HTN Cology Flashcards
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What is hypertension?
Hypertension also known as high blood pressure is a chronic medical condition characterized by the persistent elevation of blood pressure in the arteries. It is classified based on systolic and diastolic measurements: normal (<120/80 mmHg) elevated (120-129/<80 mmHg) stage 1 (130-139/80-89 mmHg) and stage 2 (≥140/90 mmHg).
What are the classifications of hypertension?
Hypertension can be classified into two main types: 1. Primary (essential) hypertension: No identifiable cause; develops gradually over time. 2. Secondary hypertension: Caused by an underlying condition such as kidney disease hormonal disorders or medications.
What are the common risk factors associated with hypertension?
Common risk factors for hypertension include: 1. Age: Risk increases with age. 2. Family history of hypertension. 3. Obesity: Excess weight increases blood pressure. 4. Sedentary lifestyle: Lack of physical activity contributes. 5. High salt intake: Increases fluid retention and blood volume. 6. Alcohol consumption: Excessive drinking can raise blood pressure. 7. Stress: Chronic stress may contribute to increased blood pressure.
What are the four clinical stages of hypertension?
- Normal: Systolic <120 mmHg and Diastolic <80 mmHg. 2. Elevated: Systolic 120-129 mmHg and Diastolic <80 mmHg. 3. Stage 1 Hypertension: Systolic 130-139 mmHg or Diastolic 80-89 mmHg. 4. Stage 2 Hypertension: Systolic ≥140 mmHg or Diastolic ≥90 mmHg.
What factors control blood pressure?
Blood pressure is controlled by a combination of factors including: 1. Cardiac Output (CO): The volume of blood the heart pumps per minute influenced by heart rate (HR) and stroke volume (SV). 2. Total Peripheral Resistance (TPR): Resistance blood encounters in the vessels primarily determined by vessel diameter.
Explain the relationship between cardiac output heart rate stroke volume and total peripheral resistance.
Blood pressure (BP) is determined by the equation BP = CO x TPR. Cardiac Output (CO) is affected by heart rate (HR) and stroke volume (SV) so increasing HR or SV will increase CO raising BP. TPR is influenced by the constriction or dilation of blood vessels; heightened resistance leads to higher BP.
What are the five major anatomical sites controlling blood pressure?
The five major anatomical sites include: 1. Heart 2. Blood vessels (arteries and arterioles) 3. Kidneys 4. Brain (central nervous system) 5. Hormonal systems (renin-angiotensin-aldosterone system) that regulate fluid balance and vascular resistance.
What classes of antihypertensive drugs act on these sites?
- Calcium Channel Blockers: Act on blood vessels and heart. 2. ACE inhibitors: Act on kidneys and hormonal systems. 3. Angiotensin II Receptor Blockers (ARBs): Act on hormonal systems. 4. Beta-blockers: Act on the heart. 5. Diuretics: Act on kidneys.
Describe the humoral neuronal renal and vascular mechanisms that control blood pressure.
Humoral mechanisms include hormones like adrenaline and angiotensin II that influence blood pressure; neuronal mechanisms involve nerve signals regulating heart activity and vessel diameter; renal mechanisms involve fluid balance via kidney function affecting blood volume; vascular mechanisms consist of constriction or dilation of blood vessels.
What are the consequences of chronic hypertension?
Chronic hypertension can lead to serious health issues including: 1. Heart disease (hypertrophy or failure) 2. Stroke (due to weakened vessels or blockage) 3. Kidney disease (damage from high pressure) 4. Vision loss (damage to blood vessels in the eyes).
What is the difference between primary essential hypertension and secondary hypertension?
Primary essential hypertension has no identifiable cause typically developing gradually. Secondary hypertension is the result of an underlying condition (e.g. kidney disease hormonal disorders) and may be reversible if the condition is treated.
What classes of diuretics are used for the treatment of hypertension?
The classes of diuretics include: 1. Thiazide diuretics (e.g. Hydrochlorothiazide) 2. Loop diuretics (e.g. Furosemide) 3. Potassium-sparing diuretics (e.g. Spironolactone) 4. Osmotic diuretics (e.g. Mannitol).
Explain the mechanisms of action for the different classes of diuretics.
- Thiazide diuretics inhibit sodium reabsorption at the distal convoluted tubule leading to increased urine output. 2. Loop diuretics inhibit the sodium-potassium-chloride cotransporter in the loop of Henle leading to significant diuresis. 3. Potassium-sparing diuretics block aldosterone’s effect on the distal nephron preventing potassium loss while promoting sodium and water excretion. 4. Osmotic diuretics increase osmolarity of the filtrate promoting water excretion through osmotic diuresis.
What are the major clinical indications for diuretics in hypertension treatment?
Diuretics are primarily indicated for: 1. Initial treatment of mild to moderate hypertension. 2. Reducing edema associated with heart failure or liver disease. 3. Managing hypertension in patients with concurrent conditions like diabetes.
What are the different classes of diuretics used for the treatment of hypertension?
The main classes of diuretics used for treating hypertension include:
- Thiazide diuretics (e.g. Hydrochlorothiazide Chlorthalidone)
- Loop diuretics (e.g. Furosemide Bumetanide)
- Potassium-sparing diuretics (e.g. Spironolactone Eplerenone Amiloride)
What are sympatholytics?
Sympatholytics are drugs that inhibit the sympathetic nervous system reducing blood pressure and heart rate by blocking the effects of catecholamines like norepinephrine and epinephrine.
What are the main classes of sympatholytics?
The main classes of sympatholytics include: 1. Alpha-1 blockers (e.g. Prazosin Doxazosin) 2. Alpha-2 agonists (e.g. Clonidine Guanfacine) 3. Beta blockers (e.g. Propranolol Atenolol) 4. Mixed alpha and beta blockers (e.g. Carvedilol Labetalol).
What is the mechanism of action of Alpha-1 blockers?
Alpha-1 blockers inhibit alpha-1 adrenergic receptors on vascular smooth muscles leading to vasodilation decreased peripheral resistance and lowered blood pressure.
What are the therapeutic applications of Alpha-1 blockers?
Alpha-1 blockers are primarily used in the treatment of hypertension and benign prostatic hyperplasia (BPH).
What are the major adverse effects of Alpha-1 blockers?
Adverse effects include orthostatic hypotension reflex tachycardia nasal congestion due to vasodilation and dizziness.
What is the mechanism of action of Alpha-2 agonists?
Alpha-2 agonists bind to alpha-2 adrenergic receptors in the brain leading to decreased sympathetic outflow and reduced heart rate and blood pressure.
What are the therapeutic applications of Alpha-2 agonists?
Alpha-2 agonists are used for hypertension attention deficit hyperactivity disorder (ADHD) and opioid withdrawal.
What are the major adverse effects of Alpha-2 agonists?
Adverse effects include sedation dry mouth rebound hypertension upon abrupt withdrawal and severe bradycardia.
What is the mechanism of action of Beta blockers?
Beta blockers block beta-adrenergic receptors primarily reducing heart rate myocardial contractility and conduction velocity.
What are the therapeutic applications of Beta blockers?
Beta blockers are used for hypertension heart failure arrhythmias and to prevent migraines.
What are the major adverse effects of Beta blockers?
Adverse effects include bradycardia fatigue depression bronchospasm (especially in non-selective beta blockers) and exacerbation of asthmatic conditions.
What is the role of the RAAS system in blood pressure regulation?
The Renin-Angiotensin-Aldosterone System (RAAS) regulates blood pressure by promoting vasoconstriction and sodium retention which increases blood volume.
How do diuretics reduce blood pressure?
Diuretics promote sodium and water excretion decreasing blood volume which leads to reduced cardiac output and lower blood pressure.
What are the types of diuretics?
The main types of diuretics include: 1. Thiazide diuretics (e.g. Hydrochlorothiazide) 2. Loop diuretics (e.g. Furosemide) 3. Potassium-sparing diuretics (e.g. Spironolactone).
What are the pharmacological effects of thiazide diuretics?
Thiazide diuretics inhibit sodium reabsorption in the distal convoluted tubule promoting diuresis and decreasing blood pressure.
What are the major adverse effects of thiazide diuretics?
Adverse effects include hypokalemia hyperglycemia hyperuricemia and dehydration.
What is the typical mechanism of action for Loop diuretics?
Loop diuretics inhibit the Na+/K+/2Cl- co-transporter in the thick ascending limb of the loop of Henle which increases urine output.
What are the major adverse effects of Loop diuretics?
Adverse effects include significant electrolyte imbalances (especially hypokalemia) dehydration and ototoxicity.
What is the role of resistance vessels in blood pressure regulation?
Resistance vessels (arterioles) are crucial for maintaining systemic vascular resistance and blood pressure; they respond to physiological and pharmacological stimuli.
How does stimulation of alpha-1 receptors affect vascular resistance?
Stimulation of alpha-1 receptors causes vasoconstriction leading to increased vascular resistance and heightened blood pressure.
What are the effects of reducing preload on cardiac function?
Reducing preload decreases stroke volume and cardiac output which can help the heart manage workload and alleviate heart failure symptoms.
What strategies can be employed to reduce blood pressure short-term?
Short-term strategies to reduce blood pressure include the use of diuretics sympatholytics and directly acting vasodilators.
What is the effect of vagal nerve control on heart rate?
Vagal nerve stimulation decreases heart rate by enhancing parasympathetic activity through acetylcholine release promoting heart relaxation.
What is the relationship between venous return and cardiac output?
Decrease in venous return leads to a decrease in stroke volume which consequently decreases cardiac output and blood pressure.
What are sympathoplegic drugs and their effects on the cardiovascular system?
Sympathoplegic drugs include central sympatholytics adrenergic neuron blockers ganglionic blockers alpha (1) blockers and mixed blockers. They decrease peripheral resistance and cardiac output by reducing heart rate and contractility leading to increased venous pooling in capacitance vessels resulting in lowered blood pressure.
What are the types of direct vasodilators and their mechanisms of action?
Direct vasodilators include arterial vasodilators venous vasodilators and calcium channel blockers (CCBs). They promote relaxation of vascular smooth muscle dilate resistance vessels increase venous capacitance and decrease venous return thereby lowering blood pressure.
What role do Inhibitors of the Renin-Angiotensin-Aldosterone System (RAAS) play in hypertension treatment?
Inhibitors of RAAS include renin inhibitors ACE inhibitors and angiotensin II receptor blockers (ARBs). They block the synthesis and action of angiotensin II leading to decreased peripheral resistance and potential reduction in blood volume which lowers blood pressure.
How do sympathoplegic drugs affect heart rate and contractility?
Sympathoplegic drugs decrease heart rate and myocardial contractility which reduces cardiac output and thereby lowers blood pressure.
Define the term ‘peripheral resistance’ in the context of blood circulation.
Peripheral resistance refers to the resistance encountered by blood flow in the systemic circulation largely influenced by the size and tone of the arterioles. Decreased peripheral resistance results in lower blood pressure.
What is the effect of calcium channel blockers (CCBs) on vascular smooth muscle?
Calcium channel blockers induce relaxation of vascular smooth muscle leading to vasodilation in both arterial and venous systems which helps decrease blood pressure.
What are the benefits of using angiotensin II receptor blockers (ARBs) in treating hypertension?
ARBs block the action of angiotensin II leading to vasodilation reduced secretion of aldosterone and lower blood pressure through decreased peripheral resistance and possibly reduced blood volume.
What is meant by ‘increased venous pooling’ and how does it impact blood pressure?
Increased venous pooling refers to the accumulation of blood in the capacitance vessels which reduces the volume of blood returning to the heart (venous return) subsequently decreasing stroke volume and blood pressure.
Explain the significance of renal function and sodium reabsorption in the control of blood pressure.
Renal function and sodium reabsorption are crucial in regulating blood volume. Effective sodium reabsorption increases blood pressure whereas blockers that reduce sodium reabsorption can lead to decreased blood volume and lower blood pressure.
What is the primary effect of diuretics on urine composition?
Diuretics increase the excretion of sodium (Na) and water resulting in increased urine volume.
How do diuretics decrease sodium reabsorption?
Diuretics decrease the reabsorption of sodium and an accompanying anion usually chloride (Cl) from the filtrate in the nephron.
What secondary effect occurs due to increased sodium chloride (NaCl) excretion?
Increased water loss is secondary to the increased excretion of NaCl a process known as natriuresis.
What are the two mechanisms by which diuretics can act on the nephron?
Diuretics can act either directly on the cells of the nephron or indirectly by modifying the content of the filtrate.
What is the clinical application of diuretics in hypertension?
Diuretics are effective in lowering blood pressure by approximately 10-15 mm Hg in most patients.
In what scenarios are diuretics commonly used outside of hypertension treatment?
Diuretics are often used in conjunction with other medications to manage conditions such as heart failure edema and certain kidney disorders.
What is the long-term effect of aldosterone blockers on potassium levels?
Aldosterone blockers are potassium-sparing diuretics which help retain potassium in the body.
What is the relationship between increased elimination of substances by diuretics and osmolarity of urine?
Increasing the elimination of substances such as sodium leads to a higher osmolarity of urine.
How do diuretics impact blood pressure through vascular mechanisms?
Diuretics reduce blood pressure by decreasing total peripheral resistance (TPR) and inhibiting the sympathetic nervous system (SNS) leading to vasodilation and reduced venous return.
What is the impact of diuretics on cardiac output?
Diuretics can act on the brain to decrease cardiac output by reducing heart rate and promoting vasodilation.
What is moderate essential hypertension?
Moderate essential hypertension refers to an increase in blood pressure without a secondary cause and it is characterized by systolic blood pressure readings generally between 140-159 mmHg and/or diastolic blood pressure readings between 90-99 mmHg.
What are diuretics used for in hypertension treatment?
Diuretics are used to lower blood pressure primarily by depleting body sodium stores thereby reducing blood volume which in turn lowers cardiac output.
What is the initial mechanism of action (MOA) of diuretics in hypertension?
Initially diuretics lower blood pressure by reducing blood volume and cardiac output; however peripheral vascular resistance may increase in the early stages of treatment.
What happens to cardiac output and peripheral vascular resistance over time when using diuretics?
After 6-8 weeks of treatment cardiac output typically returns to normal while peripheral vascular resistance declines contributing to the maintenance of the hypotensive effect.
How does baroreceptor reflex affect the action of diuretics over time?
Initially the hypotensive effects of diuretics are mediated by the reduction of blood volume. However as baroreceptors adapt to stable volume conditions the hypotensive effects become less mediated by diuretics and more by the reduction of total peripheral resistance (TPR).
What can occur as a result of the body’s response to diuretics in terms of sodium retention?
Sometimes due to the effects of diuretics the body may attempt to retain sodium to counteract vasodilation leading to water retention and possible edema.
What are considered first-line medications in more severe hypertension management?
In more severe hypertension diuretics are combined with sympathoplegic agents and vasodilators to help control hypertension effectively.
What are loop diuretics?
Loop diuretics are a class of diuretics that act on the ascending loop of Henle in the kidneys and are typically used for their potent diuretic effects in managing fluid retention and hypertension.
What is the primary effect of diuretics on total peripheral resistance (TPR)?
Diuretics eventually lead to a decline in total peripheral resistance (TPR) contributing to the stabilization of blood pressure after the initial reduction from blood volume depletion.
Why may the effectiveness of diuretics change over time in hypertensive patients?
The effectiveness of diuretics may change due to compensatory mechanisms in the body that attempt to restore blood pressure such as baroreceptor reflex adaptations and sodium retention.
What are the inhibitors of the Na-K-2Cl symporter in the ascending limb of the nephron?
Furosemide Bumetanide Ethacrynic Acid.
What are the thiazide diuretics that act on the distal tubule?
Chlorothiazide Hydrochlorothiazide Chlorthalidone Indapamide.
What are the potassium-sparing diuretics acting on the distal tubule and collecting duct?
- Inhibitors of renal epithelial Na channels: Amiloride Triamterene. 2. Aldosterone antagonists: Spironolactone Eplerenone.
How are diuretics classified?
Diuretics are classified into three major classes based on their site of action in the nephron: 1. Loop diuretics 2. Thiazide diuretics 3. Potassium-sparing diuretics.
What is the mode of action of loop diuretics?
Loop diuretics reduce the excretion of free water and act on the ascending limb of the Loop of Henle.
What are the 2 classes of diuretics used for glaucoma and how do they work?
- Osmotic diuretics that reduce intraocular pressure. 2. Carbonic anhydrase inhibitors that assist in reducing fluid production.
What are osmotic diuretics and give examples?
Osmotic diuretics are substances that promote diuresis through osmotic force. Examples include Mannitol Urea Isosorbide and Glycerin.
What are carbonic anhydrase inhibitors and provide examples?
Carbonic anhydrase inhibitors are diuretics that prevent the enzyme from facilitating the reversible reaction between carbon dioxide and water leading to diuresis. Examples include Acetazolamide Methazolamide and Dichlorophenamide.
What is the main site of action for thiazide diuretics?
Thiazide diuretics act primarily on the distal convoluted tubule of the nephron.
What biochemical process do potassium-sparing diuretics inhibit?
They inhibit sodium channels in the kidney and/or block the action of aldosterone which promotes sodium retention and potassium excretion.
Explain the significance of diuretics in hypertension management.
Diuretics help manage hypertension by reducing blood volume through increased urine production thereby lowering blood pressure.
What contraindications or side effects are associated with loop diuretics?
Possible side effects include electrolyte imbalance (hypokalemia hyponatremia) dehydration and ototoxicity.
What is the role of aldosterone in the kidney?
Aldosterone promotes sodium reabsorption and potassium excretion in the distal tubule and collecting ducts essential for fluid and electrolyte balance.
Which diuretic class is particularly effective in patients with heart failure?
Loop diuretics are particularly effective in managing fluid overload in patients with heart failure.
How do potassium-sparing diuretics differ from other diuretic classes in terms of potassium retention?
Potassium-sparing diuretics help to retain potassium in the body while other diuretics generally promote potassium excretion.
What are the clinical indications for carbonic anhydrase inhibitors?
Clinical indications include the treatment of glaucoma altitude sickness and metabolic alkalosis.
Name the mechanism of action for furosemide as a loop diuretic.
Furosemide inhibits the Na-K-2Cl symporter in the thick ascending limb of the Loop of Henle leading to increased excretion of sodium chloride and water.
What is the therapeutic action of thiazides beyond diuresis?
Thiazides can lower blood pressure and are also used in heart failure management by reducing fluid overload.
How can the effectiveness of diuretics vary from patient to patient?
Differences in renal function age body mass comorbidities and concurrent medications can influence the effectiveness of diuretics.
What is the primary action of loop diuretics on the renal system?
Loop diuretics inhibit sodium (Na) reabsorption at the thick ascending limb of the loop of Henle leading to increased urine output and electrolyte loss.
What effect do thiazide diuretics have on sodium reabsorption?
Thiazide diuretics inhibit sodium reabsorption at the distal convoluted tubules promoting diuresis and affecting the balance of electrolytes.
What metabolic state develops as a result of loop and thiazide diuretic use?
A form of metabolic alkalosis develops due to the loss of chloride (Cl) in the urine which leads to an increase in bicarbonate (HCO3-) concentration in the plasma.
How do loop diuretics and thiazide diuretics affect potassium levels?
Both classes of diuretics increase the delivery of sodium to the distal nephron which leads to the loss of potassium (K) due to its regulation by aldosterone resulting in hypokalemia.
Describe the mechanism of potassium loss in relation to sodium-potassium ATPase. How does this affect H+ ion secretion?
In the late distal tubule and collecting duct for every 3 sodium ions reabsorbed by Na-K ATPase only 2 potassium ions are excreted. To maintain electrical neutrality hydrogen ions (H+) are also excreted which contributes to further metabolic alkalosis.
What ions are primarily reabsorbed in the thick ascending limb of the loop of Henle?
The thick ascending limb primarily reabsorbs sodium (Na) potassium (K) and chloride (Cl) ions.
What is the role of aldosterone in the context of diuretics?
Aldosterone regulates the reabsorption of sodium and the secretion of potassium in the distal nephron and diuretics can disrupt this balance leading to electrolyte imbalances.
What is the relevance of bicarbonate (HCO3-) in the context of acid-base balance in the body?
Bicarbonate acts as a crucial buffer in the blood to maintain pH; its levels may increase during diuretic therapy contributing to metabolic alkalosis.
What is hypokalemia and what are its potential consequences?
Hypokalemia refers to low potassium levels in the blood which can lead to muscle weakness cramping arrhythmias and overall disturbances in the function of various organs.
How does the use of diuretics impact blood pH?
The use of diuretics can lead to an increase in blood pH resulting in alkalosis primarily due to the loss of sodium and potassium and the consequent increase in bicarbonate levels.
Explain how diuretics influence the excretion of protons in relation to acid-base balance.
Diuretics promote the excretion of sodium leading to aldosterone-driven loss of potassium; this coupled with the need to maintain electroneutrality causes increased secretion of protons (H+) impacting acid-base balance.
What happens to HCO3- levels in relation to alkalosis?
If HCO3- levels increase it can lead to alkalosis.
What is the relationship between hypokalemia and aldosterone?
Due to loss of potassium (hypokalemia) aldosterone will compensate for the loss of sodium.
What is the effect of potassium-sparing diuretics on K secretion?
Potassium-sparing diuretics prevent potassium (K) secretion by antagonizing the effects of aldosterone in the collecting tubules.
How do potassium-sparing diuretics inhibit K secretion?
They inhibit K secretion either through direct pharmacologic antagonism of mineralocorticoid receptors (like spironolactone and eplerenone) or by inhibiting sodium (Na) influx through ion channels in the luminal membrane (like amiloride and triamterene).
Name the inhibitors of renal epithelial Na channels.
Amiloride and Triamterene are inhibitors of renal epithelial Na channels.
What is the mechanism of action of amiloride and triamterene in potassium-sparing diuretics?
These diuretics block Na entry into the cell through the principal cell’s epithelial Na channels leading to reduced K secretion into the lumen via K channels in the luminal membrane.
What are examples of potassium-sparing diuretics?
Examples of potassium-sparing diuretics include amiloride triamterene spironolactone and eplerenone.
What are aldosterone antagonists (AAs)?
Aldosterone antagonists such as spironolactone and eplerenone competitively inhibit the binding of aldosterone to the cytosolic mineralocorticoid receptor.
How do potassium-sparing diuretics and aldosterone antagonists differ in their mechanisms?
Potassium-sparing diuretics may inhibit Na influx through ion channels while aldosterone antagonists inhibit the binding of aldosterone to its receptor.
Why is potassium-sparing diuretics advantageous in treating patients with hypokalemia?
Potassium-sparing diuretics help retain potassium levels preventing further hypokalemia while addressing fluid and electrolyte imbalances.
What is the role of MR antagonists in relation to endogenous aldosterone levels?
The clinical efficacy of MR antagonists is dependent on the levels of endogenous aldosterone. Higher levels of aldosterone lead to a more significant therapeutic effect from MR antagonists on urinary excretion.
List the K-sparing diuretics mentioned and their characteristics.
The K-sparing diuretics mentioned include: 1. Amiloride - helps decrease sodium reabsorption without causing potassium loss. 2. Triamterene - has similar effects to amiloride and prevents potassium excretion. 3. Spironolactone - an MR antagonist that inhibits aldosterone-induced protein synthesis which promotes sodium reabsorption and potassium excretion. 4. Eplerenone - a more selective MR antagonist with fewer side effects compared to spironolactone.
What is the effect of aldosterone binding to its receptor?
When aldosterone binds to its receptor it promotes the expression of aldosterone-induced proteins (AIPs) that increase sodium reabsorption and potassium excretion in the kidneys.
What are the major adverse effects of thiazide diuretics?
The major adverse effects of thiazide diuretics include: 1. Hyponatremia 2. Hypokalemia 3. Hypomagnesemia 4. Metabolic alkalosis 5. Hypercalcemia 6. Possible beneficial effects for osteoporosis management 7. Risk of hyperglycemia 8. Increased plasma lipids including elevated LDL and total cholesterol.
Explain the relationship between aldosterone levels and the efficacy of mineralocorticoid receptor antagonists (MRAs).
The efficacy of MRAs increases with higher endogenous aldosterone levels. This means that MRAs have a greater impact on sodium and potassium transport in conditions where aldosterone levels are elevated.
What types of diuretics are classified as potassium-sparing and how do they function in the body?
Potassium-sparing diuretics including amiloride triamterene spironolactone and eplerenone function by inhibiting sodium reabsorption at the distal convoluted tubule or collecting duct of the nephron while preserving potassium levels in the blood.
What are some implications of thiazide diuretics for patients with a history of osteoporosis?
Thiazide diuretics can be useful in osteoporosis management since they can increase calcium reabsorption from the urine potentially improving bone mineral density.
Define Aldosterone-Induced Proteins (AIPs) and their significance.
Aldosterone-Induced Proteins (AIPs) are proteins that are synthesized in response to aldosterone binding to its receptor. They are significant because they play a crucial role in the reabsorption of sodium and the excretion of potassium in renal tubules.
What is the mechanism of action of spironolactone and eplerenone?
Spironolactone and eplerenone act as mineralocorticoid receptor antagonists blocking the action of aldosterone. This results in decreased sodium reabsorption and decreased potassium excretion thereby producing a diuretic effect.
Discuss the causes and consequences of metabolic alkalosis as a side effect of thiazide diuretics.
Metabolic alkalosis can occur due to thiazide-induced loss of hydrogen ions in the urine and volume contraction. This can lead to symptoms such as muscle cramps fatigue and potentially severe disturbances in acid-base balance.
What is hyperuricemia and how is it related to gout?
Hyperuricemia refers to an elevated level of uric acid in the blood which can lead to the formation of urate crystals. These crystals deposit in joints and tissues leading to a painful inflammatory condition known as gout.
What are loop diuretics and how do they impact calcium levels?
Loop diuretics are a class of diuretics that act on the Loop of Henle in the kidneys. They are similar to thiazide diuretics but can cause hypocalcemia which is low calcium levels in the blood.
What are the side effects of loop diuretics particularly Ethacrynic acid?
Common side effects of loop diuretics include ototoxicity tinnitus hearing impairment deafness vertigo and a sense of fullness in the ears. Ethacrynic acid is noted for carrying the highest risk for ototoxicity among loop diuretics.
What are potassium-sparing diuretics and their risks related to potassium?
Potassium-sparing diuretics are diuretics that help the body retain potassium while losing sodium and water. They pose a risk of causing hyperkalemia which is a life-threatening condition of elevated potassium levels in the blood.
Who should avoid potassium-sparing diuretics?
Patients with hyperkalemia or at increased risk of developing hyperkalemia such as those with renal failure patients on ACE inhibitors or ARBs or patients taking potassium supplements should avoid potassium-sparing diuretics.
What is the clinical use and side effects of diuretics?
Diuretics are clinically used for conditions such as hypertension and edema. Their side effects include electrolyte imbalances (like hypokalemia or hyperkalemia) dehydration dizziness and in some cases ototoxicity with loop diuretics.
What are sympatholytic drugs?
Sympatholytic drugs are medications that depress the sympathetic nervous system leading to decreased heart rate and blood pressure. They are also used in the treatment of certain psychiatric conditions like depression.
Name some central acting sympatholytics and their cardiovascular effects.
Central acting sympatholytics include clonidine methyldopa guanabenz and guanfacine. Clonidine lowers heart rate and cardiac output more than methyldopa.
What is the site of action for central acting sympatholytics?
Central acting sympatholytics primarily act on the central nervous system particularly at the medullary cardiovascular centers thereby reducing sympathetic outflow.
What is the mechanism of action of clonidine?
Clonidine functions as a direct alpha-2 adrenergic agonist which means it binds to and activates alpha-2 receptors leading to reduced sympathetic tone and decreased heart rate.
What is the mechanism of action of methyldopa?
Methyldopa is converted to alpha-methyl norepinephrine in the body which activates alpha-2 adrenergic receptors in the central nervous system leading to reduced sympathetic outflow and lower blood pressure.
What is the mechanism of action of thylnorepinephrine?
Thylnorepinephrine acts as a false neurotransmitter stimulating presynaptic alpha-2 receptors in the brain stem. This stimulation leads to decreased norepinephrine release resulting in reduced sympathetic outflow.
What are the physiological effects of thylnorepinephrine on the cardiovascular system?
Thylnorepinephrine reduces cardiac output heart rate peripheral vascular resistance and blood pressure.
What are the side effects of thylnorepinephrine?
Side effects include drowsiness irritability nightmares trouble sleeping constipation dry mouth lack of appetite and dizziness.
In what setting is thylnorepinephrine especially effective and why?
Thylnorepinephrine is especially effective in emergency settings due to its resemblance to norepinephrine specifically its action on alpha-2 receptors which work on the upper centers of the nervous system.
What is a ganglionic blocker?
A ganglionic blocker is a drug that competitively blocks nicotinic cholinoceptors on postganglionic neurons in both sympathetic and parasympathetic ganglia.
What are the common side effects of ganglionic blockers?
Common side effects of ganglionic blockers include dry mouth constipation urinary retention blurred vision and orthostatic hypotension.
What is trimehtaphan camsylate used for?
Trimehtaphan camsylate is a ganglionic blocker used to manage hypertensive emergencies by decreasing sympathetic outflow.
What does parasympatholytic mean?
Parasympatholytic refers to actions that inhibit the parasympathetic nervous system often resulting in effects like increased heart rate and decreased glandular secretions.
What is orthostatic hypotension and how is it related to ganglionic blockers?
Orthostatic hypotension is a form of low blood pressure that happens when you stand up from sitting or lying down. It can be a side effect of ganglionic blockers due to their ability to inhibit autonomic responses.
What is hypotension caused by blocking sympathetic ganglia?
Hypotension results from the diminished cardiovascular reflexes including vasoconstriction caused by drugs that block sympathetic ganglia.
What happens to blood vessels when a person stands up if sympathetic ganglia are blocked?
When a person stands up there is a failure to adequately constrict blood vessels leading to a sudden drop in blood pressure termed orthostatic hypotension which can cause dizziness or lightheadedness.
What are the effects of drugs that block sympathetic ganglia?
These drugs inhibit the action of acetylcholine (ACh) and diminish sympathetic nervous system activity which reduces vasoconstriction and consequently can lead to hypotension.
What are guanadrel and guanethidine?
Guanadrel and guanethidine are adrenergic neuron blockers that act as false neurotransmitters replacing norepinephrine (NE) but being inactive at adrenergic receptors.
How do guanadrel and guanethidine affect norepinephrine stores?
They are transported by the norepinephrine transporter (NET) and stored in neurotransmitter vesicles gradually depleting NE stores and consequently inhibiting NE release from sympathetic nerve endings.
What is the mechanism of action of guanadrel and guanethidine?
These drugs prevent the release of norepinephrine by interrupting the nerve impulse which leads to decreased alpha-1 mediated vasoconstriction.
What happens to blood pressure as a result of decreased alpha-1 mediated vasoconstriction?
There is a decrease in peripheral resistance and blood pressure due to decreased alpha-1 mediated vasoconstriction.
What are the potential adverse effects of sympathetic ganglia blockers?
Potential adverse effects include orthostatic hypotension dizziness and lightheadedness upon standing due to impaired cardiovascular reflexes.
How do neuroreceptors respond to acetylcholine and nicotine?
Neuroreceptors respond to both ACh and nicotine; if blocked their transduction process is interrupted leading to diminished sympathetic activity.
What role does the norepinephrine transporter (NET) play in the action of adrenergic neuron blockers?
NET transports guanadrel and guanethidine into the sympathetic nerve endings where they are stored causing the depletion of norepinephrine stores.
Explain the concept of orthostatic hypotension in detail.
Orthostatic hypotension is the failure of blood vessels to adequately constrict during the transition from lying down or sitting to standing resulting in a sudden drop in blood pressure leading to symptoms such as dizziness lightheadedness or fainting.
What is the relationship between sympathetic ganglia blocking agents and cardiovascular reflexes?
Sympathetic ganglia blocking agents inhibit the normal cardiovascular reflexes particularly those involved in the compensatory mechanisms for maintaining blood pressure during positional changes.
What neurotransmitters are affected by adrenergic neuron blockers like guanadrel and guanethidine?
These adrenergic neuron blockers primarily affect norepinephrine (NE) and inhibit its release from sympathetic nerve endings.
What are the effects of Postural hypotension?
Postural hypotension also known as orthostatic hypotension can lead to symptoms such as dizziness lightheadedness fainting fatigue and blurred vision when standing up from a sitting or lying position.
What drugs are associated with postural hypotension and impaired ejaculation?
Guanethidine Guanadrel and Reserpine are associated with postural hypotension and impaired ejaculation.
How do Guanethidine and Guanadrel work?
Guanethidine and Guanadrel work by depleting stores of catecholamines and preventing the normal physiologic release of norepinephrine (NE) from post-ganglionic sympathetic neurons.
What is the role of false neurotransmitters in the action of these drugs?
False neurotransmitters act similarly to norepinephrine but do not produce the same physiological effects ultimately interfering with the normal function of adrenergic transmission.
What is the mechanism of action of Reserpine?
Reserpine depletes vesicular stores of norepinephrine and inhibits the NE uptake mechanism by blocking the vesicular monoamine transporter (VMAT2) leading to increased metabolism of norepinephrine by mitochondrial monoamine oxidase (MAO) and depleting norepinephrine from adrenergic terminals.
What plant is the alkaloid Reserpine extracted from?
Reserpine is extracted from the roots of the Indian plant Rauwolfia serpentina.
What is the clinical significance of Reserpine?
Reserpine was one of the first effective drugs used on a large scale for the treatment of hypertension especially before the advent of newer antihypertensive medications.
Which receptors do the norepinephrine and related drugs affect?
These drugs primarily affect the alpha (α) and beta (β) adrenergic receptors in the sympathetic nervous system.
What are the symptoms and consequences of impaired ejaculation?
Impaired ejaculation can result in difficulties with sexual satisfaction potential infertility and emotional impacts such as stress or anxiety related to sexual performance.
What is the name of the transporter that Reserpine blocks?
Reserpine blocks the vesicular monoamine transporter (VMAT2) which is responsible for the uptake of amines into storage vesicles.
What class of medication does Reserpine belong to?
Reserpine belongs to the class of medications known as rauwolfia alkaloids or antihypertensives.
Explain the physiological impact of catecholamine depletion.
Depletion of catecholamines leads to reduced sympathetic nervous system activity which can cause decreased heart rate reduced vasoconstriction concomitant blood pressure drops (such as postural hypotension) and potential sexual dysfunction like impaired ejaculation.
What is the main action of alpha blockers in the treatment of hypertension and benign prostatic hyperplasia (BPH)?
Alpha blockers function primarily as antagonists at alpha-1 adrenergic receptors on vascular smooth muscle. This blockade leads to dilation of resistance arterioles which reduces total peripheral resistance (TPR) and capacitance of venules thereby decreasing venous return and cardiac output (CO).
What are some non-selective alpha-1 blockers and their uses?
Non-selective alpha-1 blockers include Phenoxybenzamine and Phenotolamine. These are used to manage hypertension often in patients with pheochromocytoma and they can help alleviate symptoms of BPH although selective blockers are generally preferred for the latter.
What are some selective alpha-1 blockers and what are their primary indications?
Selective alpha-1 blockers include Prazosin Terazosin and Doxazosin. They are primarily indicated for the treatment of hypertension and symptoms associated with benign prostatic hyperplasia (BPH) in men.
What is the mechanism of action for alpha-1 adrenergic blockers?
Alpha-1 adrenergic blockers act as competitive antagonists at post-synaptic alpha-1 receptors located on vascular smooth muscle. This action leads to vasodilation of arterioles reduction in total peripheral resistance (TPR) decreased venous return and subsequently lowered cardiac pressure.
What are the adverse effects of alpha blockers?
Adverse effects of alpha-1 blockers can include sedation depression hypotension and reflex tachycardia. These side effects are primarily due to the systemic vasodilation caused by the blockade of the alpha-1 receptors.
What role does norepinephrine (NE) play in the function of alpha blockers?
Norepinephrine is a key neurotransmitter involved in vasoconstriction. In cases of severe depletion of NE in the brain often due to degradation by monoamine oxidase (MAO) alpha blockers may lead to decreased vasoconstrictor tone contributing to potential hypotensive effects.
How does administration of an alpha blocker affect cardiac output (CO)?
Administration of an alpha blocker reduces venous return (due to decreased vascular resistance) which in turn reduces cardiac output (CO). This process is mediated by the reduction in preload on the heart as less blood returns to the heart chambers.
Explain how a1-blocker mechanisms lead to reducing blood pressure.
Alpha-1 blocker mechanisms lead to reduced blood pressure through post-synaptic receptor blockade which causes vasodilation of both resistance arterioles and capacitance venules leading to decreased TPR and reduced venous return. This culminates in lowered blood pressure.
Describe the indirect effects that alpha blockers have on the sympathetic nervous system.
While alpha-1 blockers primarily affect vascular smooth muscle their systemic effects can lead to reduced sympathetic tone. This can result in compensatory mechanisms such as reflex tachycardia due to the drop in systemic vascular resistance ultimately causing the cardiovascular system to adapt to maintain blood flow.
Why are selective alpha blockers preferred in the management of BPH?
Selective alpha blockers are preferred for BPH as they provide similar therapeutic effects in reducing urinary symptoms associated with prostate enlargement without the systemic side effects that come from non-selective agents such as significant cardiovascular effects.
What are the two types of alpha blockers?
- Non-selective alpha blockers: Phenoxybenzamine Phentolamine. 2. Selective alpha-1 blockers: Prazosin Terazosin Doxazosin.
What are some common adverse effects associated with alpha blockers?
- Drowsiness 2. Weakness 3. Orthostatic hypotension especially with first dose so nighttime administration is preferred. 4. Nausea vomiting diarrhea.
What is a significant adverse effect of non-selective alpha blockers related to heart function?
Reflex tachycardia which can precipitate angina in patients with coronary disease.
How can the administration of selective alpha-1 blockers differ from non-selective blockers for patients with coronary disease?
Selective alpha-1 blockers generally cause reflex tachycardia less frequently than non-selective agents reducing the risk of precipitating angina.
What are some examples of non-cardio-selective beta blockers?
- Propranolol 2. Nadolol.
List some examples of cardio-selective beta blockers.
- Metoprolol 2. Atenolol 3. Esmolol 4. Betaxolol 5. Bisoprolol.
What are partial agonist beta blockers?
Beta blockers that act as partial agonists include: 1. Pindolol 2. Acebutolol 3. Penbutolol.
What is the mechanism of action of beta blockers?
Beta blockers primarily block beta-adrenergic receptors which results in decreased heart rate and myocardial contractility leading to reduced cardiac workload and oxygen demand.
Explain the significance of nighttime administration of alpha blockers.
Nighttime administration is significant to minimize the effects of orthostatic hypotension which can be particularly pronounced after the first dose.
What effect does reflex tachycardia have on patients with coronary artery disease?
Reflex tachycardia can lead to increased heart rate which may precipitate angina due to greater myocardial oxygen demand.
What gastrointestinal side effects can occur with oral administration of alpha blockers?
Oral administration of alpha blockers can lead to nausea vomiting and diarrhea.
Why might beta blockers be beneficial for patients with angina or atherosclerosis?
Beta blockers can decrease heart rate and myocardial contractility thus reducing oxygen demand and helping to prevent angina attacks.
What mechanisms do alpha blockers use to function in the body?
Alpha blockers work by antagonizing alpha-adrenergic receptors leading to vasodilation and reduced peripheral resistance.
How do alpha-1 blockers affect blood pressure?
Alpha-1 blockers lower blood pressure by preventing vasoconstriction in blood vessels.
What is the effect of 1-adrenoceptor blockers on the heart?
Reduction of myocardial contractility and heart rate leading to a decrease in cardiac output (CO) and blood pressure (BP).
How do 1-adrenoceptor blockers in the kidney affect the juxta-glomerular apparatus?
They reduce renin release and angiotensin II production which results in decreased total peripheral resistance (TPR) and blood pressure (BP).
What differentiates drugs without intrinsic sympathomimetic activity (ISA) from those with ISA?
Drugs without ISA are non-selective and 1-selective blockers that cause a significant decrease in cardiac output (CO) while drugs with ISA act as partial agonists producing a lesser decrease in CO.
What mechanisms contribute to the decrease in blood pressure (BP) when using drugs with ISA?
There is a decrease in peripheral resistance due to 2-agonist activity that leads to vasodilation contributing to lowered BP.
What is intrinsic sympathomimetic activity (ISA) in beta blockers?
ISA refers to the partial agonist activity of certain beta blockers which can provide benefits such as bronchodilation in asthma patients and a moderate effect on lipid metabolism.
What benefits do beta blockers with ISA provide for asthma patients?
They cause bronchodilation and have a moderate lower effect on lipid metabolism and lesser vasospasms which may be beneficial for patients with asthma.
What is a potential adverse effect of beta blockers?
Beta blockers may induce some vasoconstriction as an adverse effect.
What is the role of beta-blockers on myocardial contractility?
Beta-blockers generally decrease myocardial contractility which can lead to a reduction in heart rate and cardiac output.
Explain the term ‘negative inotropic effect’ in relation to beta blockers.
Negative inotropic effect refers to the reduction in the strength of heart muscle contraction which is a common effect of beta blockers.
What impact do beta blockers have on peripheral resistance?
Beta blockers can decrease peripheral resistance due to their effects on the vascular system particularly through the blockade of adrenergic receptors.
What is the significance of dose adjustment for patients taking beta blockers with ISA?
Because these drugs have partial agonist activity doses may need adjusting to balance therapeutic effects while minimizing potential adverse effects.
What are the cardiovascular adverse effects of beta-blockers?
Cardiovascular adverse effects associated with beta-blockade include: 1. Bradycardia 2. Asthmatic attacks in patients with airway disease 3. Increased plasma lipids (not observed with partial agonists) 4. Glucose inhibition of receptor-mediated glucose metabolism in the liver.
What are the contraindications for beta-blocker use?
The contraindications for the use of beta-blockers include: 1. Asthma 2. Diabetes 3. Bradycardia 4. Chronic Obstructive Pulmonary Disease (COPD).
What are the indications for using beta-blockers as antihypertensive drugs?
Beta-blockers are indicated as antihypertensive drugs in the following situations: 1. To prevent reflex tachycardia caused by direct vasodilators. 2. For hypertensive patients with tachycardia angina myocardial infarction coronary artery disease and heart failure.
Which beta-blocker is ultra-short acting and what is its primary use?
Esmolol is an ultra-short-acting cardio-selective beta-blocker that requires constant IV perfusion. Its primary use is for the management of hypertensive emergencies and during surgical operations.
What is the importance of selecting a cardio-selective beta-blocker?
The importance of selecting a cardio-selective beta-blocker like Esmolol is to prevent patients from experiencing adverse effects such as bradycardia especially in those with non-selective Beta-2 blockade which can exacerbate respiratory conditions.
What are mixed alpha and beta-blockers?
Mixed alpha and beta-blockers are drugs that concurrently block both alpha and beta-adrenergic receptors. They are utilized for managing conditions where both types of receptor blockade provide benefits such as hypertension and heart failure.
What effect do partial agonists have on plasma lipids?
Partial agonists do not lead to an increase in plasma lipids differentiating them from non-partial beta blockers which may raise plasma lipid levels.
Why is it important to monitor patients taking beta-blockers who have asthma or COPD?
Patients with asthma or COPD taking beta-blockers must be monitored closely because these medications can provoke bronchoconstriction and worsen respiratory symptoms due to non-selective beta-receptor blockade.
What is reflex tachycardia and how do beta-blockers prevent it?
Reflex tachycardia is a compensatory increase in heart rate that occurs as a reaction to a drop in blood pressure. Beta-blockers prevent this by reducing heart rate and myocardial contractility thereby counteracting the body’s attempt to increase heart rate in response to vasodilation.
How do beta-blockers affect glucose metabolism?
Beta-blockers can inhibit receptor-mediated glucose metabolism in the liver which may complicate glucose homeostasis especially in diabetic patients.
What is Labetalol classified as and what are its main functions?
Labetalol is classified as a non-selective beta-blocker with intrinsic sympathomimetic activity (ISA) and selective alpha-1 blocker activity. It decreases peripheral resistance without significant effects on cardiac output (CO) and has a rapid effect making it useful for emergency treatment of hypertension.
What are the key characteristics and clinical uses of Carvedilol?
Carvedilol is a non-selective beta-blocker with alpha-1 blocking activity. It is useful for patients with hypertension and heart failure as it reduces mortality associated with these conditions.
Describe the mechanism of action of Nebivolol and its unique properties.
Nebivolol is a selective beta-1 blocker that has vasodilating properties not mediated by beta-1 blockade activity. Its mechanism of action involves the release of nitric oxide (NO) from the endothelium leading to relaxation of arterial smooth muscle.
What are the common adverse effects associated with beta-blockers such as Labetalol Carvedilol and Nebivolol?
Common adverse effects include orthostatic hypotension gastrointestinal upset nervousness dry mouth and fatigue.
What does ISA stand for and what is its significance in beta-blockers?
ISA stands for Intrinsic Sympathomimetic Activity. It indicates that certain beta-blockers like Labetalol can partially activate beta-adrenergic receptors while blocking them which may attenuate some of the adverse effects such as bradycardia.
List the diuretics mentioned and their primary action on the body.
The diuretics mentioned include thiazide diuretics loop diuretics and potassium-sparing diuretics. Their primary action is to promote sodium (Na) and water (H2O) excretion leading to a decrease in blood volume and venous return.
What are the pharmacological effects of diuretics in treating hypertension?
Diuretics decrease blood volume and venous return which helps in lowering blood pressure making them effective in the treatment of hypertension.
How does the mechanism of action of Labetalol differ from that of Nebivolol?
Labetalol acts through non-selective beta-blockade and alpha-1 blockade which decreases peripheral resistance and heart rate. In contrast Nebivolol selectively blocks beta-1 receptors and causes vasodilation primarily through nitric oxide release reducing blood pressure without the same degree of heart rate reduction.
What patient conditions can benefit from the use of Carvedilol due to its unique properties?
Carvedilol can benefit patients with hypertension and heart failure due to its ability to lower blood pressure and reduce mortality in these populations.
What effects do thiazide diuretics have compared to loop diuretics?
Thiazide diuretics primarily act on the distal convoluted tubule and are effective in moderately lowering blood pressure and preventing fluid retention. Loop diuretics are more potent and work on the ascending loop of Henle effectively managing fluid overload in conditions like heart failure.
What is stroke volume and how does it affect cardiac output?
Stroke volume is the amount of blood pumped by the left ventricle with each heartbeat. A decrease in stroke volume leads to a decrease in cardiac output (CO) which is the volume of blood the heart pumps per minute. Cardiac output can be calculated as CO = Stroke Volume x Heart Rate.
What are the effects of decreased cardiac output on blood pressure?
A decrease in cardiac output typically results in lower blood pressure (BP) because there is less volume being pumped into the arteries with each heartbeat.
What are sympathoplegic drugs and their mechanism of action?
Sympathoplegic drugs are medications that inhibit the sympathetic nervous system. They include central sympatholytics adrenergic neuron blockers and ganglionic blockers which lead to decreased peripheral resistance reduced heart rate and contractility thereby lowering cardiac output and blood pressure.
What are central sympatholytics?
Central sympatholytics are a class of drugs that act on the central nervous system to reduce sympathetic outflow. They result in decreased peripheral resistance decreased cardiac output and lower blood pressure.
What are adrenergic neuron blockers?
Adrenergic neuron blockers are medications that inhibit the release of norepinephrine from sympathetic neurons reducing sympathetic tone and leading to decreased blood pressure and cardiac output.
What are ganglionic blockers?
Ganglionic blockers are drugs that inhibit transmission in the autonomic ganglia leading to a decrease in both sympathetic and parasympathetic outflow resulting in reduced peripheral resistance and blood pressure.
What are mixed blockers in the context of antihypertensive therapy?
Mixed blockers are medications that simultaneously block both alpha and beta adrenergic receptors leading to reduced heart rate decreased myocardial contractility and decreased peripheral resistance resulting in lowered blood pressure.
What are direct vasodilators?
Direct vasodilators are a class of antihypertensive drugs that directly relax the vascular smooth muscle leading to dilation of resistance vessels increasing venous capacitance and decreasing blood return to the heart effectively lowering blood pressure.
What are calcium channel blockers (CCBs) and their function?
Calcium channel blockers (CCBs) are medications that prevent calcium from entering the smooth muscle cells of the arteries leading to muscle relaxation and vasodilation which decreases peripheral resistance and blood pressure.
What is the Renin-Angiotensin-Aldosterone System (RAAS) and its role in hypertension?
RAAS is a hormone system that regulates blood pressure and fluid balance. Disorders of RAAS often lead to hypertension through increased blood volume and peripheral resistance.
What are renin inhibitors?
Renin inhibitors are a class of drugs that directly inhibit the activity of renin an enzyme that initiates the RAAS cascade ultimately leading to decreased production of angiotensin I and II therefore reducing blood pressure.
What are ACE inhibitors and how do they function?
Angiotensin-converting enzyme (ACE) inhibitors are medications that prevent the conversion of angiotensin I to angiotensin II thereby blocking its effects which include vasoconstriction and increased blood volume leading to lower blood pressure.
What are angiotensin II receptor blockers (ARBs)?
Angiotensin II receptor blockers (ARBs) are drugs that block the receptors for angiotensin II preventing its vasoconstrictive and aldosterone-secreting actions resulting in decreased blood pressure and reduced blood volume.
How do antihypertensive agents lead to decreased blood pressure?
Antihypertensive agents lower blood pressure through various mechanisms including reducing peripheral resistance decreasing cardiac output inhibiting the RAAS and relaxing vascular smooth muscle.
Explain the classification of antihypertensive agents based on mode of action.
Antihypertensive agents can be classified into several categories including: 1) Sympathoplegic Drugs (such as central sympatholytics adrenergic neuron blockers and ganglionic blockers) 2) Direct Vasodilators (including direct arterial and mixed vasodilators) 3) Calcium Channel Blockers 4) Inhibitors of the Renin-Angiotensin-Aldosterone System (such as renin inhibitors ACE inhibitors and ARBs).
What are the different types of arterial vasodilators?
- Arterial Hydralazine
- Minoxidil
- Diazoxide
- Fenoldopam
What is Sodium nitroprusside (SNP)?
Sodium nitroprusside (SNP) is an arterial-venous vasodilator that dilates both arteries and veins decreasing peripheral vascular resistance and affecting cardiac output by reducing venous return.
What are dihydropyridines and give examples?
Dihydropyridines are a class of vasodilators that primarily act on blood vessels. Examples include:
- Nifedipine
- Amlodipine
- Felodipine
- Isradipine
- Nicardipine
- Nisoldipine
What characterizes non-dihydropyridines and list two examples?
Non-dihydropyridines primarily affect the heart more than blood vessels. Examples include:
- Verapamil
- Diltiazem
What are vasodilators and how do they function?
Vasodilators are drugs that dilate blood vessels and decrease peripheral vascular resistance by acting on smooth muscle cells leading to reduced blood pressure.
How do vasodilators affect calcium channels in the heart and smooth muscles?
Vasodilators act on calcium channels in the heart and smooth muscles leading to decreased intracellular calcium levels reduced contractility and relaxation of vascular smooth muscle.
What is the significance of reflex tachycardia in vasodilator use?
Many vasodilators while reducing blood pressure can lead to reflex tachycardia as a compensatory mechanism by the body to maintain cardiac output despite lower systemic vascular resistance.
What is the anti-hypertensive action of vasodilators mediated by?
The anti-hypertensive action of vasodilators is primarily mediated by vasodilation leading to a decrease in total peripheral resistance (TPR). However Sodium nitroprusside (SNP) has an additional effect of changing venous return.
What are the effects of vasodilation on cardiac output (CO)?
Vasodilation reduces venous return which can lead to decreased cardiac output (CO) under certain circumstances due to lower volume returning to the heart.
What effects does nitric oxide (NO) have in vasodilators?
Nitric oxide is a potent vasodilator that increases vasodilation by stimulating the production of cyclic GMP in smooth muscle cells leading to relaxation.
What are the systemic effects (SIE) associated with vasodilators?
The systemic effects associated with vasodilators may include blood pressure lowering reflex tachycardia and potential fluid retention.
Explain the mechanism by which vasodilators reduce resistance and blood pressure?
Vasodilators reduce resistance and blood pressure primarily through the relaxation of smooth muscles in the blood vessels leading to an increase in the diameter of the vessels thus lowering total peripheral resistance.
What happens to MLC (myosin light chain) during relaxation?
MLC will be dephosphorylated so it cannot bind with actin leading to relaxation.
Does the diagram discuss any drug actions regarding direct vasodilators?
No the diagram does not discuss any drug direct vasodilator actions.
What is the mechanism of action (MOA) of Hydralazine?
Hydralazine causes direct relaxation of arteriolar smooth muscle. The exact MOA is unclear but may involve a decrease in intracellular Ca2+ and/or release of nitric oxide (NO) from the endothelium.
How is Hydralazine metabolized?
Hydralazine is metabolized by acetylation and it is noted that rapid acetylators have greater metabolism of this drug.
What pharmacological effects does Hydralazine have?
Hydralazine has an anti-hypertensive effect.
What are Minoxidil and Diazoxide classified as?
Minoxidil and Diazoxide are classified as Potassium Channel Openers.
What is the active metabolite of Minoxidil and where is it formed?
The active metabolite of Minoxidil is Minoxidil sulfate which is formed in the liver.
How do Minoxidil and Diazoxide induce relaxation of arterial smooth muscle?
They activate ATP-modulated K+ channels by opening K+ channels in the smooth muscle membrane permitting K+ efflux which leads to hyperpolarization and relaxation of the arterial smooth muscle.
What is the function of Fenoldopam?
Fenoldopam is an agonist of peripheral dopamine D1 receptors.
What are the effects of activating the D1 receptors by Fenoldopam?
Activation of D1 receptors results in dilation of peripheral arteries and induces natriuresis.
What physiological effect do potassium channel openers have on membrane potential?
Potassium channel openers stabilize the membrane at its resting potential by bringing the action potential to its resting values.
What is the effect of acetylation on muscle cell polarization?
Acetylation of cells can affect the polarization state by influencing the activity of various ion channels and transporters.
Define depolarization in the context of muscle cells.
Depolarization refers to a change in the membrane potential of a cell that makes it more positive moving away from the resting membrane potential.
What is the role of sodium (Na+) in the depolarization of muscle cells?
Sodium ions (Na+) play a crucial role in depolarization by entering the cell through sodium channels causing a rapid increase in positive charge inside the cell.
What does hyperpolarization mean in muscle cells?
Hyperpolarization is the process by which the membrane potential becomes more negative than the resting potential making it less likely for the cell to fire an action potential.
How does hyperpolarization allow potassium (K+) to exit the cell?
During hyperpolarization increased permeability of the cell membrane to potassium ions (K+) allows these ions to flow out of the cell contributing to the more negative membrane potential.
What is the significance of less calcium (Ca2+) in smooth muscle cells?
Lower levels of calcium in smooth muscle cells result in reduced contraction strength which can lead to hypotensive effects.
Explain the hypotensive effect related to smooth muscle cells.
The hypotensive effect occurs when smooth muscle relaxation results in vasodilation leading to lower blood pressure.
What is the relationship between sodium excretion and hypotension?
Increased sodium excretion typically leads to decreased fluid volume in the body which can further contribute to lowering blood pressure.
Describe the mechanism by which beta-adrenergic agonists induce relaxation in smooth muscle.
Beta-adrenergic agonists activate cyclic AMP (cAMP) signaling pathways which lead to phosphorylation of proteins that decrease calcium levels and promote smooth muscle relaxation.
List common uses of medications that induce smooth muscle relaxation. Why are they important?
Medications such as beta-agonists nitrates and calcium channel blockers are used to treat conditions like asthma and hypertension as they promote bronchodilation or vasodilation respectively.
Discuss the importance of maintaining a balance of sodium and potassium in the body.
Maintaining a balance of sodium and potassium is essential for proper cellular function electrolyte balance muscle contraction and maintaining fluid levels influencing overall blood pressure and heart function.
