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Obat Antihipertensi

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ANTI HYPERTENSION

DRUGS
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,Chlorothiazid
e,Chlorthalidone,Indapamide,Metolaz
one.
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,Hypo
natremia,Alkalosis,H
ypokalemia.
Loop diuretics Hypokalcemia,Alkalo
sis,Otot-
oxicity,Hypokalemia.
Carbonic
Acidosis,Hypokalemi
anhydrase a
inhibitors
K+ Sparing (or)
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,Diazoxid
e,Sodium 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 Alpha blockers


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

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