Pharmacology Lecture Hypertension 2014

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A. Blood Pressure
1. What is Blood Pressure?
a.k.a: Arterial Pressure – the pressure exerted by the circulating volume of blood on the walls of the arteries and veins and on the chambers of the
heart
− pressure exerted by the blood on the walls of a blood vessel


2. Types of Blood Pressure
a. Systole – pressure exerted by the heart to pump out blood
− contraction of the heart driving blood into the aorta and pulmonary arteries
− refers to the upper number, in mmHg
− ventricular contraction
b. Diastole – pressure when the heart is at rest; exerted against the walls of the blood vessels
− period within contractions of the atria or the ventricles during which blood enters the relaxed chambers from the systemic circulation and
the lungs
− refers to the lower number, in mmHg
− ventricular relaxation
Normal: 120/80 Range:


3. Hydrostatic equation
According to the hydrostatic equation, arterial blood pressure (BP) is directly proportional to the product of the blood flow (CO) and the
resistance to passage of blood through precapillary arterioles (PVR).
BP = CO x PVR

*Cardiac Output – volume of blood ejected from the left ventricle/right ventricle into the aorta/pulmonary trunk each minute. Cardiac output equals
the stroke volume (volume of blood ejected by the ventricle during each contraction) multiplied by the heart rate (number of heartbeats per
minute)
CO = SV x HR
*Peripheral Vascular Resistance – force of the blood pressure; the opposition to blood flow due to friction between blood and the walls of blood
vessels. (size of BV lumen, blood viscosity, total BV length)


4. Classification of Blood Pressure by JNC (Joint National Committee)
Systole Diastole
Normal ≤ 120 ≤ 80
Prehypertension 121 - 139 81 – 89
Stage 1 140 - 159 90 – 99
Stage 2 ≥ 160 ≥ 100


5. Regulation of BP
Organs involved include: heart, blood vessels, ANS-SANS

Neural Regulation of Blood Pressure
a. Baroreceptor Reflexes - a sensory receptor located in the aorta, internal carotid arteries (found in the neck that supplies blood in the
brain), and other large arteries in the neck and chest; regulate BP
Stimuli ↓BP Baroreceptors CV Center (+)inotropy-F of contraction ↑SV & HR ↑BP
(+)chronotropy-HR ↑PVR
(+)dromotropy-conduction of impulse
(+)bathmotropy-excitability,sensitive impulse
− change in body position particularly form sitting to standing position – blood will rush below the heart detected by baroreceptors
b. Chemoreceptor Reflexes - a sensory receptor that monitor the chemical composition of blood, are located close to the baroreceptors of
the carotid sinus and arch of aorta

detects changes in O2(hypoxia=↓ O2), CO2(hypercapnia=↑ CO2), and H
+
(acidosis=↑ H
+
conc)

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Stimuli chemoreceptors CV Center ↑sympathetic ↑vasoconstriction ↑BP
(arterioles & veins)


Hormonal Regulation of BP
a. Renin-angiotensin-aldosterone (RAA) System

b. Epinephrine and Norepinephrine – adrenal medulla
Epi & Nor (+)chronotropy ↑CO ↑BP
(+)inotropy
c. Antidiuretic hormone (ADH) – aka vasopressin; pdc by hypothalamus and released by posterior pituitary in response to dehydration
and ↓BV
ADH vasoconstriction ↑BP
H2O to bloodstream ↑BV,↓urine
d. Atrial Natriuretic Peptide – released by cells in the atria of the heart
ANP loss of NaCl and H2O ↓BV,vasodilation ↓BP


Autoregulation of BP
− Ability of a tissue to automatically adjust its blood flow to match its metabolic demands
a. Physical changes – warming promotes vasodilation, cooling causes vasoconstriction
b. Vasodilating and vasoconstricting chemicals
Vasodilating: K
+
, H
+
, lactate, ATP, NO, kinins, histamine
Vasoconstricting: thromboxane, A2, superoxide radicals, serotonin, endothelins


B. Hypertension
1. What is Hypertension?
− persistent elevation of blood pressure after 3-4 occasions
− elevated systemic arterial blood pressure
− cardiovascular disease risk factor (not a disease)
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2. Types
a. Primary/Idiopathic/Essential htn
− no identifiable cause
Theories:
i. Age
− body systems ↓efficiency
− elasticity of BV is lost
− NP = ↓ release as you age because there are no peptides that control
ii. RAAS
− aldosterone is an end product therefore reabsorption of sodium ions
eg. Black Race – can’t efficiently handle sodium ions; ACE inibitors is not used in the management of htn
iii. Na⁺
− Normal: [135-145 mEq/L] [135-145 mmol/L]
− excess NP = urine is salty
iv. ANS/SANS
− Stresses? ↑release of catecholamines which act on CVS causing hypertension
v. Ca
2+

− Calcium ions plus contractile CHONs (actin and myosin) leads to vasoconstriction thereby increasing PVR and thus,
increase in BP

b. Non-essential/Secondary htn
i. Renal/glomerular dse
ii. DM
iii. Cushing’s Syndrome/pheochromocytoma
iv. Excessive ROH intake
v. Heart dse
vi. Coarctation of the aorta
vii. Drugs – NSAIDS, SANS, Adrenergic Drugs
c. White coat htn – anxiety induced when BP is taken by a HCP
d. Pregnancy-induced htn – because of ↑BP; hormonal; 2 circulations
e. Isolated systolic htn – SBP >140 with DBP <90
− occurs in elderly


3. Risk Factors
a. Age
b. Obesity
c. Sedentary lifestyle – no exercise
d. Smoking
e. Excessive ROH intake
f. Diet - ↑cholesterol/fatty foods, ↑Na, ↑Ca
g. Stress
h. Drugs = NSAIDS, steroids
i. Family history
j. Co-morbid dse – chronic dse such as kidney, heart,
DM
k. Black race / ethnicity


4. Management
a. Interview – F Hx, s/s (asymptomatic)
s/s
o nape pain
o chest pain
o dizziness
o palpitations
o fatigue
o HA
o epistaxis
o fainting
o shortness of breath
o tinnitus
b. Get BP
− 3 separate occasions (3-4 mos interval)
− BP remains elevated

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c. Lab Tests – identify the organs involved in htn
Eg. Blood glucose –DM
Blood lipids – cholesterol/triglycerides
Urinalysis – kidneys, BUN
ECG – heart is normal or enlarged
CXR - lungs


5. Treatment
Principle involved in treating hypertension
a. Individualization – dependent on the individual characteristics (age, gender, race, height and weight, co-morbid factors)
b. Stepped Care Approach/Laddered Approach



a. Non-PCOL – modify their lifestyle
i. DASH diet
fruits, vegetables, wheat, whole grains, low-fat dairy foods
↑K – balance the amount of sodium in cells
↓Na in diet – 1,500 mg a day for hypertensive patients (2,300 mg for healthy individuals); retain fluid
ii. Limit alcohol intake – moderateROH can raise BP even in healthy individuals
iii. Maintain a healthy weight – more weight means more blood needed to supply oxygen and nutrients to your tissues thus, BV
increases and so does pressure
iv. Regular exercise – brisk walking; 30 mintues of physical activity a day
 Not active? Tend to have higher heart rates; the higher HF, the harder the heart must work with each contraction and the
stronger the force on the arteries. Also increase the risk of being overweighed
v. Stop smoking – injures blood vessel walls causing it to narrow; speeds up the process of hardening of the arteries
vi. Manage stress – muscle relaxation, deep breathing, plenty of sleep

b. PCOL
i. Alpha-adrenergic blockers
ii. ACE inhibitors
iii. Beta-Blockers
iv. Calcium Channel Blockers
v. Diuretics
vi. Sympatholytics
vii. Vasodilators
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C. Drugs for Hypertension
1. Diuretics
MOA ADR Agents Brand Name
Thiazide/Thiazide-like Diuretics





Promotes excretion of Na
+

Prevents Na
+
reabsorption
Decrease in BV
Decrease in CO
Decrease in BP
hypokalemia
hyponatremia
hyperuricemia
orthostatic hypotension
hypercalcemia
hyperglycemia
hyperlipidemia
Bendroflumethiazide
HCTZ / CTZ
Chlorthalidone
Indapamide
Metolazone
Naturetin
Hytaz
®
Diuzid
®
Urilzid
®

ThalitoneTenoretic
®
(+Atenolol)
Natrilix
®
Zaroxolyn
®

Loop Diuretics ototoxicity
hyperuricemia
acute hypovolemia
hypokalemia
hypomagnesemia
Furosemide
Torsemide
Bumetanide
Ethacrynic acid
Metazolide
Lasix
®
Fretic
®
Frusema
®
Demadex
®

Bumex
®
BurinexFontego
®
Edecrin
®


Potassium-sparing Diuretics gastric upset
gynecomastia
menstrual irregularities
hyperkalemia
nausea
lethargy
mental confusion
Spirinolactone
Eplerenone
Aldactone
®
Inspra
®




2. Sympatholytics
 aka anti-adrenergics (targets the SANS)
MOA ADR Agents Brand Name
β-Blockers
Types:
a. Cardioselective
b. Non-cardioselective

Blocks α/β receptors
preventing the reaction of
catecholamines
↓CO by (-)inotropy,
chronotropy, dromotropy,
bathmotropy
↓BP

↓renin = ↓angiotensinogen
to ↓aldosterone
hypotension
bradycardia
arrhythmia
bronchospasm
dyspnea
sedation
↓HDL
fatigue
insomnia
sexual dysfunction
Acebutolol
Atenolol
Carvedilol
Labetalol
Metoprolol
Nadolol
Propranolol
Timolol
Sectral
®

Tenormin
®

Coreg
®
Carvid
®

Normodyne
®
Trandate
®

Neobloc
®

Corgard
®

Inderal
®
Hemangeol
®
InnoPran
®

Blocadren
®

α-Blockers
DI: Sit for 10-15 min before
getting up to avoid postural
hypotension
Best given at HS
Inhibit/block α asdrenergic
receptors at vascular
tissues (blood vessels)
causing vasodilation
↓PVR
↓BP
orthostatic hypotension
edema
bradycardia
lightheadedness
syncope
HA
reflex tachycardia
salt and water retention
Prazosin
Terazosin
Doxazosin
Phentolamine
Phenoxybenzamine
Minipress
®

Hytrin
®

Cardura
®

OraVerse
®
Regitine
®

Dibenzyline
®

Centrally-acting α
agonists
Blocks sympathetic
outflow in the brain stem
to cause vasodilation
↓PVR
↓BP
sedation
drowsiness
hemolytic anemia
bradycardia
constipation
dry mouth
edema
Clonidine – with renal dse
Methyldopa – PIH
Guanfacine
Guanabenz
Catapres
®
Kapvay
®
Jenloga
®

Aldomet
®
Aldoclor
®
Medopa
®

Intuniv
®
Tenex
®
Estulic
®

Wytensin
®

Adrenergic Neuron Depletes norepinephrine depression (CI to Px with Reserpine
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Blocker from circulation





depression)
sexual dysfunction
(↓libido)
orthostatic hypotension
angina
bradycardia



3. Agents that suppress RAAS
MOA ADR Agents Brand Name
ACE Inhibitors
“prils”
Inhibits conversion of
Angiotensin I to Angiotensin
II to Aldosterone




hyperkalemia
dry cough
angioedema
proteinuria
dysgeusia
ACE: rash, fever
ARB: diarrhea
Benazepril
Captopril
Enalapril
Fosinopril
Lisinopril
Moexipril
Quinalapril
Ramipril
Trandolapril
Lotensin
®

Capoten
®

Vasotec
®
Epaned
®

Monopril
®

Zestril
®
Prinivil
®

Univasc
®

Accupril
®

Altace
®

Mavik
®

ARBs
“sartans”
Inhibits release of renin so
no conversion of
angiotensinogen into
aldosterone
Candesartan
Eprosartan
Irbesartan
Losartan
Olmesartan
Telmisartan
Valsartan
Blopress
®
Atacand
®
Candez
®

Teveten
®

Aprovel
®
Avapro
®

Cozaar
®
Losart
®

Benicar
®

Micardis
®

Diovan
®





4. Calcium Channel Blockers
− usually non-selective since it affects all muscles
MOA ADR Agents Brand Name
Dihydropyridines
Inhibits entry of Ca
2+

Inhibit rxn with contractile
CHONs into myocardial and
vascular cells to promote
vasodilation

Also cause relaxation of
other cells – skeletal and
smooth muscles



Constipation
Weakness
Periopheral edema
Reflex tachycardia
(-)inotropy – can lead to HF
Amlodipine
Felodipine
Isradipine
Nicardipine
Nifedipine
Nimodipine
Nisoldipine
Norvasc
®
Amvasc
®

Plendil
®

Dynacirc
®

Cardene
®

Adalat
®
Procardia
®
Nifediac
®

Nimodin
®
Nymalize
®

Sular
®

Non-dihydropyridines
 Diphenylalkylamine –
Verapamil
 Benzothiazepines –
Diltiazem
Diltiazem
Verapamil
Dilzem
®
Cardizem
®
Dilacor
®

Isoptin
®
Covera-HS
®
Calan
®




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5. Vasodilators
MOA: acts directly on blood vessels (arteries and veins) to ↓PVR leading to ↓BP
Brand Name Notes Specific ADR General ADR
Hydralazine Apresoline
®


Drug that undergoes
acetylation polymorphism
which is a part of Phase II
metabolism
Rapid/slow acetylators
Drug-induced SLE
Type II allergic reactions






postural hypotension
epinephrine reversal –
reflex tachycardia
palpitation
HA
arrhythmia
peripheral neuropathy
edema
Minoxidil Loniten
®
Hyoertrichosis
Hirsutism
Diazoxide Proglycem
®

Hyperstat
®

Inhibits insulin release from
the pancreas
Hyperglycemia
Fenoldapam Corlopam
®
Targets the dopamine
receptors
Dilation of peripheral
arteries
Natriuresis
Na Nitroprusside Nitropress
®
Nitroprusside = enzyme
rhodanase, liver metabolize
to inactive substance
↓Rhodanase ]= metabolize
to toxic subs
*Thiocyanate has the
tendency to accumulate in
the blood causing
methemoglobinemia
(0xidize)
Reducing agent:
Methylene blue – urine blue
CN toxicity
Antidote: Na2S2O3