

Table 15 2hoing classification of hypertension $6bate et al.' ())-%.

7any factors can affect blood pressure such as ho much ater and salt present in the body8 the

condition of &idneys' ner!ous system' or blood !essels8 and the le!els of different body

hormones $9a et al.' ())1%. 2ome causes of higher ris& of hypertension are5

: Obesity

: stressed or an"ious

: Too much salt inta&e

: ;amily history: Diabetes

: 2mo&e

7ost of the time' there are no symptoms of hypertension. Hoe!er' symptoms that may occur

include confusion' ear noise or buasodilators

1
http://en.wikipedia.org/wiki/MmHghttp://en.wikipedia.org/wiki/Pascal_(unit)http://en.wikipedia.org/wiki/Medicationhttp://en.wikipedia.org/wiki/Hypertensionhttp://en.wikipedia.org/wiki/Antihypertensive_drug#Diureticshttp://en.wikipedia.org/wiki/Antihypertensive_drug#Adrenergic_receptor_antagonistshttp://en.wikipedia.org/wiki/Antihypertensive_drug#Calcium_channel_blockershttp://en.wikipedia.org/wiki/Antihypertensive_drug#Renin_Inhibitorshttp://en.wikipedia.org/wiki/Antihypertensive_drug#ACE_inhibitorshttp://en.wikipedia.org/wiki/Antihypertensive_drug#Angiotensin_II_receptor_antagonistshttp://en.wikipedia.org/wiki/Antihypertensive_drug#Aldosterone_antagonistshttp://en.wikipedia.org/wiki/MmHghttp://en.wikipedia.org/wiki/Pascal_(unit)http://en.wikipedia.org/wiki/Medicationhttp://en.wikipedia.org/wiki/Hypertensionhttp://en.wikipedia.org/wiki/Antihypertensive_drug#Diureticshttp://en.wikipedia.org/wiki/Antihypertensive_drug#Adrenergic_receptor_antagonistshttp://en.wikipedia.org/wiki/Antihypertensive_drug#Calcium_channel_blockershttp://en.wikipedia.org/wiki/Antihypertensive_drug#Renin_Inhibitorshttp://en.wikipedia.org/wiki/Antihypertensive_drug#ACE_inhibitorshttp://en.wikipedia.org/wiki/Antihypertensive_drug#Angiotensin_II_receptor_antagonistshttp://en.wikipedia.org/wiki/Antihypertensive_drug#Aldosterone_antagonists


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Figure 15 The potential site of action for antihypertensi!e drugs $#iasci&'())%.

DIUR=TIC2

Diuretic drugs increase urine output by the &idney $i.e.' promote diuresis%. This is accomplished

by altering ho the &idney handles sodium. If the &idney e"cretes more sodium' then ater

e"cretion ill also increase. In general' the primary goal of diuretic therapy is to reduce

e"tracellular fluid !olume in order to loer blood pressure. 7ost diuretics produce diuresis by

inhibiting the reabsorption of sodium at different segments of the renal tubular system

$?labunde' ()**%. Types of diuretics are5@ 9oop diuretics5 2ome drugs of this group are5 ;urosemide

=thacrynic acid

Bumetanide

Torsemide

@ Thia


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Figure 25 2pecific segments in the nephron targeted by diuretics $Thomas' ()))%.

7=CH6NI27 O; 6CTION5

*% 9oop diuretics5

Figure 35 Inhibition of sodium@potassium@chloride cotransporter by loop diuretics.

9oop diuretics inhibit the sodium@potassium@chloride cotransporter in the thic& ascending limb.

This transporter normally reabsorbs about (-A of the sodium load8 therefore' inhibition of this

pump can lead to a significant increase in the distal tubular concentration of sodium' reducedhypertonicity of the surrounding interstitium' and less ater reabsorption in the collecting duct.

This altered handling of sodium and ater leads to both diuresis $increased ater loss% and

natriuresis $increased sodium loss%. By acting on the thic& ascending limb' hich handles a

significant fraction of sodium reabsorption' loop diuretics are !ery poerful diuretics. 9oop

diuretics cause an increase in the renal blood flo by this mechanism. This diuresis lea!es less

ater to be reabsorbed into the blood' resulting in a decrease in blood !olume $#iasci&'())%.

3


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(% Thia


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The HCO1@is transported across the basolateral membrane. His secreted into the tubular lumen

in e"change for Na. The Hcombines ith a filtered HCO1@$using C6% to form H(CO1hich

immediately dissociates into H(O and CO(that is reabsorbed. Therefore' filtered bicarbonate isreabsorbed for e!ery Hsecreted $2upuran and 2co


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muscle cramps

s&in rash

raised uric acid le!els $that can lead to &idney problems and gout%

raised blood sugar le!els $Blood #ressure 6ssociation' ())+%

Feneric name Brand name Dosage form Type 7anufactured by

Hydrochlorothia


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Figure 75 The mechanism of adrenergic receptors. Figure 85 6drenergic receptor subtype

characteri


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7=CH6NI27 O; 6CTION5 @bloc&ers are pharmacological agents that act as receptor

antagonists of @adrenergic receptors $@adrenoceptors%.

It acts by binding ith the @adrenergic receptors and bloc&s noradrenaline$norepinephrine% or

adrenaline$epinephrine% from binding ith the receptors. Thus@

: It decreases arterial and !enous !asoconstriction and conseuently decrease of peripheral

resistance and loering of arterial pressure

: It decreases platelet aggregation

: It facilitates bladder e!acuation $;lynn' ()*)%

B=T6@B9OC?=R25 J@bloc&ers are the drugs that competiti!ely bloc& beta@adrenergic

substances $endogenous catecholamines , eg. adrenaline% to bind ith the beta receptors of the

in!oluntary ner!ous system $autononomic ner!ous system% $Cruic&shan&' ()*)%.

7=CH6NI27 O; 6CTION5 This specific class of drugs or&s to bloc& the binding sites for

epinephrine and norepinephrine on the adrenergic receptors $J* and J(% found on myocardial

tissue. By bloc&ing the binding sites of these catecholamines' the o!erall effect is leads toreduced heart rate' along ith increased !asodilation of blood !essels resulting in a loering of

blood pressure $;reemantle et al.' *+++%

Figure 95 The mechanism of action of beta@bloc&ers

Generic name Brand name Dosage form Type Manufactured by

Bisoprolol

;umarate

Bisocor Tablet

Beta Bloc&ers 2uare #harmacuetics6tenolol Cardipro Tablet

Car!edilol Durol Tablet7i"ed 6lpha

Beta bloc&ers

7etoprolol

tartrate

#resonilTablet

Beta Bloc&ersIncepta #harmacuetics

Table 35 2hoing some diuretics a!ailable in Bangladesh $Incepta #harmaceuticals 9td.' *+++8

2uare #harmaceuticals 9td.' *+0-).

8
http://en.wikipedia.org/wiki/Noradrenalinehttp://en.wikipedia.org/wiki/Adrenalinehttp://www.inceptapharma.com/view-product.php?pid=104http://en.wikipedia.org/wiki/Noradrenalinehttp://en.wikipedia.org/wiki/Adrenalinehttp://www.inceptapharma.com/view-product.php?pid=104


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C69CIU7 CH6NN=9 B9OC?=R2

Calcium channel or !oltage@dependent calcium channel is an ion channel hich displaysselecti!e permeability to calcium ions. 6t physiologic or resting membrane potential' channels

are normally closed. They are acti!ated $i.e.' opened% at depolari


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less contraction of the !ascular smooth muscle

increase in arterial diameter $CCBs do not or& on !enous smooth muscle%' a

phenomenon called !asodilation

blood pressure drops $Nelson' ()*)%.

2ide effects of Calcium Channel Bloc&ers are5

Di


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6ldosterone causes the tubules of the &idneys to increase the reabsorption of sodium and ater

into the blood. This increases the !olume of fluid in the body' hich also increases blood

pressure. If the renin@angiotensin@aldosterone system is too acti!e' blood pressure ill be toohigh $Ba&ris' ())/%.

Figure 115 The renin@angiotensin@aldosterone system $R662%

7=CH6NI27 O; 6CTION5 Renin inhibitors are antihypertensi!e drugs that inhibit the first

stepof the renin@angiotensin@aldosterone system$R662%. Renin inhibitors bind to the acti!e siteof renin and inhibit the binding of renin to angiotensinogen. By inhibiting the R662 at the

beginning renin inhibitors pre!ent the formation of 6ng I and 6ng II. This pre!ents ater and

salt retention and arteriolar !asoconstriction. Thus renin inhibitors are effecti!e in loering

blood pressure $Bron' ())-%.

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http://genewikiplus.org/wiki/Renin_inhibitorhttp://genewikiplus.org/index.php?title=Antihypertensive_drug&action=edit&redlink=1http://genewikiplus.org/wiki/Enzyme_inhibitorhttp://genewikiplus.org/wiki/Rate-determining_stephttp://genewikiplus.org/wiki/Rate-determining_stephttp://genewikiplus.org/wiki/Renin-angiotensin-aldosterone_systemhttp://genewikiplus.org/wiki/Active_sitehttp://genewikiplus.org/wiki/Renin_inhibitorhttp://genewikiplus.org/index.php?title=Antihypertensive_drug&action=edit&redlink=1http://genewikiplus.org/wiki/Enzyme_inhibitorhttp://genewikiplus.org/wiki/Rate-determining_stephttp://genewikiplus.org/wiki/Rate-determining_stephttp://genewikiplus.org/wiki/Renin-angiotensin-aldosterone_systemhttp://genewikiplus.org/wiki/Active_site


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2cientists ha!e been trying to de!elop potent inhibitors ith acceptable oral bioa!ailability

$Fross et al.' *+/(%. The process as difficult and too& about three decades. The first and second

generations faced problems li&e poor bioa!ailability and lac& of potency. ;inally the third

generation as disco!ered. Thesecompoundsere non@peptidicrenin inhibitors' had acceptable

oral bioa!ailability and ere potent enough for clinical use. The first drug in this class as

alis&iren hich recei!ed a mar&eting appro!al in ())/. 6s of anuary ()*(' it is the only renin

inhibitor on the mar&et $ensen et al.' ())0%

6C= INHIBITOR2 G 6NFIOT=N2IN R=C=#TOR B9OC?=R2

6s discussed pre!iously that in renin@angiotensin@aldosterone system $R662%' the &idneys

produce renin for maintaining normal blood pressure. The renin stimulates the formation of the

protein' angiotensin I' hich is then con!erted to angiotensin II by the angiotensin@ con!ertingen


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Figure 125 The mechanism of action of 6C=.Common ad!erse drug reactionsof 6C= inhibitors include5 hypotension'cough' hyper&alemia'

headache' di


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Figure 135 The mechanism of action of 6RB.

Generic name Brand name Dosage form Type Manufactured by

9osartan #otassium 6ngiloc& Tablet

6RB

2uare

#harmacueticsOlmesartan7edo"omil

Olmecar Tablet

6mlodipine Besylat

e and Olmesartan

7edo"omilBizoran

Tablet6RB and calcium

channel bloc&er

Be"imco

#harmacuetics

Table 65 2hoing some 6RB a!ailable in Bangladesh $Be"imco #harmaceuticals 9td' 2005;

2uare #harmaceuticals 9td.' *+0-).

>62ODI96TOR2

>asodilators are medications that open $dilate% blood !essels. They or& directly on the muscles

in the alls of your arteries' pre!enting the muscles from tightening and the alls from

narroing. 6s a result' blood flos more easily through the arteries' the heart doesnLt ha!e to

pump as hard and your blood pressure is reduced $Fuyton and Hall' ())%.

7=CH6NI27 O; 6CTION5 >asodilation is the result of rela"ation in smooth muscle

surrounding the blood !essels. This rela"ation' in turn' relies on remo!ing the stimulus for

contraction' hich depends on intracellular calcium ion concentrations and' conseuently'

phosphorylationof the light chain of the contractile protein myosin. Thus' !asodilation mainly

or&s either by loering intracellular calcium concentration or the dephosphorylation of myosin

$Mebb' ())1%.

14
http://www.squarepharma.com.bd/SPL_PI_PDF/p21.pdfhttp://www.squarepharma.com.bd/SPL_PI_PDF/p455.pdfhttp://www.beximco-pharma.com/cardiovascular/353-bizoran.htmlhttp://en.wikipedia.org/wiki/Smooth_musclehttp://en.wikipedia.org/wiki/Phosphorylationhttp://en.wikipedia.org/wiki/Myosinhttp://www.squarepharma.com.bd/SPL_PI_PDF/p21.pdfhttp://www.squarepharma.com.bd/SPL_PI_PDF/p455.pdfhttp://www.beximco-pharma.com/cardiovascular/353-bizoran.htmlhttp://en.wikipedia.org/wiki/Smooth_musclehttp://en.wikipedia.org/wiki/Phosphorylationhttp://en.wikipedia.org/wiki/Myosin


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Figure 145 The mechanism of action of 7ino"idil.

>asodilators are strong medications and are generally used only as a last resort' hen other

medications ha!enLt adeuately controlled blood pressure.These medications ha!e a number of

side effects' some of hich reuire ta&ing other medications to counter those effects. 2ide effects

include5

Chest pain

Rapid heartbeat $tachycardia%

Heart palpitations

;luid retention $edema%

Nausea

>omiting

Di


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Change in lifestyle can help to loer blood pressure in some cases li&e losing eight if one is

o!ereight' regular physical acti!ity' a healthy diet' cutting bac& if you drin& a lot of alcohol'

stopping smo&ing' and a lo salt and caffeine inta&e $Milliams' ())1%.

If one does some physical acti!ity on fi!e or more days of the ee&' for at least 1) minutes' for

e"ample' bris& al&ing' simming' cycling' dancing' etc.' it can reduce systolic blood pressureby (@*) mm Hg. =ating a !ariety of fruit and !egetables and starch@based foods $such as cereals'

holegrain bread' potatoes' rice' pasta%8 not eating much fatty food such as fatty meats' cheeses'

full@cream mil&' fried food' butter' etc.8 limiting salt in diet8 using !egetable oil to fry and lean

meat can help can loer systolic blood pressure by up to ** mm Hg. Cutting bac& on hea!y

drin&ing to the recommended limits $i.e. one unit is in about half a pint of normal@strength beer'

or to thirds of a small glass of ine' or one small pub measure of spirits% can loer a high

systolic blood pressure by up to *) mm Hg. It is estimated that dietary and e"ercise inter!entions

that are discussed can reduce blood pressure by at least *) mm Hg in about * in 3 people ith

high blood pressure $#atient.co.u&' *++/%.

If lifestyle changes are ineffecti!e to loer blood pressure then it is ad!ised to loer blood

pressure ith the help of medication. Blood pressure !accinations are no being trialed and may

become a treatment option for high blood pressure in the future $Bron' ())+%.

R=;=R=NC=

6bate' 7.' 6bel' 2.' R.' 6c&ermann' B.' 9. et al $())-%&emi'gto' T!e "cie'ce a'$ ractice o*

!armac+. (*thedn. (nd!olume. #hiladelphia5 9ippincott Milliams G Mil&ins.

Be"imco #harmaceuticals 9td $())-% ,ur ro$uct &a'ge -ar$ioa"cularP/ailable at

http5EE.be"[email protected]@productsEour@product rangeEcardio!ascular.html

$6ccessed5 (nd 6pril ()*(%

Blood #ressure 6ssociation $())+% iuretic" bloo$ re""ure me$icatio'.P6!ailable at5

http5EE.bpassoc.org.u&EBlood#ressureandyouE7edicinesE7edicinetypesEDiuretics$6ccessed5 (nd 6pril ()*(%.

Bron' 7 $())+%. 2uccess and failure of !accines against renin@angiotensin system

16
http://www.bpassoc.org.uk/BloodPressureandyou/Medicines/Medicinetypes/Diureticshttp://www.bpassoc.org.uk/BloodPressureandyou/Medicines/Medicinetypes/Diuretics


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components.Pature reie". -ar$iolog+ $*)%5 1+,3/.

Bron' 7. . $())%. Direct renin inhibition Q a ne ay of targeting the renin system.P

our'al o* &e'i'/'giote'"i'/l$o"tero'e +"tem' /$( suppl%' 2/@2**.

Brunton' 9.' 9. $ed.% $()**% oo$ma' a'$ ilma'" t!e !armacological ba"i" o* t!eraeutic".*(thedn. (nd!olume. Ne or&5 7c Fra Hill.

Chen@I


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?labunde, R., 2. "#$))& Cardiovascular Physiology Concepts#ndedn. Ne or&5 9ippincott

Milliams G Mil&ins

?umar' 6. and ;austo' 6. $()*)%.at!ologic Ba"i" o* i"ea"e0thedn. #hiladelphia5 2aunders

=lse!ier. p. 3+1.

9a' 7.' Mald' N.' and 7orris' . $())1% 9oering blood pressure to pre!ent myocardial

infarction and stro&e5 a ne pre!enti!e strategy.Pealt! Tec!'ol /""e""%/ $1*%5 *,+3.

9ee' Hon@Cheung $())% K#harmacology of Diuretic Drugs.K */ No!. Uni!ersity of 7innesota

Ma6off, D. $())-% 6RBs G 6C= Inhibitors...#oerful Blood #ressure Treatments.P >eb

Na

Documents

There Are Many Classes of Antihypertensives