7. Groups of Antihypertensive Drugs
Diuretics
β Blockers
ACE
Inhibitors
Angiotensin II
Receptor
Blockers
Ca Channnel
Blockers
α1 Blockers
Centrally α2
agonist
Direct
Vasodilator
others
8. Diuretics
Trigger the excretion of water and
electrolytes from the kidneys
Blood Volume
Peripheral Retention
Sodium water retention
Cardiac Output
Decrease Blood Pressure
10. Continue...
III. Potassium Sparing Diuretic
• Diuretics that do not promote secretion of
potassium in the urine.
• As adjunctive drugs, combination with other
drugs
• Actions :
– Aldosterone antagonis : spironolactone,
eplerenone
– Block sodium channel : amiloride, triamteren
11. Thiazide Diuretics
• Diuretic that most widespread use. Derived from
sulfonamides.
• Thiazide diuretics are absorbed rapidly but
incompletely from the GI tract. Cross the
placenta and are secreted in breast milk.
• Therapeutic Uses : long-term treatment of
hypertension. Particularly useful in the treatment
of black or elderly. Also used to treat edema.
• Not effective in patient with inadequate kidney
function (Cr Cl < 50 mL/min).
• Decrease the level of calcium in urine prevent
the development and recurrence of renal calculi.
12. Continue...
• Side effects : hyperurecemia (70%),
hyperglycemia (10%), hypomagnesemia.
Increase the excretion of chloride, potassium,
and bicarbonate electrolyte imbalance
• Potassium levels should be monitored closely
in patient who are predisposed to arrhythmias
or using digitalis glycosides.
13. Loop Diuretics
• Highly potent diuretics. Loop diuretics, with the
exception of ethacrynic acid, contain sulfa.
• Act on proximal tubule the thick, ascending loop
of Henle.
• Cause decreased renal vascular resistance,
increase renal blood flow, increase Ca2+ content
of urine.
• Used to treat edema, hypertension (usually with
a potassium-sparing diuretic or potassium
supplement to prevent hypokalemia)
14. CALCIUM CHANNEL BLOCKERS
Blocking the slow calcium channel in
myocardial and vascular smooth
muscle cell membranes
Inhibits the influx of
extracellular calcium ions
No Contraction =
Dilatation
Have intrinsic
natriuretic effect
Decrease Blood Pressure
15. Pharmacokinetics
• When administered orally, calcium channel
blockers are absorbed quickly and almost
completely.
• Because of the first -pass effect, however, the
bioavailability of these drugs is much lower.
• The calcium channel blockers are highly bound
to plasma proteins.
17. Differences
Classes /Drugs Properties
Verapamil Has significant effect on both
cardiac and vascular smooth
muscle
Diltiazem Affect both cardiac and vascular
smooth muscle, but less
pronounced negative inotropic
effect compare to verapamil
Nifedipine etc Much greater affinity for
vascular smooth muscle
18.
19. Continue...CCB
• Useful in the treatment of hypertensive (mild-
moderate) who also have asthma, diabetes,
angina, peripheral vascular disease.
• Side effects: constipation (10%), dizzines,
headache, feeling fatique. Verapamil
contraindication for congestive heart failure
due to its negative inotropic effects.
24. Actions
• Block the binding of angiotensin II to the AT1
receptor This prevents angiotensin II from
exerting its vasoconstricting properties and
from promoting the excretion of aldosterone -
lowered blood pressure.
25. Continue...
• Valsartan may also be used for the
management of heart failure.
• Decrease nephrotoxicity of diabetes
therapy in hypertensive diabetics (Irbesartan
and losartan).
• Losartan is also used to reduce the risk of
stroke in high-risk patients with hypertension
and left ventricular hypertrophy.
• Side effect similar with ACEI, but risk of cough
and angiodema sigificantly decrease
27. Continue...
• Selective β1 Blockers : metoprolol, atenolol
• Non selective β Blockers (block β1 & β2) :
Propanolol
• May take several (1-2) weeks to develop full
effects
28. Continue...
• Side effect : bradycardia, fatique, insomnia,
hallucination, hypotension, decrease libido, cause
impotence, disturb lipid metabolism, decreasing
HDL, increasing Trigliseride, drug withdrawl
(rebound hypertension should be tapering off)
• Caution in obstructive lung disease, chronic
congestive heart failure, severe symptomatic
occlusive peripheral vascular disease, acute heart
failure, diabetes.
29. α1 Blocker
• Actions : competitive block α1 adrenoceptor relaxation
arterial and venous smooth muscle decrease peripheral
vascular resistance and lower arterial blood pressure.
• Have minimal change in cardiac output, renal blood flow,
glomerular filtration rate.
• Cause short term effect of reflex tachycardia to blunt this
effect concomitant use of β blocker may be needed.
• Prazosin, doxazosin, terazosin.
• Side effect : postural hypotention, reflex tachycardia, first
dose syncope.
30. α-1 and β Blockers
• Actions : blocking both α-1 and β receptors in
the body lowers blood pressure.
• Carvedilol, labetalol
• Contraindication : heart block, heart failure,
asthma, obstructive airway disease, severe
slow heartbeat, severe low blood pressure
31. Clonidine
• It is α2 presinaptic agonist, work centrally
• Action: inhibit the released of noradrenaline
from symphatetics nerves.
• Does not decrease renal blood flow & GFR
Useful in the treatment of hypertention
complicated by renal disease.
• Causes sodium and water retention usually
used in combination with diuretic.
• Side effect : sedation, drying nasal mucosa,
rebound hypertention in abrupt withdrawal
(should be withdrawn slowly)
32. α methyldopa
• It Inhibits dopa decorboxylase and deplete
norepinephrine
• Also valuable in treating hypertensive patient
with renal insufficiency.
• Reduce total peripheral resistance and
decreased blood pressure.
• Cardiac output not decreased Does not
decrease renal blood flow & GFR
• Side effect : sedation, drowsiness.
33. Direct Vasodilators
• Actions : act on arteries, veins, or both.
• Include :
–Diazoxide
–Hydralazine
–Minoxidil
–Nitroprusside
34. Continue...Indications
• They’re usually combined with other drugs to
treat the patient with moderate to severe
hypertension (hypertensive crisis).
• Hydralazine and minoxidil are usually used to
treat resistant or refractory hypertension.
• Diazoxide and nitroprusside are reserved for use
in hypertensive crisis.
• Hydralazine monotherapy accepted method for
controlling blood pressure in pregnancy-induced
hypertension.
35. Continue... Side effect
• Produce reflex stimulation of heart
increased myocardial contractility, heart rate,
oxygen consumption may prompt angina
pectoris, MI, cardiac failure in predisposed
individuals.
• Increase plasma renin concentration
sodium and water retention
• Those undesirable side effects can be blocked
by concomitant use of diuretic and β blocker.
41. Causes of Resistant Hypertension
• Improper BP measurement
• Excess sodium intake
• Inadequate diuretic therapy
• Medication:
– Inadequate doses
– Drug actions and interactions (e.g., nonsteroidal anti-
inflammatory drugs (NSAIDs), illicit drugs,
sympathomimetics, oral contraceptives)
– Over-the-counter (OTC) drugs and herbal supplements
• Excess alcohol intake
• Identifiable causes of hypertension
42. Recommendations for initiating and modifying
pharmacotherapy for patients with elevated
blood pressure (BP) : "2014 Evidence-Based
Guideline for the Management of High Blood
Pressure in Adults: Report From the Panel
Members Appointed to the Eighth Joint National
Committee (JNC 8), published online Dec. 18 by
JAMA: The Journal of the American Medical
Association
43. Initiation pharmacologic treatment (1)
Population Blood Pressure
In the general population
aged ≥60 years
SBP ≥150 mm Hg or DBP
≥90 mm Hg
In the general population
<60 years
SBP ≥140 mmHg or at DBP
≥90 mmHg
In the population aged
≥18 years with chronic
kidney disease (CKD)
SBP ≥140 mmHg or DBP
≥90 mmHg
44. Initiation pharmacologic treatment (2)
Population Drugs
In the general nonblack
population, including those
with diabetes
a thiazide-type diuretic,
calcium channel blocker
(CCB), angiotensin-
converting enzyme inhibitor
(ACEI), or angiotensin
receptor blocker (ARB).
In the general black
population
a thiazide-type diuretic or
CCB.
In the population aged ≥18
years with CKD
ACEI or ARB
45. Evaluation
Initiate with 1 drugs for 1
month
If goal BP cannot be reached ,
increase the dose of the
initial drug or add a second
drug .
If goal BP cannot be reached
with 2 drugs, add and titrate
a third drug .
Referral to a hypertension
specialist may be indicated
for patients in whom goal BP
cannot be attained using the
above strategy or for the
management of complicated
patients
Do not
combine
together ACEI
and an ARB
46. CRISIS HYPERTENSIVE
• Rarely but life threatening situation
(emergency)
• DBP > 150 mmHg in healthy person; DBP >130
mmHg in individual with preexixting
complication (encelopathy, cerebral
hemorrhage, left ventricular failure, aortic
stenosis)
• Therapeutic goal : Rapidly reduce blood
pressure choose drugs with rapid onset
47.
48. Sodium Nitroprusside.
• Administered IV
• Cause reflex tachycardia
• Acting equally in arterial and veous smooth
muscle can reduce cardiac preload.
• Metabolized rapidly require continuous
infusion to maintain hypotensive action.
• Metabolit : cyanide ion
49. • Labetalol
– α and βblocker
– Administered by IV bolus or infusion.
– Does not cause reflex tachycardia
• Fenoldopam
– Peripheral dopamine- 1 receptor agonist.
– Administerd by IV infusion
– Lower blood pressure and also increase renal
perfusion
– Contraindicated in patient with glucoma.
50. • Nicardipne
– Can be given as intravenous infusion.
• Minoxidil
– Dilatation of arteriole but not venules.
– For severe to malignant hypertention that is
refractory to other drugs.
– Concomitant with other drug to diminish side
effect.
– Side effect : hypertrichosis, water nad sodium
retention.
51. Post Test
1. Candesartan adalah obat antihipertensi golongan ....
2. Lisnopril adalah obat antihipertensi golongan ....
3. Furosemid adalah obat antihipertensi golongan ....
4. Amlodipine adalah obat antihipertensi golongan ....
5. Penderita hipertensi denngan penyakit ginjal kronis, maka pilihan obat
antihipertensinya adalah ....
6. Untuk hipertensi emergensi dipilih obat antihipertensi yang ........,
contoh : .....
7. Efek samping kaptopril antara lain ...
8. Seorang pasien hipertensi derajat 1 dengan riwayat asma bronkiale,
golongan obat antihipertensi yang harus dihindari adalah ...
9. Seorang pasien terdiagnosis hipertensi dan edema pretibial. Obat
antihipertensi yang juga dapat menurunkan edemanya adalah ....
10. Seorang pasien 50 tahun dengan riwayat hipertensi, pada
pemeriksaan tekanan darah didapatkan 200/150 mmHg. Obat
antihipertensi pilihan untuk pasien tersebut adalah ....
52. Tuliskan Resep
• Ny. T, 50 tahun. Hasil pemeriksaan tekanan
darah masih tinggi setelah dilakukan
modifikasi gaya hidup. Tekanan darah terakhir
: 150/90 mmHg. Tidak ada penyakit komorbid
lainnya. Berikan resep obat antihipertensi
untuk Ny. T.
53. Rumusan Masalah :
1. Bagaimana pedoman pemilihan obat
antihipertensi yang akan diberikan kepada
pasien yang terdiagnosis hipertensi ?
2. Apakah ada golongan obat antihipertensi yang
lebih superior dibandingkan golongan
antihipertensi lainnya?
Tugas : Buat Artikel
Editor's Notes
Arterial Blood Pressure is directly proportional to the product of cardiac output (CO) dan peripheral vascular ressitance.
Most antihypertensive drugs lower bllod preesure by reducing cardiac output and/ decreaseing in peripheral resistance.
CO and peripheral resistance controlled by barofeflexes (sympathetic nervous system) and renin Angitensin Aldosteron System.
Typically begins with a thiazide diuretic or a calcium channel blocker.
a primary choice in the treatment of renal disease, edema, hypertension, and heart failure.
Initially, diuretic drugs decrease circulating blood volume, leading to reduced cardiac output. However, if therapy is maintained, cardiac output stabilizes but plasma fluid volume decreases.
With long-term use, thiazide diuretics also lower blood pressure by causing arteriolar vasodilation.
decrease blood pressure in both supine & standing position, rarely cuse postural hypotention except in elderly. Useful for combination with others antihypertensive agents, particularly useful in the treatment of black or elderly.
All thiazide are ligands for organic acid secretory system of nephron may compete with uric acid for elimination.
This generation differ in pharmacokinetics, uses and drug interactions. Amlodipine and nicardipine show little interaction with other cardiovascular drugs (ex. Digoxin or warfarin)
Some calcium channel blockers (diltiazem and verapamil) also reduce the heart rate by slowing conduction through the SA and AV nodes.
High dose of short acting CCB should be avoided increased risk myocardial infarction.
Bradykinin is a vasodilator.
patients taking ACE inhibitors should avoid taking all NSAIDs. Besides decreasing the antihypertensive effect of ACE inhibitors, NSAIDs may alter renal function.
antacids may impair the absorption of fosinopril.
quinapril may reduce the absorption of tetracycline
all are highly bound to plasma proteins.
When losartan is taken with fluconazole, an increased blood level of losartan may result, leading to hypotension.
NSAIDs reduce the antihypertensive effects of ARBs.
Rifampin may increase metabolism of losartan and decrease its antihypertensive effect.
Candesartan may increase blood levels of lithium, leading to lithium toxicity.
When digoxin is taken with telmisartan, an increased blood level of digoxin may occur, possibly leading to digoxin toxicity.
Potassium supplements may increase the risk of hyperkalemia when used with ARBs.
Symphatolytics drugs
Effective but have some contraindications.
In the general population ages ≥ 60, pharmacologic treatment to lower BP should be initiated at a systolic blood pressure (SBP) of 150 mmHg or higher or a diastolic blood pressure (DBP) of 90 mmHg or higher. Patients should be treated to a goal SBP lower than 150 mmHg and a goal DBP lower than 90 mmHg. If treatment results in lower achieved SBP and is not associated with adverse effects, treatment does not need to be adjusted.
In the general population younger than age 60, initiate pharmacologic treatment at a DBP of 90 mmHg or higher or an SBP of 140 mmHg or higher and treat to goals below these respective thresholds.
In the population ages 18 years or older with diabetes or CKD, initiate pharmacologic treatment at an SBP of 140 mmHg or higher or a DBP of 90 mmHg or higher and treat to goals below these respective thresholds.
