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Therapeutics P2 > Exam 1 lecture 4 > Flashcards

Exam 1 lecture 4 Flashcards

1
Q

What are diuretics?

A

Agents that help get rid of sodium (naturesis) and water (diuresis)

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2
Q

Why do diuretics decrease BP?

A

because of a decrease in plasma volume.

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3
Q

What are some indication (uses) of diuretics

A

HTN
Edema
Heart failure
Acute renal failure

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4
Q

Is caffeine a diuretic

A

Not really, Only has a diuretc action for a short period of time, then body habituates to it.

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5
Q

Drugs usually target what type of transporter

A

Active

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6
Q

What are the classifications of diuretics based on MOA

A
  1. Inhibitors of carbonic anhydrase
  2. Osmotic diuresis
  3. Inhibitors of Na-K-2Cl symport
  4. inhibitors of Na-Cl symport
  5. Inhibitors of renal epithelial Na channels
  6. mineralocortecoid receptor antagonists
  7. vasopressin antagonists
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7
Q

WHat factors does glomerular filtration rate (GFR) depend on

A

Size of drug
extent of plasma protein binding of diuretic. (only unbound drug filtered)

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8
Q

carbonic anhydrase location

A

proximal tubule

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9
Q

example of carbonic anhydrase

A

acetazolamide

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10
Q

what do CAI do to Bicarbonate excretion

A

Increase urine output by increasing NaHCO3 excretion

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11
Q

What is an example of osmotic diuretic

A

Mannitol (increase h20 excretion)

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12
Q

How do Na-K-Cl inhibitors affect ions (loop diuretics)

A

Increase Na, K, CL excretion

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13
Q

What are Na-Cl inhibitors also known as

A

Thiazide diuretics

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14
Q

Mineralocorticoid receptor antagonists and inhibitors of renal epithelial Na channels work in what way

A

Increase K retention (K sparing)

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15
Q

CAI work in

A

PCT

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16
Q

Loop diuretics work in

A

Thick ascending limb

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17
Q

Why do diuretic drugs find it difficult to pass through glomerulus

A

Because they are protein bound (albumin).

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18
Q

If diuretics can not go into glomerulus, how do they get into tubules?

A

They undergo active drug secretion across to the proximal tubule

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19
Q

Where does active drug secretion happen

A

Proximal tubule

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20
Q

where does drug reabsorption happen?

A

Distal tubule

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21
Q

renal excretion of drugs is a major route of elimination for what percentage of drugs?

A

25-30%

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22
Q

Is the secretion of drugs in PCT active or passive

A

Active

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23
Q

What are the name of the transporters that aid in active secretion in proximal tubule

A

Organic anion transporter (OAT)
Organic cation transporter (OCT)

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24
Q

steps of active transport of drug into proximal tubule

A

Diffusion out of capillary into interstitial space
transport across basolateral membrane
secretion across luminal membrane

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25
What are main sites for drug-drug interaction? WHY?
OAT/OCT transporters. SInce they are non selective, drugs can interact with each other here.
26
Some drugs that use OAT
Furosemide, penicillin, probenecid
27
How can we use the competition of drugs for these organic transporters therapeutically?
Like what probenecid + penicillin was used for in WW II, we can saturate the transporters in the kidney with another drug to increase the availability of the drug we want in the blood.
28
location of carbonic anhydrase inhibitors
Proximal tubule
29
what does carbonic anhydrase do?
Reabsorption of bicarbonate
30
What doe carbonic anhydrase inhibitors do?
block reabsorption of NaHCO3
31
example of CA-I
Acetazolamide (Diamox)
32
clinical use of CA-I
Acute mountain sickness Diuretic (weak)
33
toxicities of CA-I
Hyperchloremic acidosis renal potassium wasting
34
WHy are CA-I useful for mountain sickness
metabolic acidosis produced by excretion of bicarbonate counteracts the respiratory alkylosis that results from hyperventilation
35
Give an example of osmotic diuretic
Mannitol
36
what is mannitol? how does it work?
Mannitol is a large, pharmacologically inert molecule that is not reabsorbable. This forces water to rush into it.
37
location of osmotic diuretic action
proximal tubule and decending loop of henle
38
is mannitol IV or PO
IV
39
Orally active osmotic diuretics
glucose, glycine
40
Location of loop diuretic action?
ascending thick loop of henle
41
which transporter do loop diuretics affect?
Na, K, Cl symporter
42
T/F Loop diuretics must act on basolateral membrane for diuretic activity
False must act on luminal membrane
43
which are the most potent class of diuretics
loop diuretics
44
Is energy required for Na-k-cl symporter?
No, K and Na are going down concentration gradient and they take Cl with them
45
How is the gradient maintained in Na-K-Cl symporter
ATP-ase keeps pumping Na & K to keep gradient normal
46
which class of diuretics lower urica acid
loop diuretics
47
Loop diuretics also have weak _________ properties
CA-I
48
Give examples of loop diuretics
furosemide bumetanide
49
Most loop diuretics structure are derived from
sulfonamide groups
50
which is the only loop diuretic that did not derive from sulfonamide
Ethacrynic acid
51
use of loop diuretics
edema, HTN, heart failure
52
what is the main toxicity of loop diuretics
Ototoxicity
53
Effect of loop diuretics on potassium
Hypokalemia (potassium wasting)
54
are loop diuretics potassium sparing or wasting
Potassium wasting
55
location of action for thiazides
DCT
56
What do thiazides target (transporter)
Na-Cl transporter
57
Does the Na-Cl transporter in thiazides require ATP
No, Na is going down Concentration gradient and takes Cl with it. gradient is maintained by ATP-ase
58
What percent of NA is reabsorbed from DCT
10%
59
thiazides structure derives from
sulfanilamide
60
effect of thiazides on potassium
potassium wasting
61
WHich two classes of diuretics are potassium wasting
Thiazides and loop diuretics
62
examples of thiazides
Chlorothiazide, hydrochlorothiazide
63
use of thiazide
HTN, HF, nephrogenic diabetes insipidus
64
toxicities thiazides may cause
hypokalemia hyperuricemia impaired carbohydrate tolerance hyperlipidemia
65
why are loop diuretics more effective than thiazides
more Na is physiologically reabsorbed at loop of henle than at DCT
66
Which two diuretics are potassium sparing
Inhibitors of renal epithelia Na channels mineralcorticoid receptor antagonist (MRA)
67
where do inhibitors of renal epithelia Na channels operate
Late distal tubule and collecting duct
68
Which channel do inihitors of renal epithelia in NA channel act on
Na-k channels ( they are also used in combination with other diuretics)
69
how do inhibitors of renal epithelia affect movement of K and Na
They inhibit K excretion and Na entrance
70
examples of inhibitors of renal epithelia
Amiloride, triamtrene
71
Clinical use of amiloride and triamtrene
Used in adjunctive tretament with thiazides and loop diuretics in HF and HTN
72
Toxicities related to inhibitors of renal epithelia
hyperkalemia
73
Contraindications while taking inhibitors of renal epithelia
K+ supplements ACE inhibitors
74
What are the only diuretics that do not act within the tubular lumen
MRA (mineralocorticoid receptor antagonists)
75
Where do MRA drugs act
Cytosol.
76
What do mineralocortecoid receptors do?
Produce mRNA and produce Na channel
77
MRA mechanism of action
Binds mineralocorticoid receptor in late distal tubule and collecting duct
78
give an example of MRA drug
Spironolactone
79
Uses of MRA drugs
HTN, HF aldosteronism
80
Toxicities related to using MRA drugs
Hyperkalcemia gynecomastia
81
Contraindications of MRA drugs
K supplements and ACE inhibitors
82
K supplements and ACE inhibitors are contraindications related to which two diuretics
MRA and inhibitors of renal epithelia NA
83
hyperkalemia is a toxicity related to which twodiuretics
The potassium sparing ones (MRA, inhibitors of renal epithelia)
84
What is vasopressin
Antidiuretic hormone
85
How to vasopressin antagonists work?
antagonize vasopressin
86
main objective of vasopressin is to
increase BP
87
Two vasopressins and their functions
V1- constrict blood vessels V2- Fluid reabsorption from kidney
88
mechanism by which Vasopressin increases renal conservation of H20
V2 receptors insert aquaporins into membrane, increasing permeability of water, causing BP to increase. Vasopressin blockers block this action
89
Examples of vasopressin blockers
conivaptan tolvaptan
90
site of action if luminal side for drugs except for which two types
aldosterone inhibitors and vaptan inhibitors
91
how does renal failure affect diuretic action
secretion of diuretics decrease with renal failure, reducing effectiveness.
92
are diuretics secreted or filtered
secreted
93
why are diuretics secreted and not filtered
because CA-I, thiazides and loop diuretics are highly bound to proteins
94
hydrochlorothiazide effect on blood glucose
May increase it
95
hydrochlorothiazide effect on ca
Decreases Calcium
96
which one is more effective, increasing a dose for a single diuretic or combining diuretics with different mechanisms
Combining diuretics with different mechanisms
97
explain braking phenomenon
diuretics decrease body weight due to Na excretion exceeding intake, this increases water excretion leading BW and ECFV to decrease. A new steady state is achieved when Na intake and excretion are equal but at a lower ECFV and weight. This results from activation of RAAS and SNS. when diuretic is DX, BW and ECFV rise where Na intake exceeds excretion. New steady state reached.
98
how do thiazides affect uric acid levels
thiazides increase uric acid
99
amiloride causes hyper or hypo kalemia
Hyperkalemia
100
Triamtrene effect on K
K increasing
101
hydrochlorothiazide effect on Ca
Decreases Ca
102
Hydrochlorothiazide effect on blood glucoseq
Increases BG
103
what drug can furosemide not be used wuth
Gentamicin
104

Therapeutics P2 (41 decks)

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