ANTI HYPERTENSION DRUGS

Santun Bhekti Rahimah., dr., M.Kes

 Hipertensi
Hipertension adalah penyakit kardiovascular yang paling
umum.
The prevalence varies with age, race, education, and many
other variables.
Sustained arterial hypertension damages blood vessels in
kidney, heart, and brain and leads to an increased incidence
of renal failure, coronary disease, cardiac failure, and stroke.
Effective pharmacologic lowering of blood pressure has been
shown to prevent damage to blood vessels and to
substantially reduce morbidity and mortality rates.
Lokasi anatomi yang mengontrol
tekanan Darah
Tekanan Darah Normal
BHS Classification of BP Levels

Category Systolic BP Diastolic BP

(mmHg) (mmHg)
Optimal BP <120 <80
Normal BP <130 <85
High Normal BP 130-139 85-89

Grade 1 Hypertension (mild) 140-159 90-99

Subgroup: Borderline 140-149 90-94
Grade 2 Hypertension (moderate) 160-179 100-109
Grade 3 Hypertension (severe) >180 >110

Isolated Systolic Hypertension >140 <90

Subgroup: Borderline 140-149 <90

This classification equates with that of the WHO/ISH (2) and is based on clinical BP values. If SBP and DBP
fall into different categories the higher value should be taken for classification.
 Suggested target blood pressures during antihypertensive treatment
Systolic and diastolic should both be attained eg <140/85 mmHg means less than 140 mmHg
systolic and less than 85 mmHg diastolic

Clinic BP (mmHg) Mean day-time ABPM or

home BP (mmHg)
No Diabetes Diabetes No Diabetes Diabetes

Optimal BP <140/85 <140/85 <130/80 <130/75

Audit Standard <150/90 <140/85 <140/85 <140/80

Audit standard reflects the minimum recommended levels of BP control

Despite best practice, the Audit Standard will not be achievable in all treated hypertensives
 Classification
1.Sympatholytics : a) Alpha 2 agonists
b) Alpha 1 antagonists
c) Beta blockers
d) Adrenergic neuron
blockers.
2.Diuretics
3.Angiotensin inhibitors
4.Vasodilators
5.Calcium channel blockers
Obat Hipertensi
 Sympatholytics
a) Alpha 2 agonists : Alpha Methyl dopa,
Clonidine.
1)Alpha Methyl dopa : converted to Alpha
methyl NE, Activates alpha2 receptors in
medulla. NE in vasomotor centre of
medulla PVR.
High 1st pass metabolism
Safe in Pregnancy and renal failure.
Side effects:Sedation, Prolactin Lactation,
Hemolytic anemia with positive coombs
test,drug fever,edema.
2)Clonidine: Alpha2 agonist in vasomotor
centre in medulla. PVR.
Uses:1. HTN 2.Rx of withdrawl symptoms of
Opiates(morphine)
Side effects:Dry mouth, sedation, edema,
Rebound HTN.
b) Alpha1 antagonists:
Prazocin,Doxazocin,Terazocin.
Competitively blocks alpha1 receptors on
arterioles and veins. NE action on blood
vessels PVR.
Uses : 1.HTN 2.Bening prostatic
hyperplasia.
Side effects:1st dose syncope,orthostatic
hypotension,Edema,Reflex tachycardia.
 C)Beta 1 antagonists.
Cardioselective beta blockers
CV effects: HR
cond.Velocity
contractility
.

Toxicity: Arrythmias, heart block, systolic cardiac

failure,Edema.
 Cardioselective (B1)beta blockers
Atenolol
Acebutolol
Betoxalol
Esmolol
Metaprolol
 Non selective Beta blockers
Pindolol
Timolol
Nadolol
Propranolol
 Nonselective beta blockers
Other toxic effects of nonselective beta blockers:
Bronchospasm
Peripheral vascular disease,impotence
Hypoglysemia( Glycogenolysis and Glucagon)
hyperlipidemia .

Clinical uses:Rx of Diastolic cardiac failure, IHD, Arrhythmias,

HTN,Migrane (Propranolol), anxiety, glaucoma(Timolol),
Hyperthyroidism(Propronolol),Bening essential tremors.
Contraindications:Asthma,peripheral vascular diseases.
d)Adrenergic neuron blockers:
1)Reserpine:
Mech: Inhibits granular(vesicle) uptake of NE in
presynaptic nerve terminal.
Side effects: Depression,Sedation, Parkinsonism like
symptoms,Diarrhea.
2)Guanethidine:
Mech: Inhibits granular(vesicular) release of NE
from presynaptic nerve terminal.
Side effects:Postural hypotension, Diarrhea,
Retrograde ejaculation,edema.
Synthesis and release of NE
 Diuretics
Thiazides
Loop diuretics
Carbonic anhydrase inhibitors
K+ sparing diuretics
Osmotic diuretics
Action of Diuretics
 Diuretics
1.Thiazide diuretics:
Mech:Inhibits Na+,Cl-cotransporter in distal
convoluted tubule.
Uses:Rx of 1.HTN 2.Congestive Heart
failure 3.Nephrolithiasis 4.Nephrogenic
Diabetes insipidus.

Ex:Hydrochlorothiazide,Chlorothiazide,Chlort
halidone,Indapamide,Metolazone.
 Side effects: 1.Hypokalemia 2.Metabolic
alkalosis 3.Hyperuricemia 4.Hyponatremia
5.Hyperglycemia 6.Hyperlipidemia
7.Hypercalcemia. 8.Allergic reactions.

Drug interactions: 1.Increases toxicity of

Digoxin (Due to Hypokalemia).
2.Cross hypersensitivity
with drugs with sulphar group.
2.Loop diuretics:
Mech: Inhibits Na,k,2Cl Cotransporters in
thick ascending loop.
Uses:1.Acute pulmonary edema 2.HTN
3.Acute renal failure 4.Anion overdosage 5.Heart
failure 6.Hypercalcemia
Ex:Furosemide,Ethacrinic acid,Bumetanide.
 Adverse effects: 1.Hypokalemia 2.Metabolic
alkalosis 3.ototoxicity 4.Hyperuricemia
5.Hypocalcemia.6.Allergic reactions(skin
rash,intertitial nephritis,esinophilia).

Drug interactions: 1.Aminoglycosides +Loop

diuretics Ototoxicity .
2.Increases toxicity of
Digoxin(Due to Hypokalemia).
3.k+ Sparing Diuretics:
Spironolactone : Aldosterone antagonist
Amiloride &Triamterene: Na channel blockers
Acts at Collecting tubules.
Uses: 1.Hyper aldosteronism 2.HTN 3.Heart failure.
Adverse effects:Hyperkalaemia, Metabolic acidosis,
Gynaecomastia,Nephrolithiosis (Triamterene).
Drug interactions: 1 Digoxin action
2.Along with Beta blockers and
ACE inhibitors causes Severe Hyperkalaemia
4.Carbonic anhydrase inhibitors:
Acetazolamide,Dorzolamide.
Acts at Proximal convoluted tubule.
Uses:Rx of Glaucoma,Metabolic alkalosis,Acute
mountain sickness,Elimination of acidic drugs.
Adverse effects:1.Metabolic acidosis 2.Renal
stones 3.Hypokalemia.
Drug interaction: Digoxin toxicity (Due to
Hypokalemia)
5.Osmotic diuretics:
Mech: Decreases absorption of water in
proximal convoluted tubules and descending
limb of loop of henle.
Ex: Mannitol
Uses: Rx of1.Cerebral edema
2.Glaucoma.
Side effects: Dehydration,Hypernatremia.
 Diuretic Adverse effect

Thiazides Hypercalcemia,Hyponatremi
a,Alkalosis,Hypokalemia.
Loop diuretics Hypokalcemia,Alkalosis,Otot-
oxicity,Hypokalemia.
Carbonic anhydrase
Acidosis,Hypokalemia
inhibitors
K+ Sparing (or)
Acidosis,Hyperkalemia
Aldosterone antagonists
Osmotic diuretics Dehydration,Hypernatremia
 Angiotensin inhibitors
ACE inhibitors:
Mech: Angiotensin I
ACE
Angiotensin II
Ex: Enalapril,Lisinopril,Captopril,Ramipril,
Benazepril,,,,
Uses: Heart failure,HTN, Post MI.
Adverse effects:1st dose hypotension,
Hyperkalemia,drycough, Neutropenia ,
Angioedema ,rash,Acute renal failure.
 Note: dry cough and angioedema are caused
by Bradykinin.
Contraindications: 1.Bilateral renal artery
stenosis 2.Pregnancy.
Angiotensin II antagonists:
Losartan,Valsartan.
No dry cough and angioedema.
Inhibitor Angiotensin
 Vasodilators
Arterial:Hydralazine,Minoxidil,Diazoxide,Sodiu
m nitropruside.
Venular :Nitrates,Sodium nitropruside.
Adverse effects:
Headache,Flushing,Edema, SLE like
rash(Hydralazine),Reflex tachycardia,
Hypertrichosis(Minoxidil),Cyanide
poisoning(Sodium nitro pruside).
 Diazoxide and Sodium nitropruside are useful
in Rx of HTN emergencies.
Diazoxide useful in Rx of Insulinoma.
Obat Vasodilator
 Ca channel blockers
1.Dihydropyridines :block Ca channels only in blood vessels
Nifedipine, Nimodipine , Amlodipine

2.Verapamil & Diltiazem : block Ca channels both in blood vessels and

heart

3.Biperidin : blocks Ca channels in blood vessels

 Clinical uses
Angina
Hypertension
Supraventricular tachycardia
Subarachanoid hemorrhage
raynauds syndrome
Preterm labor
Congestive heart failure
 Adverse effects
Hypotension, headache, flushing
Tachycardia[ only vascular selective agents]
Fluid retention
Heart block, CCF (only with diltiazem & verapamil)
Constipation
Gingival hyperplasia, proteinuria (only with
dihydropyridines)
Torsade de pointes (only with biperidin)
 Anti-HTN drugs in co-morbid
conditions
Comorbid condition Anti-HTN drug of choice

Angina Beta blockers, Ca channel

blockers
Heart failure Angiotensin inhibitors

Post MI Beta blockers

Diabetes Angiotensin inhibitors

Benign prostatic hyperplasia Alpha blockers

(BPH)
Dyslipidemias Alpha blockers, Ca channel
 Drugs useful in Rx of HTN emergencies:
Sodium nitropruside
Diazoxide
Labetalol
TERIMA KASIH