Pharmacology Module 3: Drugs Treating Impaired Perfusion PDF

**Dugs that Treat Impaired Perfusion** ---------------------- -------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------...

**Dugs that Treat Impaired Perfusion** ---------------------- ---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- Concept of perfusion **Perfusion** refers to the process by which blood is delivered to tissues and organs in the body through the circulatory system. It is a critical function because it ensures that tissues receive adequate oxygen and nutrients while also allowing for the removal of waste products like carbon dioxide. Effective perfusion is essential for maintaining healthy tissue function and overall bodily homeostasis ---------------------- ---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- +-----------------------------------+-----------------------------------+ | Adequate blood and oxygen | | | perfusion is essential for | | | delivering oxygen and nutrients | | | to tissues and organs while | | | removing waste products. Several | | | components and processes work | | | together to ensure effective | | | perfusion. Below are the key | | | components and processes | | | required: | | +===================================+===================================+ | Components needed for adequate | **Heart, blood vessels, blood, | | blood and oxygen perfusion | and lungs** are the major | | | components responsible for | | | adequate perfusion | | | | | | **Heart**: | | | | | | - - | | | | | | **Blood Vessels**: | | | | | | - - - - | | | | | | **Blood**: | | | | | | - - - | +-----------------------------------+-----------------------------------+ | Processes needed for adequate | Processes such as **cardiac | | blood and oxygen perfusion | output, blood pressure | | | regulation, oxygen transport, and | | | cellular respiration** ensure | | | that tissues receive the oxygen | | | and nutrients they need. | | | | | | **Cardiac Output (CO)**: | | | | | | - - - | | | | | | Blood Pressure (BP): | | | | | | - - - | | | | | | Oxygen Transport: | | | | | | - - - | +-----------------------------------+-----------------------------------+ +-----------------------------------+-----------------------------------+ | Learned pathophysiological | The pathophysiological concepts | | concepts to perfusion | of **hypertension, fluid balance | | | alterations, heart failure, | | | angina, hypercholesterolemia, | | | blood clots, and anemia** are | | | closely related to perfusion, as | | | each affects the ability of blood | | | to adequately deliver oxygen and | | | nutrients to tissues. Here\'s how | | | each condition impacts perfusion: | +===================================+===================================+ | Hypertension | ### **Hypertension (High Blood Pr | | | essure):** | | | | | | **--Effect on Perfusion**: | | | Hypertension increases the force | | | exerted on artery walls, causing | | | damage to the blood vessels over | | | time. This leads to stiffening | | | and narrowing of arteries, | | | reducing blood flow to tissues | | | and organs, thereby impairing | | | perfusion. | | | | | | **--Hypertension**: Damages blood | | | vessels, reducing their ability | | | to perfuse tissues properly and | | | increasing the risk of ischemia. | +-----------------------------------+-----------------------------------+ | Alterations in fluid balance | ### **Alterations in Fluid Balanc | | | e:** | | | | | | **--Hypovolemia** (low blood | | | volume) reduces the amount of | | | blood available for perfusion. | | | This can result from dehydration, | | | blood loss, or excessive diuresis | | | (fluid loss through urination). | | | Decreased blood volume leads to | | | reduced **cardiac output**, | | | impairing the delivery of oxygen | | | to tissues. | | | | | | **--Hypervolemia** (excess fluid | | | volume) can cause fluid overload, | | | leading to increased blood | | | pressure and vascular congestion, | | | especially in conditions like | | | **congestive heart failure**. | | | Excess fluid can leak into | | | tissues, causing **edema** and | | | further impairing perfusion by | | | compressing capillaries. | | | | | | --**Edema**: Fluid accumulation | | | in tissues can impair the | | | diffusion of oxygen and nutrients | | | across capillaries, leading to | | | inadequate tissue perfusion. | | | | | | **--Alterations in Fluid | | | Balance**: Hypovolemia reduces | | | blood volume and perfusion; | | | hypervolemia causes vascular | | | congestion and edema, impairing | | | tissue oxygenation. | +-----------------------------------+-----------------------------------+ | Heart failure | ### **Heart Failure:** | | | | | | **--Effect on Perfusion**: In | | | heart failure, the heart\'s | | | ability to pump blood efficiently | | | is reduced, resulting in | | | **decreased cardiac output**. As | | | a result, perfusion to vital | | | organs and tissues is | | | compromised, leading to symptoms | | | like fatigue, shortness of | | | breath, and poor organ function. | | | | | | **--Heart Failure**: Impaired | | | cardiac output leads to systemic | | | perfusion deficits, affecting | | | organs and tissues. | +-----------------------------------+-----------------------------------+ | Angina | ### **Angina:** | | | | | | **--Effect on Perfusion**: Angina | | | is chest pain caused by | | | **ischemia** (reduced blood flow) | | | to the heart muscle, typically | | | due to **coronary artery | | | disease** (CAD) or | | | atherosclerosis. The narrowed | | | coronary arteries limit blood | | | flow to the myocardium (heart | | | muscle), especially during times | | | of increased oxygen demand (e.g., | | | physical exertion or stress). | | | | | | **--Angina**: Reduced coronary | | | perfusion limits oxygen supply to | | | the heart, impairing cardiac | | | function and systemic perfusion. | +-----------------------------------+-----------------------------------+ | Hypercholesterolemia | ### **Hypercholesterolemia (High | | | Cholesterol):** | | | | | | **--Effect on Perfusion**: High | | | levels of **low-density | | | lipoprotein (LDL)** cholesterol | | | contribute to the formation of | | | **atherosclerotic plaques** | | | within blood vessels. These | | | plaques narrow and stiffen | | | arteries, reducing blood flow and | | | impairing perfusion. | | | | | | **--Atherosclerosis**: | | | Atherosclerosis is a key factor | | | in conditions like coronary | | | artery disease, peripheral artery | | | disease, and cerebrovascular | | | disease. It can significantly | | | reduce perfusion to the heart, | | | legs, brain, and other organs, | | | leading to ischemia and tissue | | | damage. | | | | | | **--Increased Risk of | | | Thrombosis**: Plaques can | | | rupture, leading to blood clots | | | that further obstruct blood flow, | | | worsening perfusion deficits. | | | | | | **--Hypercholesterolemia**: Leads | | | to atherosclerosis, which narrows | | | arteries and reduces perfusion to | | | critical tissues. | +-----------------------------------+-----------------------------------+ | Blood clots | ### **Blood Clots (Thrombosis):** | | | | | | **--Effect on Perfusion**: Blood | | | clots (thrombi) can form in veins | | | (deep vein thrombosis) or | | | arteries (arterial thrombosis). | | | When they obstruct blood vessels, | | | they restrict blood flow to | | | tissues, causing **ischemia** and | | | impairing oxygen delivery. | | | | | | **--Blood Clots**: Block blood | | | vessels, causing ischemia and | | | impaired perfusion in affected | | | tissues or organs. | +-----------------------------------+-----------------------------------+ | Anemia | ### **Anemia:** | | | | | | **--Effect on Perfusion**: Anemia | | | is a condition characterized by a | | | decrease in red blood cells or | | | hemoglobin, resulting in reduced | | | oxygen-carrying capacity of the | | | blood. | | | | | | **--Impaired Oxygen Delivery**: | | | Even if perfusion (blood flow) is | | | adequate, the reduced amount of | | | hemoglobin in anemia means less | | | oxygen is delivered to tissues. | | | This can cause symptoms like | | | fatigue, weakness, and shortness | | | of breath, especially during | | | activities that increase oxygen | | | demand. | | | | | | **--Anemia**: Reduces the | | | oxygen-carrying capacity of the | | | blood, impairing the ability to | | | deliver adequate oxygen to | | | tissues, despite normal blood | | | flow. | +-----------------------------------+-----------------------------------+ **Drugs that Treat Hypertension and Fluid Balance** +-----------------------------------+-----------------------------------+ | Hypertension | **Hypertension** (commonly known | | | as high blood pressure) is a | | | chronic medical condition in | | | which the **force of the blood | | | against the walls of the arteries | | | is consistently too high**. This | | | increased pressure makes the | | | heart work harder than normal to | | | pump blood, which can lead to | | | damage to the heart, blood | | | vessels, and other organs over | | | time. Hypertension is a | | | significant risk factor for | | | cardiovascular diseases, | | | including heart attack, stroke, | | | and kidney disease | | | | | | Blood pressure is measured using | | | two values: | | | | | | **Systolic Blood Pressure | | | (SBP)**: The pressure in the | | | arteries when the heart beats | | | (when the heart contracts and | | | pumps blood). | | | | | | **Diastolic Blood Pressure | | | (DBP)**: The pressure in the | | | arteries when the heart is at | | | rest between beats. | +===================================+===================================+ | How it is diagnosed | Hypertension is diagnosed based | | | on consistently high blood | | | pressure readings. A single high | | | reading does not necessarily mean | | | hypertension; it must be measured | | | over time and under various | | | conditions. | +-----------------------------------+-----------------------------------+ +-----------------------------------+-----------------------------------+ | Modifiable risk factors of | ### **Modifiable Risk Factors:** | | hypertension | These are lifestyle and environme | | | ntal factors that can be changed | | | or managed to reduce the risk of | | | hypertension. | | | | | | **Diet**: High intake of **sodium | | | (salt)** can raise blood pressure | | | by causing the body to retain | | | water. Diets low in | | | **potassium**, **magnesium**, and | | | **calcium** can increase the risk | | | of hypertension. | | | | | | **Physical Inactivity**: A | | | sedentary lifestyle leads to | | | weight gain and can make the | | | heart work harder, increasing the | | | risk of hypertension. | | | | | | **Obesity**: Being overweight or | | | obese increases the strain on the | | | heart, requiring more effort to | | | pump blood, which raises blood | | | pressure. | | | | | | **Excessive Alcohol | | | Consumption**: Drinking large | | | amounts of alcohol over time can | | | lead to increased blood pressure. | | | Limiting alcohol intake can help | | | lower the risk. | | | | | | **Tobacco Use**: Smoking or using | | | tobacco products raises blood | | | pressure and damages the lining | | | of blood vessels, making them | | | more prone to narrowing and | | | stiffening. | | | | | | **Chronic Stress**: Stress | | | triggers the release of hormones | | | (like cortisol and adrenaline) | | | that temporarily increase blood | | | pressure. | | | | | | **Poor Sleep Patterns**: Sleep | | | disorders, such as **sleep | | | apnea**, can lead to an increase | | | in blood pressure due to | | | interrupted breathing during | | | sleep. | | | | | | **Excessive Caffeine Intake**: | | | Caffeine can cause a temporary | | | spike in blood pressure, and | | | regular heavy consumption may | | | contribute to sustained high | | | blood pressure in some | | | individuals | +===================================+===================================+ | Nonmodifiable risk factors of | **Age**: The risk of hypertension | | hypertension | increases with age, particularly | | | after the age of 40. As people | | | age, blood vessels become | | | stiffer, leading to higher blood | | | pressure. | | | | | | **Gender**: Until the age of | | | about 64, men are more likely to | | | develop hypertension than women. | | | After age 65, women are at | | | greater risk. | | | | | | **Family History (Genetics)**: A | | | family history of hypertension | | | increases the likelihood of | | | developing the condition, as high | | | blood pressure can run in | | | families due to shared genetics. | | | | | | **Ethnicity**: Certain ethnic | | | groups are at higher risk of | | | developing hypertension. For | | | example, African Americans are | | | more likely to develop high blood | | | pressure at an earlier age and | | | often have more severe | | | hypertension than other racial | | | groups. | | | | | | **Underlying Health Conditions**: | | | Conditions like **chronic kidney | | | disease**, **diabetes**, or | | | **thyroid disorders** can | | | contribute to the development of | | | hypertension. | +-----------------------------------+-----------------------------------+ +-----------------------------------+-----------------------------------+ | non-pharmacological methods to | --Dietary changes (reducing | | prevent, manage, or treat | sodium, following the DASH diet, | | hypertension | increasing potassium). | | | | | | --Physical activity (aerobic | | | exercise, resistance training). | | | | | | --Weight management (maintaining | | | a healthy weight). | | | | | | --Limiting alcohol and quitting | | | smoking. | | | | | | --Stress management (relaxation | | | techniques, reducing chronic | | | stress). | | | | | | --Improving sleep quality and | | | addressing sleep disorders. | | | | | | --Limiting caffeine and reducing | | | sugar intake. | | | | | | --Self-monitoring blood pressure | | | at home. | +-----------------------------------+-----------------------------------+ +-----------------------------------+-----------------------------------+ | Normal blood pressure controls, | | +===================================+===================================+ | Renin-angiotensin-aldosterone | The **RAAS** is a hormonal system | | system (RAAS) | that plays a key role in | | | regulating blood pressure, blood | | | volume, and electrolyte balance. | | | It primarily responds to low | | | blood pressure or low blood | | | volume. Responds to low blood | | | pressure or low blood volume, | | | leading to vasoconstriction and | | | increased blood volume via | | | aldosterone and ADH. | | | | | | #### **Steps in RAAS Activation:* | | | * | | | | | | **--Renin Release**: When blood | | | pressure drops or the kidneys | | | sense decreased blood flow (low | | | perfusion), the juxtaglomerular | | | cells in the kidneys release | | | **renin**, an enzyme. | | | | | | **--Angiotensinogen Conversion**: | | | Renin converts | | | **angiotensinogen** (a protein | | | produced by the liver) into | | | **angiotensin I**. | | | | | | **--Angiotensin I to Angiotensin | | | II**: Angiotensin I is converted | | | into **angiotensin II** by the | | | enzyme **angiotensin-converting | | | enzyme (ACE)**, primarily in the | | | lungs. | | | | | | #### | | | | | | #### **Actions of Angiotensin II: | | | ** | | | | | | **Vasoconstriction**: Angiotensin | | | II causes blood vessels to | | | constrict (narrow), increasing | | | vascular resistance and raising | | | blood pressure. | | | | | | **Aldosterone Release**: | | | Angiotensin II stimulates the | | | adrenal glands to release | | | **aldosterone**, a hormone that | | | increases sodium and water | | | reabsorption in the kidneys, | | | which raises blood volume and | | | blood pressure. | | | | | | **ADH Release**: Angiotensin II | | | also promotes the release of | | | **antidiuretic hormone (ADH)** | | | (also called vasopressin) from | | | the pituitary gland, which | | | increases water retention by the | | | kidneys, further raising blood | | | volume and pressure. | +-----------------------------------+-----------------------------------+ | Osmoreceptors | **Osmoreceptors** are specialized | | | cells located primarily in the | | | hypothalamus of the brain that | | | detect changes in blood | | | osmolality (the concentration of | | | solutes in the blood). They play | | | a key role in regulating blood | | | pressure through fluid balance | | | and the control of **antidiuretic | | | hormone (ADH)**. Regulate blood | | | pressure through control of fluid | | | balance and ADH release, | | | affecting blood volume. | | | | | | #### **Function of Osmoreceptors: | | | ** | | | | | | **--ADH Release**: When the | | | osmolality of the blood increases | | | (indicating dehydration or a high | | | concentration of solutes), | | | osmoreceptors signal the | | | posterior pituitary gland to | | | release **ADH**. ADH causes the | | | kidneys to retain water, | | | decreasing blood osmolality and | | | increasing blood volume. | | | | | | **--Fluid Balance**: By | | | increasing water reabsorption in | | | the kidneys, osmoreceptors help | | | to maintain blood volume, which | | | in turn influences blood | | | pressure. If blood osmolality | | | decreases (too much water), ADH | | | secretion is reduced, leading to | | | increased urine production and | | | decreased blood volume. | +-----------------------------------+-----------------------------------+ | Baroreceptors | **Baroreceptors** are | | | stretch-sensitive receptors | | | located in the walls of large | | | blood vessels, including the | | | **aortic arch** and **carotid | | | sinuses**. They respond to | | | changes in blood pressure by | | | detecting the stretch or tension | | | of the vessel walls. Detect | | | changes in blood vessel stretch | | | due to high or low blood pressure | | | and adjust heart rate, | | | vasodilation, or vasoconstriction | | | to normalize blood pressure. | | | | | | **High Blood Pressure**: When | | | blood pressure increases, the | | | walls of the blood vessels | | | stretch more. Baroreceptors | | | detect this increased stretch and | | | send signals to the | | | cardiovascular control centers in | | | the brainstem (the **medulla | | | oblongata**). If there is | | | sufficient pressure in these | | | vessels, the baroreceptors are | | | stimulated, sending that | | | information to the brain. | | | | | | **Low Blood Pressure**: When | | | blood pressure drops, | | | baroreceptors sense the reduced | | | stretch and signal the brain to | | | activate the **sympathetic | | | nervous system**. If the pressure | | | falls, the stimulation of the | | | baroreceptors falls off. That | | | information is also sent to the | | | brain. | +-----------------------------------+-----------------------------------+ ---------------------------------------------------------------- -------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- Various drugs used to treat hypertension affect these controls Drugs used to treat hypertension (high blood pressure) target the physiological controls that regulate blood pressure, including the **renin-angiotensin-aldosterone system (RAAS)**, **osmoreceptors**, **baroreceptors**, and other mechanisms. These medications work by lowering blood pressure through various means, such as reducing vascular resistance, decreasing blood volume, or influencing heart function. ---------------------------------------------------------------- -------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- +-----------------------------------+-----------------------------------+ | Thiazide diuretics | **Action**: Block the chloride | | (hydrochlorothiazide) | pump. Sodium stays in tubule. | | | Sodium excreted through urine | | **Hydrochlorothiazide** | | | | **Therapeutic actions**: | | Methyclothiazide | **Antihypertensive**: | | | Hydrochlorothiazide lowers blood | | *ENDING:* "Thiazide" | pressure primarily by reducing | | | blood volume and, over time, | | | through a decrease in vascular | | | resistance. **Diuretic**: It | | | promotes the excretion of sodium | | | and water, which helps reduce | | | fluid retention. | | | | | | **Prevention of kidney stones**: | | | By reducing calcium excretion in | | | the urine, it can help prevent | | | the formation of calcium-based | | | kidney stones | | | | | | **Indications**: | | | **Hypertension**: | | | Hydrochlorothiazide is often used | | | as a first-line treatment, either | | | alone or in combination with | | | other antihypertensives (e.g., | | | ACE inhibitors, ARBs, calcium | | | channel blockers). **Edema**: | | | Associated with heart failure, | | | liver cirrhosis, nephrotic | | | syndrome, or corticosteroid use. | | | **Kidney stone prevention**: | | | Particularly in patients with | | | recurrent calcium-based kidney | | | stones (hypercalciuria). | | | | | | **Heart failure**: Used to manage | | | fluid overload in mild to | | | moderate heart failure. | | | | | | **Pharmacokinetics:** Absorption: | | | Well absorbed orally; | | | bioavailability ranges from 60% | | | to 80%. | | | | | | - - - - - | | | | | | **Contraindications:** Anuria: | | | Thiazide diuretics are | | | contraindicated in patients with | | | no urine output (anuria), as they | | | rely on functioning kidneys to | | | exert their effects. | | | | | | Severe renal impairment: | | | Ineffective when kidney function | | | is severely compromised (e.g., | | | creatinine clearance less than 30 | | | mL/min). Hypersensitivity: | | | Patients with a known allergy to | | | sulfonamides, as thiazides have a | | | similar chemical structure. | | | Electrolyte imbalances: | | | Contraindicated in cases of | | | severe hyponatremia (low sodium), | | | hypokalemia (low potassium), or | | | hypercalcemia (high calcium), as | | | thiazides can worsen these | | | conditions. Pregnancy and | | | breastfeeding: Should be used | | | cautiously, as they may affect | | | electrolyte balance and fluid | | | status. | | | | | | **Most common adverse | | | reactions:** GI Upset. Fluid & | | | Electrolyte | | | Imbalance.HYPOKALEMIA[.]{.underli | | | ne} | | | Hypotension. Hyperglycemia. | | | Alkaline Urine. **hyponatremia**, | | | **hypercalcemia**, and | | | **hyperuricemia**. | | | | | | **Important drug--drug | | | interactions**:**ACE | | | inhibitors/ARBs**: These drugs | | | also lower blood pressure, so | | | combining them with | | | hydrochlorothiazide can have an | | | additive effect. **NSAIDs (e.g., | | | Ibuprofen, Naproxen)**: NSAIDs | | | can reduce the antihypertensive | | | effect of hydrochlorothiazide by | | | promoting sodium and water | | | retention, counteracting the | | | diuretic effect. **Lithium**: | | | Hydrochlorothiazide reduces the | | | clearance of **l**ithium, leading | | | to an increased risk of lithium | | | toxicity. **Digitalis glycosides | | | (Digoxin)**: Low potassium | | | (hypokalemia) from thiazide use | | | increases the risk of **digoxin | | | toxicity**, which can lead to | | | dangerous heart arrhythmias. | | | | | | **Corticosteroids**: Concomitant | | | use with corticosteroids (e.g., | | | prednisone) can increase the risk | | | of hypokalemia due to increased | | | potassium loss. | | | | | | **Antidiabetic medications**: | | | Thiazide diuretics can reduce the | | | effectiveness of oral | | | hypoglycemic agents (e.g., | | | sulfonylureas, insulin) by | | | raising blood sugar levels, which | | | may require dose adjustments for | | | patients with diabetes. | | | | | | **Calcium supplements**: Since | | | thiazides reduce urinary calcium | | | excretion, combining them with | | | calcium supplements can increase | | | the risk of hypercalcemia. | +===================================+===================================+ | Loop diuretics (furosemide) | **Action**: Block the chloride | | | pump in the ascending loop of | | **Furosemide (Lasix)** | henle. Sodium is reabsorbed | | | | | Torsemide | **Therapeutic actions: | | | Diuresis:** Promotes rapid | | *[ENDING:]* may end | diuresis, making it effective for | | in "MIDE" not a fool proof rule! | acute and chronic fluid overload. | | | Antihypertensive effect: Reduces | | | blood pressure primarily through | | | volume depletion and decreased | | | cardiac preload. Decreases | | | peripheral edema: Used in | | | conditions associated with edema, | | | such as congestive heart failure, | | | liver cirrhosis, and renal | | | disease. | | | | | | **Indications:** Congestive heart | | | failure: Management of fluid | | | overload and pulmonary | | | congestion. Edema: Associated | | | with conditions such as heart | | | failure, liver cirrhosis, and | | | renal disease. | | | | | | Hypertension: Particularly in | | | patients with heart failure or in | | | cases where other diuretics are | | | insufficient. Acute renal | | | failure: To manage fluid | | | overload. Hypercalcemia: To | | | promote renal excretion of | | | calcium in certain conditions | | | | | | **Pharmacokinetics:** | | | | | | Absorption: Rapidly absorbed | | | after oral administration, with a | | | bioavailability of approximately | | | 50%. Onset of action is quicker | | | when given intravenously (IV). | | | | | | Onset of action: Oral | | | administration: Effects begin | | | within 30-60 minutes. IV | | | administration: Effects can start | | | within 5 minutes. | | | | | | Peak effect: Occurs within 1-2 | | | hours for oral doses and 30-60 | | | minutes for IV doses. | | | | | | Duration of action: Lasts | | | approximately 6-8 hours with oral | | | administration and 2 hours with | | | IV administration. | | | | | | Metabolism: Minimal hepatic | | | metabolism; primarily excreted | | | unchanged by the kidneys. | | | | | | Half-life: Approximately 1-2 | | | hours, but can be prolonged in | | | cases of renal impairment | | | | | | **Contraindications:** | | | | | | Anuria: Furosemide is | | | contraindicated in patients with | | | no urine output due to severe | | | renal failure. | | | | | | Severe electrolyte imbalances: | | | Particularly hypokalemia (low | | | potassium), hyponatremia (low | | | sodium), or hypomagnesemia (low | | | magnesium). | | | | | | Hypersensitivity: Known allergy | | | to furosemide or other | | | sulfonamide-derived drugs. | | | | | | Pregnancy: Should be used | | | cautiously; can cause electrolyte | | | imbalances in the fetus. | | | | | | Hepatic coma: Furosemide should | | | be used cautiously in patients | | | with hepatic failure as it may | | | worsen fluid and electrolyte | | | imbalances. | | | | | | **Most common adverse | | | reactions:** Fluid & Electrolyte | | | Imbalance:HYPOKALEMIA, Alkalosis, | | | Hypocalcemia, Hypotension | | | | | | **Important drug--drug | | | interactions:** | | | | | | Aminoglycoside antibiotics (e.g., | | | gentamicin, tobramycin): | | | Concurrent use can increase the | | | risk of ototoxicity. | | | | | | NSAIDs: Nonsteroidal | | | anti-inflammatory drugs can | | | decrease the diuretic effect of | | | furosemide and may increase the | | | risk of acute kidney injury. | | | | | | Lithium: Furosemide can decrease | | | renal clearance of lithium, | | | increasing the risk of lithium | | | toxicity. | | | | | | Antihypertensives: Other | | | antihypertensive agents can have | | | an additive effect, increasing | | | the risk of hypotension. | | | | | | Digitalis glycosides (e.g., | | | digoxin): The risk of digoxin | | | toxicity increases with | | | hypokalemia caused by furosemide. | | | | | | Corticosteroids: Concomitant use | | | can increase the risk of | | | hypokalemia. | | | | | | Other diuretics: Concurrent use | | | of other diuretics can lead to | | | electrolyte imbalances and | | | increased risk of renal | | | impairment. | +-----------------------------------+-----------------------------------+ | Potassium-sparing diuretics | **Action:** Blocks aldosterone. | | (spironolactone) | Loss of sodium while retaining | | | potassium. Inhibition of sodium | | **Spironolactone (Aldactone)** | reabsorption: By blocking | | | aldosterone, spironolactone | | Amiloride | prevents sodium reabsorption and | | | promotes sodium and water | | *[Potassium | excretion, leading to increased | | Retainers!!!!]* | urine output. Potassium | | | retention: Unlike other | | | diuretics, spironolactone | | | promotes the retention of | | | potassium in the kidneys, thereby | | | preventing hypokalemia. | | | | | | **Therapeutic actions:** | | | | | | Diuresis: Increases urine | | | production, helping to reduce | | | fluid overload. | | | | | | Antihypertensive effect: Lowers | | | blood pressure, particularly in | | | patients with heart failure and | | | hypertension. | | | | | | Heart failure management: | | | Improves symptoms and outcomes in | | | patients with heart failure by | | | decreasing preload and reducing | | | cardiac workload. | | | | | | Hormonal effects: Has | | | anti-androgenic effects, which | | | can be beneficial in conditions | | | like hirsutism and acne. | | | | | | **Indications:** | | | | | | Hypertension: Often used in | | | combination with other | | | antihypertensives for better | | | control. | | | | | | Heart failure: Used to manage | | | fluid retention and improve | | | survival in heart failure | | | patients. | | | | | | Edema: Associated with liver | | | cirrhosis, nephrotic syndrome, or | | | heart failure. | | | | | | Primary hyperaldosteronism: | | | Diagnosis and treatment of | | | conditions characterized by | | | excessive aldosterone production. | | | | | | Polycystic ovary syndrome (PCOS): | | | Used off-label for treating | | | hirsutism and acne in women due | | | to its anti-androgenic effects. | | | | | | **Pharmacokinetics:** | | | | | | Absorption: Well absorbed orally, | | | but bioavailability is variable | | | (\~60-80%). | | | | | | Onset of action: Diuretic effect | | | begins within 24-48 hours of oral | | | administration. | | | | | | Peak effect: Occurs approximately | | | 2-3 days after starting therapy. | | | | | | Duration of action: Effects can | | | last for 24-48 hours, which | | | allows for once-daily dosing. | | | | | | Metabolism: Primarily metabolized | | | by the liver via the cytochrome | | | P450 system (CYP3A4), producing | | | active metabolites. | | | | | | Excretion: Excreted mainly | | | through the kidneys; however, | | | active metabolites can be | | | excreted in urine as well. | | | | | | Half-life: Approximately 1.4 | | | hours, but the effects can last | | | longer due to active metabolites. | | | | | | **Contraindications:**Anuria, | | | Severe renal impairment. | | | | | | Hyperkalemia, Hypersensitivity, | | | Pregnancy | | | | | | **Most common adverse | | | reactions:** | | | | | | Hyperkalemia: Elevated potassium | | | levels are the most significant | | | risk, potentially leading to | | | serious cardiac complications. | | | | | | Gynecomastia: Due to its | | | anti-androgenic properties, | | | spironolactone can cause breast | | | enlargement in men. | | | | | | Menstrual irregularities: May | | | cause changes in menstrual cycles | | | or breast tenderness in women. | | | | | | Dehydration and hypotension: | | | Excessive diuresis can lead to | | | volume depletion and low blood | | | pressure. | | | | | | Gastrointestinal disturbances: | | | Nausea, vomiting, diarrhea, and | | | abdominal cramps may occur. | | | | | | Dizziness and fatigue: Common, | | | particularly in the context of | | | volume depletion or hypotension | | | | | | **Important drug--drug | | | interactions:** Salicylates, ACE | | | inhibitors and ARBs, Nonsteroidal | | | anti-inflammatory drugs (NSAIDs, | | | Lithium Digoxin, Corticosteroids | +-----------------------------------+-----------------------------------+ | Beta-blockers (metoprolol) | **Action: :** Block Beta Cells in | | | smooth muscle of heart (cardio | | **"OLOL"** | selective) = Lower BP | | | | | ***EX:** metoprolol (Lopressor), | **Therapeutic actions:** | | atenolol (Tenormin), timolol* | | | | Antihypertensive: Lowers blood | | | pressure through reduced cardiac | | | output and inhibition of renin | | | release from the kidneys. | | | | | | Anti-anginal: Relieves angina | | | symptoms by decreasing heart | | | workload and oxygen demand. | | | | | | Heart rate control: Effective in | | | managing tachyarrhythmias by | | | slowing heart rate. | | | | | | Heart failure management: | | | Improves left ventricular | | | function and reduces mortality in | | | chronic heart failure patients. | | | | | | Post-myocardial infarction (MI): | | | Reduces the risk of reinfarction | | | and mortality in patients after a | | | heart attack. | | | | | | **Indications:** | | | | | | Hypertension: First-line | | | treatment, often used in | | | combination with other | | | antihypertensives. | | | | | | Angina pectoris: Management of | | | chronic stable angina. | | | | | | Heart failure: As part of a | | | comprehensive treatment plan for | | | chronic heart failure. | | | | | | Arrhythmias: Management of atrial | | | fibrillation and other | | | tachyarrhythmias. | | | | | | Post-myocardial infarction: | | | Reduces mortality risk and | | | recurrent events. | | | | | | Migraine prophylaxis: Off-label | | | use for preventing migraines**.** | | | | | | **Pharmacokinetics:** | | | | | | Absorption: Well absorbed orally, | | | with a bioavailability of | | | approximately 40% due to | | | first-pass metabolism in the | | | liver. | | | | | | Onset of action: Takes about 1 | | | hour after oral administration | | | for blood pressure reduction. | | | | | | Peak effect: Reached within 2-4 | | | hours after dosing. | | | | | | Duration of action: Lasts | | | approximately 6-12 hours, | | | depending on the formulation | | | (immediate-release vs. | | | extended-release). | | | | | | Metabolism: Primarily metabolized | | | by the liver via the cytochrome | | | P450 system (CYP2D6). | | | | | | Excretion: The metabolites are | | | primarily excreted via the | | | kidneys. | | | | | | Half-life: Approximately 3-7 | | | hours, but it can be longer in | | | individuals with liver | | | impairment. | | | | | | **Contraindications:** severe | | | bradycardia, hypotension, | | | cardiogenic shock, and | | | hypersensitivity, Severe asthma | | | or chronic obstructive pulmonary | | | disease (COPD) | | | | | | **Most common adverse | | | reactions:** CNS Effects, Cardiac | | | Effects, Bronchospasms, | | | Hyperglycemia, Masks the symptoms | | | of Hypoglycemia. Bradycardia: | | | Slowed heart rate can occur, | | | especially at higher doses. | | | Hypotension: May lead to | | | dizziness, lightheadedness, or | | | fainting. Fatigue and lethargy: | | | Common side effects due to | | | reduced cardiac output and | | | overall central nervous system | | | effects. Dizziness: Often related | | | to changes in blood pressure or | | | heart rate. Depression: Some | | | patients report mood changes, | | | including depression. Cold | | | extremities: Due to reduced | | | peripheral blood flow. | | | Gastrointestinal disturbances: | | | Nausea, vomiting, and diarrhea | | | may occur. Sexual dysfunction: | | | May lead to decreased libido or | | | erectile dysfunction. | | | | | | **Important drug--drug | | | interactions:** | | | | | | Calcium channel blockers (e.g., | | | verapamil, diltiazem): Concurrent | | | use can lead to significant | | | bradycardia and hypotension. | | | | | | Other antihypertensives: Additive | | | effects may cause hypotension; | | | monitoring is necessary. | | | | | | Digoxin: Can enhance the effects | | | of digoxin and increase the risk | | | of bradycardia. | | | | | | NSAIDs: Nonsteroidal | | | anti-inflammatory drugs can | | | reduce the antihypertensive | | | effect of metoprolol by promoting | | | sodium and water retention. | | | | | | Antidiabetic medications: May | | | mask the symptoms of | | | hypoglycemia, making it harder | | | for patients to recognize low | | | blood sugar. | | | | | | MAO inhibitors: Use with caution, | | | as they can increase the effects | | | of metoprolol and potentially | | | cause severe hypertension. | | | | | | Rifampin: May decrease metoprolol | | | levels due to increased | | | metabolism, reducing its | | | effectiveness. | | | | | | Nursing Consideration: First Dose | | | Effect,Use cautiously in patients | | | with COPD | +-----------------------------------+-----------------------------------+ | ACE inhibitors (captopril) | **Action**: Block ACE from | | | converting A1 to A2 = Decreased | | *captopril (Capoten), lisinopril | systemic vascular resistance | | (Zestril)* | (afterload), Lower blood | | | pressure, Reduced fluid | | | retention. | | | | | | **Therapeutic actions:** ACE | | | inhibitors act in the lungs to | | | prevent ACE from converting | | | angiotensin I to angiotensin II, | | | a powerful vasoconstrictor and | | | stimulator of aldosterone | | | release. This action leads to a | | | decrease in BP and in aldosterone | | | secretion with a resultant | | | increase in serum potassium and a | | | loss of serum sodium and fluid. | | | | | | **Indications**: Treatment of | | | hypertension, heart failure, | | | diabetic nephropathy, and left | | | ventricular dysfunction after MI. | | | | | | **Pharmacokinetics:** All of the | | | ACE inhibitors are administered | | | orally. Enalapril also has the | | | advantage of parenteral use | | | (enalaprilat) if oral use is not | | | feasible or rapid onset is | | | desirable. These drugs are well | | | absorbed, widely distributed, | | | metabolized in the liver, and | | | excreted in the urine and feces. | | | They have been detected in human | | | milk, are known to cross the | | | placenta, and have been | | | associated with serious fetal | | | abnormalities so they should not | | | be used during pregnancy. | | | | | | **Contraindications:** ACE | | | inhibitors are contraindicated in | | | people with a history of allergic | | | reaction (including angioedema) | | | to any of the ACE inhibitors and | | | to prevent hypersensitivity | | | reactions. Caution should be used | | | in patients with impaired renal | | | function, which could be | | | exacerbated by the effects of | | | this drug in decreasing renal | | | blood flow; with acute heart | | | failure exacerbation because the | | | change in hemodynamics could be | | | detrimental in some cases; and | | | with salt/volume depletion, which | | | could be exacerbated by the drug | | | effects. | | | | | | **Most common adverse | | | reactions**: Allergic reactions, | | | angioedema, neutropenia, | | | hypotension, tachycardia, rash, | | | pruritus, gastric irritation, | | | aphthous ulcers, peptic ulcers, | | | dysgeusia, proteinuria, bone | | | marrow suppression, cough, renal | | | impairment, hyperkalemia. | | | | | | **Important drug--drug | | | interactions**: The risk of | | | hypersensitivity reactions | | | increases if these drugs are | | | taken with allopurinol. There is | | | a risk of decreased | | | antihypertensive effects if taken | | | with nonsteroidal | | | anti-inflammatory drugs, and | | | there are additive | | | antihypertensive effects if taken | | | with diuretics and other | | | antihypertensive medications; | | | patients should be monitored. | | | Potassium supplements and | | | potassium-sparing diuretics | | | increase the risk of | | | hyperkalemia. There is increased | | | risk of lithium toxicity with | | | coadministration, so levels need | | | to be monitored carefully. The | | | combination of drugs used to | | | alter the RAAS is not recommended | | | due to potentially serious | | | adverse effects and should not be | | | combined with other ACE | | | inhibitors, ARBs, or a renin | | | inhibitor. | | | | | | NURSING CONSIDERAT:Take on an | | | empty stomach, NSAIDS reduce | | | medication effectiveness, Use | | | cautiously in clients with severe | | | CHF IONS: | +-----------------------------------+-----------------------------------+ | Angiotensin II receptor blockers | **Action**: Selectively blocks | | (losartan) | the binding of angiotensin II to | | | specific tissue receptors found | | **"SARTAN"** | in the vascular smooth muscle and | | | adrenal glands; blocks the | | ***EX:** zilsartan (Edarbi), | vasoconstriction and release of | | candesartan (Atacand), irbesartan | aldosterone associated with the | | (Avapro), losartan (Cozaar), | RAAS. | | olmesartan (Benicar), telmisartan | | | (Micardis), and valsartan | **Therapeutic actions:** The ARBs | | (Diovan)* | selectively bind with the | | | angiotensin II receptors in the | | | vascular smooth muscle of the | | | blood vessels and in the adrenal | | | cortex to block vasoconstriction | | | and the release of aldosterone. | | | These actions block the | | | BP-raising effects of the RAAS | | | and lower BP. | | | | | | **Indications:** Alone or as part | | | of combination therapy for the | | | treatment of hypertension; | | | treatment of diabetic nephropathy | | | with elevated serum creatinine | | | and proteinuria in patients with | | | type 2 diabetes and hypertension. | | | | | | **Pharmacokinetics:**These agents | | | are all given orally. They are | | | well absorbed and undergo | | | metabolism in the liver by the | | | cytochrome P-450 system. They are | | | excreted in the feces and urine. | | | The ARBs cross the placenta. It | | | is not known whether they enter | | | human milk during lactation | | | | | | **Contraindications:** The ARBs | | | are contraindicated in the | | | presence of allergic reaction, | | | including angioedema, to any of | | | these drugs to prevent | | | hypersensitivity reactions. These | | | drugs are also contraindicated | | | during pregnancy because of | | | association with serious fetal | | | abnormalities and even death. | | | Although it is not known whether | | | the ARBs enter human milk during | | | lactation, these drugs should not | | | be used during lactation because | | | of the potential for serious | | | adverse effects on the neonate. | | | Patients who can become pregnant | | | should be advised to use barrier | | | contraceptives to avoid | | | pregnancy; if a pregnancy does | | | occur, the ARB should be | | | discontinued immediately. | | | | | | **Most common adverse | | | reactions:** Hypotension, | | | Hyperkalemia, Dizziness or | | | lightheadedness, Fatigue, Renal | | | impairment, Angioedema | | | | | | **Important drug--drug | | | interactions:** ARBs will have | | | increased effect if used with | | | other antihypertensive | | | medications, so BP response | | | should be monitored carefully. | | | There is increased risk of | | | hyperkalemia when administered | | | with potassium supplements or | | | potassium-sparing diuretic | | | medication. There is increased | | | risk of lithium toxicity, so | | | lithium levels should be closely | | | monitored. Coadministration with | | | NSAIDs increases risk of renal | | | impairment and decreases | | | antihypertensive effects. | | | | | | Nursing Conciduration: ​​Use | | | cautiously with Hepatic or Renal | | | dysfunction, Decreases | | | effectiveness of Phenobarbital, | | | Cardizem decreases ARB's | | | effectiveness | +-----------------------------------+-----------------------------------+ | Calcium channel blockers | **Action**: Inhibits Ca Ions | | (diltiazem) | across cardiac muscle = Lower BP | | | + Decrease Cardiac Workload. | | **"DIPINE"** | Inhibits the movement of calcium | | | ions across the membranes of | | ***EX:** mlodipine (Katerzia, | cardiac and arterial muscle | | Norvasc), diltiazem (Cardizem