-
A SBP <120 and a DBP <80 is considered what BP Classification?
1. Normal
-
A SBP 120-135 and a DBP 80-89 is considered what BP Classification?
1. Prehypertension
-
A SBP 140-159 and a DBP 90-99 is considered what BP Classification?
1. Stage I Hypertension
-
A SBP >160 and a DBP >100 is considered what BP Classification?
1. Stage II Hypertension
-
A SBP greater than or equal to 140 and a DBP greater than or equal to 90 is classified as what?
1. Hypertension
-
Normal BP is what?
1. A SBP <120 and a DBP <80
-
Prehypertension is what?
1. A SBP 120-135 and a DBP 80-89
-
Stage I Hypertension is what?
1. A SBP 140-159 and a DBP 90-99
-
-
1. A SBP greater than or equal to 140 and a DBP greater than or equal to 90
-
Heart Rate x Stroke Volume equals what?
1. Cardiac Output
-
Cardiac Output is equal to what?
1. Heart Rate x Stroke Volume
-
End Diastolic Volume - End Systolic Volume equals what?
1. Stroke Volume
-
What is stroke volume influenced by?
- 1. Preload
- 2. Contractility
- 3. Afterload
-
Cardiac Output x Stroke Volume is equal to what?
1. Blood Pressure
-
What is determined by viscosity and vessel length an diameter?
1. Resistance
-
BP is maintained in a moment-to-moment fashion. As these moments add up, the risk of what can occur?
1. End organ damage increases exponentially
-
What percentage of patients can a specific cause of hypertension be established in?
1. 10-15 %
-
Patients in whom no specific cause of hypertension can be found are said to have what?
1. Essential or primary hypertension (The majority of patients are this)
-
Patients with a specific etiology are said to have what?
1. Primary Hypertension
-
Carbonic Anhydrase Inhibitors, Loop, Thiazide, K+ Sparing are all considered what?
1. Diuretics
-
Examples of Diuretics are (list them)?
- 1. Carbonic Anhydrase Inhibitors
- 2 Loop
- 3. Thiazide
- 4. K+ Sparing
-
Examples of Sympathoplegics are what (list them)?
- 1. Centrally Acting
- 2. Ganglion-blocking,
- 3. Alpha and Beta Adrenoreceptor Antagonists
-
Centrally Acting, Ganglion-Blocking, α and β Adrenoreceptor Antagonists are considered what?
1. Sympathoplegics
-
Examples of Vasodilators are what (list them)?
1. Direct and Ca++ Channel Blockers
-
Direct and Ca++ Channel Blockers are considered what?
1. Vasodiators
-
Angiotensin Production / Action Blocking Agents
-
What will lower blood pressure by depleting the body of sodium and reducing blood volume and perhaps by other mechanisms.
1. Diuretics
-
Diuretics will do what?
1. Lower blood pressure by depleting the body of sodium and reducing blood volume and perhaps by other mechanisms.
-
What will lower blood pressure by reducing peripheral vascular resistance, inhibiting cardiac function, and increasing venous pooling in capacitance vessels. These agents are further subdivided according to their putative sites of action in the sympathetic reflex arc.
1. Sympathoplegic Agents.
-
Sympathoplegic Agents will do what?
- 1. lower blood pressure by reducing peripheral vascular resistance,
- 2. which will nhibiting cardiac function, (This effect may reduce cardiac output)
- 3. and increasing venous pooling in capacitance vessel (This effect may reduce cardiac output)
-
Direct Vasodilators will do what?
1. reduce pressure by relaxing vascular smooth muscle, thus dilating resistance and-to varying degrees - increasing capacitance as well
-
What will reduce pressure by relaxing vascular smooth muscle, thus dilating resistance and-to varying degrees - increasing capacitance as well?
1. Direct Vasodilators
-
Agents that block production of action of angiotensin will do what?
1. Reduce peripheral vascular resistance and (potentially) blood volume
-
Sites of Action of the major classes of Anti-Hypertensive Drugs; What acts on the Sympathetic nerve terminals?
- 1. Guanethidine
- 2. Guanadrel
- 3. Reserpine
-
Sites of Action of the major classes of Anti-Hypertensive Drugs; What acts on the Beta Receptors of the Heart?
- 1. Propranolol and other
- 2. Beta Blockers
-
Sites of Action of the major classes of Anti-Hypertensive Drugs; What acts on the Angiotensin receptors of vessels?
- 1. Losartan and other
- 2. Angiotensin Receptor Blockers
-
Sites of Action of the major classes of Anti-Hypertensive Drugs; What acts on the Alpha Receptor of Vessels?
- 1. Praxosin and other
- 2. Alpha 1 blockers
-
Sites of Action of the major classes of Anti-Hypertensive Drugs; What acts on the Kidney tubules?
1. Thiazides, etc
-
Sites of Action of the major classes of Anti-Hypertensive Drugs; What acts on the Beta Receptors of juxtaglomerular cells that release renin?
- 1. Proparanolol and other
- 2. Beta Blockers
-
Sites of Action of the major classes of Anti-Hypertensive Drugs; What acts on the Vascular smooth muscle?
- 1. Hydralazine
- 2. Minoxidil
- 3. Nitroprusside
- 4. Diazoxide
- 5. Verapamil and other Calcium channel Blockers
- 6. Fenoldopam
-
Sites of Action of the major classes of Anti-Hypertensive Drugs; What acts on the Sympathetic Ganglia?
1. Trimethaphan
-
Sites of Action of the major classes of Anti-Hypertensive Drugs; What acts on the Vasomotor center?
- 1. Methyldopa
- 2. Clonidine
- 3. Guanabenz
- 4. Guanfacine
-
Sites of Action of the major classes of Anti-Hypertensive Drugs; What acts on the area after Angiotension I and before Angiotension II?
- 1. Captopril and other
- 2. ACE Inhibitors
-
When treating elevated arterial blood pressure what is manipulated?
- 1. Cardiac Output
- 2. Heart Rate
- 3. Circulating fluid Volume
- 4. Peripheral vascular resistance
- 5. and Renin Activity
-
Without Compelling Indication what are the considerations for initial pharmacological therapy for category Normal?
1. No Antihypertensive drug indicated for Category Normal
-
Without Compelling Indication what are the considerations for initial pharmacological therapy for category Pre-Hypertension?
1. No Antihypertensive drug indicated for Category Pre-hypertension
-
Without Compelling Indication what are the considerations for initial pharmacological therapy for category Stage 1 Hypertension?
- 1. Thiazide-type diuretic for most
- 2. May consider ACE Inhibitor,
- 3. ARB,
- 4. BB,
- 5. CCB or
- 6. combination of above
-
Without Compelling Indication what are the considerations for initial pharmacological therapy for category Stage 2 Hypertension?
- 1. 2-drug combination for most
- 2. Usually thiazide-type diuretic OR
- 3. ACE Inhibitor, ARB, BB OR
- 4. CCB
-
WITH Compelling Indication what are the considerations for initial pharmacological therapy for category Normal?
1. Drugs for Compelling indications
-
WITH Compelling Indication what are the considerations for initial pharmacological therapy for category Pre-Hypertension?
1. Drugs for Compelling Indications
-
WITH Compelling Indication what are the considerations for initial pharmacological therapy for category Stage 1 Hypertension?
1.Drugs for Compelling Indications, Other antihypertensive drugs (diuretic, ACE inhibitor, ARB, BB, CCB) as needed
-
WITH Compelling Indication what are the considerations for initial pharmacological therapy for category Stage 2 Hypertension?
1. Drugs for Compelling Indications, Other antihypertensive drugs (diuretic, ACE inhibitor, ARB, BB, CCB) as needed
-
Pharmacologic treatments for hypertension include what?
- 1. Diuretic
- 2. Sympathoplegics - Central Acting
- 3. Sympathathetic Nerve Terminal Blockers
- 4. Alpha Blockers
- 5. Beta Blockers
- 6. Calcium Channel Blockers
- 7. Parenteral Vasodilators
- 8. RAAS - ACE, ARB, Renin Inhibitors
-
The purpose for using Diuretics to treat Hypertension is what?
1. Increase volume of urine
-
What is the difference between a Diuretic and Natriuretic?
- 1. Diuretic - Increases urine Volume
- 2. Natriuretic - Increases renal Na+ excretion
-
Name the sub classes of Diuretics.
- 1. Carbonic Anhydrase Inhibitors
- 2. Loop
- 3. Thiazides
- 4. K+ Sparing
- 5. Osmotics?
-
When using Diuretics to treat hypertension what are the effects?
- 1. A Decrease of Blood Pressure by 10 - 15 mm Hg
- 2. Thiazide - do NOT see greater results with higher doses
- 3. Loop - DO see greater results with higher doses
-
When using Diuretics to treat hypertension what are the Side Effects?
- 1. K+ loss (except for potassium sparing)
- 2. Mg+ loss
- 3. Increase lipid concentrations
- 4. Impaired glucose tolerance
-
When using Diuretics to treat hypertension what are the CONTRAINDICATIONS?
- 1. Use Caution with Diabetes due to impaired glucose tolerance
- 2. Hyperlipidemia due to the increase lipid concentrations
- 3. Gout
- 4. Renal Insuficiency
- 5. Beware of Drug interactions: Digitalis, ACE
-
Functions of the segment of the nephron Glomerulus are:
- 1. Formation of glomerular filtrate
- 2. water permeability in the Glomerulus is Extremely High
-
Functions of the segment of the nephron Proximal convoluted tubule (PCT) are:
- 1. Reabsorption of 65% of filtered Na+/K+/CA2+ and Mg+
- 2. 85% of NaHCO3, and
- 3. Nearly 100% of glucose and amino acids.
- 4. Isosmotic reabsorption of water
- 5. Water permeability in the Proximal convoluted tubule (PCT) is very high
-
Functions of the segment of the nephron Proximal tubule, straight segment are:
- 1. Secretion and reabsorption of organic acids and bases
- 2. including uric acid and most diuretics
- 3. Water permeability in the Proximal tubule, straight segment is very high
-
Functions of the segment of the nephron Thin descending limb of Henle's Loop are:
- 1. Passive reabsorption of water
- 2. Water permeability in the Descending limb of Henle's loop is High
-
Functions of the segment of the nephron Thick ascending limb of Henle's Loop (TAL) are:
- 1. Active reabsorption of 15-25% of filtered Na+/K+/Cl-
- 2. Secondary reabsorption of Ca2+ and Mg+
- 3. Water permeability in the Thick ascending limb of Henle's Loop (TAL) is Very Low
-
Functions of the segment of the nephron Distal Convoluted Tubule (DCT) are;
- 1. Active reabsorption of 4-8% of filtered Na+ and Cl-
- 2. Ca2+ reabsorption under parathyroid hormone control
- 3. Water permeability in the Distal Convoluted Tubule (DCT) is very low
-
Functions of the segment of the nephron Cortical Collecting tubule (CCT) are:
- 1. Na+ reabsorption (2-5%) coupled to K+ and H+ secreation
- 2. Water permeability in the Cortical Collecting tubule (CCT) is variable
-
Functions of the segment of the nephron Medullary collecting duct are;
- 1. Water reabsorption under vasopressin control
- 2. Water permeability in the Medullary collecting duct is variable
-
Name the Diuretic (s) that have a major action at the segment of the nephron Glomerulus:
1. None - Glomerulus
-
Name the Diuretic (s) that have a major action at the segment of the nephron Proximal Convoluted Tubule (PCT):
- 1. Carbonic Anhydrase Inhibitors
- 2. Adenosine Antagonists (under investigation)
- 3. Proximal Convoluted Tubule (PCT)
-
Name the Diuretic (s) that have a major action at the segment of the nephron Proximal Tubule, straight segments;
1. None - Proximal Tubule, straight segments
-
Name the Diuretic (s) that have a major action at the segment of the nephron Thin Descending limb of Henle's loop:
1. None - Thin Descending limb of Henle's loop
-
Name the Diuretic (s) that have a major action at the segment of the nephron Thick ascending limb of Henle's Loop (TAL):
1. Loop Diuretics - Thick ascending limb of Henle's Loop (TAL)
-
Name the Diuretic (s) that have a major action at the segment of the nephron Distal Convoluted Tubule (DCT)
1. Thiazides - Distal Convoluted Tubule (DCT)
-
Name the Diuretic (s) that have a major action at the segment of the nephron Cortical Collecting Tubule (CCT):
- 1. K+ sparing Diuretics
- 2. Adenosine Antagonists (Under Investigation)
- 3. Cortical Collecting Tubule (CCT)
-
Name the Diuretic (s) that have a major action at the segment of the nephron Medullary Collecting Duct:
1. Vasopressin Antagonists - Medullary Collecting Duct
-
What segment of the nephron is the site for formation of glomerular filtrate, is highly permeable to water, has no transporters and no clinical site of action for diuretics?
1. Glomerulus
-
What is the Renal Tubule Transport Mechanisms for the Proximal Convoluted Tubule (PCT):
- 1. NaHCO3, NaCl, glucose, AAs reabsorbed via specific transport systems in proximal convoluted tubule (PCT).
- 2. K+ reabsorbed via paracellular pathway
- 3. Water reabsorbed passively
-
Proximal Convoluted Tubule (PCT) Reabsorption is:
- 1. Na+ 66%
- 2. NaHCO3 85%
- 3. K+ 65%
- 4. H2O 60%
- 5. Glucose 100%
- 6. Amino Acids 100%
-
In the Proximal Convoluted Tubule (PCT) the Na+H+ exchanger (NHE3) initiates what?
1. NaHCo3 reabsorption
-
In the Proximal Convoluted Tubule (PCT) Carbonic Anhydrase activity drives what?
- 1. HCO3 reabsorption
- 2. If blocked, no exchange of Na+ for H+, thus lose NA+ and thus more urine is produced
- 3. Site of action for CAIs (acetazolamide)
-
What is located in the outer medulla and composed of Thin Descending (dl), Thin Ascending (al), and the Thick ascending limbs (TAL)
1. Loop of Henle
-
The Thin Descending limb of Henle's loop has
1. Water extracted from Thin descending (dl) by osmosis d/t hypertonic medullary intertitium
-
Which segment of Loop of Henle is impermeable to water?
1. Thin ascending limb of Henles loop
-
Thick ascending limb of Henle's Loop (TAL):
- 1. Actively reabsorbs c. 25% of filtered NaCl from lumen, but nearly impermeable to water.
- 2. Na+K+2Cl- cotransporter (NKCC2)
-
The site of action for Loop diuretics is what?
1. Thick ascending limb of Henle's Loop (TAL):
-
What is selectively blocked by loop diuretics at the Thick ascending limb of Henle's Loop (TAL):
1. NKCC2
-
About 10% of filtered NaCl is reabsorbed where?
1. Distal Convoluted Tubule (DCT)
-
Distal Convoluted Tubule (DCT) is relatively impermeable to water, thus the reabsorption of NaCl will do what?
1. Further dilutes the tubular fluid
-
Distal Convoluted Tubule (DCT) is the site of action for what?
- 1. Thiazide Diuretics
- 2. NaCl transporter: Na+ and Cl- cotransporter (NCC)
- 3. NCC Blocked by thiazide diuretics
-
Collecting Tubule System does connects what and is composed of what?
- 1. Connects DCT to the renal pelvis and ureter.
- 2. Composed of connecting tubule, collecting tubule, and collecting duct (formed from connection of 2 collecting tubules).
-
Only 2-5% of NaCl reabsorption occurs here:
1. Collecting tubule system
-
The 2 cell types responsible for ion transport in the Collecting Tubule System
- 1. Principal cells: Na+, K+ and Water
- 2. Intercalated cells; H+ and HCO3- secretion
-
Collecting tubule System Transport Mechanisms:
- 1. Principal cells = epithelial Na+ channel (ENaC).
- 2. Intercalated cells = H+ATPase and Cl/HCO3- exchanger
-
Site of action for K+ sparing Diuretics is what?
1. Cortical Collecting Tubule (CCT)
-
What is Carbonic Anhydrase Inhibitor's mechanism of Action?
1. Blocks dehydrogenation of carbonic acid in PCT > Sodium Bicarb secretion > diuresis
-
What are the indications for carbonic Anhydrase Inhibitor?
- 1. Urinary Alkalinization - weak acid OD, Pure uric acid stones, hemoglobinuria (heat stroke)
- 2. Glaucoma
- 3. Acute Mountain sickness
- 4. Metabolic Alkalosis
-
Urinary Alkalinization, Glaucoma, Acute Mountain Sickness and Metabolic alkalosis are all indications for what?
1. Carbonic Anhydrase Inhibitor
-
What is a Carbonic Anhydrase Inhibitor Drug Name?
1. Acetazolamide (Diamox)
-
Pharmacokinetics of Carbonic Anhydrase Inhibitor include what?
- 1. Onset diuresis 30 min
- 2. Peaks in 2 hours
- 3. Half life 10-15 hours
-
Side Effects of Carbonic Anhydrase Inhibitor are what?
- 1. Drowsiness
- 2. Anorexia
- 3. Paresthesias
-
Cautions / contraindications for carbonic Anhydrase Inhibitor include what?
- 1. Calcium Calculi
- 2. Acidosis
- 3. Renal Potassium wasting
- 4. Cirrhosis (decreased NH4 excretion)
-
The mechanism of action for Loop Diuretics is what?
- 1. Blocks reabsorption of NaCl in the Thick ascending limb of Henle's Loop (TAL) by interfering with Na/K/CL transporter
- - 25% of Na reabsorption occurs in TAL
- - Interfering with K+ recycling > Ca++ and Mg++ excretion
- - Encourages prostaglandin synthesis > PGE2 inhibits salt transport > diuresis >
-
Clinical Indications for Loop diuretics include?
- 1. Edema
- 2. Hypercalcemia
- 3. acute renal failure
- 4 Hyperkalemia
- 5. Anion Over Dose
-
Bumetanide, Furosemide, torsemide, ethacrynic acid are drug names for what?
1. Loop diuretics
-
What are some drug names for loop diuretics?
- 1. Bumetanide
- 2. Furosemide
- 3. torsemide
- 4. ethacrynic acid
-
Pharmacokinetics of Loop Diuretics include what?
- 1. Onset and clearance depend on delivery method and renal function
- 2. Rapidly absorbed and not inhibited by acidosis
-
Cautions / Contraindications for Loop Diuretics include What?
- 1. slight chance of hypersensitivity with sulfa allergy
- 2. Hyperuricemia
- 3. Ototoxicity (concurrent use of aminoglycosides)
- 4. Hypomagnesemia / Hypokalemic Metabolic Alkalosis
-
Usual dosing for Loop Diuretics are dependent upon what?
1. delivery method and renal function
-
What are the Side effects for Loop diuretics?
- 1. Dizziness
- 2. Photosensitivity
- 3. Orthostatic Hypotension
-
The mechanism of action for Thiazides include what?
- 1. Block Reabsorption of NaCl in DCT
- 2. Enhance Ca2+
- 3. Compete with uric acid secretion in PCT
-
What are the clinical indications for Thiazides?
- 1. Hypertension
- 2. Heart Failure
- 3. Calculi - Hypercalciuria
- 4. Nephrogenic diabetes insipidus
-
Hypertension, Heart Failure, Calculi - Hypercalciuria, and Nephrogenic diabetes insipidus are all indications for what diuretic?
1. Thiazides
-
What are some drug names for Thiazides?
- 1. HCTZ
- 2. Chlorothiazide
- 3. Chlorthalidone et al
-
What is the usual dosing for Thiazides?
1. The usual dosing for Thiazides is oral HCTZ 12.5mg - 100mg PO
-
What are the side effects of Thiazides?
- 1. Orthostatic Hypotension
- 2. Photosensitivity
- 3. Electrolyte imbalance
-
Orthostatic Hypotension, Photosensitity, electrolyte imbalance are all side effects for what drug?
1. Thiazides
-
What is the Pharmacokinetics for Thiazides?
- 1. HCTZ - Onset 2 hours Peak 4-6 Duration 6-12 hours
- May take up to 3 weeks to see full effect with initial treatment
- 2. Chlorthalidone - Onset 2 hours duration up to 72 hours
-
Cautions / Contrindications for Thiazides are what?
- 1. Hypomagnesemia / Hypokalemic Metabolic Alkalosis
- 2. Slight chance of hypersensitivity with Sulfa Allergy
- 3. Hyperuricemia
- 4. Hyperglycemia / hyperlipidemia
-
The mechanism of action for Potassium Sparing Diuretics include what?
- 1. Prevent K+ secretion by opposing aldosterone in DCT
- Antagonism of mineralcorticoid receptors or block Na influx
-
What are the clinical indications for Potassium Sparing Diuretics?
- 1. Hypertension
- 2. Hyperaldosteronism primary or secondary
- 3. Edema
-
Hypertension, Hyperaldosteronism, and edema are all clinical indications for what diuretic drug?
1. Potassium Sparing Diuretics
-
What are some drug names for Potassium Sparing Diuretics?
- 1. Spironolactone
- 2. Triamterene
- 3. Amiloride
- 4. Eplerenone
-
What are the usual dosing for Potassium Sparing Diuretics?
- 1. Can use in combination with Thiazide
- 2. Spironolactone, Amiloride and triamterene have black box warnings
-
What are some side effects for Potassium Sparing Diuretics?
- 1. Hyperkalemia
- 2. gynecomastia
- 3. N / D
- 4. Sexual Dysfunction
- 5. rénal calculi (triamterene)
-
Hyperkalemia, gynecomastia, N / D, Sexual Dysfunction and rénal calculi (triamterene) are side effects of what diuretic?
1. Potassium Sparing Diuretics
-
What is the Pharmacokinetics of Potassium Sparing Diuretics?
1. Mechanism of action dependent
-
What are some contraindications / cautions for Potassium Sparing Diuretics?
- 1. Concomitant use of Beta Blockers, ACE
- 2. Hepatic Impairment
- 3. NO K+ supplementaiton
-
What is the mechanism of action for Osmotic Diuretics?
- 1. Proximal and descending Loop of Henle
- 2. Osmotic flow after filtration in the glomerulus
-
What are the clinical indications for Osmotic Diuretics?
- 1. Water > Na excretion
- Hemolysis, rhabdomyolysis
- 2. Decrease Intracellular volume
-
What is a drug name for Osmotic Diuretics?
1. Mannitol (parental only)
-
What is the usual dosing for Osmotic Diuretics?
1. 12.5-25g IV
-
Side effects for osmotic diuretics are what?
- 1. Headache
- 2. N/V
- 3. Dizziness
-
What are the Pharmacokinetics for Osmotic Diuretics?
1. Poor GI Absorption - osmotic diarrhea
-
What are some cautions / contraindications for Osmotic diuretics?
- 1. Initial Extracellular Volume Expansion
- 2. Dehydration,
- 3. hyperkalemia,
- 4. hyper/hyponatremia
-
What are some considerations with diuretics?
- 1. Most renal diseases cause retention of Na and water
- 2. Cirrhotic conditions are not greatly impacted by loop diuretics but are responsive to Spironolactone and Eplerenone
- 3. 80% of renal calculi contain calcium
- 4. Heart failure treatment is a balance between stimulating cardiac output with adequate filling pressure and decreasing the fluid volume load
-
Diuretic Toxicity (slide 41)
- 1. Diuretic toxicity is related to the differing mechanisms of action and clinical indications.
- 2. Hint: Pay attention to the ion exchange, tranport, and cotransport mechanisms (Figures 15-2, 3, 4, 5, p. 253-254)
-
Discuss some of the Diuretic uses for Carbonic Anhydrase Inhibitors:
- 1. Glaucoma (reduces aqueous humor formation)
- 2. Urinary Alkalinazation for cystinuria (Increases urinary pH from 7.0 to 7.5 and increases cystine reabsorption)
- 3. Metabolic Alkalosis, esp. in CHF pts (due to excessive diuresis, volume replacement contraindicated, aczetaloamide used to correct alkalosis and add additional diuresis
- 4. Acute Mtn Sickness (Mild S&S- weakness, dizziness, insomnia, HA. Serious S&S- pulm or cerebral edema. CAIs decrease CSF formation and pH, thus causing increase ventilation, diminish symptoms of sickness.
-
When a Carbonic Anhydrase Inhibitor is used to treat Glaucoma what are the expected results
1. Reduces aqueous humor formation
-
When a Carbonic Anhydrase Inhibitor is used to treat Urinary Alkalinazation for cystinuria what are the expected results
1. Increases urinary pH from 7.0 to 7.5 and increases cystine reabsorption
-
When a Carbonic Anhydrase Inhibitor is used to treat Metabolic Alkalosis, esp. in CHF pts, what are the expected results
1. due to excessive diuresis, volume replacement contraindicated, aczetaloamide used to correct alkalosis and add additional diuresis
-
When a Carbonic Anhydrase Inhibitor is used to treat Acute Mtn Sickness what are the expected results
1. Mild S&S- weakness, dizziness, insomnia, HA. Serious S&S- pulm or cerebral edema. CAIs decrease CSF formation and pH, thus causing increase ventilation, diminish symptoms of sickness.
-
Discuss Diuretic Toxicity for Carbonic Anhydrase Inhibitors for the following conditions: Hyperchloremic Metabolic Acidosis, Renal stones and renal K+ wasting:
- 1. Hyperchloremic Metabolic Acidosis: Results from chronic loss of HCO3-
- 2. Renal Stones: Calcium salts insoluble with relatively alkaline pH, thus increased risk of renal stones
- 3. Renal K+ wasting: occurs secondary to increased Na+ and HCO3- delivered to collecting tubule- Na+ reabsorbed and K+ secreted
-
Discuss the diuretic uses for Loop:
- 1. Primary- Acute Pulmonary Edema, other edema, Hypercalcemia.
- 2. Hyperkalemia (increase urinary excretion of K+)
- 3. Acute Renal Failure (increase rate of urine flow and K+ excretion)
- 4. Anion Overdose (tx toxic ingestion of substances reabsorbed in TAL- bromide, fluoride, iodide, etc. Must be used with Saline to offset Na+ loss)
-
Discuss slide 45 Diuretic Toxicity: Loop
- 1. Hypokalemic Metabolic Alkalosis: Inhibits NaCl reabsorption leads to increased NaCl delivered to collecting duct, thus increased secretion of K+ and H+.
- 2. Ototoxicty: Dose-related hearing loss, usually reversible. Worsened with other ototoxic agents (aminoglycosides, etc.)
- 3. Hyperuricemia: Hypovolemia induced gout from increased uric acid reabsorption in proximal tubule. Prevent by using low dose loop diuretics to avoid hypovolemia.
- 4. Hypomagnesemia: Results from chronic use of loop diuretics. Tx with oral magnesium supplements.
- 5. Loop diuretics except ethacrynic acid are sulfonamides. Therefore, reactions can involve Sulfa allergy S&S: skin rash, eosinophilia, interstitial nephritis.
- 6. Severe dehydration, hyponatremia, hypocalcemia and secondary parathyroidism.
-
Diuretic use for Thiazides include what?
- 1. HTN
- 2. Heart Failure
- 3. Nephrolithiasis from idiopathic hypercalcuria
- 4. Nephrogenic diabetes insipidus
-
Discuss slide 47 Diuretic Toxicity: Thiazides:
- 1. Hypokalemic Metabolic Alkalosis & Hyperuricemia (similar to loop)
- 2. Impaired CHO Tolerance d/t impaired pancreatic release of insulin and diminished tissue utilization of glucose
- 3. Hyperlipidemia: Increase of 5-15% in total serum cholesterol and LDLs.
- 4. Hyponatremia: Occurs from combination of hypovolemia-induced increase in ADH, reduced renal diluting capacity, and increased thirst.
- 5. Thiazides also sulfonamides, thus cross-reactivity. Rare- photosensitivity, dermatitis. Extremely rare- hemolyitic anemia, thrombocytopenia, and acute necrotizing pancreatitis.
-
Discuss the diuretic use of Potassium Sparing
- 1. Useful in mineralocorticoid excess or hyperaldosteronism whether primary (Conn’s syndrome, ectopic adrenocorticotropic hormone production) or secondary (heart failure, cirrhosis, nephrotic syndrome, or other conditions from decreased intravascular volume).
- 2. Used when other diuretic classes, loop and thiazide, may exacerbate secondary mineralocorticoid excess from volume contraction. Blunt the K+ secretion response.
-
Discuss diuretic Toxicity for Potassium Sparing
- 1. Hyperkalemia: Exacerbated in renal disease or by concomitant use of drugs that reduce renin (B Blockers, NSAIDS, etc.) or angiotensin II activity (ACE, ARB).
- 2. Hyperchloremic Metabolic Acidosis: Inhibited H+ secretions in parallel with K+ secretion- mimics type IV renal tubular acidosis.
- 3. Gynecomastia (impotence, BPH): Caused by spironolactone exerting steroidal effects on other receptors. Has not been reported with with eplerenone (more selective for mineralocorticoid receptors and inactive on androgen/progesterone receptors).
- 4. Acute Renal Failure: Triamterene combined with indomethacin has been reported to precipitate ARF.
- 5. Kidney Stones: Triamterene slightly soluble and precipitates in urine, leading to stones.
-
What is the purpose of Sympathoplegics - central acting?
1. Block Vasoconstriction
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What medications are considered Sympathoplegics - central acting?
1. Primarily Methyldopa and Clonidine
-
What are the mechanism of action for Sympathoplegics - central acting?
1. Impair Baroreceptor reflexes
-
What is the half life of Sympathoplegics - central acting?
- 1. Varies by drug
- 2. Methyldopa - 2 hours
- 3. Clonidine - 8-12 hours
-
What are some side effects for Sympathoplegics - central acting?
- 1. Sedation
- 2. postural hypotension
- 3. mental fog
- 4. dry mouth
-
Sympathoplegics - central acting? Slide 51
- 1. Specific MoA of Clonidine:
- 2. Lowers BP by reduction of cardiac output due to heart rate decrease, relaxation of capacitance vessels, and decrease in PVR.
- - d/t direct stimulation of α adrenoreceptors in arterioles and in the medulla of the brain and inhibits other pressor effects of αlpha agonists as a partial agonist at αlpha receptors.
- - In animals, hypotensive effect blocked by centrally acting α antagonists. Clonidine reduces sympathetic and increases parasympathetic tone- decreased BP and bradycardia.
- - Higher affinity for presynaptic α2 adrenergic receptors, thought to reduce norepinephrine release in the brain.
-
What are some contraindications / cautions for Sympathoplegics - central acting?
- 1. Depression
- 2. SLOW taper off Clonidine!
-
What are some toxicity for the use of Central Acting Sympathoplegics? CAS
- 1. Most common undesirable effect of CAS is pronounced sedation
- 2. Long term tx with CAS has been linked to the following:
- 1. Persistent mental lassitude
- 2. Impaired concentration
- 3. Nightmares, depression, vertigo.
- 4. EPS can occur, but infrequent.
- 5. Lactation in men and women from increased prolactin (associated with hypothalamic dopaminergic inhibition associated with methyldopa-
- + Coombs test for 10-20% of pts tx’d for >12 mos. Can make blood cross-matching difficult, associated with hemolytic anemia, and fever.
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The purpose of Sympathetic Nerve Terminal Blockers is what?
1. Block vasoconstriction
-
List some examples of Sympathetic Nerve Terminal Blockers:
-
What is the mechanism of action for Sympathetic Nerve Terminal Blockers?
1. Block nicotinic acetylcholine channels on sympathetic and parasympathetic ganglia
-
What are some side effects / Toxicity for Sympathetic Nerve Terminal Blockers?
- 1. Profound orthostatic hypotension
- 2. Sexual dysfunction
- 3. depression
- 4. nightmares
- 5. diarrhea
- 6. Parkinsonian extrapyramidal effects
-
What are some contraindications for Sympathetic Nerve Terminal Blockers?
1. This drug is rarely used
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What is the purpose of Beta Blockers?
- 1. Block beta receptor activity
- 2. Reduce mortality post MI, in CHF
-
What are some subclasses of Beta Blockers?
- 1. Nonselective – Propranolol
- 2. Cardioselective (non β2)– Metoprolol, Atenonlol, Esmolol
- 3. Nonselective with ISA (-TPR, mod – HR/CO)- Pindolol Acebutolol
- 4. Mixed α and β – labetalol, carvedilol and nebivolol
-
Which beta blocker is nonselective?
1. Propranolol
-
Which beta blocker is cardioselective (non beta 2)?
- 1. Metoprolol
- 2. Atenonlol
- 3. Esmolol
-
What beta blocker is nonselective with ISA?
1. Pindolol Acebutolol
-
What beta blocker is mixed alpha and beta?
- 1. Labetalol
- 2. carvedilol
- 3. nebivolol
-
What is the mechanism of action for Beta Blockers?
- 1. Negative Ionotropic effect
- 2. Negative chronotropic effect
- 3. block renin production
-
What is the half life of Beta Blockers?
1. 3-30 hours depending
-
What are some side effects of Beta Blockers?
- 1. Headach
- 2. rash
- 3. Dizziness
-
What are some contraindications / Cautions for Beta Blockers?
- 1. Arrhythmias
- 2. Nonselective beta Blocker - Asthma / COPD
- 3. Bradycardia
- 4. Severe CHF
-
What is the purpose of Alpha Blockers?
1. Vasodilation
-
What is the Benefit of Alpha Blockers?
- 1. BPH
- 2. Bladder obstruction
-
What is the mechanism of action for Alpha Blockers?
1. Block Alpha Receptor at arterioles and venues
-
What is the half life of Alpha Blockers?
1. 3-22 hours
-
What are the side effects of Alpha Blockers?
- 1. NaCl and water Retention
- 2. Orthostatic hypotension (dosing)
- 3. Dizziness
- 4. headache
-
What are some contraindications / cautions for Alpha Blockers?
1. Primarily used as adjunctive therapy (use with Beta blocker, diuretic)
-
What is the purpose of Vasodilators: Calcium Channel Blockers?
- 1. Decrease SVR
- 2. May Decrease HR, Cardiac Output
- 3. decrease Cardiac muscle oxygen demand
- 4. Works best in combination
-
What are some subclasses of Vasodilators: Calcium Channel Blockers?
- 1. Dihdropyridine - smooth muscle
- 2. Non-dihydropyridine (cardiac) Verapamil and Diltiazem
-
What is the mechanism of acton for Vasodilators: Calcium Channel Blockers?
- 1. Decrease Ca++ influx
- 2. Decrease conduction and contractility
- 3. Relaxation of arteriole smooth muscle
- 4. Sympathetic and RAAS reflexive systems intact
-
What are the side effects from Vasodilators: Calcium Channel Blockers?
- 1. Slight reflex tachycardia (with dihydropyridines)
- 2. Edema
- 3. Increase generally as dose increases
-
What are the contraindications for Vasodilators: Calcium Channel Blockers?
- 1. NO short acting
- 2. Not as single treatment
-
What is the mechanism of action for the Calcium Channel Blockers: Diltiazem?
- 1. Voltage gated L-type calcium channels in cardiac and smooth muscle
- - Composed of several subunits, chiefly a1 and a2
- - 4 variants of a1: Diltiazem and verapamil don’t occupy same receptors as dihydropyridines, but on same a1-subunit.
- - Act similarly to Na+ channel blockade by local anesthetics- Drugs act from inner side of membrane and bind more effectively to open channels and inactivated channels.
- - Drug binding reduces frequency of opening in response to depolarization.
- -Results in marked decrease in transmembrane calcium current and long-lasting relaxation in smooth muscle and decreased contractility and SA & AV nodal conduction velocity in cardiac muscle.
-
What is the purpose of Vasodilator Hydrazaline?
1. Decease PVR
-
What is the mechanism of action for the Vasodilator Hydrazaline?
1. Arteriole Dilation only
-
What are some uses for the Vasodilator Hydrazaline?
- 1. Adjunctive use with Severe HTN/CHF particularly in AA
- 2. Dose ranges from 40 mg/d to 200 mg/d, 2-3xs daily
- 3. Higher the dose – greater effect
-
What are some side effects for Vasodilator Hydrazaline?
1. SLE like syndrome with high doses (400 mg/d)
-
What are some cautions with Vasodilator Hydrazaline?
- 1. Ischemic CAD - provoke angina from reflex
- 2. Tachycardia and sympathetic stimulation
-
What is the purpose of Parental Vasodilators?
- 1. Decrease PVR
- 2. Work best in combination (Beta Blocker and Diuretics)
- 3. hypertensive emergencies
-
Name some Parental Vasodilators Drugs:
- 1. Diazoxide
- 2. Fenoldopam
- 3. Nitroprusside
-
What is the mechanism of action for Parental Vasodilators?
- 1. Relaxation of arteriole smooth muscle
- 2. Sympathetic and RAAS reflexive systems intact (Figure 11-4, page p. 174)
-
What are some cautions for Parental Vasodilators?
- 1. Reflexive tachycardia
- 2. Rapid toxicity
-
Discuss the Parental Vasodilators Sodium Nitroprusside: slide 62
- 1. Sodium Nitroprusside
- - Used for HTN emergencies and heart failure.
- -Dilates both arterial and venous vessels= reduced PVR.
- -Activates guanylyl cyclase by nitric oxide release and direct enzymatic stimulation. Increases cGMP which relaxes vascular smooth muscle.
- -Doses: 0.5 mcg/kg/min to 10 mcg/kg/min.
- -High doses can lead to cyanide toxicity.
- -Complex of iron, cyanide groups, and nitroso moiety.
- -Rapidly metabolized by RBC uptake, cyanide metabolized by rhodanase to thiocyanate, to ecf, kidneys. -High doses overwhelm this, lead to increased cyanide levels.
- -Must protect from light.
-
What is the purpose of ACE Inhibitors?
- 1. Decrease TPR
- 2. Does not stimulate reflexive tachycardia
-
Name some ACE Inhibitors: "pril"
- 1. captopril
- 2. enalapril
- 3. lisinopril
- 4. benazepril
-
What are the mechanism of action for ACE Inhibitors?
- 1. Blocks conversion of Angiotensin I into Angiotension II
- 2. Inactivates bradykinin
- 3. improves glomerular flow by decreasing resistance and pressure
-
What is the Pharmacokinetics for the ACE Inhibitor: Captopril?
- 1. (h) - 2.2 hours
- 2. Bioavailability: 65%
- 3. Initial dose: 50-75 mg/d
- 4. usual Maintenance Range: 75-150 mg/d
- 5. Reduce dose in moderate renal insuficiencey (Cr Cl < 30 ml/min)
-
What is the half life for ACE Inhibitors?
- 1. Generally about 12 hours
- 2. Excreted via kidneys
-
What are the side effects for ACE Inhibitors?
- 1. Hypotension
- 2. ARF = stenosis
- 3. Hyperkalemia (more often renal dz/diabetes)
- 4. Cough & Angioedema (bradykinin and substance P)
-
What are some contraindications / cautions for ACE Inhibitors?
- 1. Pregnancy, 1st trimester (teratogen), 2nd/3rd trimesters (fetal hypotension, anuria, renal failure, malformations, death)
- 2. Interaction with NSAIDS- Block bradykinin/prostaglandin-mediated vasodilation
-
What is the purpose of an ARB?
- 1. Prevent Vasoconstriction
- 2. Prevent Aldosterone secretion
-
What is the drug names for ARB?
- 1. "sartan"
- 2. losartan
- 3. valsartan
- 4. irbesartan, etc…
-
What is the mechanism action for ARB?
- 1. No bradykinin activity
- 2. Compete with Angiotensin II at receptor sites
- 3. Improves glomerular flow by decreasing resistance and pressure
-
What is the half life of an ARB?
- 1. Generally about 12 hours
- 2. Excreted via kidneys
-
What are the side effects of ARB?
- 1. Hypotension
- 2. ARF=stenosis
- 3. hyperkalemia
- 4. Cough - less than ACE
- 5. Angioedema - Less than ACE
-
What are some contraindications / cautions for ARB?
1. Pregnancy
-
What are the goals when treating a Hypertensive Emergencies?
- 1. Reduce BP by 25%,
- 2. NOT normalization.
- 3. Maintain DBP at no less than 100-110 mm Hg.
-
What is required when treating a patient with an Hypertensive Emergencies?
- 1. Monitoring with continuous arterial BP, Meticulous I/O, daily weights.
- 2. Parenteral antihypertensive agents (direct vasodilators- Na+ nitroprusside, Ca++ channel blockers, etc.) for rapid correction.
- 3. Initiate oral BP agents for smoother long-term management.
-
What is the initial therapy options for a compelling indication of: Heart Failure?
- 1. Thiaz
- 2. BB
- 3. ACEI
- 4. ARB
- 5. ALDO ANT
-
What is the initial therapy options for a compelling indication of: Postmyocardial Infarction?
-
What is the initial therapy options for a compelling indication of: High CAD risk?
- 1. THIAZ
- 2. BB
- 3. ACE
- 4. CCB
-
What is the initial therapy options for a compelling indication of: Diabetes?
- 1. THIAZ
- 2. BB
- 3. ACEI
- 4. ARB
- 5. CCB
-
What is the initial therapy options for a compelling indication of: Chronic Kidney Disease?
-
What is the initial therapy options for a compelling indication of: Recurrent stroke prevention?
-
Latest Evidence …. JNC 8 previews
- 1. Aggressive BP reduction to <120/80 is not beneficial
- 2. Treatment of very elderly <150/80 is not beneficial
- 3. Treatment of very elderly does prevent stroke
- 4. ACE and ARB are not recommended in combination
- 5. Combination therapy is recommended
-
Review tie it all together slide:
1. Slide 73
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