Diuretics Flashcards
(144 cards)
1
Q
metabolic acidosis as SE
A
Sulfanilamide
2
Q
prototype drug
A
Acetazolamide
3
Q
- limited usefulness as diuretics
A
CAIs
4
Q
- forerunners of diuretics
A
CAIs
5
Q
Zn metalloenzyme found in proximal tubular epithelial cells (where too??)
A
Carbonic Anhydrase
- Luminal and basolateral membranes (type IV)
- Cytoplasm (type III)
6
Q
first to discover CA in mammalian kidneys
A
Davenport and Willhelmi (1941)
7
Q
Key role in NaHCO3 reabsorption and acid secretion
A
Carbonic anhydrase
8
Q
Inhibit the enzyme carbonic anhydrase, blocking NaHCO3 reabsorption in PCT
A
Carbonic anhydrase Inhibitors MOA
9
Q
MOA of Carbonic Anhydrase Inhibitors
A
Inhibit the enzyme carbonic anhydrase, blocking NaHCO3 reabsorption in PCT
collecting duct as secondary site of action (blocking and secretion)
10
Q
collecting duct as secondary site of action (blocking and secretion)
A
MOA of Carbonic Anhydrase Inhibitors
11
Q
Extrarenal action of CAIs
A
Extrarenal actions:
- Decreases rate of formation of aqueous humor -> reduces IOP
- Frequently causes paresthesias and somnolence
- Anticonvulsant (acetazolamide)
- Increases CO2 levels in peripheral tissues; decreases CO2 levels in expired gas
- Reduce gastric acid secretion (large doses)
12
Q
Decreases rate of formation of aqueous humor -> reduces IOP
A
CAIs
13
Q
Frequently causes paresthesias and somnolence
A
CAIs
14
Q
Anticonvulsant
A
acetazolamide
15
Q
Increases CO2 levels in peripheral tissues; decreases CO2 levels in expired gas
A
CAIs
16
Q
Reduce gastric acid secretion (large doses)
A
CAis
17
Q
Dose Acetazolamide
A
125 mg half, 250 mg and quarter-scored tablets
18
Q
1% ophthalmic suspension
A
Brinzolamide
19
Q
2% ophthalmic suspension
A
Dorzolamide
20
Q
primary indication is Glaucoma, no diuretic effect, no systemic effect and ↓IOP
A
Brinzolamide, Dorzolamide Topical agents
21
Q
open-angle glaucoma
A
CAIs
22
Q
CHF-associated and drug induced edema
A
acetazolamide
23
Q
Epilepsy
A
(acetazolamide)
24
Q
symptomatic relef and/or prophylaxis for acute mountain or altitude sickness
A
CAIs
*used nightly for 5 days before climbing to prevent weakness, breathlessness
25
familial periodic paralysis
CAIs
26
correction of metabolic alkalosis (diuretic-induced H+ excretion)
CAIs
27
bone marrow depression, skin toxicity, sulfonamide-like renal lesions, hypersensitivity reactions (SJS)
AE - CAIs
28
signs on bulla skin, deadly if on mucosa
SJS
29
drowsiness and paresthesias
AE - CAIs
30
Hepatic encephalopathy
AE - CAIs
31
( diversion of ammonia of renal origin from urine into the systemic circulation -> induce or worsen hepatic encephalopathy therefore drugs are contraindicated to patients with hepatic cirrhosis
AE - CAIs
Hepatic encephalopathy
32
calculus formation, ureteral colic
AE - CAIs
33
(owing to ppt of calcium phosphate salts in an alkaline urine)
AE - CAIs
| Calculus formation, ureteral colic
34
worsening of metabolic or respiratory acidosis
AE - CAIs
35
Drugs are contraindicated in patients with hyperchloremic acidosis or severe COPD
AE - CAIs
| worsening of metabolic or respiratory acidosis
36
Na+ and K+ wasting
AE - CAIs
37
CI for patients w/ Na+ or K+ depletion)
AE - CAIs
| CI for patients w/ Na+ or K+ depletion)
38
- Most effective diuretics available
LOOP DIURETICS
39
- High-ceiling diuretics
LOOP DIURETICS
40
Highest efficacy in mobilizing Na+ and Cl- from the body
LOOP DIURETICS
41
*produce copious amounts of urine
LOOP DIURETICS
42
Act directly on the thick ascending limb of the loop of Henle to inhibit sodium and chloride reabsorption
LOOP DIURETICS
43
MOA of Loop diuretics
Act directly on the thick ascending limb of the loop of Henle to inhibit sodium and chloride reabsorption
44
Increase renal prostaglandins, resulting in the dilation of blood vessels and reduced peripheral vascular resistance (↑ renal blood flow)
LOOP DIURETICS
45
– impt role in mediating renin release reponse to loop diuretics
Prostacyclins
| LOOP DIURETICS
46
Prostaglandins have a role in their diuretic action and NSAIDS like indomethacin that interfere in prostaglandin synthesis can reduce the diuretic action of these agents
LOOP DIURETICS
47
Decrease renal vascular resistance and increase renal blood flow
LOOP DIURETICS
48
Other actions of loop diuretics
1. Increase renal prostaglandins, resulting in the dilation of blood vessels and reduced peripheral vascular resistance (↑ renal blood flow)
* Prostacyclin – impt role in mediating renin release reponse to loop diuretics
* Prostaglandins have a role in their diuretic action and NSAIDS like indomethacin that interfere in prostaglandin synthesis can reduce the diuretic action of these agents
2. Decrease renal vascular resistance and increase renal blood flow
49
Lasix dosage form
Tablet and ampule
50
– greater S/E therefore limited use (a loop diuretic)
Ethacrynic acid
51
more potent than furosemide , ↑ use
Bumetanide
52
DOC: acute pulmonary edema of HF
LOOP diuretics
| given parenterally due to rapid action
53
Ind: Hypercalcemia (+hydration)
LOOP DIURETICS
54
Ind: - Hyperkalemia
LOOP DIURETICS
55
Ind: Hyponatremia
| (+ hypertonic saline
LOOP DIURETICS
56
Ind: Acute renal failure
| oliguric to nonoliguric
LOOP DIURETICS
57
Ind: - Forced diuresis in drug overdose
LOOP DIURETICS
58
Ind: Hypertension refractory to other diuretics or antihypertensives
LOOP DIURETICS
59
Administered orally or parenterally
LOOP DIURETICS
60
rapid onset of action (IV)
LOOP DIURETICS
61
duration of action is relatively brief (2 to 4 hrs)
LOOP DIURETICS
62
secreted into urine
LOOP DIURETICS
63
A/E Hypokalemia
| TX?
Tx: Potassium-sparing diuretics or dietary supplementation with K+
LOOP DIURETICS
64
A/E Hypomagnesemia
(chronic use + low dietary intake of Mg 2+) = Elderly
| LOOP DIURETICS
65
A/E Hyperuricemia
furosemide, ethacrynic acid compete with uric acid for the renal and biliary secretory systems, thus blocking its secretion and inturen causing or exacerbating gouty attacks)
LOOP DIURETICS
66
A/E Ototoxicity
(+aminoglycosides; rapid IV > PO)
*Tinnitus- hearing impairment deafness, vertigo, sense of fullness in the ears
*vestibular function too affected
LOOP DIURETICS
67
A/E - Sulfonamide-related hypersensitivity rxns
(Furosemide and Bumetanide)
| LOOP DIURETICS
68
- synthesized to enhance potency of CAIs
Thiazides
69
- discovered to increase NaCl excretion
Thiazides
70
- Benzothiadiazine derivatives (chlorothiazide) are
Thiazides
71
- Most widely used diuretic drugs for tx of Hypertension
Thiazides
72
- Sulfonamide derivatives; related in structure to CAIs
- Significantly greater diuretic activity than acetazolamide
Thiazides
73
- Affect the distal convoluted tubule
Thiazides
74
- All have equal max diuretic effects, differing only in potency(expressed on a per-milligram basis) -> “ceiling diuretics”
*Even if increase dose of drug, it will not give ↑/enhance therapeutic action but only toxic actions
Thiazides
75
Act mainly in the cortical region of the ascending loop of Henle and the distal tubule to decrease the reabsorption of Na+, apparently by inhibition of a Na+/Cl- co-transporter on the luminal membrane of the tubules
Thiazides
76
- first modern diuretic that was active orally and was capable of affecting the severe edema of cirrhosis and heart failure w/ a min. of S/E
Chlorothiazide
77
- less ability to inhibit CA than chlorothiazide
Hydrochlorothiazide
78
- Newer derivative used more commonly
Hydrochlorothiazide
79
- more potent (required dose is considerably lower)
Hydrochlorothiazide
80
- efficacy is exactly the same as that of the parent drug
Hydrochlorothiazide
81
IND: - mainstay of antihypertensive medication
Thiazides
82
IND:- HF (when additional diuresis is needed)
Thiazides
83
IND:- Hypercalciuria
Thiazides
84
IND:- Nephrogenic diabetes insipidus (substitute for ADH)
Thiazides
85
- Effective orally
Thiazides
86
- Most thiazides take ___ wks to produce a stable reduction in BP
1 to 3 wks
87
- Exhibit a prolonged biologic half-life
Thiazides
88
- secreted by the organic acid secretory system of the kidney
Thiazides
89
A/E - Hypokalemia (↑common)
Thiazides
90
A/E - Hyponatremia
Thiazides
91
A/E - Hyperuricemia
- increase serum uric acid by decreasing the amt of acid excreted by the organic acid secretory system
Thiazides
92
A/E - Hypercalcemia
Thiazides
93
A/E - Hyperglycemia
- due to impaired release of inculin and tissue uptake of glucose
Thiazides
94
A/E - Hyperlipidemia
Thiazides
95
A/E - Volume depletion
Thiazides
96
A/E - Hypersensitivity rxns
Thiazides
97
- compounds that lack the thiazide structure but like thiazides they have the unsubstituted sulfonamide groups and share same MOA
Thiazide -like
98
- Non-thiazide derivatives that behaves like HCTZ
Chlorthalidone
99
- very long duration of action ; therefore, is often used to tx Hypertension
Chlorthalidone
100
- given 1/d for this in
Chlorthalidone
101
- more potent than thiazides
Metolazone
102
- causes Na+ excretion in advanced renal failure
Metolazone
103
- lipid-soluble, nonthiazide diuretic that has a long duration of action
Indapamide
104
- at low doses, shows significant antihypertensive action w/ min diuretic effects
Indapamide
105
- metabolized and excreted by the GIT and kidneys
Indapamide
106
- less likely to accumulate in patients w/ renal failure
Indapamide
107
- act in the collecting tubule to inhibit Na reabsorption and K+ excretion
Potassium-sparing diuretics/ Na-channel inhibitors
108
- Major use: Tx of hypertension, most often in combination w/ a thiazide
Potassium-sparing diuretics/ Na-channel inhibitors
109
- discontinue exogenous K supplementation
Potassium-sparing diuretics/ Na-channel inhibitors
110
- close monitory of serum K levels
Potassium-sparing diuretics/ Na-channel inhibitors
111
- avoided in patients with renal dysfunction because of increased risk of hyperkalemia
Potassium-sparing diuretics/ Na-channel inhibitors
112
- synthetic steroid that antagonizes aldosterone at intracellular cytoplasmic receptor sites
Spironolactone
113
- Inactive spironolactone-receptor complex (does not bind to DNA -> inhibition of protein synthesis)
Spironolactone
114
- mediator proteins not present to stimulate Na+/K+ exchange sites
Spironolactone
115
- Inhibition of Na+ reabsorption and K+/H+ secretion
Spironolactone
116
*in patients with no significant circulating levels of aldosterones, like with Addison disease (primary adrenal deficiency) , no diuretic effect of the drug occur
Spironolactone
117
(Spironolactone + HCTZ)
ALDAZIDE
118
- often given in conjunction w/ a thiazide or loop diuretic to prevent the K+ excretion
Aldosterone Antagonist
119
- diuretic of choice in patients with hepatic cirrhosis
Aldosterone Antagonist
120
- secondary hyperaldosteronism
Aldosterone Antagonist
121
- completely absorbed orally
Aldosterone Antagonist
122
- strongly bound to proteins
Aldosterone Antagonist
123
- rapidly converted to an active metabolite, canrenone (has mineralocorticoid-blocking activity)
Aldosterone Antagonist
124
- induces hepatic cytochrome P450
Aldosterone Antagonist
125
- Gastric upsets -> peptic ulcers
Aldosterone Antagonist
126
- Gynecomastia in male patients; menstrual irregularities in female patients (high doses on chronic use)
Aldosterone Antagonist
127
- Hyperkalemia, nausea, lethargy and mental confusion
Aldosterone Antagonist
128
- block Na+ transport channels, resulting in a decrease in Na+/K+ exchange
Triamterene and Amiloride
129
- ability to block the Na+/K+ - exchange site does not depend on the presence of aldosterone
Triamterene and Amiloride
130
- not very efficacious diuretics
Triamterene and Amiloride
131
- commonly used in combination with other diuretics usually for their potassium-sparing properties
Triamterene and Amiloride
132
- leg cramps
Triamterene and Amiloride
133
- possibility of increased blood urea nitrogen, uric acid and K+ retention
Triamterene and Amiloride
134
- agents that are freely filtered at the glomerulus, undergo limited reabsorption by the renal tubule, and are relatively inert pharmacologically
Osmotic diuretics
135
- administered in large enough doses to increase significantly osmolality of plasma and tubular fluid
Osmotic diuretics
136
- not useful for treating conditions in which Na retention occurs
Osmotic diuretics
137
Increase the osmotic pressure at the PCT and LOH to prevent water reabsorption
Osmotic diuretics
138
what about mannitol?
- IV only
- prolonged standing of mannitol (may ppt)
- subject to heat (glass bottles); shake bottles (agitate) until clear
139
- used to maintain urine flow following acute toxic ingestion of substances capable of producing acute renal failure
Osmotic diuretics
140
- mainstay treatment for patients with increased intracranial pressure or acute renal failure due to shock, drug toxicities and trauma
Osmotic diuretics
141
- extracellular water expansion
Osmotic diuretics
142
- dehydration
Osmotic diuretics
143
- hypo- or hypernatremia
Osmotic diuretics
144
*The expansion of extracellular water results because the presence of mannitol in the extracellular fluid extracts water from the cells and causes hyponatremia until diuresis occurs.
Osmotic diuretics
