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Flashcards in Pharmacology Deck (36):
1

Diuretics in the Proximal Tubule

-mannitol
-acetazolamide

2

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

3

Acetazolamide

- Carbonic Anhydrase Inhibitor
- induces metabolic acidosis
- used for glaucoma and prevention/treatment of high altitude sickness

4

Loop Diuretic MOA

-inhibits Na/K/2Cl pump in ascending loop of henle

5

Loop Diuretic List

-furosemide- most commonly used
-bumetanide
-torsemide- impoved bioavailability with data in HF
-ethacrynic acid- only nonsulfa containing loop or thiazide

6

Loop Diuretic Uses

-volume overload
-heart failure
-BP reduction
-pulm edema

7

Loop Diuretic Adverse Effects

-dec. K/Mg
-hypocalcemia
-precipitate gout attack
-metabolic alkalosis

8

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

9

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

10

Thiazide List

-chlorthalidone
-hydrochlorothiazide (HCTZ)
-indapamide
-metolazone
-metalozone

11

K Sparing Diuretics MOA

• Bind to the aldosterone dependent Na/K exchange site
• Spironolactone and eplerenone competitively inhibit the mineralocorticoid receptor
– Eplerenone more specific

12

Aldosteronism causes:

- Increase Na/H20 reabsorption (K loss)

13

RAS Inhibitors

-ACE
-ARB

14

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

15

ARBs

Side effects:
- hyperkalemia
- rise in serum creatinine (transient) - angioedema
INDICATIONS: 1st line therapy HTN, CKD, HF, DM nephropathy

16

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

17

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.

18

Ca Channel Blockers: NDHP

NDHP (verapamil/diltiazem) • Negativeinotropicactivity
• Coronary and peripheral vasodilator
• SE: constipation, bradycardia, nausea

NDHP – Primarily reserved for neg inotropic activity

19

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

20

Beta Blocker Side Effects

• Side effects: decrease libido, bradycardia,
bronchospasm, glucose/lipid changes

21

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

22

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

23

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

24

Effects of AngII in Kidney

-efferent vasoconstriction: inc GFR inititally, but dec. renal blood flow

25

Effects of Norepinephrine on Kidney

-efferent vasoconstriction: inc GFR inititally, but dec. renal blood flow
-afferent vasoconstriction: dec GFR, dec. RBF

26

Effect of Dopamine (or caffeine) on Kidneys

-afferent vasodilation: inc. GFR, inc. RBF
-this is how caffeine causes diuretic effect

27

Effect of ACEi or ARBs on Kidneys

-efferent vasodilation: dec. GFR, inc. RBF

28

Effect of NSAIDS on Kidney

-afferent vasoconstriction: dec. GFR, dec. RBF

29

Effect of Prostaglandins on Kidney

-efferent vasodilation

30

Recombinant Erythropoeitin

-tx for anemia
-MOA: simple replacement
-side effects: well tolerated, if HgB > 12 there is inc. risk of CV events and mortality

31

Iron Products

-tx for anemia
-MOA: parenteral or supplement
-side effects: GI, hypotension, allergic rxns

32

Phosphate Binding Agents

-calcium compounds that bind PO4 to prevent bone disease due to renal osteodystrophy
-side effects: hypercalcemia

33

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

34

Calcimimetics

-alternative to vitamin D if pt develops hypercalcemia
-reduce release of PTH
-side effects: hypocalcemia
-DDIs: potent inhibitor of CYP2D6

35

Drugs That Can Cause Hyperkalemia

-potassium sparing diuretics
-ACE inhibitors
-ARBs
-digoxin (toxic, not therapeutic, doses)

36

How to Treat Hyperkalemia

C-calcium gluconate or chloride
B-B2 agonist
I- insulin
G- glucose
K- kayexalate