Pharmacology Flashcards
Diuretics in the Proximal Tubule
- mannitol
- acetazolamide
Mannitol
- non metabolized, non reabsorbed osmotic diuretics
- draws free water out of the tissue and into the circulation, where it is excreted by the kidneys
- used in management of elevated ICP
Acetazolamide
- Carbonic Anhydrase Inhibitor
- induces metabolic acidosis
- used for glaucoma and prevention/treatment of high altitude sickness
Loop Diuretic MOA
-inhibits Na/K/2Cl pump in ascending loop of henle
Loop Diuretic List
- furosemide- most commonly used
- bumetanide
- torsemide- impoved bioavailability with data in HF
- ethacrynic acid- only nonsulfa containing loop or thiazide
Loop Diuretic Uses
- volume overload
- heart failure
- BP reduction
- pulm edema
Loop Diuretic Adverse Effects
- dec. K/Mg
- hypocalcemia
- precipitate gout attack
- metabolic alkalosis
Thiazide Diuretic MOA
• Inhibit Na/Cl cotransporter in distal tubule
– Smaller portion of filtrate and less diuretic effect
• Antihypertensive effect secondary to dec plasma volume and dec CO
– Secondary mild vasodilation
Thiazide Side Effects
- hyperuricemia
- metabolic alkalosis
- hypokalemia
- hyperglycemia
- lose efficacy in later stages of CKD as less drug reaches site of action as kidney fails
- more efficacious loop diuretic need as GFR
Thiazide List
- chlorthalidone
- hydrochlorothiazide (HCTZ)
- indapamide
- metolazone
- metalozone
K Sparing Diuretics MOA
• Bind to the aldosterone dependent Na/K exchange site
• Spironolactone and eplerenone competitively inhibit the mineralocorticoid receptor
– Eplerenone more specific
Aldosteronism causes:
- Increase Na/H20 reabsorption (K loss)
RAS Inhibitors
- ACE
- ARB
ACE Inhibitors
Side effects: - cough (secondary to increase bradykinin and substance P) - hyperkalemia - rise in serum creatinine (transient) - angioedema -hypotension -category D pregnancy INDICATIONS: 1st line therapy HTN, CKD, HF, DM nephropathy
ARBs
Side effects:
- hyperkalemia
- rise in serum creatinine (transient) - angioedema
INDICATIONS: 1st line therapy HTN, CKD, HF, DM nephropathy
Ca Channel Blockers MOA
• Block L-type Calcium Channels
– Arterial vasodilation and decrease PVR
• Dihydropyridines (amlodipine, felodipine, -pine)
– Potent vasodilators with no effect on cardiac contractility
• Non-Dihydropyridines (verapamil, diltiazem)
– Less potent vasodilators with greater depressive effect on cardiac conduction
Ca Channel Blockers: DHP
DHP (“-pines”)
• Reflex tachycardia
• Coronary and peripheral vasodilator
• SE: Peripheral edema, inc HR, gingival hyperplasia
DHP - well tolerated and provide effective BP control. Good 2nd line agents for BP reduction.
Ca Channel Blockers: NDHP
NDHP (verapamil/diltiazem) • Negativeinotropicactivity
• Coronary and peripheral vasodilator
• SE: constipation, bradycardia, nausea
NDHP – Primarily reserved for neg inotropic activity
Beta Blockers MOA
- block peripheral adrenergic receptors therapy decreasing CO
- dec. sympathetic output
Keys:
– Labetalol and carvedilol (alpha and beta blocker)
– Metoprolol – renal and hepatic elimination
– Atenolol – renal elimination
Beta Blocker Side Effects
• Side effects: decrease libido, bradycardia,
bronchospasm, glucose/lipid changes
Vasodilators (hydralazine, minoxidil)
- MOA
- side effects
- keys
• MOA:
– Increase intacellular cGMP relaxation of arterial smooth muscle decrease systemic pressure and contractility
• Side effects: edema, tachycardia, lupus rash (hydralazine), neuropathy, hair growth (minoxidil)
• Keys:
– Minoxidil is a 3 drug drug
– Dosed BID
– Third/fourth line therapy. EFFECTIVE
Alpha 1 Receptor Blockers
(terazosin, doxazosin, prazosin)
• MOA:
– peripheral postsynaptic blockade decrease in arterial
tone
– relaxes the smooth muscle of the bladder neck
• Side effect: postural hypotension, dizziness, somnolence, nasal congestion/rhinitis, and impotence
• Keys:
– Primarily used for BPH symptoms
– ALLHAT study arm discontinued early secondary to increase CV events vs. thiazide
Alpha 2 Receptor Blockers
(Clonidine, methyldopa)
• MOA: stimulate presynaptic alpha 2 receptor decrease sympathetic tone
– Decrease PVR and CO
• Side effects: dry mouth, depression, lipid
abnormalities, sedation
• Keys:
– Clonidine patch available to increase compliance – Methyldopa is DOC in pregnancy
– Clonidine off label: smoking cessation, ADHD, – Used 3rd/4th line
Effects of AngII in Kidney
-efferent vasoconstriction: inc GFR inititally, but dec. renal blood flow
Effects of Norepinephrine on Kidney
- efferent vasoconstriction: inc GFR inititally, but dec. renal blood flow
- afferent vasoconstriction: dec GFR, dec. RBF
Effect of Dopamine (or caffeine) on Kidneys
- afferent vasodilation: inc. GFR, inc. RBF
- this is how caffeine causes diuretic effect
Effect of ACEi or ARBs on Kidneys
-efferent vasodilation: dec. GFR, inc. RBF
Effect of NSAIDS on Kidney
-afferent vasoconstriction: dec. GFR, dec. RBF
Effect of Prostaglandins on Kidney
-efferent vasodilation
Recombinant Erythropoeitin
- tx for anemia
- MOA: simple replacement
- side effects: well tolerated, if HgB > 12 there is inc. risk of CV events and mortality
Iron Products
- tx for anemia
- MOA: parenteral or supplement
- side effects: GI, hypotension, allergic rxns
Phosphate Binding Agents
- calcium compounds that bind PO4 to prevent bone disease due to renal osteodystrophy
- side effects: hypercalcemia
Vitamin D Compounds
- decreases PTH relsease indirectly and directly
- side effects; hypercalcemia
- note: paracalcitol acts selectively at D3 receptors on PT gland- not at intestint- so ho hypercalcemia
Calcimimetics
- alternative to vitamin D if pt develops hypercalcemia
- reduce release of PTH
- side effects: hypocalcemia
- DDIs: potent inhibitor of CYP2D6
Drugs That Can Cause Hyperkalemia
- potassium sparing diuretics
- ACE inhibitors
- ARBs
- digoxin (toxic, not therapeutic, doses)
How to Treat Hyperkalemia
C-calcium gluconate or chloride B-B2 agonist I- insulin G- glucose K- kayexalate
