Term
|
Definition
Mannitol
Glycerin
Urea
(Isosorbide) |
|
|
Term
Osmotic
Diuretics
MOA
Effects |
|
Definition
Loop of Henle: washout of NaCl & urea
Proximal tubule: osmotic effect
interfere w/ ability of kidney to [ ] urine
Effects:
Expand extracellular fluid volume (including plasma)
Increase excretion of Na+, K+, Ca2+, Mg2+,HCO3-, H2PO4-
Increase renal blood flow
Moderate diuresis (~5% FENa) |
|
|
Term
Osmotic
Diuretics
Toxicity/ ADR |
|
Definition
Heart failure, pulmonary congestion
Mannitol: cranial bleeding |
|
|
Term
Carbonic
Anhydrase
Inhibitor
Agents |
|
Definition
Acetazolamide
Dichlorphenamide
Methazolamide
Dorzolamide,
brinzolamide
(topical for glaucoma) |
|
|
Term
Carbonic Anhydrase Inhibitors
Uses
|
|
Definition
Glaucoma
Acute Mountain Sickness
Prophylaxis and treatment
Decreases CSF formation
Decreases pH of CSF àincreased ventilation
Alkalosis from increased H+ excretion (diuretics)
Urinary alkalinization Absence seizures
↑ excretion HCO3 , Na, K, H2PO4
diuresis moderate |
|
|
Term
Carbonic Anhydrase Inhibitor
Toxicities |
|
Definition
Metabolic acidosis
Stones
Potassium wasting
Contraindicated in hepatic cirrhosis
(decreases NH4+ excretion)
Hypersensitivity reactions
|
|
|
Term
|
Definition
Furosemide
Bumetanide
Torsemide
Ethacrynic acid
Site: Thick Ascending Limb
Mechanism: Inhibit Na+-K+-2Cl-symporter
requires transport by organic anion transporter
↑ excretion of Na, K, H, Ca, Mg, Cl
diuresis profound |
|
|
Term
|
Definition
Acute pulmonary edema
Hyperkalemia, hypercalcemia
Congestive heart failure (venous capacitance)
Acute renal failure
Hypertension
|
|
|
Term
Loop Diuretics
Pharmacokinetics |
|
Definition
All: highly protein bound, tubular secretion
Furosemide: elimination by kidneys, t1/2 ~1hr
Bumetanide: hepatic and renal elimination , t1/2 ~1hr
Torsemide: hepatic and renal elimination , t1/2 ~3.5 hr
Ethacrynic acid: hepatic and renal elimination ,
t1/2 ~1hr |
|
|
Term
Loop
Diuretics
Toxicities/ ADR |
|
Definition
Depletion of Na+, loss of ECF volume, circulatory collapse
Hypokalemia, hypomagnesemia, hypocalcemia
Increase LDL and triglycerides, decrease HDL
(effect on lipids less than thiazides)
Hyperglycemia, precipitate diabetes
(less than thiazides)
Hyperuricemia
Ototoxicity (especially ethacrynic acid)
Hypersenstivity: furosemide and bumetamide |
|
|
Term
Thiazides
thiazide-like
Diuretics
Agents
Site / MOA |
|
Definition
Chlorothiazide,
Hydrochlorothiazide
Chlorthalidone
Indapamide
Metolazone
↑ excretion of Na, K, H, HCO3, Cl, H2PO4
Site: Distal convoluted tubule
Mechanism: Inhibit Na+-Cl-symporter
requires transport by organic anion transporter |
|
|
Term
Thiazide Diuretics
Uses &
Toxicities/ ADR |
|
Definition
Edema
Hypertension
Toxicity/Adverse Effects:
Hyperuricemia (chronic use)
Hypokalemic metabolic alkalosis
Hyponatremia
Increased LDL, total cholesterol, triglycerides
(tend to normalize w/ chronic use)
Decreased insulin secretion, impaired glucose tolerance
Hypersensitivity reactions (rare)
Erectile dysfunction |
|
|
Term
K sparing:
Mineralocorticoid Antagonists
Agents
Site / MOA |
|
Definition
Spironolactone
Eplerenone
Site: late distsal tubule & collecting duct
Antagonist for aldosterone rp
↑ excretion of Na, Cl
↓ excretions of K, H, Ca, Mg |
|
|
Term
K sparing
Mineralocorticoid Antagonists
Uses / Toxicities |
|
Definition
in combination with loop or
thiazide to maintain Plasma K+
Hyperaldosteronism
Edema from hepatic cirrhosis
Toxicity/Adverse Effects:
Hyperkalemia
Spironolactone: gynecomastia, impotence, decreased libido, hirsutism, etc.
Spironolactone: diarrhea, gastritis, gastric bleeding, peptic ulcers (contraindication)
Eplerenone: GI
Eplerenone: interaction with CYP3A4 inhibitors |
|
|
Term
K sparing Diuretics
ENaC Inhibitors
Agents
Site / MOA |
|
Definition
Triamterene
Amiloride
Site: Late distal tubule and early collecting duct
Mechanism: Inhibit Epithelial Na+Channel
(this prevents activation of K+ secretion)
↑ excretion of Na, Cl
↓ excretion of K, H, Ca, Mg
Mild diuresis |
|
|
Term
K sparing Diuretics
ENaC Inhibitors
Uses
Toxicities / MOA |
|
Definition
In combination with loop or thiazide to maintain plasma K+
Hypertension due to polymorphism of ENaC
Cystic fibrosis: aerosol
Toxicity/Adverse Effects:
Hyperkalemia: ACE Inhibitors, NSAIDs
Triamterene: impaired glucose tolerance
Both: CNS, GI, musculoskeletal effects |
|
|
Term
Antidiuretic
Hormone
Antagonist
Agent/ site / MOA |
|
Definition
Conivaptan
Tolvaptan
Site: Collecting duct
Mechanism: Antagonize Antidiuretic Hormone
(ADH, aka arginine vasopressin) at V2 receptor
↑ excretion of H2O
↑ Urine output
↓ urine osmolality
|
|
|
Term
Antidiuretic Hormone Antagonist
Uses / Toxicities / MOA |
|
Definition
Hyponatremia (hyper~ or euvolemic)
Clinically significant
SIADH, cirrhosis, heart failure (tolvaptan)
Toxicity/Adverse Effects
CYP3A4: use with strong inhibitors contraindicated
Conivaptan: strong inhibitor of CYP3A4
Neurologic sequelae from rapid correction of sodium
Dehydration, hypovolemia
Hyperkalemia with K+ sparing drugs (tolvaptan)
Hyperglycemia |
|
|
Term
RAS
4 ways to decrease the activity
of AT II |
|
Definition
(1) inhibit the release of renin (b-blockers)
(2) inhibit the activity of renin
(3) inhibit the formation of AT-II by ACE
(4) block the AT1 receptors for AT-II. |
|
|
Term
Renin
Inhibitor
Aliskiren |
|
Definition
¯ PVR and ¯ blood pressure
increase renal blood flow
¯ secretion of aldosterone
preserve potassium
¯ stimulation of AT2 receptors
Does not effect::
Angiotensin (1-7)
renin activity
kinins |
|
|
Term
|
Definition
Captopril (active form with an active metabolite)
Enalapril (ester prodrug)/Enalaprilat (active metabolite)
Lisinopril (active form is excreted) |
|
|
Term
Competitive AT 1
Antagonists
ARBs
|
|
Definition
Losartan,
Irbesartan,
Valsartan |
|
|
Term
Therapeutic
Applications
RAS Drugs |
|
Definition
Hypertension
–do not trigger reflex tachycardia
–very effective when combined with a diuretic
–can be effective even with low renin
Congestive Heart Failure
–improved hemodynamics
–slows hypertrophy/remodeling
–improved left ventricular systolic function
Myocardial Infarction
–prevent excessive remodeling of cardiac tissue
–begin immediately after an infarction
Slowing of diabetic nephropathy |
|
|
Term
|
Definition
severe hypotension, including postural hypotension, in patients who are hypo-volemic, salt-depleted, or have CHF (especially with the first dose)
hyperkalemia in patients with impaired renal function or when combined with potassium-sparing diuretics
problems associated with kinins (ACE inhibitors only)
–cough, angioedema
fetopathic after first trimester of pregnancy
can induce acute renal failure in a patient with bilateral renal artery stenosis |
|
|
Term
Two
Major Systems that regulate
Blood
Pressure |
|
Definition
SNS
Sympathatic Nervous System
RAS
Renin Angiotensin System |
|
|
Term
When the SNS is activated,
NE (the sympathetic neurotransmitter)
is released from sympathetic nerve terminals and
stimulates: |
|
Definition
4beta1 receptors in the heart to
increase HR and contractility
4beta1 receptors in the kidney to
activate the RAS
4alpha1 receptors in the vasculature to
cause vasoconstriction (á TPR) |
|
|
Term
|
Definition
nonselective (block beta1 and beta2 receptors)
propranolol,
timolol,
nadolol,
carteolol,
penbutalol
and pindolol
“cardioselective” (block only beta1)
metoprolol,
atenolol,
acebutolol,
betaxolol,
bisoprolol
and esmolol; (used i.v. only)
intrinsic sympathomimetic activity (ISA; weak partial agonist activity) pindolol, penbutalol,
carteolol, acebutolol |
|
|
Term
|
Definition
4Decrease CO by decreasing chronotropy and inotropy
(â HR and â SV)
4Inhibit the RAS by blocking renal beta1 receptors |
|
|
Term
|
Definition
maculopapular rash due to captopril (free sulfhydryl); less common with pro-drug ACE inhibitors
Fever
Dry cough results from inhibition of BK metabolism in the lung;
Angioedema (mediated by BK); can be fatal
Hypotension (first-dose effect); especially in high renin patients
Orthostatic (postural) hypotension (more common when used in combination with diuretic |
|
|
Term
|
Definition
Constipation
Headache
Dizziness
Edema
Fatigue
Bradycardia (especially verapamil and diltiazem)
AV block (especially verapamil)
Contraindications:
4CHF (especially verapamil due to cardiac depressant effect; negative inotrope)
4SA or AV bradyarrhythmias (verapamil and Diltiazem)
4SA or AV tachyarrhythmias (nifedipine-like) |
|
|
Term
|
Definition
First-dose hypotension, especially in high renin patients and when given with diuretics (like ACE inhibitors)
Contraindicated in pregnancy
Better tolerated than ACE inhibitors due to preservation of the BK degredation pathway (ACE-mediated)
4 less cough
4less angioedema |
|
|
Term
|
Definition
|
|
Term
Two Drugs
used for
Hypertensive Crisis |
|
Definition
Fenoldopam
i.v. only
A selective Dopamine DA1 agonist; dilates arterioles
Causes renal vasodilation
Also dilates mesenteric and cerebral vascular beds, and lowers BP
Increases RBF while lowering BP unlike other vasodilators
Most useful in patients with renal insufficiency
Diazoxide
i.v. for hypertensive emergencies
Potassium channel opener; dilates arterioles
Produces reflex activation of SNS
(á HR and edema due to RAS activation) |
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|
