Pharm 2025 > Diuretics E3 Start > Flashcards

Diuretics E3 Start Flashcards

Exam 3 (81 cards)

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1
Q

What are diuretics useful for?

A

HTN
Fluid build up in body

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2
Q

DIuretic vs Natriuretic ?

A

Diuretic- Inc UO
Natriuretic- Inc sodium ion secretions (inc water secretion- osmosis)

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3
Q

What are the main targets of diuretics?

A

1) Membrane transport proteins
2) Water permeable segments of nephron
3) Enzyme inhibition
4) Interference with hormone receptors (ADH)

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4
Q

What are the difference classes of diuretics?

A

1) Carbonic Anhydrase Inhibitors
2) Loop Diuretics
3) Thiazides
4) Potassium Sparing Diuretics
5) Agents that Alter Water Excretion
6) SGLT2 Inhibitors (also antidiabetic meds)

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5
Q

What is the functional unit of the kidney?

A

Nephron

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6
Q

SGLT2 MOA

A

Primarily- Anti-diabetic meds

Inc glucose secretion in urine output

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7
Q

T/F: A nephron consists of a renal corpuscle and associated tubules, except the collecting ducts.

A

TRUE

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8
Q

Explain where nephron starts and ends.

A

Nephron starts at glomerulus= ends where urine is produced.

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9
Q

The 3 principal activities of nephrons in producing urine:

A

1) Filtration
2) Reabsorbs water, electrolytes, and glucose back into the blood.
3) Secretes substances (H+, K+,, NH3 and certain drugs) from the blood into the urine from the tubules.

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10
Q

Glomerulus is apart of what?

A

The vasculature

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11
Q

Bowmans capsule is apart of what?

A

Part of the nephron

Also known as glomerular capsule

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12
Q

What is a sign of kidney disease?

A

Protein in urine; too big, does not usually exit in glomerulus

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13
Q

Explain flow of urine in the nephron within kidney

A

Glomerulus–> Bowmans capsule–> Proximal Convoluted tubule–> Loop of Henle–> Distal convoluted tubule–> collecting tubule —> collecting duct

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14
Q

Vascular pole is what?

A

Where vasculature comes in (blood comes into kidney)

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15
Q

Urinary pole is what?

A

Where urine goes out

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16
Q

What is the cortex of the kidney?

A

Outer portion of the kidney

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17
Q

Where is the medulla of a kidney? What features of the nephron are here?

A

More towards the middle

Collecting duct and loop of Henle

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18
Q

Where does reabsorption occur within kidneys?

A

1) Between tubules and the peritubular capillaries

2) Loop of Henle and Vasaracta

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19
Q

Where does Filtration occur?

A

At the glomerulus

(water soluble and small from glomerulus to bowman’s capsule)

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20
Q

How much % at glomerular & urine?

A

100% produced at Bowmans capsule

1% of it goes out into the urine

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21
Q

What are the components of the JGA?

A

1) Macula densa
2) Juxtaglomerular cells
3) Extraglomerular mesanginal cells

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22
Q

What does the macula densa (MD) do? Where is it?

A

Location: Occurs in distal convoluted tubule

Function: Senses osmolality and volume/pressure of fluid in distal tubule

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23
Q

What activates the juxtaglomerular cells to secrete renin?

A

Low Na and H2O flow within kidneys

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24
Q

What do the Juxtaglomerular cells do (JG)?

A

1) Can constrict or dilate afferent arteriole

2) Release renin= activates RAAS

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25
Know how body autoregulates GFR.
1) Renal auto regulation- controls arterial diameter 2) Neural regulation- sympathetic & parasympathetic pathway = RAAS 3) Hormonal regulation: Aldosterone
26
What is absorbed at the proximal tubule through transporters?
Sodium bicarbonate (NaHCO3), NaCl, glucose, amino acids, organic solutes, K+, water
27
What meds are targeted at the proximal tubule?
Target: NaCl, NaHCO3 1) Carbonic anhydrase inhibitor 2) Caffeine- blocks adenosine receptors (excess Na secretion)
28
Where and how do we reabsorb Bicarb?
Prox Convoluted Tubule 1) Na/H Exchanger (NHE3)- Na in, H out (of prox tubule) 2) H binds with Bicarb in lumen-urine= Carbonic acid formed (H2CO3) 3) Carbonic Anhydrase= breaks H2CO3 into CO2 & water 4) CO2 diffuses back into convoluted tubule= excess CO2 in cell 5) CO2 combines w water= Carbonic Anydrase enzyme makes H2CO3 (Carbonic acid again) 6) Carbonic acid excess= breaks into H ions & bicarb 7) Bicarb Transporter= Bicarb back into bloodstream= helps pH
29
Carbonic Anhydrase Inhibitor (CAIs) Drug Example
Acetazolamide
30
How do CAIs work?
Blocks carbonic acid anhydrase= carbonic acid won't convert into CO2= stays & excreted in urine
31
What does the S2 segment do?
Secretion of larger substances into luminal fluid Uric acid NSAIDs Diuretics Antibiotics etc…
32
Loop of Henle: Parts & Function
Descending: Water reabsorption Ascending : impermeable to water; movements of ions (K, Na, Cl---> NKCC2)
33
Why must the water reabsorption equal Na reabsorption in the proximal tubule?
To keep osmotic gradient equal
34
Loop Diuretics MOA, Ex? Potential Side effect?
MOA: Inhibits NaCl reabsorption= inhibits NKCC2 Transporter (Reduction in NaCl absorption, lose KIncrease secretion (loss) of Mg2+ and Ca2+) SIde effect: Potential alkalosis Ex: Furosemide (sulfonamide)
35
Loop Diuretic Contraindications, Toxicity risk?
Allergic reactions- All are sulfonamides Avoid in patients with sulfa allergies Rash, eosinophilia Nephritis Resolves rapidly
36
Thiazides MOA, Lose, Ex?
MOA: Inhibit NaCl transport in DCT (NCC: Na/Cl co transporter) Some minimal CA inhibition Lose: Na, Cl-, HCO3- Ex: Hydrochlorothiazide (prototype)
37
Where is the final site of sodium reabsorption? What gets lost here?
Collecting tubule; Lost of K here if wasn't reabsorbed earlier
38
T/F: First part is collecting duct then collecting tubule.
FALSE Collecting tubule THEN collecting duct
39
List the segments of the nephron.
1) Renal Corpuscle: Glomerulus 2) Renal tubule 3) Collecting Ducts
40
Explain the afferent and efferent blood vessels of the kidney.
Afferent blood vessels feeding it Efferent blood vessels coming away from it
41
What is the glomerulus? What surrounds it?
-Collection fo capillaries (leaky) - Surrounded by Bowmans capsule
42
What is the last part of the nephron?
Collecting tubule
43
What is within the cortex of the kidney?
Glomerulus, proximal tubule, distal tubule, collecting tubule
44
What is in the medulla of the kidney?
Loop of Henley Collecting Duct
45
What are the peritubules and vasa recta?
Peritubules : blood vessels around proximal & distal tubules Vasa Recta: blood vessels around loop of henle
46
How does the macula densa play a role in the size of the afferent arteriole?
Senses high pressure= SHRINK afferent arteriole= STOP NO production LOW PRESSURE= increase secretion of NO to dilate arteriole
47
What are the JG cells?
Modified smooth muscle cells in the afferent arteriole
48
How do CAIs effect Na?
Fewer H inside due to blocking Carbonic anhydrase= NHE3 slows down So Na stays in urine= more water to stay in tubules
49
Issues with CAIs?
K+ depletion Acidosis due to loss of bicarb
50
What else can CAIs be used for?
1) Alkalosis 2) Pressure on brain d/t high altitude sickness
51
T/F: There is an osmotic gradient in the medulla.
TRUE; Cortex osmolality= 300 Medulla Osmo= 1200
52
What kind of diuretic is Mannitol?
Osmotic (Keeps osmolality high= keeps water in tubule= stay in urine)
53
Why is the ascending loop of henle impermeable to water?
TO balance out osmotic gradient (Transports Na, K, Cl)
53
Why does the descending loop of henle have a high water reabsorption?
Hypertonic Medullary Interstituim: much higher degree of solutes up to 1200 mOsmo/kg
54
What transporter is in the ascending loop of henle?
Sodium Potassium 2 Chloride Transporter (NKCC2)
55
After the NKCC2 puts Na, K, Cl into the cell what happens?
Na/K Pump= pumps Na back into blood K/Cl= Pumps Cl back into blood K+ = Goes back into urine= helps drive Mg & Ca back into blood
56
Why is there little water movement in the distal convoluted tubule? What ions does it reabsorb well & poorly?
Back to balance osmolality (around 300 mOsmo) Low Na reabsorption, high Ca reabsorption
57
Parathyroid hormone vs Calcitonin action
PH: low Ca= PH inc = reabsorb Ca at DCT Calcitonin- high Ca= calcitonin inc= Ca stored into bone
58
Where does aldosterone work?
At collecting tubule (influenced by mineral corticoids)
59
What does the principal cell do in the collecting tubule?
Site for water, Na, K transport
60
Explain what happens at the collecting tubule.
1) ENaC- Na transporter = absorbs Na into tubule 2) Na/K pump= moves Na into blood (***Inc with aldosterone) 3) Na++ build up in tubule= more K leaves into urine 4) gNormally Cl- moves through paracellular channel back into bloodstream due to net neg of Na leaving
61
Understand why diuretics that affect bicarb cause more K loss than diuretics affecting Cl-
Bicarb bigger and more negative = more net negative = makes more K come out into lumen of urine even MORE
62
What makes K go into lumen of urine in collecting tubule?
Cl: net neg (-) attracts K to lumen of urine Na: coming in pushes K out
63
Explain how aldosterone works at the collecting tubule
Binds to aldosterone receptor → inc Na absorption (ENaC) → inc Na/K pump→into vasculature H20 follows Na→ inc blood volume → inc BP
64
Explain potassium sparing diuretics : MOA, drug example
Works at collecting tubule Antagonizes the effect of aldosterone → blocks aldosterone receptors Dec Na coming in= dec K loss in urine ex: Spironolactone
65
Common use for K sparing diuretic
Primary : Conn's syndrome (adrenal cortex issue) , Ectopic ACTH production (pituitary gland issue) Secondary: CHF (be careful) , Nephrotic syndrome, other diuretics Anything with excess production of mineralocorticoid excess
66
Contraindications/Toxicity for K sparing
Contra: Liver diease Tox: Hyperkalemia (need to be aware of other drugs that may affect K if they are taking any)
67
What hormone works at the collecting DUCT ? What causes this to be released?
ADH - Vasopressin Released by pituitary in response to low BP, inc osmolality
68
What does ADH do?
Binds to V2 (ADH-R) which are GPCR that inc cAMP → causes vesicles to merge with urine lumen= H2O channels (AQP2) allowing for H2O to come in
69
Explain change with presence of ADH
70
ADH: Agonist & Antagonist
Agonist: Vasopressin Antagonist : Conivaptan
71
Where do osmotic duretics work at?
PCT primarily (but effects entire tubule; anywhere that tube is permeable to H2O)
72
Mannitol primary uses
1) Reduce intracranial pressure 2) Promote removal of renal toxins ( hemolysis, rhabdo)
73
Mannitol Pharmacokinetics
A: POOR (induces diarrhea); given IV M: Not metabolized E: Glomerular filtration (30-60 min); no sig reabsorption or secretion
74
How does mannitol work?
Counters osmotic force→ very high osmolality within tubule so water stays in urine
75
Mannitol Toxicity
Dehydration, hypernatremia, hyperkalemia, hyponatremia (renal pt) Extracellular volume expansion → will push water & solutes into ECF compartments (prior to diuresis; will resolve after diuresis)
76
What diuretics are used in DI?
Neurogenic- give Vasopressin Nephrogenic- Thiazide diuretic
77
Types of DI
Neurogenic- Pituitary gland (not ADH) Nephrogenic -issue of kidney
78
Explain pathway of thiazides in DI
Dec plamsa volume= dec GFR= H2O & NaCl reabsorption)
79
What areas are water permeable within the kidney?
PCT Descending loop of henle DCT Collecting tubule Collecting duct
80
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