HYPERTENSION

Rudy Salam
DEPARTEMEN FARMASI KLINIS
PRODI FARMASI FAKULTAS KEDOKTERAN
UNIVERSITAS BRAWIJAYA
WHAT IS BLOOD PRESSURE (BP)?
WHAT IS HIPERTENSION (HTN)?
EPIDEMIOLOGY
 EPIDEMIOLOGY

The U.S. Census Bureau and the

National Health and Nutrition
Examination Survey (NHANES).

Percentage of
Hypertensives with
Controlled BP
CVD RISK
ETIOLOGY
 WHITE COAT HYPERTENSION
Clinic BP reading
Night Time Period

Systolic BP

Diastolic BP
Normal Bands
White coat window

24 h ABPM confirms the presence of white coat hypertension in this patient

(www.abdn.ac.uk/medical/ bhs/booklet/whitcoat.htm)
PATHOPHYSIOLOGY
A. RAAS
RENIN-ANGIOTENSIN-ALDOSTERONE SYSTEM (RAAS)

- Renin  catalyzes convertion angiotensinogen – angiotensin I – angiotensin II 

receptor AT1 & AT2
- Circulating angiotensin II
a. pressor
catecholamine – adrenal medulla; centrally mediated increase in
sympathetic activity)
b. volume effect
stimulate aldosterone synthesis  Na & water retension   plasma
volume, TPR  BP
- Local RAAS in the heart (not blocked by ACEI)   contractility – cardiac hyperthropy
- Local RAAS in the brain   production & release hypothalamic & pituitary hormones 
sympathetic outflow from medulla oblongata
- Peripheral tissue – angiotensin + other humoral + endothelium growth factor  
vascular resistance
Natriuretic Hormone

Insulin Resistance &

Hyperinsulinemia
 2. NEURONAL MECHANISM
a. Autonomic nervous system  play role of BP regulation
• 2 presynaptic receptor – negative inhibition;  presynaptic receptor - positive
feedback to the norepinephrine containing vesicles
• Postsynaptic -receptor stimulation (1)  vasocontriction; Stimulation
postsynaptic 1 – HR & contractility; 2 – vasodilatation

b. Baroreceptor reflex system

• Major negative feedback mechanism - controls sympathetic activity
• Nerve ending lying in the wall of large arteries (carotid arteries & aortic arch)
• Change BP – activate baroreceptors – impulses – 9th cranial & vagus nerves –
brain stem
•  BP – stimulate baroreceptors – reflex vasoconstriction,  HR, force cardiac
contraction
• Blunted in the elderly & those with diabetes
 NEURONAL MECHANISM
c. Central nervous system
• Stimulation certain areas eg. Nucleus tractus solitarius, vagal nuclei, vasomotor
center and the area postrema   or  BP
• Stimulation 2-receptor within CNS decreases BP through inhibitory effect
vasomotor center; Angiotensin II -  sympathetic outflow from the vasomotor
center
 3. PERIPHERAL AUTOREGULATORY
COMPONENTS
Renal or tissue autoregulatory abnormalities  HTN
• Volume-pressure adaptive mechanism by kidneys
• BP drops, increase sodium & water retention  Plasma volume
expansion  increase BP
• BP rise, increase sodium & water excretion  decrease CO + BP
• Local autoregulatory process
• Maintain tissue oxygenation
• O2 demand normal to low  arteriolar bed remains relatively
vasocontricted
• Increase metabolic demand  trigger arterioral vasodilatation 
lower peripheral vascular resistance, increase blood flow and O2
through autoregulation
• Renal adaptive mechanism defect  plasma volume expansion
& increased blood flow  local tissue autoregulatory process that
vasoconstrict then would be activated to offsett the increased
blood flow  increase peripheral resistance and if sustained 
thickening arterial walls in long term
VASCULAR ENDOTHELIAL MECHANISM

 vasodilating
substance (prostacyclin
and bradykinin)

HTN
 vasoconstricting
substances (angiotensin II
and endothelin I)

 nitric oxide
ELECTROLYTES AND OTHER CHEMICALS
BENEFITS OF LOWERING BP
 JNC-7 CLASSIFICATION

• Classification determined based on the average of two or more properly

measured seated blood pressure measurements from two or more clinical
encounters
CLINICAL EVALUATION
ROUTINE DIAGNOSTICS
 TREATMENT OF HTN

Goals of Therapy

Lifestyle modification/Nonpharmacologic treatment

Classification and management of BP for adults

Pharmacologic treatment

Compelling indications for individual drug classes

Follow-up and monitoring

GOALS OF THERAPY
ALGORITHM FOR TREATMENT OF HTN

http://hin.nhlbi.nih.gov/nhbpep_slds/menu.htm
CLASSIFICATION & MANAGEMENT OF BP FOR ADULTS
LIFESTYLE MODIFICATION
(NONPHARMACOLOGIC THERAPY)
 LIFESTYLE MODIFICATION

• Works best in motivated individuals

• Initiate at prehypertension classification
• Obesity  risk for HTN and DM
• If > 20% over ideal body weight (IBW) – considered obese
• IBW females = 100 lbs + 5 lb/every inch over 5’
• IBW females = 106 lbs + 6 lb/every inch over 5’
• 3500 calories = 1lb
• Decrease intake by 500 cal/day
• Increase exercise and activity
 LIFESTYLE MODIFICATION

• Sodium restriction and other diet aids

• Usual salt intake 10 gm/d = 4 gm Na+
• Reduce to 2.4 gm Na+/day
• Caution – salt substitutes contain K+
• Fish oils and garlic – beneficial in HTN ?
• Alcohol consumption
• Exercise/Activity
• 30-40 minutes 3-4x/wk, optimal 5x/wk
• Stress reduction
• Smoking cessation – explain benefit, many therapies & aids
PHARMACOLOGIC TREATMENT
DIURETICS
DIURETICS
THIAZIDE DIURETICS
LOOP DIURETICS
POTASSIUM SPARING DIURETICS
DRUG INTERACTIONS - DIURETICS
 RAAS

ARB’s
ACEI’s

Renin Blocker
ACE INHIBITORS
ARB’S
 RENIN BLOCKERS

MoA Agents SE
Decreases Aliskiren (Do: Hyperkalemia,
plasma renin 150-300 mg PO GERD, diarrhea,
activity qd elevated BUN/Cr

Interfering Pregnancy:
conversion of
angiotensinogen fetal/neonatal
to angiotensin I harm/death

Avoid
combinations
with ACEI/ARB
SIDE EFFECTS & INTERACTIONS
ACEI’S/ARB’S
BETA (Β) BLOCKERS
BETA (Β) BLOCKER AGENTS
SIDE EFFECTS & INTERACTIONS
BETA BLOCKERS
CALCIUM CHANNEL BLOCKERS
CALCIUM CHANNEL BLOCKERS

clevidipine
SIDE EFFECTS & DRUG INTERACTION
CCB’S
CENTRAL ALPHA-2 AGONIST
PERIPHERAL ALPHA-1 BLOCKERS
DIRECT VASODILATORS
OTHERS ANTIHYPERTENSIVES
 5. COMPELLING INDICATIONS
Compelling Indication Initial Therapy Options Clinical Trial Basis

Heart failure Thiazide, BB, ACEI, ACC/AHA HF Guidelines, Merit-

ARB, ALDO-Ant HF, Copernicus, CIBIS, SOLVD,
AIRE, TRACE, ValHeft, Rales

MI BB, ACEI, ALDO-Ant ACC/AHA Guidelines, BHAT,

SAVE, Capricorn, Ephesus

High CAD risk Thiazide, BB, ACEI, CCB ALLHAT, HOPE, LIFE, Convince

Diabetes BB, ACE, ARB, CCB NKF-ADA Guideline, UKPDS,

ALLHAT

Chronic Kidney Dz ACE, ARB NKF Guideline, Captopril

trial, RENAAL, IDNT, REIN,
AASK
Recurrent Stroke
Thaizide, ACEI PROGRESS
Prevention
ANTIHYPERTENSIVES TX FOR COMPELLING
POPULATIONS
COMBINATION THERAPY
RESISTANT HTN
FOLLOW-UP AND MONITORING
 PROMOTE PATIENT COMPLIANCE
Educate pt regarding proper use of medicine as well as disease state

Include social support networks

Include the patient in decision making

Avoid drugs with numerous side effects

Simplify the drug regimenminimize the number of pills, frequency, and

inconvenience

Provide positive reinforcement

Maintain continuity of care and avoid polypharmacy

Individualize treatment
HYPERTENSIVE URGENCIES
AND EMERGENCIES
 HYPERTENSIVE URGENCIES
AND EMERGENCIES

Hypertensive Urgencies Hypertensive Emergencies

managed by adjusting maintenance Require immediate BP reduction to limit

therapy by adding a new antihypertensive new or progressing target-organ damage
and/or increasing the dose of a present
medication The goal is not to lower BP to less than
Very rapid reductions in BP to goal values 140/90 mm Hg; rather, a reduction in
should be discouraged because of mean arterial pressure of up to 25%
potential risks within minutes to hours is the initial target
Acute administration of a short-acting oral Required parenteral therapy
antihypertensive (captopril, clonidine or
labetalol)
Oral or sublingual immediate-release
nifedipine for acute BP lowering is
dangerous
AGENT FOR HYPERTENSIVE EMERGENCIES