Diuretics Flashcards
(135 cards)
1
Q
where are beta1 receptors located?
A
the heart and kidney
2
Q
what do stimulated beta1 receptors lead to?
A
in heart: increased HR, increased contractility, and increased SV leading to increased CO
in kidneys: increase renin release
3
Q
where are alpha1 receptors located?
A
blood vessels
4
Q
what do stimulated alpha1 receptors lead to?
A
increased vasoconstriction, and increased peripheral resistance
5
Q
equation for cardiac output
A
HR X SV
6
Q
what does increased renin release imply?
A
increased conversion of angiotensinogen to angiotensin I
7
Q
how is angiotensin I converted to angiotensin II?
A
ACE
8
Q
how does angiotensin II impact the adrenal cortex?
A
increases aldosterone release
9
Q
how does angiotensin II impact the posterior pituitary?
A
increases vasopressin or antidiuretic hormone
10
Q
function of aldosterone
A
act on late distal tubule and collecting duct, directly impacts Na absorption and K excretion
11
Q
what does increased Na channels and Na-K ATPase in the nephron imply?
A
increased passive diffusion of na into na channels on the luminal side (into the blood vessels), increased active transport of na into blood and K into cell via basolateral na-k atpase
NET EFFECT: sodium absorption into blood cells from lumen of nephron
12
Q
function of vasopressin (ADH)?
A
act on V2 receptors of distal or collecting tubules, and generates aquaporin-2 (and encourages aquaporin-2 migration to luminal membrane of tubule cells), water then reabsorbed from urine to the blood stream.
13
Q
end product of ADH?
A
water resorption, concentration of urine, reduces urine volume, increases blood volume
14
Q
overall impact of aldosterone and ADH increase?
A
increased Na and H2O retention = increased blood pressure
15
Q
site of action of carbonic anhydrase inhibitors?
A
proximal convoluted tubule
16
Q
example of carbonic anhydrase inhibitor?
A
acetazolamide
17
Q
site of action of osmotic diuretics?
A
thin descending limb, PCT, collecting duct (places where water is permeable)
18
Q
class of mannitol?
A
osmotic diuretic
19
Q
class of urea?
A
osmotic diuretic
20
Q
class of glycerin?
A
osmotic diuretic
21
Q
class of furosemide?
A
loop diuretic
22
Q
class of bumetanide?
A
loop diuretic
23
Q
class of torsemide?
A
loop diuretic
24
Q
class of ethacrynic acid?
A
loop diuretic
25
site of action of loop diuretics?
thick ascending limb
26
class of metolazone?
thiazide
27
class of indapamide?
thiazide
28
site of action of thiazides?
distal convoluted tubule
29
class of triamterene
potassium sparing diuretic
30
class of eplerenone
potassium sparing diuretic
31
class of canrenone
potassium sparing diuretic
32
class of spironolactone
potassium sparing diuretic
33
class of amiloride
potassium sparing diuretic
34
site of action of potassium sparing diuretics
collecting ducts
35
class of demeclocycline
vasopressin antagonist
36
class of vaptans
vasopressin antagonist
37
site of action of vasopressin antagonists?
collecting ducts
38
what do most diuretics block in the renal tubules?
transporters on the luminal membrane of tubular cells
39
how do most diuretics reach the site of action?
secretion by the organic acid secretory system in the proximal convoluted tubule
40
do diuretics ever block na-k-ATPase?
NO
41
4 biological actions of most diuretics?
increased urine volume and flow, decreased na reabsorption (increased na in urine), decreased water reabsorption indirectly (increased water concentration in urine), changing urine and plasma concentration of ions
42
5 major ions affected by diuretics?
sodium, chloride, potassium, calcium, magnesium
43
what are diuretics majorly used to treat?
htn, heart failure
44
where is the organic acid secretory system located?
proximal convoluted tubule
45
reabsorption in the proximal convoluted tubule?
most reabsorption of na, k, and ions and water; nearly all glucose, AA; sodium bicarb
46
organic acid secretory system
secretes uric acid, antibiotics, and para-aminohippuric acid into lumen
47
reabsorption in thin descending tubule?
water (permeable) (urine increases in concentration), NO SALT
48
reabsorption in thick ascending tubule?
Na, Ca, Mg reabsorption, water impermeable (urine concentration decreased - losing ions but no water)
49
urine concentration in thin descending tubule?
increased concentration
50
urine concentration in thick ascending tubule?
decreased concentration
51
reabsorption in distal convoluted tubule?
Na and Ca, water impermeable
52
where in the nephron is water impermeable?
thick ascending tubule, distal convoluted tubule
53
where in the nephron is water permeable
PCT, thin descending, collecting duct
54
collecting duct reabsorption
Na, water if ADH and aldosterone
55
site of action of aldosterone and ADH
collecting ducts
56
where is Na NOT resabsorbed?
thin limb of loop of henle
57
what is the passive step of Na reabsorption?
passive movement of na from lumen into tubular cell mediated by transporter mechanisms
58
what is the active step of na resorption?
movement of na from the tubular cell through the ECF to the blood, mediated by Na/K ATPase in basolateral membrane
59
where is the basolateral membrane?
between the tubular cell and the interstitial fluid (extracellular fluid)
60
% of Na reabsorption in PCT?
67%
61
passive step of Na reabsorption in PCT?
Na/H exchanger
62
active step of Na reabsorption in PCT, thick ascending, DCT and collecting duct?
Na/K ATPase
63
Na reabsorption in thin descending limb?
NONE
64
%Na reabsorption in thick ascending limb?
25%
65
passive step of Na reabsorption in thick ascending limb?
Na/K/2Cl transporter
66
% Na reabsorption in DCT?
6%
67
passive step of na reabsorption in DCT?
NaCl transporter
68
% na reabsorption collecting tubule?
2%
69
passive step of na reabsorption in collecting tubule?
na ion channels
70
which step do diuretics block for Na reabsorption?
passive steps (Na/K/2Cl, NaCl transporters and Na ion channels)
71
2 routes that diuretics reach site of actions?
blood to site, tubular fluid to site
72
which is the only diuretic that utilizes blood transport?
aldosterone antagonists (spironolactone)
73
how do most diuretics travel from the tubular fluid to the site of action?
drug binds to OASS and is transported from the blood directly into the tubular lumen in the PCT
74
how do aldosterone antagonists (spironolactone) reach the site of action?
directly from blood to site
75
how do osmotic diuretics reach the site of action?
filtration of the substance at the glomerulus
76
what large or extensively bound molecules are transferred from the blood to the renal tubules through the OASS?
diuretics, penicillin, uric acid, NSAIDs
77
what is the effect of diuretics with frequent gout attacks?
diuretics compete with endogenous substances for transfer into tubular fluid and can lead to decreased uric acid secretion and increased uric acid concentrations in blood (increased uric acid in plasma, buildup of uric acid)
78
most potent loop diuretic
bumetanide
79
2 most notable characteristics of loop diuretics?
1. most powerful diuretic that produce lots of urine (highest efficacy in producing na and water loss)
2. very rapid onset of action
80
benefit of very rapid onset of action of loop diuretics?
can be used in emergency situations (edema from heart failure)
81
loop diuretic access to site of action?
to the tubular fluid via OASS in the PCT
82
nephron site of action of loop diuretic?
thick ascending limb
83
transporter site of action loop diuretics
Na/K/2Cl transporter on the luminal membrane of thick ascending limb
84
which ions can move directly from lumen to blood?
calcium and magnesium
85
5 major physiological events in thick ascending limb?
1. increased Na reabsorption
2. increased Cl reabsorption
3. increased water reabsorption
4. increased Ca reabsorption
5. increased Mg reabsorption
86
explain K accumulation in the thick ascending limb CELL
Na/K/2Cl transporter increases the [K], Na-K ATPase increases [K] in cell, which then causes the concentration gradient to move back into the lumen. this buildup of +charge drives Ca and Mg out of the lumen and into the blood.
87
what is the major reason for Ca and Mg reabsorption at the thick ascending limb?
the buildup of + charge from K secretion into the lumen driving out the Ca and Mg
88
6 pharmacological effects of loop diuretics on thick ascending limb
1. decreased na reabsorption (directly)
2. decreased cl reabsorption (directly)
3. decreased water reabsorption
4. decreased Ca reabsorption (indirectly)
5. decreased Mg (indirectly)
reabsorption
6. decreased K reabsorption (directly)(abolishes K back diffusion into the lumen, prevents + charge buildup in luminal side, removes driving force for Ca and Mg reabsorption)
89
pharmacology of loop diuretics on thick ascending limb
blocks Na/K/2Cl transporter
90
considerations for loop diuretics?
hypocalcemia, hypokalemia
91
drug interaction of loop diuretics?
NSAID decreases overall efficacy of diuretic, risk of kidney failure
92
why are NSAIDs and loop diuretics contraindicated?
NSAID blocks renal prostaglandins (PGE2), which contribute to the diuretic effects of loop diuretics
93
loop diuretic impact on prostaglandins?
loop diuretics increase PGE2, which decreases na and water reabsorption, decreasing blood volume and blood pressure
94
what adverse side effect can the loop diuretic action of decreasing K reabsorption have?
decreased K plasma concentration, increasing risk of hypokalemia
95
what adverse side effect can the loop diuretic action of decreasing Na and H2O reabsorption have?
decreases blood volume, therefore decreasing blood pressure, increasing risk of hypovalemia (orthostatic hypotension and lightheaded)and hyponatremia
96
what adverse side effect can the loop diuretic action of increasing uric acid reabsorption have?
increased plasma uric acid concentration, increases risk for hyperuricemia and gout
97
chlorthiazide classq
thiazide diuretic
98
HCTZ class
thiazide diuretic
99
chlorthalidone class
thiazide-like diuretic
100
metolazone class
thiazide like diuretic
101
indapamide class
thiazide like diuretic
102
onset of action speed?
slower than loop diuretics
103
which class is the most effective diuretic in lowering BP and is the first line HTN tx?
thiazide and thiazide-like diuretics
104
thiazide/TLD nephron side of action?
distal convoluted tubule
105
transporter targeted by thiazides?
NaCl transporter on luminal membrane of DCT
106
how do thiazides/TLD access the DCT?
tubular fluid via organic acid secretory system (OSS in the PCT)
107
4 major physiological events in the distal tubule?
1. increased Na reabsorption
2. increased Cl reabsorption
3. increased water reabsorption (direct and indirect)
4. increased Ca reabsorption
108
where does Ca reabsorption occur in the distal convoluted tubule?
Na/Ca exchanger, driven by energy derived from the steep Na gradient (high Na outside the cell makes high Ca outside the cell, optimizing reabsorption)
109
Thiazide diuretics and NaCl transporter relationship??
thiazide blocks NaCl channel, decreasing Na and Cl reabsorption directly, decreasing intracellular Na directly
110
thiazide NaCl transporter effect on Ca?
increases Ca reabsorption indirectly via reduction in intracellular Na (blocked NaCl) d/t increased movement of Na from blood to cell at the Na/Ca exchanger which equals more energy input to Ca transport )increase rate of Ca movement from cell into blood) = rise in blood Ca levels
111
Thiazide/TLD effect on arterioles?
work directly on smooth muscle cells, promote smooth muscle relaxation, most responsible for long term reduction in blood pressure
112
physiologic response to smooth muscle relaxation in the arterioles?
vasodilation, decreased peripheral resistance, decreased blood pressure
113
where is thiazide/TLD active?
orally
114
onset of action of thiazides?
1-3 weeks before stable BP reduction
115
duration of action of thiazides?
long duration (d/t vasodilation mostly and volume reduction)
116
5 main effects of thiazides/TLD?
1. decreased Na and H2O reabsorption
2. relaxation of smooth muscle in arterioles
3. decreased K reabsorption
4. increased Ca reabsorption
5. uric acid reabsorption
117
risk of decreased K reabsorption?
decreased plasma K concentration, leading to increased risk of hypokalemia
118
risk of increased Ca reabsorption?
increased plasma Ca concentration, increasing bone mineral density and decreasing risk of hip fractures
119
risk of uric acid reabsorption?
increased plasma uric acid concentration, leading to hyperuricemia and increased gout risk
120
risk of the combination decreased Na, H2O absorption and decreased peripheral resistance?
decreased BP that could lead to hypovolemia, orthostatic hypotension and light headedness, and hyponatremia
121
what makes potassium sparing diuretics special?
actually increases K reabsorption, not decreased
122
what are the two classes of potassium sparing diuretics?
1. Na channel blockers
| 2. aldosterone antagonists
123
amiloride class
K sparing, na channel blocker
124
triamterene class
na channel blocker, Ksparing diuretic
125
spironolactone class
aldosterone antagonist ,K sparing
126
canrenone class
aldosterone antagonist, K sparing
127
eplerenone class
aldosterone antagonist, K sparing
128
K sparing diuretic site of action?
collecting ducts
129
aldosterone antagonist transporter site of action
block aldosterone receptors in cytoplasm of collecting duct cells
130
Na channel blocker transporter site of action?
block Na channels on luminal membrane of collecting duct
131
aldosterone antagonist access to site of action?
transported through the blood and then directly through the lipid membrane of collecting duct cells to cytoplasmic aldosterone receptor
132
na channel antagonist access to site of action?
tubular fluid via OASS in the PCT
133
3 major aldosterone effects?
1. decreased K reabsorption
2. increased Na reabsorption
3. increased water reabsorption (decreased water output) (passive and indirect)
134
what 2 things (genetically) occur when aldosterone is released?
1. binds to and activates cytoplasmic aldosterone receptor
| 2. aldosterone-receptor complex migrates to nucleus and binds to DNA
135
what does aldosterone-receptor complex binding to DNA cause? (3)
1. increased Na channel expression
2. increased Na channel activity
3. increased K channel expression
