| 1- centrally acting sympatholytics |
4- ACE inhibitors :is
Zn containing glycoprotein *SAR *common side effects 1-hypotension 2-hyperkalemia 3-dry cough (due to inhibition og
bradykinin & PG syn) *formulations 1-ACE + diuretic [captopril .hydrochlorothiazide] 2-ACE
,Ca channel blocker (enalapril & diltiazem) |
| methyldopate HCl (aldomet) |
mechanisms of action 1-inhibitor of dopa
decarboxylase enz involved in the biosyn of NE &
E 2-metab to a-methyl NE w
displace NE in nerve terminals and act as false
transmitter 3-most acceptable ;a-methyl NE considered as centrally acting a2
agonist *methyl dopa suitable for oral use ,is zwitter ion and is not sol enough for parentral use this
problem was solved by masking the ester leaving the amine free to form water sol HCL salt |
Thiol
** Captopril |
*metab :cysteine disulphide (inactive
metabolite) *contain thiol gp w bind to Zn *SH not only
excellent inhibiting action of enz but also cause SE
eg skin rashes ,metalic taste so use of other drugs not
contain SH gp |
| 2- agents depletes neurotransmitter store
eg RESERPINE : deplete catecholamine at adrenergic neurons
by inhibiting active transport Mg -ATPase respons for sequestring NE ,DA e in
the storage vesicles *depleted catecholamine are metab by MAO > ! Amine
content |
A) dicarboxylate inhibitor 1-Enalapril |
*it is prodrug must
be activate dby esterase enz >enalaprilate >very poor abs .despite of excellent IV activity it has very poor oral bioav
>estrification of
enalaprilate >enalapril has superior oral bioav *combination of 2cooH ,NH (zwitter ion ) >so low lipophilicity a poor oral
bioav *enalapril maleate >long acting ACE inhibitor *devoid of S.E of captopril (no sH gp) |
| 3- direct acting vasodilators
; K channel agonist (opener) 1-arterial as hydralazine ,minoxidil
,diazoxide 2-arterial & venous >sod nitroprusside |
activate ATP sensitive K
channels w lead to !
Intracellular Ca & ! Excitability of s.m the 1ry
action of these cpds is due to open K channels in plasma memb of vascular s.m |
| Diazoxide |
sod 7-chloro-3-methyl-2H-1,2,4-benzothiadiazine
1,1dioxide *it is structurally related to chlorothiazde (des sulphamoyl drv) *used as IV injection as rapidly acting antihypertensive for emergency ! B.P in hospitialized
patients |
2-Lisinopril (Zestril) |
active drug *metab >exc unchanged] |
| Hydralazine HCL |
1-hydralazinophthalazine mono hydrochloride *action :1-relax
s.m of vascular wall e +
in P.R to bl flow 2-+
renal bl flow w is important in patient e renal
insuffiency *metab >N-acetylation or
hydroxylation (both inactive) *syn > |
3-Benazepril (lotensin) |
*inactive *benzazepine str
*ester ><prodrug >esterase *metab >glucorunate
conjugation |
| minoxidil
|
2,4-diamino-6-piperidinopyrimidine-3-
oxide *effect similar to hydralazine *it self inactive >activated by sulfotransferase to minoxidil sulfate (active) *used as topical soln in severe hypertension that difficult to
control by other agents *S.E 1-water & Na
retension so req coadm e diuretics 2-cause reflex tacchycardia so used e B
blocker |
B)phosphorate containing inhibitors *Fosinopril |
* prodrug >esterase |
| 5- Angiotensin II antagonist ****Losartan |
2-butyl -4-chloro[p-(o-1H-tetrazol -5-ylphenyl)
benzyl] imidazole -5-methanol *used as K salt *metab >oxidation of CH2OH >COOH
(active metabolite) |
| sodium nitroprusside(Nipride) |
*one of the most potent bl pr lowering drug >its use is limited in emergency due to
short duration *active moity (NO) *mech as organic nitrates & nitrites *use :in emergency as infusion in hypertensive crisis *S.E
>cn ,scn may accum in blood >toxic effect >so
monitoring of cn in bl |
|
6-diuretics 7- Ca channel blocker 8
-sympatholytics (eg B-blocker ,,a1 -blocker) |
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