cular resistance and blood pressure. Alpha-receptor antagonists may be reversible or irreversible with regards to receptor bind- ing (Katzung, 2018, p. 156). Reversible alpha-receptor antago- nists may be disassociated with elevated agonist concentrations though remains primarily dependent upon the chemical signature half-life. In contrast, irreversible alpha-receptor antagonist effects require production of new receptors, which often requires a pe- riod of days. In contrast, beta-receptor antagonists may be partial or full antagonists. Beta-receptor antagonists are also common- ly associated with reducing hypertension and are often termed “beta-blockers.” Beta-blockers are commonly associated with decreasing frequency of cardiac angina, especially with regards to cardiac stress-associated with exercise. Despite colloquial pre- scription, the mechanism of action for beta-receptor antagonists is less understood when compared to alpha-receptor antagonists. Cardiovascular effects of this drug class are postulated to involve inhibition of renin release in the CNS. Common side effects of beta-blockers may include bronchial smooth muscle spasm. Thus, applying these drugs in the presence of chronic obstructive pul- monary disease is often contraindicated and/or managed care- fully depending on the therapeutic net value. In addition, beta- receptor blockers restrict sympathetic nervous system stimulation of lipolysis, and may be employed to treat acute hypoglycemia, an example of which is glucagon (Katzung, 2018, p. 165). Diuretics While the complete effects of diuretics are still subjects of clinical research, the common understanding is that they reduce blood pressure by lowering the body’s sodium content, and thereby lowering blood volume. The primary mechanism of action is an increase in urine volume. Diuretics are often effective in treatment of mild to moderate hypertension, reducing blood pressure by an average of 10 to 15 mmHg (Katzung, 2018, p. 177). This course will primarily discuss diuretics based on common administration in the acute hospital setting, and include loop diuretics, thiazides, potassium-sparing diuretics and osmotic diuretics. Loop diuretics are the most commonly employed version of this pharmaceutical class, and are often prescribed in the presence of edema, whether pulmonary or otherwise. They are also useful to reduce potassium levels in the body and increase urine flow in the presence of renal failure, as well as treatment following inges- tion of certain toxic compounds. Thiazides prohibit reabsorption of sodium chloride (NaCl); a common example includes hydro- chlorothiazide. Primary toxic effects of loop diuretics, as well as thiazides, are caused by excessive influx of sodium into the renal collecting duct, which can lead to hypokalemia and metabolic al- kalosis. Potassium-sparing diuretics reduce potassium loss either by antagonizing mineralocorticoid receptors associated with po- tassium secretion, or by inhibiting sodium influx through the lu- minal membrane. Common examples include spironolactone and amiloride (Katzung, 2018, p. 265). In contrast, the primary toxic ef- fect of this drug subgroup is acute hyperkalemia, which can be fa- tal in the presence of chronic renal insufficiency as well as liver fail- ure. Osmotic diuretics, such as mannitol, promote water retention in the proximal tubule and loop of Henle, which in turn promotes water diuresis. Loop agents are often used in combination with thiazides to prevent refractory response, while potassium-sparing diuretics may be prescribed in combination with loop diuretics or thiazides to reduce hypokalemic effects. Diuretics are commonly prescribed for treatment and/or medical management of edema, heart failure, mild renal failure, hepatic cirrhosis, hypertension, nephrolithiasis, hypercalcemia, and diabe- tes insipidus. While diuretics are effective in mobilizing interstitial edema, application requires continuous monitoring of blood vol- ume as well as blood pressure, often in a hospital setting, to en- sure that vital organs remain perfused. By reducing blood volume, diuretics also reduce venous pressure and ventricular preload, which ultimately reduce heart size and improve pump efficiency. The downside of this process is consequent reduction in venous
compounds , this class of pharmaceuticals causes CNS stimulation, tachycardia and bronchodilation (Katzung, 2018, p. 130). Atropine once served as the sole drug therapy to treat Parkinson’s disease, prior to the development of levodopa. Scopolamine is another popular antimuscarinic drug, used to treat motion sickness. Adrenoreceptor agonists bind either directly to epinephrine and norepinephrine receptors, or augment the actions of endogenous catecholamines, thereby initiating sympathetic neural responses. Termed sympathomimetic drugs, this pharmaceutical class gener- ally initiates localized “fight or flight” responses at various sites of action. When applied to cardiac function, they are said to have a positive chronotropic effect, meaning they can increase heart rate by affecting the sinoatrial electrical node conduction rate. In addition, adrenoreceptor agonists generally increase cardiac muscle contractile force, vascular smooth muscle contraction, re - nal blood vessel dilation, bronchodilation, and urinary sphincter contraction. Common examples include direct application of epi- nephrine in the presence of cardiac arrest and/or anaphylaxis, and dobutamine to induce controlled cardiac stress testing (Katzung, 2018, p. 152). Adrenoreceptor antagonist drugs bind to alpha- and beta-re- ceptors, primarily outside the CNS, preventing their activation by catecholamines and/or similar agonists. The most well-known effect of alpha-receptor antagonists is reducing peripheral vas-
ANTI-HYPERTENSIVE PHARMACEUTICALS
Hypertension is more often than not a multi-factorial pathology. Contributing factors may be genetic, environmental, dietary and/ or psychological. Common considerations include smoking, obe- sity, diabetes and emotional stress, as well as pathologies such as Cushing’s disease. Current research has also associated hyperten- sion with daily consumption of red meat. Primary hypertension indicates that no clear-cut etiology exists for a patient, while sec- ondary hypertension can be attributed to a specific cause and is diagnosed in roughly 10 to 15 percent of patients (Katzung, 2018, p. 175). Blood pressure is the physiologic product of cardiac output against peripheral vascular resistance. In the absence of patho- logical conditions, blood pressure is regulated on a moment-to- moment basis in the heart, arterioles and postcapillary venules. The kidney provides additional chronic pressure regulation in the form of intravascular fluid management. Nephrotic blood volume control is achieved by varying reabsorption rates of blood and water. Dynamic blood pressure adaptation occurs in the form of baroreflexes. Baroreceptors in the carotid sinus and aortic arch initiate inhibitory autonomic sympathetic responses to increases in arterial wall pressure. This process is reduced in the presence of reduced arterial wall pressure, commonly observed in the pres- ence of positional changes from lying down to sitting up and/ or acute vasodilation. Four categories of anti-hypertensive drugs include diuretics, sympathoplegic agents, direct vasodilators, and angiotensin blocking agents. Hypertension is managed across inpatient and outpatient medical settings. Primary conservative measures are non-pharmacologic and may include reduced dietary salt intake, prescribed exercise and weight loss. This increases the value of physical therapy to compliment treatment of hypertension. While pharmaceutical management of mild hypertension may include prescription of a single drug, more severe presentations lead to prescriptions of two or more. Physical therapy thus requires clinical application that accounts for the pathophysiology of hypertension and asso- ciated comorbidities. While physical therapists treating patients with hypertensive urgency in the acute hospital setting follow up with examination and treatment of patients who have been medi- cally optimized, therapists in outpatient settings must be familiar with a patient’s prescription for antihypertensive agents and pre- pare for potential adverse effects during prescribed exercise by recording blood pressure in variable positions and activities.
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