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Medical Pharmacology Lectures:  Cardiovascular Pharmacology, Antihypertensive Agents Slide1

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Table of Contents

  • Essential Hypertension

  • Classification of Arterial Hypertension

  • Control of Blood Pressure

  • Antihypertensive Drug Mechanisms

  • Baroreceptor Reflexes

  • Antihypertensive Drugs and Anesthesia

  • Hypertension:  Organ Systems Effects:

    • Cardiovascular Effects

    • Pathogenesis

    • Secondary Hypertension

    • Effects on Cardiac Function

    • CNS Effects-stroke

    • Renal Effects

    • Chronic Hypertension: Perioperative Issues

  • Pharmacological Management of Hypertension

    • Hypertensive Crisis

  • Diuretics

  • Sympatholytics

  • Vasodilators

    • Hydralazine (Apresoline)

    • Minoxidil (Loniten)

    • Management of Hypertensive Crisis

    • Adverse Effects

    • Nitroprusside (Nipride)

      • Overview

      • Mechanism of Action

      • Metabolism

      • Organ System Effects

        • Cardiovascular

      • Clinical Uses

  • Calcium Channel Blockers

  • Angiotensin Converting Enzyme Inhibitors (ACE inhibitors)

  • Drug Classes

 

 

 

Essential Hypertension (greater than 90% of cases)

  • Occurs in patients who have arterial hypertension without a clear, definable cause.

  • Essential hypertension is also referred to as primary or idiopathic hypertension.

Classification of Arterial Hypertension

I. Systolic hypertension

  • (with wide pulse pressure) can be caused either by conditions of decreased aortic compliance, often due to arteriosclerosis or to increased stroke volume.

  •  Some conditions that increase stroke volume:

    • Thyrotoxicosis

    • Fever

    • Aortic regurgitation

II. Systolic and Diastolic hypertension

  • (increased peripheral vascular resistance)

Renal 

  • Renovascular stenosis or renal infarction

  • Polycystic kidney disease

  • Acute and chronic glomerulonephritis

  • Chronic pyelonephritis

  • Renin-producing tumors

  • Other severe renal diseases)

Endocrine 

  • Adrenocortical hyperactivity (Cushing's disease, primary hyperaldosteronism)

  • Oral contraceptives

  • Pheochromcytoma

  • Acromegaly

  • Myxedema

Neurogenic

  • Psychogenic

  • Polyneuritis

  • Elevated intracranial pressure

  • Familial dysautonomia

Miscellaneous

  • Increased intravascular volume

  • Polyarteritis nodosa

  • Hypercalcemia

  • Aortic coarctation

 

 

Unknown Etiology

  • Toxemia of pregnancy

  • Acute intermittant porphyria

  • Essential Hypertension (> 90% of all cases of hypertension

 

 

Control of Blood Pressure

Arterial pressure is determined by a number of interacting factors

Physiological Factors Influencing Arterial Pressure

  • Preload & Contractility:

    • As blood volume returning to the heart increases, preload increases and there is enhanced filling with ventricular dilation.

    • According to Starling's Law, increased ventricular stretch usually leads to increased contractility.

    • Increased preload and increased contractility lead to increased stroke volume and ultimately an increase in arterial pressure, all other factors remaining equal.

    • Some antihypertensive drugs decrease preload.

  • Heart rate: Since the product of heart rate and stroke volume equals cardiac output, an increase in heart rate will increase arterial blood pressure, all other factors remaining equal.

    • Some antihypertensive agents decrease heart rate (-adrenergic receptor antagonists, e.g.).

  • Heart Rate X Stroke Volume = Cardiac Output

  • Cardiac Output X Peripheral Resistance = Arterial Pressure

  • Peripheral resistance: For a given cardiac output, blood pressure depends only on peripheral resistance. Some antihypertensive drugs act to reduce peripheral resistance.

Baroreceptor Reflexes

  • A principal mechanism for arterial blood pressure control is the baroreceptor reflex.

  • The reflex is initiated by activation of stretch receptors located in the wall of most large arteries of the chest and neck.

  • A high density of baroreceptors is found in the wall of each internal carotid artery (just above the carotid bifurcation i.e. carotid sinus) and in the wall of the aortic arch.

 

  • As pressure rises and especially for rapid increases in pressure:

    • baroreceptor input to the tractus solitarius of the medulla results in inhibition of the vasoconstrictor center and excitation of the vagal centers and therefore:

    • a vasodilatation of the veins and arterioles in the peripheral vascular beds and negative chronotropic and inotropic effects on the heart occurs. (slower heart rate with reduced force of contraction)

 

 

Antihypertensive Drugs and Anesthesia

  • There is probably excessive concern about interaction potential between anesthetics and antihypertensive drugs.

  • Areas of concern for administration of anesthetic to patients treated with antihypertensive medications:

    • Reduced sympathetic nervous system activity--manifestations:

      • Orthostatic hypotension

      •  Excessive systemic blood-pressure responses (decreases) to:

        1. acute blood loss

        2. body position changes

        3. decreased venous return cause by positive-pressure ventilation

      • Reduced sensitivity to indirect-acting sympathomimetic agents (cause by antihypertensive drugs that deplete norepinephrine from nerve terminals

      • Possible enhanced response to catecholamines and direct-acting sympathomimetics following sympathetic nervous system blockade (reduced alpha-adrenergic receptor tone with loss of tonic stimulation)

    • Altered physiological response to sympathomimetic agents

    • Sedation

  • Maintenance of antihypertensive drug treatment during perioperative time frame:

    • Fewer systemic blood-pressure and heart rate fluctuations during anesthesia

    • Decreased likelihood of cardiac dysrhythmias

    • Conclusion:

      • Previously effective antihypertensive drug therapy should be continued during the perioperative period.

      • The pharmacology of the particular antihypertensive drug should be considered in the development of the anesthesia plan.

Stoelting, R.K., "Antihypertensive Drugs", in Pharmacology and Physiology in Anesthetic Practice, Lippincott-Raven Publishers, 1999, 302-312.

 

 
 
 
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