Antihypertensive Drugs.pdf

Introduction to hypertension
Classification of drugs
Mode of Action of Drugs

1. ANTIHYPERTENSIVEDRUGS

2. Drugsusedintreatmentofhypertension.
Persistantelevationofbloodpressurefromnormallevel
iscalledhypertension.
Bloodpressureisapressureofthebloodexertedagainst
thebloodvessels.
NormalBP:120(systolic)/80mm(diastolic)Hg.
AlsoknownasSILENTKILLERassometimespersonis
nothavingwarningsignsorsymptomsinitially.
IncreasedBPmayleadtofurthercomplicationslike
myocardialinfarctionandstroke.

3. Types of Hypertension (Based on Measurement of diastolic pressure)
Mild Hypertension: If BP is between 90-110
Moderate Hypertension: If BP is between 110-130
Severe Hypertension: If BP is between 130-140.
If BP exceeds above 140mm it leads to Hypertensive crisis (State of
emergency)
Based on cause
Primary Hypertension (Essential/ Idiopathic): When cause or origin of
disease is unknown.
Secondary Hypertension: When cause is known i.e. it may be due to
any disease like renal artery disease, pregnancy, pheochromocytoma
etc.

4. CAUSES/ ETIOLOGYOFHYPERTENSION
Neural factors (Stress/ emotions)
Hormonal factors (Renin)
Electrolytic imbalance
Genetic factors
Environmental factors like smoking, obesity

5. Neural Factors
Increase in sympathetic outflow, increase release of
Adrenaline and Nor-Adr
So, there is increase in BP.
Drugs effective will be: Sympatholytic drugs like
prazosin, propranolol

6. Renin (Juxtaglomerular cells
of kidney)
Angiotensinogen
(Liver)
Angiotensin-I
(Inactive)
Angiotensin-II
(Active)
AT1 receptor
Aldosterone
release
Vasoconstriction
Increased sympathetic
outflow
Increased BP
ACE
Effective drugs
ACE inhibitor
AT1 receptor antagonist
Renin inhibitor

7. Electrolytic factors
Increase Sodium Retention
Increase Blood volume
Increase Peripheral
resistance
Increase BP/ Hypertension
Drugs effective: Diuretics

8. MANAGEMENT OFHYPERTENSION
Give up smoking.
Avoid sweets and coffee
Controlled salt intake
Diet control
Regular exercise
If still uncontrolled, antihypertensive drug
therapy can be the treatment

9. CLASSIFICATION
Drugseffectingsympatheticnervoussystem
Alpha(α1)-adrenergicblocker:Prazosin,Terazosin,
Phentolamine,Phenoxybenzamine
Beta(β)-adrenergicblocker:Propranolol,Metoprolol,
Atenolol,Timolol
Non-selective(α+β)blocker:Labetolol,Carvedolol
Centrallyactingdrugs(α2-agonist):Clonidine,
MethylDOPA,Guanabenz
Adrenergic neuron blockers: Reserpine,
Guanethidine

10. DrugseffectingRAASsystem
Renininhibitors:Alisekrin
ACEinhibitors:Captopril,Lisinopril,Enalapril,
Benazepril,Quinapril
AT1receptorantagonist:
Losartan,Candesartan(Non-peptideinnature)
Saralasin,Sarmesin(Peptideinnature)
oDiuretics
Thiazidediuretics:Hydrochlorthiazide
Loopdiuretics:Furosemide

11. Vasodialators
Hydralazine
Diazoxide
Sodium nitroprusside
Minoxidil
oCalcium channel blockers:
Verapamil, Amlodipine, Nifedipine
Drugs acting on Baroreceptors: Veratrum

12. ACE inhibitors
•Contraindicated with Potassium sparing diuretics, NSAIDS, Gold sodium aurothiomalate
•Common side effect is Cough.
•Decreases excretion of potassium so leads to hyperkalemia.
Captopril
1-[2-methyl-3-sulfanylpropanoyl]pyrrolidine-2-carboxylic acid
FirstACEinhibitorusedforT/tofhypertensionandCHF.
Sulfhydryl-containinganalogofproline.
Sideeffects:
Coughduetoincreaseintheplasmalevelsofbradykinin.
PosturalHypotension
Palpitation
LossofTaste(dysgeusia)

13. Lisinopril
1-[6-amino-2-[1-carboxy-3-phenylpropyl]
amino]hexanoyl]pyrrolidine-2-carboxylicacid
Enalapril
1-[1-ethoxy-1-oxo-4-phenylbutan-2-yl
aminopropanoyl]pyrrolidine-2 carboxylic
acid
Prodrugandisconvertedinto
enalaprilat(activedrug)byenzyme
esteraseinliver
Benazepril
Prodrugandisconvertedinto
benazeprilat(activedrug)byenzyme
esteraseinliver.
Quinapril
Prodrugandisconvertedinto
quinaprilat(activedrug)byenzyme
esteraseinliver.

14. DRUGS EFFECTING S YMPATHETIC
NERVOUSSYSEM
Beta BLOCKERS
Non-selective: Propranolol, Timolol
Selective beta 1 blocker: Atenolol, Metoprolol
Timololis a nonselective beta-adrenergic antagonist given in an eye drop
solution to reduce intraocular pressure. It is also used in tablet form as a
drug to treat hypertension
Acts by
Inhibiting reninrelease
Reducing sympathetic outflow and cardiac output.
Side effects include: Tiredness, slowhearbeat, cold hand and feet.
1-(tert-butylamino)-3-{[4-(morpholin-4-yl)-
1,2,5-thiadiazol-3-yl]oxy}propan-2-ol

15. CENTRALLYACTING DRUGS
α2agonist.
Clonidine, Methyl Dopa, Guanabenz
Methyl DOPA
2-amino-3-(3,4-dihydroxyphenyl)-2-methylpropanoicacid
HavingstructuralresemblancewithDOPAsoinsteadofDOPA,itwill
undergodecarboxylationtoformmethyldopamineandthenmethyl
nor-adr/adr,sononeurotransmitterreleasewillbethere,sonoIncrease
BP.

16. Tyrosine
Phenyl alanine
DOPA
Dopamine
Adr/ Nor Adr
Hydroxylase
Hydroxylase
Decarboxylase
Methyl-DOPA
Methyl-Dopamine
Methyl-Adr/Nor Adr
(False neurotransmitter)

17. Uses
In treatment of hypertension in conjugation with
diuretics.
Side Effects
Sedation
Dry mouth
Bradycardia
Constipation
Nausea and vomiting

18. Clonidine
Clonidineisanimidazolederivatethatactsasanagonistofalpha-2adrenoceptors.
N-(2,6-dichlorophenyl)-4,5-dihydro-
imidazol-2-amine
2-{[(2,6-dichlorophenyl)
methylidene]amino}guanidine
Guanabenz is an guanidine derivate that acts as an agonist of alpha-2 adrenoceptors
Guanabenz

19. ADRENERGIC NEURON BLOCKERS
Reserpine
Guanethidine
AnalkaloidfoundintherootsofRauwolfiaserpentinaandR.vomitoria.
Reserpineinhibitstheuptakeofnorepinephrineintostoragevesiclesresulting
indepletionofcatecholaminesfromperipheralsympatheticnerveendings.It
hasbeenusedasanantihypertensiveandanantipsychotic,butitsadverse
effectslimititsclinicaluse.
Sideeffectsincludenasalcongestion,nausea,vomiting,weightgain,gastric
intolerance,gastriculceration

20. Guanethidine
Antihypertensivedrug,actmainlybypreventingthe
releaseofnorepinephrineatnerveendingsandcauses
depletionofnorepinephrineinperipheralsympathetic
nerveterminalsaswellasintissues.
Sideeffectsincludeposturalhypotensionanddiarrhea.
2-[2-(azocan-1-yl)ethyl]guanidine

21. Vasodialators
Sodiumnitroprusside
Hydralazine
Minoxidil
Diazoxide

22. Sodium nitroprusside
Actsbyvasodialationasorganicnitrates
Veryrapidmodeofactionsousedtolowerbloodpressure
inhypertensivecrisis.
Sideeffectsinclude:Skinrashes,stomachache,nausea,
tinnitus,sweatingandmostimportantiscyanide
toxicity.

23. Hydrazinederivativevasodilatorusedaloneorasadjunct
therapyinthetreatmentofhypertension.
Hydralazinemayinterferewithcalciumtransportinvascular
smoothmuscletorelaxarteriolarsmoothmuscleandlowerblood
pressure.
Preventinfluxofcalciumintocells,preventingcalciumrelease
fromintracellularcompartmentssonocombinationofactinand
myosin,sonocontraction.
AlsoactasantineoplasticbyinhibitingenzymeDNAmethyl
transferaseandthusinhibitcellreplication.
Sideeffects:Headache,Anorexia,Nausea,vomiting,diarrhea.
Hydralazine
1-hydrazinylphthalazine

24. Minoxidil
Mainlyusedtotreatalopecia.
Alsousedasanhypertensiveduetoitsvasodialtioneffect.
Actaspotassiumchannelopenerleadingto
hyperpolarisationeffect.
Minoxidilisanexampleofprodrugandisconvertedinto
minoxidilsulfate(activeform).
Sideeffectsincludechestpain,drycough,nausea,
sweating,rapidweightgain,facialhair.
6-(1-Piperidinyl)pyrimidine-2,4-diamine 3-oxide

25. Diazoxide
7-Chloro-3-methyl-1,2,4-
benzothiadiazine 1,1-dioxide
Potassiumchannelopenersoincreasemembranepermeability
topotassiumionscausingvascularrelaxationinsmooth
muscle.
Alsousedtotreathypoglycemia
Althoughbelongingtothiazidesbutnodiureticaction.
Sideeffects:Nausea,lossofapetite,stomachupset.

26. Carbonic anhydrase inhibitors: Acetazolamide
Loop diuretics: Furosemide
Thiazide diuretics: Hydrochlorthiazide
Potassium sparing diuretics: Spironolactone