Unit 1.A Cardiovascular, Renal, and Hematologic Pharmacology - Lecture Notes PDF

PHARMACOLOGY II UNIT 1. Cardiovascular, Renal, and Hematologic Pharmacology Prepared by Romuelle B. Barbado, RPh Faculty, UCU College of Pharmacy Prepared by Romuelle B. Barbado, RPh - for UCU-COP students use only. Reproduction without permission is...

PHARMACOLOGY II UNIT 1. Cardiovascular, Renal, and Hematologic Pharmacology Prepared by Romuelle B. Barbado, RPh Faculty, UCU College of Pharmacy Prepared by Romuelle B. Barbado, RPh - for UCU-COP students use only. Reproduction without permission is strictly prohibited. Pre-assessment Quiz 1. Which type of receptor is involved in the activation of G-proteins and secondary messengers like cAMP, IP3, and DAG? A) Ionotropic receptors B) Metabotropic receptors C) Enzyme-linked receptors D) Nuclear receptors Prepared by Romuelle B. Barbado, RPh - for UCU-COP students use only. Reproduction without permission is strictly prohibited. Pre-assessment Quiz 2. Which neurotransmitter is primarily associated with adrenergic receptors? A) Acetylcholine B) Dopamine C) Norepinephrine D) Serotonin Prepared by Romuelle B. Barbado, RPh - for UCU-COP students use only. Reproduction without permission is strictly prohibited. Pre-assessment Quiz 3. What is the role of M2 muscarinic receptors in the heart? A) Increase heart rate B) Decrease heart rate C) Increase gastric acid secretion D) Stimulate peristalsis Prepared by Romuelle B. Barbado, RPh - for UCU-COP students use only. Reproduction without permission is strictly prohibited. Pre-assessment Quiz 4. Which drug is a direct renin inhibitor used to treat hypertension? A) Losartan B) Aliskiren C) Captopril D) Metoprolol Prepared by Romuelle B. Barbado, RPh - for UCU-COP students use only. Reproduction without permission is strictly prohibited. Pre-assessment Quiz 5. What is the primary effect of β2 adrenergic receptor stimulation in the lungs? A) Bronchodilation B) Bronchoconstriction C) Increased mucus secretion D) Vasoconstriction Prepared by Romuelle B. Barbado, RPh - for UCU-COP students use only. Reproduction without permission is strictly prohibited. Pre-assessment Quiz 6. Which receptor subtype is targeted by tiotropium in the management of Chronic Obstructive Pulmonary Disease? A) M1 receptors B) M2 receptors C) M3 receptors D) β2 receptors Prepared by Romuelle B. Barbado, RPh - for UCU-COP students use only. Reproduction without permission is strictly prohibited. Pre-assessment Quiz 7. Which type of adrenergic receptor is primarily responsible for increasing heart rate and contractility? A) α1 receptors B) α2 receptors C) β1 receptors D) β2 receptors Prepared by Romuelle B. Barbado, RPh - for UCU-COP students use only. Reproduction without permission is strictly prohibited. Pre-assessment Quiz 8. Which of the following is an example of an α2 agonist used in hypertension management? A) Clonidine B) Propranolol C) Prazosin D) Atenolol Prepared by Romuelle B. Barbado, RPh - for UCU-COP students use only. Reproduction without permission is strictly prohibited. Pre-assessment Quiz 9. What is the therapeutic goal in the treatment of Alzheimer's disease using cholinesterase inhibitors? A) Decrease acetylcholine levels in the brain B) Increase acetylcholine levels in the brain C) Increase dopamine levels in the brain D) Decrease dopamine levels in the brain Prepared by Romuelle B. Barbado, RPh - for UCU-COP students use only. Reproduction without permission is strictly prohibited. Pre-assessment Quiz 10. Which drug is a dopamine agonist commonly used in the treatment of Parkinson’s disease? A) Levodopa B) Pramipexole C) Haloperidol D) Olanzapine Prepared by Romuelle B. Barbado, RPh - for UCU-COP students use only. Reproduction without permission is strictly prohibited. Pre-assessment Quiz 11. Which receptor subtype is responsible for inducing bladder detrusor relaxation to prevent excessive urination? A. α1 B. β1 C. β2 D. β3 Prepared by Romuelle B. Barbado, RPh - for UCU-COP students use only. Reproduction without permission is strictly prohibited. Pre-assessment Quiz 12. Activation of which receptor subtype leads to vasoconstriction and is a target for migraine treatment? A. 5HT1A B. 5HT1B/1D C. 5HT2 D. 5HT3 Prepared by Romuelle B. Barbado, RPh - for UCU-COP students use only. Reproduction without permission is strictly prohibited. Pre-assessment Quiz 13. Which receptor subtype's stimulation is associated with increased gastric acid secretion in the stomach? A. H1 B. H2 C. M3 D. β1 Prepared by Romuelle B. Barbado, RPh - for UCU-COP students use only. Reproduction without permission is strictly prohibited. Pre-assessment Quiz 14. Which of the following receptors is involved in bronchoconstriction, particularly in anaphylaxis? A. H1 B. H2 C. β2 D. α1 Prepared by Romuelle B. Barbado, RPh - for UCU-COP students use only. Reproduction without permission is strictly prohibited. Pre-assessment Quiz 15. Which receptor, when activated, decreases norepinephrine release and is targeted for hypertension management? A. α1 B. α2 C. β1 D. β2 Prepared by Romuelle B. Barbado, RPh - for UCU-COP students use only. Reproduction without permission is strictly prohibited. Pre-assessment Quiz 1. Which type of receptor is involved in the activation of G-proteins and secondary messengers like cAMP, IP3, and DAG? A) Ionotropic receptors B) Metabotropic receptors C) Enzyme-linked receptors D) Nuclear receptors Answer: B Prepared by Romuelle B. Barbado, RPh - for UCU-COP students use only. Reproduction without permission is strictly prohibited. Pre-assessment Quiz 2. Which neurotransmitter is primarily associated with adrenergic receptors? A) Acetylcholine B) Dopamine C) Norepinephrine D) Serotonin Answer: C Prepared by Romuelle B. Barbado, RPh - for UCU-COP students use only. Reproduction without permission is strictly prohibited. Pre-assessment Quiz 3. What is the role of M2 muscarinic receptors in the heart? A) Increase heart rate B) Decrease heart rate C) Increase gastric acid secretion D) Stimulate peristalsis Answer: B Prepared by Romuelle B. Barbado, RPh - for UCU-COP students use only. Reproduction without permission is strictly prohibited. Pre-assessment Quiz 4. Which drug is a direct renin inhibitor used to treat hypertension? A) Losartan B) Aliskiren C) Captopril D) Metoprolol Answer: B Prepared by Romuelle B. Barbado, RPh - for UCU-COP students use only. Reproduction without permission is strictly prohibited. Pre-assessment Quiz 5. What is the primary effect of β2 adrenergic receptor stimulation in the lungs? A) Bronchodilation B) Bronchoconstriction C) Increased mucus secretion D) Vasoconstriction Answer: A Prepared by Romuelle B. Barbado, RPh - for UCU-COP students use only. Reproduction without permission is strictly prohibited. Pre-assessment Quiz 6. Which receptor subtype is targeted by tiotropium in the management of Chronic Obstructive Pulmonary Disease? A) M1 receptors B) M2 receptors C) M3 receptors D) β2 receptors Answer: C Prepared by Romuelle B. Barbado, RPh - for UCU-COP students use only. Reproduction without permission is strictly prohibited. Pre-assessment Quiz 7. Which type of adrenergic receptor is primarily responsible for increasing heart rate and contractility? A) α1 receptors B) α2 receptors C) β1 receptors D) β2 receptors Answer: C Prepared by Romuelle B. Barbado, RPh - for UCU-COP students use only. Reproduction without permission is strictly prohibited. Pre-assessment Quiz 8. Which of the following is an example of an α2 agonist used in hypertension management? A) Clonidine B) Propranolol C) Prazosin D) Atenolol Answer: A Prepared by Romuelle B. Barbado, RPh - for UCU-COP students use only. Reproduction without permission is strictly prohibited. Pre-assessment Quiz 9. What is the therapeutic goal in the treatment of Alzheimer's disease using cholinesterase inhibitors? A) Decrease acetylcholine levels in the brain B) Increase acetylcholine levels in the brain C) Increase dopamine levels in the brain D) Decrease dopamine levels in the brain Answer: B Prepared by Romuelle B. Barbado, RPh - for UCU-COP students use only. Reproduction without permission is strictly prohibited. Pre-assessment Quiz 10. Which drug is a dopamine agonist commonly used in the treatment of Parkinson’s disease? A) Levodopa B) Pramipexole C) Haloperidol D) Olanzapine Answer: B Prepared by Romuelle B. Barbado, RPh - for UCU-COP students use only. Reproduction without permission is strictly prohibited. Pre-assessment Quiz 11. Which receptor subtype is responsible for inducing bladder detrusor relaxation to prevent excessive urination? A. α1 B. β1 C. β2 D. β3 Answer: D Prepared by Romuelle B. Barbado, RPh - for UCU-COP students use only. Reproduction without permission is strictly prohibited. Pre-assessment Quiz 12. Activation of which receptor subtype leads to vasoconstriction and is a target for migraine treatment? A. 5HT1A B. 5HT1B/1D C. 5HT2 D. 5HT3 Answer: B Prepared by Romuelle B. Barbado, RPh - for UCU-COP students use only. Reproduction without permission is strictly prohibited. Pre-assessment Quiz 13. Which receptor subtype's stimulation is associated with increased gastric acid secretion in the stomach? A. H1 B. H2 C. M3 D. β1 Answer: B Prepared by Romuelle B. Barbado, RPh - for UCU-COP students use only. Reproduction without permission is strictly prohibited. Pre-assessment Quiz 14. Which of the following receptors is involved in bronchoconstriction, particularly in anaphylaxis? A. H1 B. H2 C. β2 D. α1 Answer: A Prepared by Romuelle B. Barbado, RPh - for UCU-COP students use only. Reproduction without permission is strictly prohibited. Pre-assessment Quiz 15. Which receptor, when activated, decreases norepinephrine release and is targeted for hypertension management? A. α1 B. α2 C. β1 D. β2 Answer: B PHARMACOLOGY II UNIT 1. Cardiovascular, Renal, and Hematologic Pharmacology Prepared by Romuelle B. Barbado, RPh Faculty, UCU College of Pharmacy Prepared by Romuelle B. Barbado, RPh - for UCU-COP students use only. Reproduction without permission is strictly prohibited. OUTLINE A. Antihypertensive agents I. Sympathoplegics II. Diuretics III. Calcium Channel Blockers IV. Angiotensin Antagonists V. Vasodilators B. Drugs for Angina Pectoris and Vasodilators I. Nitrates II. Beta-blockers III. Bipyridines IV. Natriuretic peptide Prepared by Romuelle B. Barbado, RPh - for UCU-COP students use only. Reproduction without permission is strictly prohibited. ANTIHYPERTENSIVE AGENTS Prepared by Romuelle B. Barbado, RPh - for UCU-COP students use only. Reproduction without permission is strictly prohibited. HYPERTENSION High blood pressure (hypertension) is a common condition in which the long-term force of the blood against your artery walls is high enough that it may eventually cause health problems, such as heart disease. Prepared by Romuelle B. Barbado, RPh - for UCU-COP students use only. Reproduction without permission is strictly prohibited. HYPERTENSION High blood pressure (hypertension) is a common condition in which the long-term force of the blood against your artery walls is high enough that it may eventually cause health problems, such as heart disease. Prepared by Romuelle B. Barbado, RPh - for UCU-COP students use only. Reproduction without permission is strictly prohibited. HYPERTENSION Joint National Committee 8 Hypertension Guideline Classification Systolic Pressure Diastolic Pressure (mmHg) (mmHg) Normal 100 *Systole - pressure when the ventricles are contracting *Diastole - pressure when the ventricles are filling 1. 120/90 2. 130/80 3. 90/60 4. 138/ 80 Prepared by Romuelle B. Barbado, RPh - for UCU-COP students use only. Reproduction without permission is strictly prohibited. Prepared by Romuelle B. Barbado, RPh - for UCU-COP students use only. Reproduction without permission is strictly prohibited. HYPERTENSION Normal Regulation of Blood Pressure According to the hydraulic equation, arterial blood pressure (BP) is directly proportionate to the product of the blood flow (cardiac output, CO) and the resistance to passage of blood through precapillary arterioles (peripheral vascular resistance, PVR): BP = CO × PVR Prepared by Romuelle B. Barbado, RPh - for UCU-COP students use only. Reproduction without permission is strictly prohibited. Peripheral Vascular Cardiac Resistance Output Prepared by Romuelle B. Barbado, RPh - for UCU-COP students use only. Reproduction without permission is strictly prohibited. Normal Regulation of ↑ Blood Blood Pressure Pressure α1 Vasoconstricti ↑PVR activatio on n SYMPATHETIC ↑ Cardiac NERVOUS Output SYSTEM ↑ Heart Rate ACTIVATION Stroke β1 volume ↑ Blood ↑ Contractility volume ADRENAL activatio MEDULLA n ↑ Renin PITUITARY Na+ Secretion reabsorption GLAND and water Angiotensinogen retention & K excretion HYPOTHALAMUS ↓Kidney Perfusion Angiotensin I Blood Vessel - Angiotensin 2 Type 1 STRESS receptor Aldosteron Angiotensin II e Adrenal Cortex - Angiotensin 2 Type 1 receptor Prepared by Romuelle B. Barbado, RPh - for UCU-COP students use only. Reproduction without permission is strictly prohibited. HYPERTENSION There are two types of Hypertension: Primary hypertension Secondary hypertension Prepared by Romuelle B. Barbado, RPh - for UCU-COP students use only. Reproduction without permission is strictly prohibited. HYPERTENSION Primary Hypertension Hypertension that happens without a clearly identifiable underlying reason. Silent killer – not clinically-evident until target-organ damage Prepared by Romuelle B. Barbado, RPh - for UCU-COP students use only. Reproduction without permission is strictly prohibited. HYPERTENSION Secondary Hypertension High blood pressure caused by an underlying conditions like: Obstructive sleep apnea Kidney disease Adrenal gland tumors Thyroid problems Certain defects you're born with (congenital) in blood vessels Certain medications, such as birth control pills, cold remedies, decongestants, over-the-counter pain relievers and some prescription drugs Illegal drugs, such as cocaine and amphetamines Prepared by Romuelle B. Barbado, RPh - for UCU-COP students use only. Reproduction without permission is strictly prohibited. HYPERTENSION Complications: Uncontrolled high blood pressure can lead to complications including: Heart attack Aneurysm which may lead to stroke Heart failure Weakened and narrowed blood vessels in your kidneys Thickened, narrowed or torn blood vessels in the eyes Metabolic syndrome Trouble with memory or understanding Prepared by Romuelle B. Barbado, RPh - for UCU-COP students use only. Reproduction without permission is strictly prohibited. HYPERTENSION DIAGNOSIS Hypertension is called the silent killer because most patients do not have symptoms Cuff Measurement −most common method to measure BP in clinical practice is the indirect measurement of BP using an oscillometer device or sphygmomanometer. −Serial BP ≥140/90 should be obtained at least 2 occasions −Unless initial BP is >210/120 or both – often associated target organ damage: changes in heart, brain, kidneys, or ocular fundi (Early Stage - hard, shiny deposits; Late Stage – Cotton wool Prepared by Romuelle B. Barbado, RPh - for UCU-COP students use only. Reproduction without permission is strictly prohibited. HYPERTENSION Prepared by Romuelle B. Barbado, RPh - for UCU-COP students use only. Reproduction without permission is strictly prohibited. HYPERTENSION DIAGNOSIS Laboratory Test (for Secondary HTN) −BUN and serum creatinine elevations = renal disease −Increased urinary catecholamines (VMA, metanephrine and normetanephrine) = pheochromocytoma −Hypokalemia = primary aldosteronism or Cushing’s disease Renal arteriography or renal venography = renal artery stenosis (for Secondary HTN) Electrocardiography (ECG) = left ventricular hypertrophy or ischemia (for Secondary HTN) Prepared by Romuelle B. Barbado, RPh - for UCU-COP students use only. Reproduction without permission is strictly prohibited. Normal Regulation of Vasodilators ↑ Blood & CCBs Blood Pressure Pressure α1 Vasoconstricti ↑PVR activatio on α1 blockersn SYMPATHETIC ↑ Cardiac NERVOUS Output SYSTEM ↑ Heart Rate α2 ACTIVATION agonists Stroke β1 volume ↑ Blood ↑ Contractility volume ADRENAL activatio MEDULLA n Beta blockers ↑ Renin PITUITARY Na+ Secretion GLAND Zilebesi reabsorptio n and water ran Angiotensinogen retention HYPOTHALAMUS Diuretics ↓Kidney Aliskerin Perfusion Angiotensin I Blood Vessel - Angiotensin 2 Type 1 STRESS receptor ACEIs Angiotensin II ARBs Aldosteron e Adrenal Gland - Angiotensin 2 Type 1 receptor Spironolactone & Eplerenone Prepared by Romuelle B. Barbado, RPh - for UCU-COP students use only. Reproduction without permission is strictly prohibited. HYPERTENSION There are five major drug classes used for Hypertension: 1. Diuretics 2. Sympathoplegic agents (a1 and beta blockers, and a2 agonists) 3. Direct vasodilators 4. Angiotensin antagonists 5. Calcium Channel Blockers Prepared by Romuelle B. Barbado, RPh - for UCU-COP students use only. Reproduction without permission is strictly prohibited. DIURETICS Diuretics lower blood pressure by depleting the body of sodium and reducing blood volume. There are different classes of diuretics: Thiazide diuretics Loop diuretics Potassium-sparing diuretics Carbonic anhydrase inhibitors Osmotic diuretics Prepared by Romuelle B. Barbado, RPh - for UCU-COP students use only. Reproduction without permission is strictly prohibited. THIAZIDE DIURETICS These are the most commonly used diuretics. They are the most effective and are derivatives of sulfonamides They have kaliuretic and Ca2+ sparing effect Hyperuricemic ~ contraindicated in gout Used for patient with normal kidney function These agents include: Hydrochlorothiazide Chlorthalidone Indapamide - have shown vasodilatory activity due to Ca channel blockade Mechanism of Action: Inhibit the Na+/Cl+ symporter in the early distal tubule Prepared by Romuelle B. Barbado, RPh - for UCU-COP students use only. Reproduction without permission is strictly prohibited. THIAZIDE DIURETICS Prepared by Romuelle B. Barbado, RPh - for UCU-COP students use only. Reproduction without permission is strictly prohibited. THIAZIDE DIURETICS Side effect(s): Hypokalemia - which may induce arrhythmia and metabolic alkalosis Hyperglycemia Hyperlipidemia Hyperuricemia - due to increased reabsorption of uric acid Hypercalcemia - beneficial for patients with osteoporosis Hypersensitivity reactions Prepared by Romuelle B. Barbado, RPh - for UCU-COP students use only. Reproduction without permission is strictly prohibited. Recall Quiz 1. A type of hypertension w/o an underlying condition. A. Essential or Primary Hypertension B. Secondary Hypertension Answer: A Prepared by Romuelle B. Barbado, RPh - for UCU-COP students use only. Reproduction without permission is strictly prohibited. Recall Quiz 2. A medical term for tumor in adrenal gland which causes an increased outflow of catecholamines. A. Pheochromocytoma B. Nephrolithiasis C. Diabetes insipidus Answer: A Prepared by Romuelle B. Barbado, RPh - for UCU-COP students use only. Reproduction without permission is strictly prohibited. Recall Quiz 3. Thiazide diuretics are beneficial to the following conditions except: A. Hypertension B. Hypocalcemia C. Gouty arthritis Answer: C Prepared by Romuelle B. Barbado, RPh - for UCU-COP students use only. Reproduction without permission is strictly prohibited. Recall Quiz 4. The following are side effects of thiazide diuretics except: A. Hypercalcemia B. Hyperglycemia C. Hypokalemia D. Hypouricemia Answer: D Prepared by Romuelle B. Barbado, RPh - for UCU-COP students use only. Reproduction without permission is strictly prohibited. Post-Lecture Quiz 1. Which diuretic class is particularly contraindicated for use in patients with gout due to its hyperuricemic effect? A) Loop diuretics B) Thiazide diuretics C) Potassium-sparing diuretics D) Osmotic diuretics Prepared by Romuelle B. Barbado, RPh - for UCU-COP students use only. Reproduction without permission is strictly prohibited. Post-Lecture Quiz 2. In the context of secondary hypertension, which laboratory finding is most indicative of a pheochromocytoma? A) Elevated serum creatinine B) Increased urinary catecholamines C) Hypokalemia D) Elevated BUN levels Prepared by Romuelle B. Barbado, RPh - for UCU-COP students use only. Reproduction without permission is strictly prohibited. Post-Lecture Quiz 3. The inhibition of which specific transporter is central to the mechanism of action of thiazide diuretics? A) Na+/K+ ATPase B) Na+/K+/2Cl- cotransporter C) Na+/Cl- symporter D) Ca2+/Na+ exchanger Prepared by Romuelle B. Barbado, RPh - for UCU-COP students use only. Reproduction without permission is strictly prohibited. Post-Lecture Quiz 4. Which antihypertensive drug class is most associated with causing hyperkalemia as a side effect? A) Thiazide diuretics B) Loop diuretics C) Potassium-sparing diuretics D) Beta-blockers Prepared by Romuelle B. Barbado, RPh - for UCU-COP students use only. Reproduction without permission is strictly prohibited. Post-Lecture Quiz 5. What is the role of the adrenal cortex in the regulation of blood pressure, particularly in response to angiotensin II? A) It increases Na+ excretion B) It secretes aldosterone, leading to Na+ reabsorption C) It triggers the release of norepinephrine D) It produces cortisol, which decreases blood pressure Prepared by Romuelle B. Barbado, RPh - for UCU-COP students use only. Reproduction without permission is strictly prohibited. Post-Lecture Quiz 6. During the stress response, which sequence correctly describes the activation of the sympathetic nervous system leading to increased blood pressure? A) Hypothalamus → Pituitary Gland → Adrenal Medulla → α1 activation B) Adrenal Medulla → Pituitary Gland → Hypothalamus → β1 activation C) Hypothalamus → Adrenal Cortex → α1 activation → Increased PVR D) Pituitary Gland → Hypothalamus → Adrenal Cortex → α2 activation Prepared by Romuelle B. Barbado, RPh - for UCU-COP students use only. Reproduction without permission is strictly prohibited. Post-Lecture Quiz 7. Which of the following is NOT a recognized complication of uncontrolled hypertension? A) Aneurysm leading to stroke B) Metabolic syndrome C) Peripheral artery disease D) Hypercalcemia Prepared by Romuelle B. Barbado, RPh - for UCU-COP students use only. Reproduction without permission is strictly prohibited. Post-Lecture Quiz 8. Which condition listed below is classified as a cause of secondary hypertension due to an identifiable underlying condition? A) Essential hypertension B) Obstructive sleep apnea C) Idiopathic intracranial hypertension D) Vasovagal syncope Prepared by Romuelle B. Barbado, RPh - for UCU-COP students use only. Reproduction without permission is strictly prohibited. Post-Lecture Quiz 9. Which statement correctly explains the relationship between cardiac output (CO), peripheral vascular resistance (PVR), and blood pressure (BP) as described by the hydraulic equation? A) BP is inversely proportional to the product of CO and PVR B) BP is directly proportional to the sum of CO and PVR C) BP is directly proportional to the product of CO and PVR D) BP is inversely proportional to CO but directly proportional to PVR Prepared by Romuelle B. Barbado, RPh - for UCU-COP students use only. Reproduction without permission is strictly prohibited. Post-Lecture Quiz 10. According to the Joint National Committee 8 Hypertension Guideline, what is the blood pressure range for pre- hypertension? A) Systolic: 100 mmHg Prepared by Romuelle B. Barbado, RPh - for UCU-COP students use only. Reproduction without permission is strictly prohibited. Post-Lecture Quiz 1. Which diuretic class is particularly contraindicated for use in patients with gout due to its hyperuricemic effect? A) Loop diuretics B) Thiazide diuretics C) Potassium-sparing diuretics D) Osmotic diuretics Answer: B) Thiazide diuretics Prepared by Romuelle B. Barbado, RPh - for UCU-COP students use only. Reproduction without permission is strictly prohibited. Post-Lecture Quiz 2. In the context of secondary hypertension, which laboratory finding is most indicative of a pheochromocytoma? A) Elevated serum creatinine B) Increased urinary catecholamines C) Hypokalemia D) Elevated BUN levels Answer: B) Increased urinary catecholamines Prepared by Romuelle B. Barbado, RPh - for UCU-COP students use only. Reproduction without permission is strictly prohibited. Post-Lecture Quiz 3. The inhibition of which specific transporter is central to the mechanism of action of thiazide diuretics? A) Na+/K+ ATPase B) Na+/K+/2Cl- cotransporter C) Na+/Cl- symporter D) Ca2+/Na+ exchanger Answer: C) Na+/Cl- symporter Prepared by Romuelle B. Barbado, RPh - for UCU-COP students use only. Reproduction without permission is strictly prohibited. Post-Lecture Quiz 4. Which antihypertensive drug class is most associated with causing hyperkalemia as a side effect? A) Thiazide diuretics B) Loop diuretics C) Potassium-sparing diuretics D) Beta-blockers Answer: C) Potassium-sparing diuretics Prepared by Romuelle B. Barbado, RPh - for UCU-COP students use only. Reproduction without permission is strictly prohibited. Post-Lecture Quiz 5. What is the role of the adrenal cortex in the regulation of blood pressure, particularly in response to angiotensin II? A) It increases Na+ excretion B) It secretes aldosterone, leading to Na+ reabsorption C) It triggers the release of norepinephrine D) It produces cortisol, which decreases blood pressure Answer: B) It secretes aldosterone, leading to Na+ reabsorption Prepared by Romuelle B. Barbado, RPh - for UCU-COP students use only. Reproduction without permission is strictly prohibited. Post-Lecture Quiz 6. During the stress response, which sequence correctly describes the activation of the sympathetic nervous system leading to increased blood pressure? A) Hypothalamus → Pituitary Gland → Adrenal Medulla → α1 activation B) Adrenal Medulla → Pituitary Gland → Hypothalamus → β1 activation C) Hypothalamus → Adrenal Cortex → α1 activation → Increased PVR D) Pituitary Gland → Hypothalamus → Adrenal Cortex → α2 activation Answer: A) Hypothalamus → Pituitary Gland → Adrenal Medulla → α1 activation Prepared by Romuelle B. Barbado, RPh - for UCU-COP students use only. Reproduction without permission is strictly prohibited. Post-Lecture Quiz 7. Which of the following is NOT a recognized complication of uncontrolled hypertension? A) Aneurysm leading to stroke B) Metabolic syndrome C) Peripheral artery disease D) Hypercalcemia Answer: D) Hypercalcemia Prepared by Romuelle B. Barbado, RPh - for UCU-COP students use only. Reproduction without permission is strictly prohibited. Post-Lecture Quiz 8. Which condition listed below is classified as a cause of secondary hypertension due to an identifiable underlying condition? A) Essential hypertension B) Obstructive sleep apnea C) Idiopathic intracranial hypertension D) Vasovagal syncope Answer: B) Obstructive sleep apnea Prepared by Romuelle B. Barbado, RPh - for UCU-COP students use only. Reproduction without permission is strictly prohibited. Post-Lecture Quiz 9. Which statement correctly explains the relationship between cardiac output (CO), peripheral vascular resistance (PVR), and blood pressure (BP) as described by the hydraulic equation? A) BP is inversely proportional to the product of CO and PVR B) BP is directly proportional to the sum of CO and PVR C) BP is directly proportional to the product of CO and PVR D) BP is inversely proportional to CO but directly proportional to PVR Answer: C) BP is directly proportional to the product of CO and PVR Prepared by Romuelle B. Barbado, RPh - for UCU-COP students use only. Reproduction without permission is strictly prohibited. Post-Lecture Quiz 10. According to the Joint National Committee 8 Hypertension Guideline, what is the blood pressure range for pre- hypertension? A) Systolic: 100 mmHg Answer: B) Systolic: 120-139 mmHg, Diastolic: 80-89 mmHg Prepared by Romuelle B. Barbado, RPh - for UCU-COP students use only. Reproduction without permission is strictly prohibited. LOOP DIURETICS Characterized by its HIGH natriuretic and kaliuretic effect AKA high-ceiling diuretics (↑dose = ↑diuresis) Beneficial for patients with kidney problems, or for those who cannot tolerate thiazides, for intensive fluid removal in pulmonary edema, and in hypercalcemia Less effective compared to thiazides These agents include: Furosemide* * Agents that are Torsemide* sulfonamide Bumetanide* derivatives Ethacrynic acid Mechanism of Action: + + - Prepared by Romuelle B. Barbado, RPh - for UCU-COP students use only. Reproduction without permission is strictly prohibited. LOOP DIURETICS Prepared by Romuelle B. Barbado, RPh - for UCU-COP students use only. Reproduction without permission is strictly prohibited. LOOP DIURETICS Side effect(s): Hypokalemia - which may induce arrhythmia and metabolic alkalosis Hyponatremia Hypomagnesemia Hypocalcemia Hypochloremia - which may induce metabolic alkalosis Hyperglycemia Hyperlipidemia Hyperuricemia - due to increased reabsorption of uric acid Adverse effect: Ototoxicity ~ greatest risk with ethacrynic acid Prepared by Romuelle B. Barbado, RPh - for UCU-COP students use only. Reproduction without permission is strictly prohibited. POTASSIUM SPARING DIURETICS These agents are combined with other diuretics to alleviate hypokalemia These agents have low natriuretic effect NO kaliuretic effect Mechanism of Action: Amiloride & Triamterene - Na channel blocker in the collecting *Spironolactone - is used for Conn’s disease (hyperaldosteronism) duct Common Spironolactone Side effect:& Eplerenone - Aldosterone receptor blocker ~ ↓Na reabsorption Hyperkalemia Adverse effect: Spironolactone - gynecomastia and impotence Prepared by Romuelle B. Barbado, RPh - for UCU-COP students use only. Reproduction without permission is strictly prohibited. POTASSIUM SPARING DIURETICS Prepared by Romuelle B. Barbado, RPh - for UCU-COP students use only. Reproduction without permission is strictly prohibited. OTHER DIURETICS Carbonic Anhydrase Inhibitors Acetazolamide Dorzolamide Dichlorphenamide Clinical Indication: Treatment of altitude sickness and glaucoma Treatment of Catamenial/Menstrual seizures (Acetazolamide) Mechanism of Action: Inhibits the enzyme carbonic anhydrase, an enzyme responsible for the breakdown of carbonic acid (H2CO3) into H+ and HCO3 and combine HCO3 with Na+ , in proximal convulated tubule Prepared by Romuelle B. Barbado, RPh - for UCU-COP students use only. Reproduction without permission is strictly prohibited. OTHER DIURETICS Carbonic Anhydrase Inhibitors H2CO3 Prepared by Romuelle B. Barbado, RPh - for UCU-COP students use only. Reproduction without permission is strictly prohibited. OTHER DIURETICS Osmotic Diuretics Mannitol Glycerol Clinical Indication: Reduction of intracranial pressure IOP reduction in glaucoma Mechanism of Action: Osmotic effect in the proximal tubule and descending limb of Henle’s loop Prepared by Romuelle B. Barbado, RPh - for UCU-COP students use only. Reproduction without permission is strictly prohibited. SYMPATHOPLEGIC DRUGS These drugs are also called sympatholytic agents Agents that alter the response of sympathetic nervous systems by inhibiting neurotransmitter outflow OR blocking the binding of NE and Epi in adrenergic receptors These agents include: α1-adrenoceptor antagonists β-adrenoceptor antagonists Centrally acting α2-adrenoceptor agonists Prepared by Romuelle B. Barbado, RPh - for UCU-COP students use only. Reproduction without permission is strictly prohibited. SYMPATHOPLEGIC DRUGS α1-Adrenoceptor Antagonists These agents include: DoxaZOSIN, PraZOSIN, TeraZOSIN These agents are not recommended as initial treatment of hypertension They are usually added in add-on therapies with beta blockers and diuretics These agents are also useful in treating patients with Benigh Prostatic Hyperplasia (enlarged prostate) as symptomatic treatment Side effects: Reflex tachycardia ~ which can be managed with beta blockers Fluid retention ~ can be managed with diuretics Prepared by Romuelle B. Barbado, RPh - for UCU-COP students use only. Reproduction without permission is strictly prohibited. SYMPATHOPLEGIC DRUGS α1a-Adrenoceptor Antagonists These agents include: AlfuZOSIN, Tamsulosin Prepared by Romuelle B. Barbado, RPh - for UCU-COP students use only. Reproduction without permission is strictly prohibited. SYMPATHOPLEGIC DRUGS Beta Adrenoceptor Antagonists Mechanism of Action: Blocks the β1 receptors in the heart → ↓HR and contractility These agents are also not usually used as first line but used in patients with other CVD Side effects: Fatigue Vivid dreams ↓ exercise capacity Prepared by Romuelle B. Barbado, RPh - for UCU-COP students use only. Reproduction without permission is strictly prohibited. SYMPATHOPLEGIC DRUGS Beta Adrenoceptor Antagonists There are various classes of beta blockers: Beta-1 selective blockers Non-selective beta blockers Mixed beta and alpha blockers Prepared by Romuelle B. Barbado, RPh - for UCU-COP students use only. Reproduction without permission is strictly prohibited. SYMPATHOPLEGIC DRUGS Beta-1 Selective Adrenoceptor Antagonists (BEAM) Nebivolol Bisoprolol Betaxolol Acebutolol Atenolol Esmolol Celiprolol Metoprolol These agents can be used in patients with hypertension and asthma. Prepared by Romuelle B. Barbado, RPh - for UCU-COP students use only. Reproduction without permission is strictly prohibited. SYMPATHOPLEGIC DRUGS Non-Selective Beta Adrenoceptor Antagonists Propranolol Nadolol others~ These agents cannot be used in patients with hypertension and asthma. Prepared by Romuelle B. Barbado, RPh - for UCU-COP students use only. Reproduction without permission is strictly prohibited. SYMPATHOPLEGIC DRUGS Mixed Alpha and Beta Adrenoceptor Antagonists Carvedilol Labetalol These agents cannot be used in patients with hypertension and asthma. Prepared by Romuelle B. Barbado, RPh - for UCU-COP students use only. Reproduction without permission is strictly prohibited. SYMPATHOPLEGIC DRUGS Lipophilic Beta-blockers These agents can enter the blood-brain-barrier These agents are: Propranolol, Metoprolol, Labetalol Due to their lipophilicity, these agents can be used as prophylaxis for migraine, specifically propranolol Polar Beta-blockers Atenolol Nadolol Sotalol - has potassium channel blocking properties in high doses Prepared by Romuelle B. Barbado, RPh - for UCU-COP students use only. Reproduction without permission is strictly prohibited. SYMPATHOPLEGIC DRUGS Other classifications of Beta-blockers: Beta-blockers with Intrinsic Sympathomimetic Activity (Partial agonists) Carteolol Celiprolol Labetalol Acebutolol Pindolol Penbutolol Oxprenolol Prepared by Romuelle B. Barbado, RPh - for UCU-COP students use only. Reproduction without permission is strictly prohibited. SYMPATHOPLEGIC DRUGS Other classifications of Beta-blockers: Beta-blockers with Membrane Stabilizing Activity - These agents can block Na channels and can induce “weak” local anesthetic effects Propranolol Labetalol - used in pregnant patients Acebutolol Metoprolol Pindolol Carvedilol Prepared by Romuelle B. Barbado, RPh - for UCU-COP students use only. Reproduction without permission is strictly prohibited. SYMPATHOPLEGIC DRUGS Centrally acting α2-Adrenoceptor Agonists These agents include: Clonidine - used in HTN crisis and as non-stimulant agent for ADHD Guanfacine - used as non-stimulant agent for ADHD Methyldopa - used in pregnant Side effects: Sedation (+) Coomb’s positive Hemolytic anemia - Methyldopa Prepared by Romuelle B. Barbado, RPh - for UCU-COP students use only. Reproduction without permission is strictly prohibited. ANGIOTENSIN INHIBITORS These agents works by inhibiting the Renin-Angiotensin- Aldosterone System (RAAS) These agents are subdivided into two classification: Angiotensin Converting Enzyme Inhibitors (ACEIs) “- pril”s Angiotensins Receptor Blockers (ARBs) “-sartan”s Prepared by Romuelle B. Barbado, RPh - for UCU-COP students use only. Reproduction without permission is strictly prohibited. ANGIOTENSIN INHIBITORS DRY COUGH Prepared by Romuelle B. Barbado, RPh - for UCU-COP students use only. Reproduction without permission is strictly prohibited. ANGIOTENSIN INHIBITORS Angiotensin Converting Enzyme Inhibitors (ACEIs) Mechanism of Action: Inhibits the conversion of angiotensin I (weak vasoconstrictor) into angiotensin II (potent vasoconstrictor) These agents include: Captopril (not a prodrug) Fosinopril (not a prodrug) Ramipril → Ramiprilat Enalapril → Enalaprilat other~ Clinical Indication: Used in hypertension with diabetic nephropathy 1st line agents in heart failure, and HTN w/o compelling Prepared by Romuelle B. Barbado, RPh - for UCU-COP students use only. Reproduction without permission is strictly prohibited. ANGIOTENSIN INHIBITORS Angiotensin Converting Enzyme Inhibitors (ACEIs) Side effects: Hyperkalemia ~ caution in patients with CKD, co- administration with K-sparing diuretics, aldosterone blockers, and ARBs Angioedema and dry cough ~ due to bradykinin accumulation Teratogenic (Renal dysgenesis) - Oligohydramnios Nephrotoxic in patients renal stenosis In cases of dry cough, switching from ACEIs to ARBs is beneficial. Prepared by Romuelle B. Barbado, RPh - for UCU-COP students use only. Reproduction without permission is strictly prohibited. ANGIOTENSIN INHIBITORS Angiotensin Receptor Blockers Mechanism of Action: Inhibits the binding of angiotensin II to the angiotensin II Type 1 receptors (AT1) These agents include: Losartan Candesartan Irbesartan others~ Clinical Indication: Used in hypertension with diabetic nephropathy 1st line agents in heart failure, and HTN w/o compelling indication Prepared by Romuelle B. Barbado, RPh - for UCU-COP students use only. Reproduction without permission is strictly prohibited. ANGIOTENSIN INHIBITORS Angiotensin Receptor Blockers Side effects: Hyperkalemia ~ caution in patients with CKD, co- administration with K-sparing diuretics, aldosterone blockers, and ACEIs Angioedema Teratogenic (Renal dysgenesis) Nephrotoxic in patients renal stenosis Prepared by Romuelle B. Barbado, RPh - for UCU-COP students use only. Reproduction without permission is strictly prohibited. VASODILATORS Vasodilators are useful in hypertension as they relax the arterioles decreasing peripheral vascular resistance These agents include the: Oral vasodilators such as Hydralazine and Minoxidil (long-term outpatient therapy) Parenteral Vasodilators such as nitroprusside, diazoxide, and fenoldopam (hypertensive emergencies) Calcium channel blockers (used for both circumstances) Prepared by Romuelle B. Barbado, RPh - for UCU-COP students use only. Reproduction without permission is strictly prohibited. VASODILATORS Calcium Channel Blockers Mechanism of Action: Reduce the Ca2+ influx in the blood vessels resulting to relaxation and dilation of vascular smooth muscle These agents are classified into two: Dihydropyridines (-dipines): Nifedipine Amlodipine Nimodipine ~ not used in HTN but useful in sub-arachnoid hemorrhage or stroke Non-dihydropyridines (Cardioselective): Verapamil Diltiazem Prepared by Romuelle B. Barbado, RPh - for UCU-COP students use only. Reproduction without permission is strictly prohibited. VASODILATORS Calcium Channel Blockers Clinical Indication: HTN with kidney disease HTN with stroke Side Effects: Non-DHPs: Verapamil - constipation DHPs: Flushing and angioedema due to vasodilation Gingival hyperplasia Headache Prepared by Romuelle B. Barbado, RPh - for UCU-COP students use only. Reproduction without permission is strictly prohibited. VASODILATORS Calcium Channel Blockers CONTRAINDICATION: Heart Failure Prepared by Romuelle B. Barbado, RPh - for UCU-COP students use only. Reproduction without permission is strictly prohibited. VASODILATORS Hydralazine Mechanism of Action: Release of nitric oxide Use: Pregnant women and resistant hypertension Side Effects: Systemic Lupus Erythematosus-like effects, reflex tachycardia, fluid retention, postural hypotension Minoxidil Mechanism of Action: Hyperpolarization of smooth muscle membrane through opening of potassium channels Use: Resistant hypertension Side Effects: Hypertrichosis, reflex tachycardia, fluid retention Prepared by Romuelle B. Barbado, RPh - for UCU-COP students use only. Reproduction without permission is strictly prohibited. VASODILATORS Diazoxide Mechanism of Action: Hyperpolarization of smooth muscle membrane through opening of potassium channels Use: Insulinoma - a condition which causes hypoglycemia Side Effects: Hyperglycemia Nitroprusside Mechanism of Action: Release of nitric oxide Use: HTN Crisis Toxic Effects: Accumulation of cyanide; metabolic acidosis, arrhythmias, excessive hypotension, and death Prepared by Romuelle B. Barbado, RPh - for UCU-COP students use only. Reproduction without permission is strictly prohibited. VASODILATORS Fenoldopam Mechanism of Action: Activation of Dopamine-1 receptors Toxic Effects: Reflex tachycardia, headache, and flushing Prepared by Romuelle B. Barbado, RPh - for UCU-COP students use only. Reproduction without permission is strictly prohibited. RENIN INHIBITOR Aliskiren Mechanism of Action: Inhibit the production of renin Toxic Effects: Renal toxicity (Renal failure) Prepared by Romuelle B. Barbado, RPh - for UCU-COP students use only. Reproduction without permission is strictly prohibited. ANGIOTENSINOGEN SYNTHESIS INHIBITORS Zilebesiran (Investigational) Mechanism of Action: decrease angiotensinogen synthesis in the liver by reducing angiotensinogen mRNA levels Dosing: 300 mg or higher, subcutaneously every 6 months Prepared by Romuelle B. Barbado, RPh - for UCU-COP students use only. Reproduction without permission is strictly prohibited. HYPERTENSIVE EMERGENCY Rare situations that require IMMEDIATE BP reduction to limit new or progressing target-organ damage Agents used for Hypertensive Emergency that are administered parenterally includes: Sodium nitroprusside Nicardipine HCl Fenoldopam mesylate Nitroglycerin Enalaprilat Hydralazine HCl Labetalol HCl Esmolol HCl Prepared by Romuelle B. Barbado, RPh - for UCU-COP students use only. Reproduction without permission is strictly prohibited. HYPERTENSION IN PREGNANCY Agents that can be used for pregnant women with hypertension includes: Labetalol Methyldopa Nifedipine Hydralazine Prepared by Romuelle B. Barbado, RPh - for UCU-COP students use only. Reproduction without permission is strictly prohibited. REFERENCE Katzung et al. (2009).Basic and Clinical Pharmacology, 11th Edition Di Piro et al.(2005). Pharmacotherapy. A Pathophysiologic Approach 6th edition