2. Hypertension – silent killer
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Heart Attack Stroke Kidney Failure
Hypertension- asymptomatic
Morbidity and mortality due to end organ
damage
3. Anti hypertensive drugs
• Patients with primary hypertension are
generally treated with drugs that 1) reduce
blood volume (which reduces central
venous pressure and cardiac output).
• Reduce systemic vascular resistance.
• Reduce cardiac output by depressing heart
rate and stroke volume.
4. Secondary hypertension
• Patients with Secondary hypertension are
best treated by controlling or removing the
underlying disease or pathology, although
they may still require antihypertensive
drugs.
5. Cardiac output
• Each time the heart beats, a volume of
blood is ejected from one ventricle .
This stroke volume (SV), times the number
of beats per minute (Heart rate HR), equals
the cardiac output (CO).
CO = SV × HR
6. Systemic vascular resistance
• Systemic vascular resistance (SVR) refers to the resistance to blood
flow offered by all of the systemic vasculature, excluding the
pulmonary vasculature.
• This is sometimes referred as total peripheral resistance (TPR).
SVR is therefore determined by factors that influence vascular
resistance in individual vascular beds.
• Mechanisms that cause vasoconstriction increase SVR, and those
mechanisms that cause vasodilation decrease SVR.
• Although SVR is primarily determined by changes in blood
vessel diameters, changes in blood viscosity also affect SVR.
7. Central venous pressure
• Venous pressure is a term that represents
the average blood pressure within the
venous compartment. The term "central
venous pressure" (CVP) describes the
pressure in the thoracic vena cava near the
right atrium
8. Determinants of Arterial Pressure
Mean Arterial
Pressure = X Arteriolar
Diameter
Blood
Volume
Stroke
Volume
Heart
Rate
Filling Pressure
Contractility
Blood Volume Venous Tone
CRITICAL POINT!
Change any physical factors
controlling CO and/or
TPR and MAP can be
altered.
9. Mechanisms Controlling CO and TPR
Artery Vein
2. Hormonal
Renal
Ang II
Adrenal
Catecholamines
Aldosterone
3. Local Factors
1. Neural
SymNS
PSNS
CRITICAL POINTS!
1. These organ systems and mechanisms control physical factors of CO and TPR
2. Therefore, they are the targets of antihypertensive therapy.
10. 2. Secondary hypertension- due to specific organ pathology
1. renal artery stenosis
2. pheochromocytoma
3. aortic coarctation
4. adrenal tumor
Summary-Types and Etiology of Hypertension
1. White coat hypertension
office or environmental
3. Essential Hypertension
No known cause.
CRITICAL POINT!
Pharmacological Therapy used
primarily for essential hypertension.
11. Summary
General Treatment Strategy of Hypertension
1. Diagnosis- 3- 6 independent measurements.
2. Determination of primary vs. secondary hypertension.
3. If secondary, treat underlying pathology.
5. Pharmacological treatment.
4. If primary, initiate lifestyle changes
smoking cessation
weight loss
diet
stress reduction
less alcohol
etc.
CRITICAL POINTS!
Goal- normalize pressure- decrease CO and/or TPR
12. Classes of Antihypertensive Agents
1. Diuretics
2. Peripheral a-1 Adrenergic Antagonists
4. b-Adrenergic Antagonists
3. Central Sympatholytics (a-2 agonists)
5. Anti-angiotensin II Drugs
6. Ca++ Channel Blockers
7. Vasodilators
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Pharmacological Treatment
CRITICAL POINTS!
1. Each designed for specific control system
2. Often used in combination
14. Diuretics (cont)
2. Mechanism of Action
Urinary Na+ excretion
Urinary water excretion
Extracellular Fluid
and/or Plasma Volume
3. Effect on Cardiovascular System
Acute decrease in CO
Chronic decrease in TPR, normal CO
Mechanism(s) unknown
1. Site of Action
Renal Nephron
15. Diuretics (cont)
4. Adverse Reactions
dizziness,
electrolyte imbalance/depletion,
hypokalemia,
hyperlipidemia,
hyperglycemia (Thiazides)
gout
5. Contraindications
hypersensitivity,
compromised kidney function
cardiac glycosides (K+ effects)
hypovolemia,
hyponatremia
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16. Peripheral a-1 Adrenergic Antagonists
Drugs: prazosin (Minipres); terazosin (Hytrin)
1. Site of Action- peripheral arterioles, smooth muscle
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CRITICAL POINT!
Major mechanism/site of SymNS control of blood pressure.
17. 2. Mechanism of Action
Competitive antagonist at a-1 receptors on vascular
smooth muscle.
3. Effects on Cardiovascular System
Vasodilation, reduces peripheral resistance
Peripheral a-1 Adrenergic Antagonists, cont.
CRITICAL POINT!
Blocking a-receptors on vascular smooth muscle allows
muscle relaxation, dilation of vessel, and reduced resistance.
18. 5. Contraindications
Hypersensitivity
Peripheral a-1 Adrenergic Antagonists, cont.
4. Adverse effects
nausea; drowsiness; postural hypotenstion;
1st dose syncope
6. Therapeutic Considerations
no reflex tachycardia; small 1st dose;
does not impair exercise tolerance
useful with diabetes, asthma, and/or
hypercholesterolemia
use in mild to moderate hypertension
often used with diuretic, b antagonist
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19. Central Sympatholytics (a-2 Agonists)
Drugs: clonidine (Catapres), methyldopa (Aldomet)
1. Site of Action
CNS medullary
cardiovascular centers
CNS a-2 adrenergic stimulation
Peripheral sympathoinhibition
Decreased norepinephrine release
2. Mechanism of Action
3. Effects on Cardiovascular System
Decreased NE-->vasodilation--> Decreased TPR
CRITICAL POINT!
Stimulation of a-2 receptors in the medulla decreases peripheral
sympathetic activity( arterial contraction), reduces tone, vasodilation
and decreases TPR.
20. 5. Contraindications
4. Adverse Effects
dry mouth; sedation; impotence;
Central Sympatholytics (a-2 Agonists); cont.
s
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21. b Adrenergic Antagonists
Drugs: propranolol (Inderal); metoprolol (Lopressor)
atenolol (Tenormin); nadolol (Corgard);
pindolol (Visken)
1. Sites of Action
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b-1 b-1
2. Mechanism of Action
competitive antagonist at b- adrenergic receptors
22. b Adrenergic Antagonists, cont.
3. Effects on Cardiovascular System
a. Cardiac-- HR, SV CO
b. Renal-- Renin Angiotensin II TPR
5. Contraindications
asthma; diabetes; bradycardia;
hypersensitivity
4. Adverse Effects
impotence; bradycardia;
fatigue; exercise intolerance;
23. Anti-Angiotensin II Drugs
Angiotensin II Formation
2. Ang II Receptor Antagonists
losartan (Cozaar);
candesartan (Atacand);
valsartan (Diovan)
1. Angiotensin Converting Enzyme-
Inhibitors
enalopril (Vasotec);
quinapril (Accupril);
fosinopril (Monopril);
moexipril (Univasc);
lisinopril (Zestril, Prinivil);
benazepril (Lotensin);
captopril (Capoten)
Ang I
Ang II
ACE
ACE
Ang II
Renin
Angiotensinogen
Ang I
AT1
AT2
Lung
VSM
Brain
Kidney
Adr Gland
24. 3. Effect on Cardiovascular System
Anti-Angiotensin II Drugs, cont
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Volume
Aldosterone
Vasopressin
CO
Angiotensin II
Vasoconstriction
TPR
SymNS
HR/SV
Angiotensin II
Norepinephrine
CO
SymNS
29. Summary
Sites and Mechanisms of Action
1. Can alter CO/TPR at number of sites and/or mechanisms.
2. Antihypertensives mechanistically specific, and alter blood
pressure through physiologically diverse effects on CO/TPR.
3. All organ systems and/or effector mechanisms are p’col targets.
3. a-2 agonists
4. b-blockers
Receptor antag.
2. a-antag.
5. ang II antag.
7. Vasodilators
6. Ca++ antag.
1. Diuretics
4. b-blockers
Other- 5. ACE inhibitors
Lung, VSM, Kidney, CNS
CRITICAL POINTS!
30. Summary Important Points
Hypertensive Agents
Each class of antihypertensive agent:
1. has as specific mechanism of action,
2. acts at one or more major organ systems,
3. on a major physiological regulator of blood pressure,
4. reduces CO and/or TPR to lower blood pressure,
5. has specific indications, contraindications, and
therapeutic advantages and disadvantages associated
with the mechanism of action.
