m1 diuretic agents (quiz 2)

EDEMATOUS STATES

Reduction of peripheral or pulmonary edema that has accumulated as a result of cardiac, renal, or vascular disease

HEART FAILURE (LEFTSIDED FAILURE)

most common type of heart failure

CAD (coronary artery disease)

left sided heart failure is mostly caused by __

loop diuretics

EDEMA associated with HEART FAILURE is generally managed with __

loop agents and thiazides

if salt and water retention is so severe in edema(heart failure), these are combined

Glomerular Filtration Rate

GFR

GFR 5-15 mL/min

for mild degree of renal insufficiency (___)

hyperkalemia

DIABETIC NEPHROPATHY is associated with development of __

loop or diazide diuretics

DIABETIC NEPHROPATHY

__ diuretics are frequently used

Nephrotic syndrome

Associated with primary retention of salt and water leading to expanded plasma volume and hypertension

Acetazolamide

KIDNEY DISEASE AND RENAL FAILURE

avoid ___ because it can exacerbate acidosis

spironolactone and eplerenone (K sparings)

Cirrhotic patients are often resistant to loop diuretics, but responsive to __

loop diuretics

Cirrhotic patients are often resistant to __, but responsive to spironolactone and eplerenone

IDIOPATHIC EDEMA

Fluctuating salt and water retention

• Hepatic Cirrhosis

• Idiopathic Edema

Other Edematous states

HEPATIC CIRRHOSIS

Associated with edema and ascites

edema and ascites

HEPATIC CIRRHOSIS is Associated with __

Spironolactone

is the diuretic of choice for patients with hepatic cirrhosis

thiazides

diuretic for mild to moderate hypertension

loop diuretic

diuretic for sever hypertension

POTASSIUM SPARING DIURETICS

Useful both to avoid excessive potassium depletion and enhance the natriuretic effects of other diuretics

Diuretics

enhance the efficacy of ACE inhibitors and vasodilators

ACE inhibitors and vasodilators

Diuretics enhance the efficacy of __

Calcium phosphate or calcium oxalate

two thirds of kidney stones contain :

nephrolithiasis

kidney stones

Kidney stone

Due to defect in proximal tubular Ca+2 reabsorption (hypercalciuria)

Thiazides

enhance Ca+2 reabsorption in the distal convulated tubule (for kidney stones)

thiazides

Reduce urinary Ca+2 concentration

HYPERCALCEMIA

high calcium in blood

loop diuretics

Reduce Ca+2 reabsorption significantly ( Can cause marked volume contraction, thus saline must be administered simultaneously)

1. Neurogenic or central diabetes insipidus

2. Nephrogenic diabetes insipidus

2 types of diabetes insipidus

Neurogenic or central diabetes insipidus

deficient production of ADH (diabetes insipidus)

Nephrogenic diabetes insipidus

inadequate responsiveness to ADH (diabetes insipidus)

thiazides

reduce polyuria and polydipsia in both types of diabetes insipidus

thiazides

has paradoxical anti-diuretic effect

• HTN

• Mild to moderate heart failure

• Chronic calcium stone formation

• Nephrogenic diabetes insipidus

Clinical Uses of Thiazide diuretics

• Acute Pulmonary edema, and other edematous condition

• Acute hypercalcemia

• Hyperkalemia

• Acute Renal Failure

• Anion overdose

Clinical Uses of Loop Diuretics

primary Hyperaldosteronism

Conn’s syndrome, ectopic ACTH production

secondary Hyperaldosteronism

evoked by heart failure, hepatic cirrhosis, nephrotic syndrome

POTASSIUM SPARING DIURETICS

diuretic for hyperaldosteronism

POTASSIUM SPARING DIURETICS

Alternative to loop and thiazide diuretics, if K+ wasting is to be avoided

Carbonic Anhydrase Inhibitors (CAIs)

reduce aqueous humor formation(glaucoma) = decr.IOP

• Glaucoma

• Urinary alkalinization

• Metabolic alkalosis

• Acute mountain sickness

clinical uses of CAIs

CAIs

decrease CSF formation and the pH of CSF and brain = increase ventilation and diminish symptoms of mountain sickness

CAIs

Adjuvants in the treatment of epilepsy

CAIs

Increase urinary phosphate excretion during severe hyperphosphatemia

 Attributable todiuretic property

Metabolic alkalosis

Hypokalemia

Hypocalcemia

Hypovolemia

Hypotension

Hypomagnesemia

 Not directly related to diuretic property

Hyperuricemia

Ototoxicity

adverse effects of furosemide

 Attributable to diuretic

property

Metabolic alkalosis

Hypokalemia

Hyponatremia

Hypercalcemia

Hypovolemia

Hypotension

Hypomagnesemia

 Not directly related to diuretic property

Hyperuricemia

Hyperglycemia

Hyperlipidemia

Adverse effects of Chlorothiazide

 Attributable to diuretic property

Metabolic acidosis

Hyperkalemia

 Not directly related to diuretic property

Menstrual disorders

Impotence/gynecomastia

Loss of libidoHirsutism

Adverse effects of Spironolactone

• Acute Renal Failure – Triamterene + Indomethacin

• Kidney stones – with triamterene

Adverse effects of Spironolactone

• Acute Renal Failure –

• Kidney stones –

mannitol

prototype agent of osmotic diuretic

osmotic diuretic

Increase urine volume

 Extracellular volume expansion

 Dehydration, Hyperkalemia, and hypernatremia

 Hyponatremia – when used with patient with diminished renal function

ADVERSE EFFECTS of osmotic diuretic

VASOPRESSIN AND DESMOPRESSIN

ANTIDIURETIC HORMONE (ADH) AGONISTS

ANTIDIURETIC HORMONE (ADH) AGONISTS - vasopressin and desmopressin

Used in the treatment of central diabetes insipidus

CONIVAPTAN and DEMECLOCYCLINE

ANTIDIURETIC HORMONE (ADH) ANTAGONISTS

ADH ANTAGONIST _ conivaptan and demeclocycline

To manage SIADH

 Nephrogenic diabetes insipidus

 Renal failure

Adverse Effects of ADH antagonist

Loop diuretics and Thiazides

diuretic combination

can mobilize a large amount of fluid

K wasting

• loop diuretic and thiazides

• loop agents or thiazeds and potassium sparing

diuretic combination

SYMPATHOPLEGICS

DRUGS THAT ALTER SYMPATHETIC NERVOUS FUNCTION

• reducing peripheral vascular resistance

• inhibiting cardiac function, and

• increasing venous pooling in capacitance vessels

sympathoplegics lower blood pressure by:

• methyldopa

• clonidine

• guanabenz

• guanfacine

Centrally Acting Sympathoplegics

a-methyldopamine and a-methylnorepinephrine

METHYLDOPA is Converted to

clonidine

 Initial effect: Brief hypertension

 Prolonged effect: Hypotension

catapres

clonidine brand name

methyldopa

Potential advantage is that it causes reduction in renal vascular resistance

mecamylamine, trimethaphan, hexamethonium

ganglionic blockers

ganglionic blockers

can be used in both hypotension and hypertension

parasympathetic (cholinergic)

○ Myocardium (atrium; S-A node) – tachycardia

○ Eye

 Iris – mydriasis

 Ciliary muscle – cycloplegia

○ GI tract – decrease in tone and motility; constipation

○ Urinary bladder – urinary retention

sympathetic (adrenergic)

 Myocardium (ventricles) – decrease in contractile force

 Arterioles – vasodilation; increase in peripheral blood flow; hypotension

 Veins – vasodilation; pooling of blood; decrease in venous return; decrease in cardiac output

 Sweat glands – decrease in secretion

Adverse Effects of Ganglionic Blockers

ADRENERGIC NEURONBLOCKING AGENTS

Lower BP by preventing the normal physiologic release of NE from postganglionic sympathetic neuron

• Guanethidine

• Guanadrel

• Reserpine

ADRENERGIC NEURONBLOCKING AGENTS

GUANETHIDINE

Rarely used because of its toxicity (“pharmacologic sympathectomy”)

Marked postural hypotension, diarrhea, and impaired ejaculation

β1 -selective blockers

• Bisoprolol, Betaxolol

• Esmolol

• Atenolol, Acebutolol

• Metoprolol

• Nadolol

• Sotalol

• Timolol

• Propranolol

Non-selective β-adrenergic antagonists

• Acebutolol

• Pindolol

β-blockers with Intrinsic Sympathomimetic Activity (ISA)

• Labetalol

• Carvedilol

β-blockers with α-blocking capacity

Esmolol

Beta-1 selective blocker

 used for management of intraoperative and postoperative hypertension

esmolol

use for hypertensive emergencies

• PRAZOSIN

• PHENTOLAMINE

• PHENOXYBENZAMINE

PRAZOSIN AND OTHER ALPHA BLOCKERS

vasodilators

Reduce pressure by relaxing vascular smooth muscle, thus dilating resistance vessels and—to varying degrees— increasing capacitance as well

• Arteriolar (direct) vasodilators

• Arterial and Venous (Nonselective) vasodilators

• Calcium channel blockers (CCBs)

VASODILATORS

Hydralazine, Nitroprusside, Nitrates

(vasodilation) drug for release of nitric oxide

Minoxidil sulfate, Diazoxide

(vasodilation) drug for Opening of potassium channels and hyperpolarization

Calcium channel blockers (Nifedipine, Diltiazem)

(vasodilation) drug for Block L-type calcium channels

Fenoldopam

(vasodilation) drug for Activation of dopamine receptors