Trachte: ADH and Diuretics

Question 1

How much plasma does the kidney filter each day?

Answer 1

180 L

Question 2

What does the kidney do?

Answer 2

1. Returns ions/nutrients to blood via specific transporters

2. Excretes toxins/metabolites in the urine

Question 3

How does using different permeabilities to water and different ionic transport processes over the course of the nephron affect the kidney?

Answer 3

It results in DRASTICALLY different OSMOLARITIES in different regions of the kidney

Question 4

Where do carbonic anyhydrase inhibitors act?

Answer 4

Proximal tubule

*Aren’t really used clincially

Question 5

Where do loop diuretics act? What do they do?

Answer 5

Ascending limb of the loop of Henle
Inhibit Na/K/2Cl pump

EXTREMELY useful

Question 6

Where do thiazide diuretics act? What do they do?

Answer 6

Distal convoluted tubule

Inhibit Na/Cl transport

Question 7

What drugs are especially useful in hypertension?

Answer 7

Thiazide diuretics

Question 8

Where do K sparing diuretics work? What do they do?

Answer 8

Cortical collecting tubule

Inhibit aldosterone receptors or block Na exchange for K and H

Question 9

Where do antidiuretic hormones work? What do they do?

Answer 9

Medullary collecting duct

Recruit aquaporin channels

Question 10

Where do osmotic diuretics work?

Answer 10

Proximal tubule or descending limb of the loob of henle

Question 11

What are the major loop diuretics?

Answer 11

Furosemide (lasix)

Bumetanide

Question 12

What normally happens in the ascending loop of henle?

Answer 12

The ascending loop of Henle normally accounts for 25% of Na reabsorption in the kidney.

NORMALLY…
Na/K/2Cl pump in the thick ascending limb of the Loop of Henle>
Na/K/CL are pumped out but water remains inside (no aquaporins)>
HYPO-OSMOLAR

Question 13

What do the loop diuretics do in the ascending loop of henle??

Answer 13

LD prevent the DECREASE in osmolarity>

greater retention of ions and water in later segments of the nephron

Question 14

What effect do loop diuretics have on urine composition?

Answer 14

1. Increased NaCl excretion

2. Increased K excretion

Question 15

What are the major uses of loop diuretics?

Answer 15

1. pulmonary edema
2. edematous conditions
3. Hyperkalemia
4. Acute renal failure
5. anion overdose (bromide, fluoride, iodide)

Question 16

What are the major thiazide diuretics?

Answer 16

Chlorthalidone
Hydrochlorothiazide
Metalazone

Question 17

What do thiazide diuretics do?

Answer 17

Block the NaCl transporter in the distal convoluted tubule

Question 18

What normally happens in the distal convoluted tubule? What happens when you block this transport mechanism?

Answer 18

Accounts for 8% of NaCl reabsorption

Blocking this mechanism results in EXCRETION of water, Na, Cl and K in urine

Question 19

Why does K get excreted with thiazide diuretics?

Answer 19

Some of the increased Na is exchanged for K in the cortical collecting tubule

Question 20

What are thiazides primarily used for?

Answer 20

1. HTN
2. HF
3. Nephrolithiasis caused by hypercalcemia
4. Nephrogenic diabetes insipidus

Question 21

What are the major SE of thiazides?

Answer 21

1. Hyperglycemia
2. Hyperuricemia
3. Hypokalemia
4. hyperlipidemia
5. hyponatremia
6. allergic rxns

Question 22

How do thiazides cause hyperglycemia?

Answer 22

Thiazides are sulfonylureas>
bind to SUR on K channel controlling insulin release>
opens the channel and hyperpolarizes the beta cell>
suppresses insulin release

Question 23

What are the K sparing diuretics and what are the mechanisms by which they act?

Answer 23

1. Inhibit aldosterone receptors (spironolactone)

2. inhibit the Na exchange for K and H in the cortical collecting duct (amiloride, triamterene)

Question 24

How do K sparing diuretics spare K?

Answer 24

By blocking the exchange of intaluminal Na for extraluminal K, less K is excreted

Question 25

What is the major use of K sparing diuretics?

Answer 25

Hyperaldosterionism or to prevent K wasing caused by other diuretics

Question 26

What does eplerenone do?

Answer 26

Prevents fibrotic changes in kidneys and hearts caused by aldosterone, and has been shown to improve survival in heart failure

Question 27

What are the side effects of K sparing diuretics?

Answer 27

Hyperkalemia Hypercholeremic metabolic acidosis Acute renal failure Kidney stones

Question 28

What K sparing diuretic causes gynecomastia?

Answer 28

Spironolactone

Question 29

What are 2 antidiuretic hormones?

Answer 29

1. Vasopressin | 2. Desmopressin

Question 30

What are antidiuretic hormones used for?

Answer 30

Treat diabetes insipidus | bed wetting!

Question 31

What is the MOA of antidiuretic hormones?

Answer 31

Stimulation of G protein coupled receptors in the collecting duct> recruits aquaporin channels> water moves by osmosis through the AQP cahnnels> hyperosmolar medullary region of the kidney

Question 32

How are vasopressin and desmopressin administered?

Answer 32

parenterally intranassally orally

Question 33

What can be used to treat syndromes involving inappropriate ADH secretion?

Answer 33

Convaptan- ADH antagonist

Question 34

What antibiotic has some activity as an ADH antagonist?

Answer 34

Demecocyline

Question 35

What is the major osmotic diuretic?

Answer 35

Mannitol

Question 36

How does mannitol cause a retention in water?

Answer 36

It's NOT reabsorbed by the nephron so it exerts an OSMOTIC effect to retain water.

Question 37

What is mannitol used for?

Answer 37

1. reduce body water | 2. reduce intracranial/intraocular pressure

Question 38

What are toxicities associated with mannitol?

Answer 38

1. Extracellular volume expansion 2. Dehydration, hyperkalemia, hypernatremia 3. hyponatremia when renal function is impaired

Question 39

What is a major carbonic anhydrase inhibitor?

Answer 39

Acetazolamide (diamox)

Question 40

Are anhydrase inhibitors useful as diuretics?

Answer 40

Not really....CA is too important of an enzyme. Blocking it leads to a number of SE.

Question 41

what are CAIs used for?

Answer 41

1. Glaucoma 2. urinary alkalinization 3. Metabolic acidosis 4. Acute mountain sickness

Question 42

What are hte SE of CAIs?

Answer 42

1. Hyperhchloremic metabolic acidosis 2. renal stones 3. renal K wasting

Question 43

What do organic anion transport inhibitors do?

Answer 43

Transport small hydrophillic molecules into or OUT of the nephron. Driven by symport or antiport exchange of molecules for dicarboxylates.

Question 44

What are OATIs used to treat?

Answer 44

Gout!

Question 45

How do you treat gout?

Answer 45

1. Reduce inflammation w/ NSAIDS (NOT salicylates) | 2. Reduce uric acid

Question 46

What drugs reduce uric acid? How do they work?

Answer 46

1. Allopurinol- inhibits xanthine oxidase | 2. Probenicid or sulfinpyrazone- inhibits a renal organic acid transporter to facilitate excretion

Question 47

What is colchicine?

Answer 47

Microtubule inhibitor with anti-inflammatory properties

Question 48

How do probenicid and sulfinpyrazone work?

Answer 48

Inhibit uric acid reabsorption by organic acid transporter

Question 49

Why are loop diuretics ototoxic?

Answer 49

Also block the pump in the ear, which is critical for K concentrations in the ear

Question 50

What do loop diuretics do to extracellular Na, K, Cl and water?

Answer 50

Decrease Na, K, Cl and reduce water

Question 51

Why are we so sensitive to K imbalance?

Answer 51

Theres very little in our extracellular fluid, so if you change it slightly it can have a large effect. There is a far greater amount of Na, so altering it does not do much.

Question 52

Why is it important to monitor electrolytes when giving loop diuretics?

Answer 52

They have the potential to be toxic

Question 53

How do thiazides prevent uric acid secretion?

Answer 53

Thiazide and UA are transported by same transporters so they interfere with the transfer of UA

Question 54

What affect do thiazides have on extracellular Na, K, Cl and water?

Answer 54

Deplete Na, K and water Much less than loop diuretics have milder affect so they're safer to use

Question 55

What part of the bp equation do thiazides affect?

Answer 55

BP= HR x SV X TPR (Decrease SV!...also decreases TPR) This affects the venous return curve

Question 56

What are the compelling reasons/perfect conditions for use of thiazides in HTN? What are ACE inhibitors good for?

Answer 56

Stroke- lower bp and reduce incidence of stroke Diabetes- they do elevate glucose, but are still ok CAD ACE inhibitors are ALWAYS GOOD b/c they are synergetic with other drugs. They have milder affects than loop diuretics

Question 57

What effects do K sparing diuretics have on extracellular na, k, cl and water?

Answer 57

Mild decrease in Na ELEVATE K levels Little affect on Cl or water

Question 58

How does aldosterone work?

Answer 58

Aldosterone works on a receptor in the cytosol. Once activated it is a transcriptional activator or inhibitor.

Question 59

Where is aldosterone synthesized?

Answer 59

Adrenal gland (glomerulosa- the outermost layer)

Question 60

What are the compelling reasons for use?

Answer 60

Heart failure | post MI

Question 61

Where does ADH come from?

Answer 61

Posterior Pituitary

Question 62

What stimulates the release of ADH?

Answer 62

``` Decrease in blood volume Increase osmolarity (osmosensor in the brain) ```

Question 63

What receptors does it stimulate?

Answer 63

Gs aplha- g protein that couples between the receptor that stimulates adenylate cyclase

Question 64

What do thiazides do to UA?

Answer 64

1. inhibit secretion of UA by OAT1 2. Serve as substrates for URAT Net effect is to INCREASE blood UA