زائر
It is nw we-estabished that hypetensin nfes an ineased isk f heat attaks and stkes and that teatment f high bd pesse edes this isk. We nw have a wide vaiety f antihypetensive agents, athgh mst an be assified int ne f five maj asses (see Pane 1). Eah f these asses has meits and disadvantages, as we as aniay ppeties that infene the hie f a patia patient. In additin, many patients eqie me than ne agent t nt thei bd pesse and ths, the hie f mbinatin theapy, with apppiate synegisti effets f the dgs, bemes simiay imptant
Pane 1: main asses f antihypetensive dgs
Dietis
beta-bkes
aim hanne bkes
AE inhibits
apha1-bkes
hie f dg
With the wide vaiety f antihypetensive agents avaiabe, whih is the idea dg t se? The yni wd age that the idea antihypetensive dg des nt eay exist. Hweve, when assessing thse that ae avaiabe t s, it is imptant t bea in mind the ppeties that make p an idea dg f the nt f hypetensin. The idea dg shd have a peditabe dse-espnse ve, as we as an aeptabe, egnised side effet pfie. Bd pesse tends t be highest fist thing in the mning and this is when the majity f adia events and, theefe, 24-h nt has been egnised as imptant. A sht-ating dg, even if taken the evening befe, may have wn ff by the time the patient ises in the mning, wheeas a dg with a nge haf-ife wd sti be pteting the patient. A dg with a ng haf-ife as has the advantage f ny being taken ne daiy. This may impve mpiane, sine p t 30 pe ent f patients miss a dse at east weeky.
As the ppse f teating hypetensin is t ede the inidene f hypetensive mpiatins (patiay nay heat disease and stke), the idea dg shd have tia evidene t pve that it ahieves these ends, as we as simpy weing bd pesse. This is nt t say that the dgs d nt pevent mpiatins bt simpy that the evidene fm age-sae tias is nt thee. Advates f the dgs an pint t edtins in sgate makes, sh as eft ventia hypetphy (VH) edtin f mipteinia, t indiate thei effetiveness. age sae tias, sh as AHAT (Antihypetensive and ipid weing Heat Attak Tia) and AST (Ang-Sandinavian tmes Tia), whih mpae newe dgs, sh as aim hanne bkes and the AE inhibits, with the we-estabished ß-bkes and dietis, ae enty in pgess.
Dietis
Thiazide dietis Thiazide dietis ede the eabsptin f sdim and hide in the eay pat f the dista nvted tbe f the kidney. This ests in the deivey f ineased amnts f sdim t the dista tbe, whee sme f it is exhanged f ptassim. The net est is ineased exetin f sdim, ptassim and wate. iating vme is diminished, eding pead n the heat and, ths, adia tpt and bd pesse. With ng-tem theapy, ategatin by the bdy’s wn mpensaty mehanisms ests in vasdiatatin, edtin f peiphea vasa esistane and etn f the adia tpt t nma. Thiazides as have sme diet vasdiaty ppeties.
Thiazides ae apidy absbed ay and pde a pnged diesis. They tend t pde a maxima espnse at eativey w dses, sh as 12.5mg hyd-hthiazide 1.25mg bendfazide. Fthe ineases in dse simpy inease side effets with itte fthe effet n bd pesse. n the whe, standad dses f thiazides we bd pesse as mh as the fist-ine antihypetensives. In sme patient gps, sh as baks and the edey, the thiazides ae patiay effiais. Hweve, they tend t be ess effetive in ynge, white patients.
Thiazides ae ne f the asses f antihypetensive that have been extensivey tested in age inia tias. In eay tias, thiazides eded the inidene f stke by 40 pe ent, athgh the edtin in nay heat disease was disappinting. This may have been de t the advese metabi effets f the age dses sed. Me eent tias, sing we dses, have demnstated impessive edtins in bth stke and nay heat disease, espeiay in the edey.
Thee is itte t hse between the vais thiazides, athgh it seems pdent t se agents, sh as hydhthiazide and bendfazide, that have been pved t be effetive at w dses in inia tias. Newe agents, sh as indapamide, have fewe metabi side effets, and may even egess hypetensive VH n ehadigaphy. Advese effets The main nens abt thiazide dietis ae thei metabi side effets, athgh, at w dses, these ae ess ikey t be a pbem. They may ase hypkaaemia de t ena ptassim wasting. Hypkaaemia may give ise t ventia ahythmias and ase advese dg effets in patients taking digxin dgs that png the QT inteva n the EG (eg, ass I antiahythmis, tiyi antidepessants, antihistamines).
Ate gt is anthe mmn side effet f thiazides, even in w dses. Hypeiaemia an be pesent in abt 30 pe ent f a hypetensives bt it is a p pedit f ate gt. Imptene may asinay be a pbem.
Thiazides an inease sem D-heste and tigyeide eves bt this is mh ess f a pbem with mden w dses. Thee is as sme evidene that dietis impai gse teane and inease insin esistane. Hweve, epts f fank diabetes ae ae. Athgh thiazides pbaby shd be avided as fist-ine dgs in patients with diabetes and thse with hypeipidaemia, thee shd be n anxiety abt adding them in whee neessay. ae side effets inde nasea, headahe, ashes, phtsensitivity and bd dysasias.
the dietis p dietis at n the asending imb f the p f Hene and inhibit the eabsptin f hide, sdim and ptassim. They pde a bisk bt sht-ived diesis and ae ths nsitabe as fist-ine agents f hypetensin, as they d nt pvide 24-h nt. Hweve, they d have a e in patients with impaied ena fntin in whm thiazides ae ineffetive, and in patients with hypetensin esistant t mtipe dg theapy, wh ae ften fid veaded. Ftheme, they may be synegisti with agents sh as the AE inhibits.
Ptassim-spaing dietis, sh as amiide and tiamteene, pde itte edtin in bd pesse themseves. They may be sef in mbinatin with the dietis t pevent hypkaaemia. Spinatne is a speifi adstene antagnist, with a patia e in pimay hypeadstenism nn’s syndme. Beta-bkes
Beta-bkes at by bking the atin f nadenaine at b adenepts thght the iaty system and esewhee. Thei maj effet is t sw the heat ate and ede its fe f ntatin. beta-bkes as ase sme edtin in enin eease and enta sympatheti tne.
Beta-bkes may be sbdivided ading t thei aniay ppeties. F exampe, b1 adiseetive agents, sh as aten, have ess atin n b2 eepts in the bnhi and peiphea vesses mpaed with nn-seetive agents, sh as ppan. This edes (bt des nt abish) b2 eept-mediated side effets. ipid-sbe agents, sh as ppan and metp, ss the bd-bain baie me eadiy and ae assiated with a highe inidene f enta side effets. Sme beta-bkes, sh as pind, have intinsi sympathmimeti ativity (ie, they stimate b eepts when bakgnd sympatheti nevs ativity is w and bk them when bakgnd sympatheti nevs ativity is high). They, theefe, ase ess badyadia and pssiby fewe pbems with d extemities than nventina beta-bkes. Hweve, in patie, they ae itte sed in the teatment f hypetensin.
abeta and avedi have bth a- and b1-bking ppeties, asing a edtin in peiphea vasa esistane, as we as swing the heat ate. In additin t its b1-bking ppeties, avedi as has antixidant effets, whih give it theetia advantages in eding endtheia damage and weing eves f highy athegeni xidised D-heste. Hweve, bth abeta and avedi have the disadvantage f pssessing the side effets f bth asses f dg.
Beta-bkes ae sef as fist-ine antihypetensive agents, athgh they tend t be ess effetive in the edey and in bak hypetensives. F the teatment f hypetensin it is best t hse a beta-bke with high adiseetivity and w ipid sbiity t ede side effets. A ng haf-ife as aws ne daiy dsing.
Advese effets Mst f the side effets f beta-bkes ae peditabe fm thei mde f atin. F exampe, they sw the ate f ndtin at the ati-ventia nde and ae ths ntaindiated in patients with send- and thid-degee heat bk. Sins badyadia is mmn and is nt a easn t stp beta-bkes ness the patient is symptmati the heat ate fas bew 40 beatsminte.
Even sma dses f ß-bkes an ase bnhspasm de t bkade f pmnay b2 eepts, athgh the pbem is ess mmn with adiseetive agents. Even s, a beta-bkes ae ntaindiated in asthma. Bkade f b eepts in the peiphea iatin ases vasnstitin, at east in the immediate tem, and the dgs ae, theefe, ntaindiated in patients with est ishaemia f the egs. Nevetheess, they ae easnaby teated in thse with esse degees f peiphea vasa disease. ipid-sbe agents an ase enta nevs system side effets f insmnia, nightmaes and fatige. Exeise apaity may be eded by beta-bkes and patients may expeiene tiedness and fatige. As with mst antihypetensives, imptene has been epted, athgh ates ae itte highe than with paeb.
ike dietis, ß-bkes an wsen gse inteane and hypeipidaemia. In diabeti patients pne t hypgyaemia, beta-bkes may, theetiay, ede the awaeness f w bd gse. Nevetheess, many diabeti hypetensives have gd easns, sh as a pevis myadia infatin, t be n a beta-bke and shd nt be denied them bease f nens abt metabi side effets.
aim hanne bkes
aim hanne bkes, thewise knwn as aim antagnists, at by intefeing with the atin f aim hannes in the e membane. This edes the infw f aim, smth mse ntatin and eetia ndtivity.
aim hanne bkes may be divided int tw asses — the dihydpyidines and the nn-dihydpyidines. The dihydpyidines, sh as nifedipine and amdipine, at pedminanty by asing peiphea vasdiatatin. The nn-dihydpyidines, sh as veapami and ditiazem, as sw the heat ate and ati-ventia nde ndtin. A aim hanne bkes ae effiais at eding bd pesse as singe agents.
The de dgs, sh as nifedipine, have sht haf-ives and may ase apid vasdiatatin, a efex tahyadia and atehamine sges. This may inease advese effets and aggavate myadia ishaemia. nge-ating agents, sh as amdipine sw-eease pepaatins f nifedipine, patiay veme these pbems.
nti atey, the aim hanne bkes aked tia evidene t sppt thei se in hypetensin. In the mid-1990s, a seies f phamasveiane ase-nt stdies sggested that the sht-ating dihydpyidine dgs (sh as nifedipine apses) atay ineased the isk f heat attaks.1 eent data fm the Syst-E tia demnstated that antihypetensive teatment f the edey with the sht-ating dihydpyidine aim hanne bke, nitendipine, nviningy eded stkes and heat attaks, witht an inease in nditins pevisy attibted t the aim hanne bkes, sh as tms, beeding and nn-adia death.2
Advese effets The main, and mst tbesme, side effet f aim hanne bkes is anke edema. This is ased by vasdiatatin, whih as ases headahe, fshing and papitatin, espeiay with sht-ating dihydpyidines. Sme f these side effets an be ffset by mbining a aim hanne bke with a b-bke.
Veapami edes intestina mtiity and, ths, an ase signifiant nstipatin. Me seisy, it an ase heat bk, espeiay in thse with ndeying ndtin pbems. Ditiazem an simiay ase gastintestina and ndtin pbems, athgh ess feqenty than veapami. Veapami, ditiazem and sht-ating dihydpyidines ae best avided in patients with heat faie.
Apha-bkes
The a1 adenept bkes pde vasdiatatin by bking the atin f n-adenaine at pst-synapti a1 eepts in bth ateies and veins. This ests in a fa in peiphea esistane, witht a mpensaty ise in adia tpt. The pttype a1-bke — pazsin — is sht ating and tends t pde peipits fas in bd pesse, bt the nge ating dxazsin mbines the advantage f a me gente edtin in bd pesse with ne daiy dsing.
The a1-bkes pde edtins in bd pesse mpaabe t fist-ine antihypetensive dgs. They seem t be patiay sef as a thid dg, pding gd fas in bd pesse whee tw agents mbined have faied. In ntast t the b-bkes and dietis, a1-bkes atay pde mdest impvements in sem ipids and gse teane bt whethe this tansates int impved tmes is nt knwn, patiay with the paity f tme data with these agents.
Advese effets a1-bkes ae, n the whe, we teated. Thei main side effet is psta hyptensin, whih is me mmny ased by shte-ating agents. In wmen, a1-bkes may ase inay inntinene. In men, they may impve the symptms f benign pstati hypetphy. ike mst antihypetensive dgs, a1-bkes an ase headahe and fatige.
AE inhibits
Angitensin nveting enzyme (AE) inhibits have beme ineasingy ppa ve the past deade. They wk by bking the enin-angitensin system, inhibiting the nvesin f the inative angitensin I t the pwef vasnstit and stimat f adstene eease, angitensin II (see Fige 1). This ests in deeased peiphea vasa esistane and as a edtin in the eves f the sdim-etaining hmne — adstene.
Fige 1: The enin-angitensin systems and its inhibits
AE inhibits as ede the beakdwn f the vasdiat badykinin, whih may enhane thei atin bt is as espnsibe f thei mst tbesme side effet f gh. Ftheme, AE inhibits may impve endtheia fntin and ede enta adenegi tne. They as have benefiia effets n ena haemdynamis, eding intagmea hypetensin, esting in impvements in pteini ena disease. AE inhibits ae effetive as singe agents in hypetensin. Thee is geneay itte t hse between the age nmbe f AE inhibits avaiabe. eenty, the aptpi Peventin Pjet (APP) stdy demnstated that aptpi was as effetive as taditina antihypetensive agents (mainy thiazides and b-bkes) in peventing advese tmes in hypetensin.3 the agents, sh as fsinpi, have the advantage f hepati as we as ena exetin and ae (theetiay, at east) ess ikey t amate in patients with ena faie. Peindpi, amipi and tandapi ae agents with ng haf-ives, whih pvide gd 24-h antihypetensive veage.
Thee is sef synegism between the AE inhibits and dietis and between AE inhibits and aim hanne bkes. The AE inhibits ae patiay sef in diabeti hypetensives, in whm they may be enptetive, as they sw the pgessin f diabeti nephpathy.4 Ftheme, these agents have shwn sme benefits in impving diabeti etinpathy and even diabeti nepathy.5,6 Hweve, the AE inhibits tend t be ess effetive as antihypetensive agents in bakAf-aibbean hypetensives and in the edey, wh tend t have we enin eves than the genea ppatin. Nevetheess, this eative ineffetiveness an be veme by sing high dses adding a dieti.
Advese effetsgh, ased by the inhibitin f badykinin beakdwn, is the mst mmn side effet f AE inhibits, ing abt five times me ften than with paeb. gh is me mmn in wmen and de patients.7 The fa me seis, bt ae, side effet f the AE inhibits is angiedema, whih s in abt 0.1 t 0.2 pe ent f patients.
Damati deteiatin in ena fntin an in patients with biatea ena atey stensis. Sem ea and eatinine shd, theefe, be heked befe and a few weeks afte stating an AE inhibit. This shd nt pevent the se f AE inhibits in thse with the fms f ena disease. In these patients, AE inhibits ae ften agents f fist hie, in view f data shwing that they sw the pgessin f diabeti and nn-diabeti nephpathy.
The AE inhibits an ase hypekaaemia bease they ede adstene and, ths, ptassim exetin. Fist-dse hyptensin is pbaby an vestated side effet f AE inhibits bt age dses f sht ating aptpi an ase sdden fas in bd pesse, espeiay in thse with vme depetin, sh as heat faie patients n age dses f dietis. ae side effets inde ash, taste distbane, bd dysasias and a symptm mpex that indes feve and vasitis.
Angitensin II antagnists
ike the AE inhibits, these dgs at n the enin-angitensin system, bking the atin f angitensin II at its peiphea eepts. As they d nt inhibit the beakdwn f badykinin, they d nt ase gh. Hweve, they may ak the additina physigia benefits that ises in badykinin eves may bing. Angitensin II antagnists have simia physigia effets t AE inhibits and pde simia fas in bd pesse. Thee is synegism f antihypetensive effet with thiazide dietis. Thee is as evidene that they may egess VH and impve pteinia.8,9
Advese effets The main advantage f the angitensin II antagnists is thei appaent ak f side effets. ike the AE inhibits, they may ase hypekaaemia, ena impaiment and hyptensin bt, thewise, they ae amst as we teated as paeb. Nevetheess, ases f angiedema have been epted with sme f these agents. de antihypetensive agents
A nmbe f de antihypetensive dgs sti have a e in sme speia sitatins (eg, pegnany) and in esistant hypetensin. These dgs ae ppa in nties whee hypetensive patients ae n w inmes and have t pay f thei wn mediatin, bease they ae heap.
enta apha-bkes These dgs stimate enta a2 adenepts, esting in a deease in enta sympatheti tne. This eads t a fa in bth adia tpt and peiphea vasa esistane. Exampes f sh dgs inde methydpa and nidine. The dgs ase sedatin, dy mth and fid etentin. Methydpa an as ase atimmne hepati deangement and haemyti anaemia. Hweve, it is safe t se in hypetensive pegnant wmen and is mmny sed in sh patients. A new entay ating dg, mxnidine, ats n enta imidazine eepts and is hped t have the benefiia effets f entay-ating dgs, witht thei side effets.
Diet vasdiats These agents at diety t eax vasa smth mse, theeby eding peiphea vasa esistane. The esting ativatin f the sympatheti nevs system means that they an ny sessfy be sed in mbinatin with dgs that bk sympatheti ativity. Exampes inde hydaazine, whse main side effet is a ps-ike syndme, and minxidi. Minxidi ases hai gwth, a side effet wemed by many midde aged men bt nt by thei femae ntepats.
Adenegi nene bkes Sh agents ae nw aey sed in the nited Kingdm. esepine and ganethidine inhibit the eease f nadenaine fm peiphea neves. This edes sympatheti tne, peiphea vasa esistane and adia tpt. They ase psta hyptensin and enta nevs system depessin. Sma dses f esepine, mbined with a dieti, fm an effetive egimen and ae sed when w sts ae paamnt, espeiay in deveping nties.
تحياتي ................هاي االمحاضره الاوللى والبقيه ان شاء الله في القريب العاجل
Pane 1: main asses f antihypetensive dgs
Dietis
beta-bkes
aim hanne bkes
AE inhibits
apha1-bkes
hie f dg
With the wide vaiety f antihypetensive agents avaiabe, whih is the idea dg t se? The yni wd age that the idea antihypetensive dg des nt eay exist. Hweve, when assessing thse that ae avaiabe t s, it is imptant t bea in mind the ppeties that make p an idea dg f the nt f hypetensin. The idea dg shd have a peditabe dse-espnse ve, as we as an aeptabe, egnised side effet pfie. Bd pesse tends t be highest fist thing in the mning and this is when the majity f adia events and, theefe, 24-h nt has been egnised as imptant. A sht-ating dg, even if taken the evening befe, may have wn ff by the time the patient ises in the mning, wheeas a dg with a nge haf-ife wd sti be pteting the patient. A dg with a ng haf-ife as has the advantage f ny being taken ne daiy. This may impve mpiane, sine p t 30 pe ent f patients miss a dse at east weeky.
As the ppse f teating hypetensin is t ede the inidene f hypetensive mpiatins (patiay nay heat disease and stke), the idea dg shd have tia evidene t pve that it ahieves these ends, as we as simpy weing bd pesse. This is nt t say that the dgs d nt pevent mpiatins bt simpy that the evidene fm age-sae tias is nt thee. Advates f the dgs an pint t edtins in sgate makes, sh as eft ventia hypetphy (VH) edtin f mipteinia, t indiate thei effetiveness. age sae tias, sh as AHAT (Antihypetensive and ipid weing Heat Attak Tia) and AST (Ang-Sandinavian tmes Tia), whih mpae newe dgs, sh as aim hanne bkes and the AE inhibits, with the we-estabished ß-bkes and dietis, ae enty in pgess.
Dietis
Thiazide dietis Thiazide dietis ede the eabsptin f sdim and hide in the eay pat f the dista nvted tbe f the kidney. This ests in the deivey f ineased amnts f sdim t the dista tbe, whee sme f it is exhanged f ptassim. The net est is ineased exetin f sdim, ptassim and wate. iating vme is diminished, eding pead n the heat and, ths, adia tpt and bd pesse. With ng-tem theapy, ategatin by the bdy’s wn mpensaty mehanisms ests in vasdiatatin, edtin f peiphea vasa esistane and etn f the adia tpt t nma. Thiazides as have sme diet vasdiaty ppeties.
Thiazides ae apidy absbed ay and pde a pnged diesis. They tend t pde a maxima espnse at eativey w dses, sh as 12.5mg hyd-hthiazide 1.25mg bendfazide. Fthe ineases in dse simpy inease side effets with itte fthe effet n bd pesse. n the whe, standad dses f thiazides we bd pesse as mh as the fist-ine antihypetensives. In sme patient gps, sh as baks and the edey, the thiazides ae patiay effiais. Hweve, they tend t be ess effetive in ynge, white patients.
Thiazides ae ne f the asses f antihypetensive that have been extensivey tested in age inia tias. In eay tias, thiazides eded the inidene f stke by 40 pe ent, athgh the edtin in nay heat disease was disappinting. This may have been de t the advese metabi effets f the age dses sed. Me eent tias, sing we dses, have demnstated impessive edtins in bth stke and nay heat disease, espeiay in the edey.
Thee is itte t hse between the vais thiazides, athgh it seems pdent t se agents, sh as hydhthiazide and bendfazide, that have been pved t be effetive at w dses in inia tias. Newe agents, sh as indapamide, have fewe metabi side effets, and may even egess hypetensive VH n ehadigaphy. Advese effets The main nens abt thiazide dietis ae thei metabi side effets, athgh, at w dses, these ae ess ikey t be a pbem. They may ase hypkaaemia de t ena ptassim wasting. Hypkaaemia may give ise t ventia ahythmias and ase advese dg effets in patients taking digxin dgs that png the QT inteva n the EG (eg, ass I antiahythmis, tiyi antidepessants, antihistamines).
Ate gt is anthe mmn side effet f thiazides, even in w dses. Hypeiaemia an be pesent in abt 30 pe ent f a hypetensives bt it is a p pedit f ate gt. Imptene may asinay be a pbem.
Thiazides an inease sem D-heste and tigyeide eves bt this is mh ess f a pbem with mden w dses. Thee is as sme evidene that dietis impai gse teane and inease insin esistane. Hweve, epts f fank diabetes ae ae. Athgh thiazides pbaby shd be avided as fist-ine dgs in patients with diabetes and thse with hypeipidaemia, thee shd be n anxiety abt adding them in whee neessay. ae side effets inde nasea, headahe, ashes, phtsensitivity and bd dysasias.
the dietis p dietis at n the asending imb f the p f Hene and inhibit the eabsptin f hide, sdim and ptassim. They pde a bisk bt sht-ived diesis and ae ths nsitabe as fist-ine agents f hypetensin, as they d nt pvide 24-h nt. Hweve, they d have a e in patients with impaied ena fntin in whm thiazides ae ineffetive, and in patients with hypetensin esistant t mtipe dg theapy, wh ae ften fid veaded. Ftheme, they may be synegisti with agents sh as the AE inhibits.
Ptassim-spaing dietis, sh as amiide and tiamteene, pde itte edtin in bd pesse themseves. They may be sef in mbinatin with the dietis t pevent hypkaaemia. Spinatne is a speifi adstene antagnist, with a patia e in pimay hypeadstenism nn’s syndme. Beta-bkes
Beta-bkes at by bking the atin f nadenaine at b adenepts thght the iaty system and esewhee. Thei maj effet is t sw the heat ate and ede its fe f ntatin. beta-bkes as ase sme edtin in enin eease and enta sympatheti tne.
Beta-bkes may be sbdivided ading t thei aniay ppeties. F exampe, b1 adiseetive agents, sh as aten, have ess atin n b2 eepts in the bnhi and peiphea vesses mpaed with nn-seetive agents, sh as ppan. This edes (bt des nt abish) b2 eept-mediated side effets. ipid-sbe agents, sh as ppan and metp, ss the bd-bain baie me eadiy and ae assiated with a highe inidene f enta side effets. Sme beta-bkes, sh as pind, have intinsi sympathmimeti ativity (ie, they stimate b eepts when bakgnd sympatheti nevs ativity is w and bk them when bakgnd sympatheti nevs ativity is high). They, theefe, ase ess badyadia and pssiby fewe pbems with d extemities than nventina beta-bkes. Hweve, in patie, they ae itte sed in the teatment f hypetensin.
abeta and avedi have bth a- and b1-bking ppeties, asing a edtin in peiphea vasa esistane, as we as swing the heat ate. In additin t its b1-bking ppeties, avedi as has antixidant effets, whih give it theetia advantages in eding endtheia damage and weing eves f highy athegeni xidised D-heste. Hweve, bth abeta and avedi have the disadvantage f pssessing the side effets f bth asses f dg.
Beta-bkes ae sef as fist-ine antihypetensive agents, athgh they tend t be ess effetive in the edey and in bak hypetensives. F the teatment f hypetensin it is best t hse a beta-bke with high adiseetivity and w ipid sbiity t ede side effets. A ng haf-ife as aws ne daiy dsing.
Advese effets Mst f the side effets f beta-bkes ae peditabe fm thei mde f atin. F exampe, they sw the ate f ndtin at the ati-ventia nde and ae ths ntaindiated in patients with send- and thid-degee heat bk. Sins badyadia is mmn and is nt a easn t stp beta-bkes ness the patient is symptmati the heat ate fas bew 40 beatsminte.
Even sma dses f ß-bkes an ase bnhspasm de t bkade f pmnay b2 eepts, athgh the pbem is ess mmn with adiseetive agents. Even s, a beta-bkes ae ntaindiated in asthma. Bkade f b eepts in the peiphea iatin ases vasnstitin, at east in the immediate tem, and the dgs ae, theefe, ntaindiated in patients with est ishaemia f the egs. Nevetheess, they ae easnaby teated in thse with esse degees f peiphea vasa disease. ipid-sbe agents an ase enta nevs system side effets f insmnia, nightmaes and fatige. Exeise apaity may be eded by beta-bkes and patients may expeiene tiedness and fatige. As with mst antihypetensives, imptene has been epted, athgh ates ae itte highe than with paeb.
ike dietis, ß-bkes an wsen gse inteane and hypeipidaemia. In diabeti patients pne t hypgyaemia, beta-bkes may, theetiay, ede the awaeness f w bd gse. Nevetheess, many diabeti hypetensives have gd easns, sh as a pevis myadia infatin, t be n a beta-bke and shd nt be denied them bease f nens abt metabi side effets.
aim hanne bkes
aim hanne bkes, thewise knwn as aim antagnists, at by intefeing with the atin f aim hannes in the e membane. This edes the infw f aim, smth mse ntatin and eetia ndtivity.
aim hanne bkes may be divided int tw asses — the dihydpyidines and the nn-dihydpyidines. The dihydpyidines, sh as nifedipine and amdipine, at pedminanty by asing peiphea vasdiatatin. The nn-dihydpyidines, sh as veapami and ditiazem, as sw the heat ate and ati-ventia nde ndtin. A aim hanne bkes ae effiais at eding bd pesse as singe agents.
The de dgs, sh as nifedipine, have sht haf-ives and may ase apid vasdiatatin, a efex tahyadia and atehamine sges. This may inease advese effets and aggavate myadia ishaemia. nge-ating agents, sh as amdipine sw-eease pepaatins f nifedipine, patiay veme these pbems.
nti atey, the aim hanne bkes aked tia evidene t sppt thei se in hypetensin. In the mid-1990s, a seies f phamasveiane ase-nt stdies sggested that the sht-ating dihydpyidine dgs (sh as nifedipine apses) atay ineased the isk f heat attaks.1 eent data fm the Syst-E tia demnstated that antihypetensive teatment f the edey with the sht-ating dihydpyidine aim hanne bke, nitendipine, nviningy eded stkes and heat attaks, witht an inease in nditins pevisy attibted t the aim hanne bkes, sh as tms, beeding and nn-adia death.2
Advese effets The main, and mst tbesme, side effet f aim hanne bkes is anke edema. This is ased by vasdiatatin, whih as ases headahe, fshing and papitatin, espeiay with sht-ating dihydpyidines. Sme f these side effets an be ffset by mbining a aim hanne bke with a b-bke.
Veapami edes intestina mtiity and, ths, an ase signifiant nstipatin. Me seisy, it an ase heat bk, espeiay in thse with ndeying ndtin pbems. Ditiazem an simiay ase gastintestina and ndtin pbems, athgh ess feqenty than veapami. Veapami, ditiazem and sht-ating dihydpyidines ae best avided in patients with heat faie.
Apha-bkes
The a1 adenept bkes pde vasdiatatin by bking the atin f n-adenaine at pst-synapti a1 eepts in bth ateies and veins. This ests in a fa in peiphea esistane, witht a mpensaty ise in adia tpt. The pttype a1-bke — pazsin — is sht ating and tends t pde peipits fas in bd pesse, bt the nge ating dxazsin mbines the advantage f a me gente edtin in bd pesse with ne daiy dsing.
The a1-bkes pde edtins in bd pesse mpaabe t fist-ine antihypetensive dgs. They seem t be patiay sef as a thid dg, pding gd fas in bd pesse whee tw agents mbined have faied. In ntast t the b-bkes and dietis, a1-bkes atay pde mdest impvements in sem ipids and gse teane bt whethe this tansates int impved tmes is nt knwn, patiay with the paity f tme data with these agents.
Advese effets a1-bkes ae, n the whe, we teated. Thei main side effet is psta hyptensin, whih is me mmny ased by shte-ating agents. In wmen, a1-bkes may ase inay inntinene. In men, they may impve the symptms f benign pstati hypetphy. ike mst antihypetensive dgs, a1-bkes an ase headahe and fatige.
AE inhibits
Angitensin nveting enzyme (AE) inhibits have beme ineasingy ppa ve the past deade. They wk by bking the enin-angitensin system, inhibiting the nvesin f the inative angitensin I t the pwef vasnstit and stimat f adstene eease, angitensin II (see Fige 1). This ests in deeased peiphea vasa esistane and as a edtin in the eves f the sdim-etaining hmne — adstene.
Fige 1: The enin-angitensin systems and its inhibits
AE inhibits as ede the beakdwn f the vasdiat badykinin, whih may enhane thei atin bt is as espnsibe f thei mst tbesme side effet f gh. Ftheme, AE inhibits may impve endtheia fntin and ede enta adenegi tne. They as have benefiia effets n ena haemdynamis, eding intagmea hypetensin, esting in impvements in pteini ena disease. AE inhibits ae effetive as singe agents in hypetensin. Thee is geneay itte t hse between the age nmbe f AE inhibits avaiabe. eenty, the aptpi Peventin Pjet (APP) stdy demnstated that aptpi was as effetive as taditina antihypetensive agents (mainy thiazides and b-bkes) in peventing advese tmes in hypetensin.3 the agents, sh as fsinpi, have the advantage f hepati as we as ena exetin and ae (theetiay, at east) ess ikey t amate in patients with ena faie. Peindpi, amipi and tandapi ae agents with ng haf-ives, whih pvide gd 24-h antihypetensive veage.
Thee is sef synegism between the AE inhibits and dietis and between AE inhibits and aim hanne bkes. The AE inhibits ae patiay sef in diabeti hypetensives, in whm they may be enptetive, as they sw the pgessin f diabeti nephpathy.4 Ftheme, these agents have shwn sme benefits in impving diabeti etinpathy and even diabeti nepathy.5,6 Hweve, the AE inhibits tend t be ess effetive as antihypetensive agents in bakAf-aibbean hypetensives and in the edey, wh tend t have we enin eves than the genea ppatin. Nevetheess, this eative ineffetiveness an be veme by sing high dses adding a dieti.
Advese effetsgh, ased by the inhibitin f badykinin beakdwn, is the mst mmn side effet f AE inhibits, ing abt five times me ften than with paeb. gh is me mmn in wmen and de patients.7 The fa me seis, bt ae, side effet f the AE inhibits is angiedema, whih s in abt 0.1 t 0.2 pe ent f patients.
Damati deteiatin in ena fntin an in patients with biatea ena atey stensis. Sem ea and eatinine shd, theefe, be heked befe and a few weeks afte stating an AE inhibit. This shd nt pevent the se f AE inhibits in thse with the fms f ena disease. In these patients, AE inhibits ae ften agents f fist hie, in view f data shwing that they sw the pgessin f diabeti and nn-diabeti nephpathy.
The AE inhibits an ase hypekaaemia bease they ede adstene and, ths, ptassim exetin. Fist-dse hyptensin is pbaby an vestated side effet f AE inhibits bt age dses f sht ating aptpi an ase sdden fas in bd pesse, espeiay in thse with vme depetin, sh as heat faie patients n age dses f dietis. ae side effets inde ash, taste distbane, bd dysasias and a symptm mpex that indes feve and vasitis.
Angitensin II antagnists
ike the AE inhibits, these dgs at n the enin-angitensin system, bking the atin f angitensin II at its peiphea eepts. As they d nt inhibit the beakdwn f badykinin, they d nt ase gh. Hweve, they may ak the additina physigia benefits that ises in badykinin eves may bing. Angitensin II antagnists have simia physigia effets t AE inhibits and pde simia fas in bd pesse. Thee is synegism f antihypetensive effet with thiazide dietis. Thee is as evidene that they may egess VH and impve pteinia.8,9
Advese effets The main advantage f the angitensin II antagnists is thei appaent ak f side effets. ike the AE inhibits, they may ase hypekaaemia, ena impaiment and hyptensin bt, thewise, they ae amst as we teated as paeb. Nevetheess, ases f angiedema have been epted with sme f these agents. de antihypetensive agents
A nmbe f de antihypetensive dgs sti have a e in sme speia sitatins (eg, pegnany) and in esistant hypetensin. These dgs ae ppa in nties whee hypetensive patients ae n w inmes and have t pay f thei wn mediatin, bease they ae heap.
enta apha-bkes These dgs stimate enta a2 adenepts, esting in a deease in enta sympatheti tne. This eads t a fa in bth adia tpt and peiphea vasa esistane. Exampes f sh dgs inde methydpa and nidine. The dgs ase sedatin, dy mth and fid etentin. Methydpa an as ase atimmne hepati deangement and haemyti anaemia. Hweve, it is safe t se in hypetensive pegnant wmen and is mmny sed in sh patients. A new entay ating dg, mxnidine, ats n enta imidazine eepts and is hped t have the benefiia effets f entay-ating dgs, witht thei side effets.
Diet vasdiats These agents at diety t eax vasa smth mse, theeby eding peiphea vasa esistane. The esting ativatin f the sympatheti nevs system means that they an ny sessfy be sed in mbinatin with dgs that bk sympatheti ativity. Exampes inde hydaazine, whse main side effet is a ps-ike syndme, and minxidi. Minxidi ases hai gwth, a side effet wemed by many midde aged men bt nt by thei femae ntepats.
Adenegi nene bkes Sh agents ae nw aey sed in the nited Kingdm. esepine and ganethidine inhibit the eease f nadenaine fm peiphea neves. This edes sympatheti tne, peiphea vasa esistane and adia tpt. They ase psta hyptensin and enta nevs system depessin. Sma dses f esepine, mbined with a dieti, fm an effetive egimen and ae sed when w sts ae paamnt, espeiay in deveping nties.
تحياتي ................هاي االمحاضره الاوللى والبقيه ان شاء الله في القريب العاجل