PHYSIOLOGY
CONTROL & REGULATION OF BLOOD PRESSURE
PATHOLOGY
HYPERTENSION
PHARMACOLOGY
ANTIHYPERTENSIVE MEDICATIONS
QUILLANO JR D. CAGADAS, M.D.
UNIVERSITY OF THE EAST RAMON MAGSAYSAY
MEMORIAL MEDICAL CENTER
At the end of this lecture, the students are expected to:
Ѱ Understand the physiologic control of blood pressure and
enumerate pathologic factors that affect it;
Ѱ Learn the significance of controlling blood pressure
particularly in a patient with dental concern; and
Ѱ Identify the drug groups, the individual member, the
mechanism of action and the adverse effects of the drugs
used in the treatment of hypertension.
Hypertension remains to be the leading cause of illness and a primary contributor to
premature death in the Philippines, projecting around 200,000 deaths yearly in the
country attributed directly or indirectly to high blood pressure.
The total number of hypertensive Filipinos is now more than 12 million, with more than
half of them are unaware of their condition. This is roughly 1 out of 4 to 5 Filipinos in
general. – DOH, 4 May 2017
HYPERTENSION
Ѱ Pressure that is exerted by the blood upon the walls of the blood
vessels and especially arteries and that varies with the:
(1) Muscular efficiency of the heart
(2) Blood volume
(3) Blood viscosity
(4) Age and health of the individual; and
(5) State of the vascular wall
Physiology of Blood Pressure Control
Renin – Angiotensin – Aldosterone System (RAAS)
Hypertension
• A sustained SBP > 140 mm Hg or a sustained DBP > 90 mm
Hg.
CLASSIFICATION OF BLOOD PRESSURE
CATEGORY SBP (mmHg) DBP (mmHg)
Normal <120 AND <80
Prehypertension 120 – 139 OR 80 – 89
Hypertension, Stage 1 140 – 159 OR 90 – 99
Hypertension, Stage 2 >160 OR >100
Hypertension
• A risk factor for:
Ѱ CKD
Ѱ CVA
Ѱ AMI
Ѱ Heart failures
Ѱ Cardiomyopathies
Ѱ Hepatic failure
Ѱ Retinopathy
Main Target Organs
Ѱ Retinopathies
Ѱ Neuropathies
Ѱ Cardiomyopathies
Ѱ Nephropathies
Ѱ Vasculopathies
Hypertensive Urgency VS Hypertensive Emergency
HYPERTENSIVE URGENCY – SBP > 220mmHg or DBP >
120mmHg without target organ damage
HYPERTENSIVE EMERGENCY – SBP > 180mmg or DBP > 120
with evidence of target organ damage.
Significance of Early Recognition and
Treatment of Hypertension
Ѱ Significant reduction of mortality and morbidity
Ѱ Prevention of damage to target organs.
Ѱ Prevention of bleeding during dental procedures.
Ѱ Reduction of risk of dying during any type of surgery
(medical or dental).
CVD INFARCT
CVD Hemorrhage
Treatment Strategies
ACE - Inhibitors
ARBs Vasodilators
ß - Blockers
Centrally – Acting Adrenergics
DIURETICS
Treatment Strategies
JNC 8: INITIAL DRUGS FOR HYPERTENSION
ACE – Inhibitors (A)
Beta Adrenergic Receptor Blockers (B)
Calcium Channel Blockers (C)
Thiazide Diuretics (D)
Treatment Strategies
Non – therapeutic Intervention
Lifestyle changes:
Ѱ Smoking Cessation
Ѱ Control blood glucose and lipids
Ѱ Diet
→ Eat healthy (i.e., DASH diet)
→ Moderate alcohol consumption
→ Reduce sodium intake to no more than 2,400 mg/day
Ѱ Physical activity
→ Moderate-to-vigorous activity 3-4 days a week averaging 40
min per session.
DIURETICS
Diuretics
Ѱ Drugs that decrease blood pressure by:
a. Depleting Na+ stores
b. Reducing blood volume and Cardiac Output
Ѱ Types:
a. Thiazide Diuretics
b. Loop Diuretics
c. Potassium – sparing Diuretics
5%
65 – 70%
25%
1 – 2%
REFERENCE: BASIC AND CLINICAL PHARMACOLOGY. 15TH ED. KATZUNG. VANDERAH.
Thiazide Diuretics
Ѱ Representative: Hydrochlorothiazide
Others: Chlorthalidone
Ѱ MOA: Inhibition of Na+ - Cl- transporter
in the luminal membrane of DCT
REFERENCE: BASIC AND CLINICAL PHARMACOLOGY. 15TH ED. KATZUNG. VANDERAH.
Thiazide Diuretics
Ѱ Useful in patients with mild to moderate hypertension
Ѱ Not useful in patients with inadequate renal function
(GFR <30mL/min/m2)
Ѱ ADR:
Hypokalemia, Hyperuricemia, Hyperglycemia,
Hypercalcemia, Hyperlipidemia
LOOP Diuretics
Ѱ Representative: FUROSEMIDE
Ѱ Others: Torsemide, Bumetamide,
Ethacrynic Acid
Ѱ MOA: Inhibition of Na+/K+/2Cl-
Transporter in the TAL
REFERENCE: BASIC AND CLINICAL PHARMACOLOGY. 15TH ED. KATZUNG.
VANDERAH.
LOOP Diuretics
:
(1) Severe hypertension where many agents with Na+ -
retaining properties are used
(2) Renal insufficiency
(3) Cardiac Failure or Cirrhosis
Symptoms of heart failure and edema
Hypokalemia; Hypotension
Potassium – Sparing
Diuretics
Ѱ Spironolactone and Eplerenone;
Amiloride and Triamterene
Ѱ MOA: Aldosterone receptor blocker
and inhibition of Na+ Transport at the DCT
and Collecting Ducts
Ѱ Useful as adjunct to K+ - wasting
Diuretics
Ѱ ADR: Hyperkalemia
REFERENCE: BASIC AND CLINICAL PHARMACOLOGY. 15TH ED. KATZUNG. VANDERAH.
B – ADRENERGIC RECEPTOR BLOCKERS
ß – Adrenergic Receptor Blockers
Ѱ Commonly known as ß – Blockers (inhibits ß receptors)
Ѱ MOA: (1) ↓↓↓ HR → ↓↓↓ Cardiac Output
(2) ↓↓↓ Sympathetic outflow from the CNS
(3) Inhibit release of renin from kidneys (↓↓↓Aldosterone)
Ѱ Prototype: Propranolol (non – selective)
Ѱ Cardio - Selective ß – Blockers:
Metoprolol
Atenolol
Nebivolol (produces nitric oxide – a vasodilator)
Esmolol (ultrashort – acting, IV)
ß – Adrenergic Receptor Blockers
Ѱ Therapeutic Uses: Ѱ ADRs
о Hypertension with concomitant heart disease о Bradycardia
о History of myocardial infarction о Hypotension
о Angina pectoris о Fatigue
о Chronic heart failure о Insomnia
о Sexual dysfunction
Ѱ Contraindications
о Bronchial Asthma
о Heart blocks
о Peripheral Vascular Disease
ANGIOTENSION – CONVERTING ENZYME
INHIBITORS
Angiotensin - Converting Enzyme Inhibitors
Ѱ Are vasodilators
Ѱ Prototype: Enalapril
Ѱ Others: Ramipril, Lisinopril, Captopril, Enalaprilat, Fosinopril
Ѱ MOA:
(1) Inhibition of Angiotensin – Converting enzyme (ACE); ↓↓↓ TPR
(2) ↓↓↓Angiotensin II (↑↑↑Vasodilation → ↓↓↓Afterload)
(3) ↓↓↓Aldosterone (↓↓↓Na and water retention → ↓↓↓ Preload)
Angiotensin - Converting Enzyme Inhibitors
Ѱ Clinical Use: Hypertension with compelling indications
(1) CAD risk (First line)
(2) Diabetes Mellitus (esp DM Nephropathy)
(3) Stroke
(4) Heart failure (First line)
(5) Myocardial infarction (Standard)
(6) CKD (First line)
Ѱ ADRs: Cough, angioedema, hyperkalemia
ANGIOTENSIN II RECEPTOR BLOCKERS
Angiotensin II Receptor Blockers
Ѱ Representative: Losartan (Lifezar)
Ѱ Others: Irbesartan, Telmisartan (Micardis), Valsartan, Candesartan,
Olmesartan (Olmetec)
Ѱ MOA: Block AT1 receptor (↓↓↓Activation of AT1 receptors by
Angiotensin II)
Ѱ Alternatives to ACE – Is
Ѱ Arteriolar and venous dilation (↓↓↓TPR = ↓↓↓Afterload)
Ѱ ↓↓↓Aldosterone secretion (↓↓↓Na and water retention=
↓↓↓Preload)
Ѱ Contraindicated in pregnancy
VASODILATORS
Vasodilators
Ѱ Hydralazine and Minoxidil
Ѱ Direct – acting smooth muscle relaxants
Ѱ NOT used primarily for hypertension
Ѱ Mechanism of Action?
Treatment Strategies
ACE - Inhibitors
ARBs Vasodilators
ß - Blockers
Centrally – Acting Adrenergics
DIURETICS
CALCIUM CHANNEL BLOCKERS
Calcium Channel Blockers
Ѱ Dihydropyridine
Representative: Nifedipine (Others:
Amlodipine, Felodipine)
Ѱ Non – dihydropyridine: Verapamil,
Diltiazem
Ѱ Moderately efficacious, orally active, well
- tolerated
CENTRALLY – ACTING ADRENERGIC AGONISTS
Centrally – Acting Adrenergics
Ѱ α2 – Selective Agonist
Ѱ Representative: Clonidine
Ѱ Other: Methyldopa
Ѱ MOA: Inhibition of sympathetic vasomotor centers → ↓↓↓
Sympathetic outflow to the periphery
Ѱ Clinical Use: For hypertension not responsive to one or two agents
(NOT as first line drug)
Ѱ REBOUND HYPERTENSION if withdrawn abruptly.
Treatment Strategies
ACE - Inhibitors
ARBs Vasodilators
ß - Blockers
Centrally – Acting Adrenergics
DIURETICS
TAKE – HOME POINTERS:
o Hypertension is a condition that can be controlled by
understanding the physiology and pathology governing this
clinical disease.
o Treatment may be achieve through pharmacologic and
non – pharmacologic methods.
o Prevention of complications, mainly cardiovascular ones, is
the ultimate goal of controlling or regulating blood
pressure.
o Regimen of treatment of hypertension should be
individualized and focused on the specific areas of blood
pressure physiology to achieve maximum drug efficacy.
THANK YOU!
