| 2689973633 | What is a diuretic? | a drug that increases the excretion of both fluids and solutes | | 0 |
| 2689974215 | What are the 2 types of diuretics? | Natriuretic: increases Na+ excretion
Kaliuretic: increases K+ excretion | | 1 |
| 2689974727 | What are the 2 modes of action of diuretics? | 1) Direct action on the cells of the nephron (more common)
2) Modification of content of the filtrate | | 2 |
| 2689975361 | Two major applications of diuretic agents: | 1) Reduce circulating fluid volume
2) Removal of excess body fluid (oedema) | | 3 |
| 2689975760 | In which conditions do we use diuretics? | - hypertension
- chronic heart failure
- liver cirrhosis
- renal disease
- premenstrual oedema
- toxic oedema
- increase elimination of drugs
- rapid weight loss (abuse)
Other actions
- glaucoma
(reduces intra-ocular pressure)
- epilepsy
(reduces pressure of CSF?) | | 4 |
| 2689977230 | Overview of fluid reabsorption in the Nephron | |  | 5 |
| 2689979218 | How much water and Na+ are reabsorbed? | 99.5%
99.4% | | 6 |
| 2689979724 | What are the 5 classes of diuretics | - Carbonic anhydrase inhibitors
- Osmotic diuretics
- Loop diuretics
- Thiazides
- Potassium-sparing diuretics
- Aldosterone antagonists
- Non-aldosterone antagonists |  | 7 |
| 2689985908 | How (where from?) do diuretics produce their effect? | Most (not all) are secreted into the proximal tubule and then produce their actions from the luminal (urine) side of the tubule | | 8 |
| 2689982090 | Where do Carbonic Anhydrase Inhibitor act? | PT |  | 9 |
| 2689982467 | Where do Osmotic Diuretics act? | PT
Descending LOH (i.e. water permeable part of the nephron) |  | 10 |
| 2689983009 | Where do loop diuretics act? | Ascending LOH |  | 11 |
| 2689983255 | Where do Thiazides act? | Early DT |  | 12 |
| 2689983820 | Where do Aldosterone antagonist Potassium sparing diuretics act? | late distal tubule |  | 13 |
| 2689983821 | Where do Non-Aldosterone antagonist Potassium sparing diuretics act? | Early Collecting Tubule |  | 14 |
| 2689987822 | Which diuretics are most effective? | Loop Diuretics | | 15 |
| 2689988147 | MOA of Loop Diuretics | Inhibit the Na+/K+/2Cl- transporters (NKCC2) in the thick ascending limb of loop of Henle
-> this reduces reabsorption of Na+, K+ and Cl-
=> Reduced Na+ reabsorption leads to rapid and profound diuresis:
=>Single dose: can increase urine volume from 200 to 1,200 ml over 3 h... |  | 16 |
| 2689991343 | Loop Diuretics : Route of Administration and Effects (Furosemide) | - Oral absorption:
diuresis in 60 minutes and persists for 4-6 hours (called Lasix as it lasts 6h)
- IV administration:
diuresis begins within 5 minutes and persists for 2 hours
- IM administration:
diuresis begins in 30 minutes | | 17 |
| 2689992775 | Clinical uses of Loop Diuretics | Acute pulmonary oedema
Chronic heart failure
Cirrhosis of the liver
Resistant hypertension
USED FOR ACUTE CONDITIONS
Nephrotic syndrome
Acute renal failure
REDUCED URINE PRODUCTION (OLIGURIA) | | 18 |
| 2689993839 | Unwanted effects of Loop Diuretics | - Dehydration
- hypokalaemia (+can potentiate effects of cardiac glycosides )
- Metabolic alkalosis
- Deafness (when used with aminoglycoside antibiotics) | | 19 |
| 2689994947 | Why can Loop Diuretics cause Hypokalaemia? | - Loop diuretics cause increased Na+ delivery to the DT
- This is exchanged for K+ in the DT which is excreted in the urine
=> This K+ loss contributes to the hypokalaemia associated with loop diuretics |  | 20 |
| 2689996969 | MOA of Thiazide Diuretics? | - Act in the distal tubule to inhibit the apical Na+/Cl- co-transporter
-> Cause moderate but sustained Na+ excretion with increased water excretion |  | 21 |
| 2689997809 | Characteristics of Thiazides | -Moderately powerful diuresis
-Well absorbed from GI tract
- long duration of action: up to 24 h | | 22 |
| 2689998807 | What is the most used Thiazide diuretic? | bendroflumethiazide (bendrofluazide)
(Neo-NaClex®, Aprinox®)
(several others available) | | 23 |
| 2690000107 | Clinical uses of Thiazide Diuretics | Hypertension
Oedema
Mild heart failure
GENERALLY USED FOR LESS ACUTE CONDITIONS | | 24 |
| 2690004861 | Unwanted Effects of Thiazide Diuretics | Hypokalaemia
Metabolic alkalosis
Increased plasma uric acid - gout
Hyperglycaemia
Increased plasma cholesterol (with long-term use)
Male impotence (reversible) | | 25 |
| 2690006720 | Why is hypokalaemia a potential problem? | Mild hypokalaemia
- fatigue, drowsiness, dizziness, muscle weakness
Severe hypokalaemia
- abnormal heart rhythm, muscle paralysis, death | | 26 |
| 2690007687 | How to avoid hypokalaemia when using diuretics? | Potassium-sparing diuretics
- Act on distal tubules to inhibit Na+ reabsorption
- However, K+ is not secreted into the distal tubule
Two subcategories:
- Aldosterone antagonists
(e.g. eplerenone, spironolactone)
- Non-Aldosterone antagonists
(e.g. amiloride, triamterene) | | 27 |
| 2690008271 | MOA of ALDOSTERONE ANTAGONISTS Potassium-sparing diuretics
[Spironolactone & Eplerenone] | - Spironolactone and Eplerenone
- Competitive antagonists of aldosterone
=> reduce Na+ channel formation
==>Reduces Na+ absorption from distal tubule
- Limited diuretic action (not as potent as loop diuretics or thiazides)
- Mechanism depends on reduction of protein expression in distal tubular cells
=>effects may take several days to develop |  | 28 |
| 2690010348 | Clinical uses of Spironolactone & Eplerenone | Heart failure
Oedema
SHORT TERM USE
Can also be used for resistant hypertension but some concerns over long-term use due to possible incidence of cancer
(note: reported in rat studies only) | | 29 |
| 2690011687 | Unwanted effects of Spironolactone & Eplerenone | - HYPERkalaemia - needs to be monitored regularly
- Metabolic acidosis (due to increased plasma H+)
- GI upsets (peptic ulceration reported)
- Gynaecomastia, menstrual disorders, testicular atrophy | | 30 |
| 2690012476 | MOA of NON-ALDOSTERONE ANTAGONISTS Potassium-sparing Diuretics
[Triamterene and Amiloride] | - Weak diuretics
- act on distal tubule
- Blocks luminal Na+ channel by which aldosterone produces its main effects
-> inhibit Na+ reabsorption + decrease K+ excretion |  | 31 |
| 2690013317 | Clinical use of Triamterene and Amiloride | - Of little therapeutic use alone
- but are useful in combination with potassium-depleting diuretics as they limit hypokalaemia | | 32 |
| 2690013897 | Main unwanted effects of Triamterene and Amiloride | - hyperkalaemia
- metabolic acidosis
- GI disturbances
- skin rashes |  | 33 |
| 2690016348 | What are the advantages of using diuretics in combination? | (1) To increase diuretic effect
- Some patients do not respond well to just one type of diuretic (e.g. loop diuretics) - reasons unknown, probably genetic
- Combinations of diuretics with different sites of action can sometimes provide a synergistic action
(2) To avoid the unwanted effects of hypokalaemia
- Combinations of loop diuretics or thiazides with potassium-sparing
diuretics
- Diuretic preparations containing K+....... | | 34 |
| 2690017430 | List the Diuretics combinations preparations | - Loop diuretics with spironolactone
Lasilactone®: furosemide + spironolactone
- Loop diuretics with amiloride or triamterene
Co-amilofruse: furosemide + amiloride
- Thiazides with spironolactone
Co-flumactone: hydroflumethiazide + spironolactone
- Thiazides with amiloride or triamterene
Co-amilozide: hydrochlorothiazide + amiloride | | 35 |
| 2690021070 | List Diuretics containing K+ | Burinex K®: bumetanide + K+
Centyl K®: bendroflumethiazide + K+
Lasikal®: furosemide + K+
Neo-NaClex-K®: bendroflumethiazide + K+ | | 36 |
| 2690022023 | MOA of Carbonic Anhydrase Inhibitors
[azetozolamide (Diamox®)] | - Blocks sodium bicarbonate (NaHCO3) reabsorption in the PT
- These were the earliest diuretic agents developed
- Causes only weak diuresis so not now commonly used as diuretic agent |  | 37 |
| 2690022856 | Clinical use of Carbonic Anhydrase Inhibitors
[azetozolamide (Diamox®)] | - glaucoma (reduces intraoccular pressure)
- epilepsy (reduces volume and pressure of CSF) |  | 38 |
| 2690023438 | Unwanted effects of Carbonic Anhydrase Inhibitors
[azetozolamide (Diamox®)] | - metabolic acidosis (due to excretion of HCO3-)
- enhances renal stone formation (due to alkaline urine) | | 39 |
| 2690025226 | MOA of Osmotic Diuretics
[Mannitol] | - Non-reabsorbable solute which undergoes glomerular filtration
-> Excreted within 30-60 min
=> Diuresis begins in 30-60 min and persists for 6-8 h | | 40 |
| 2690030062 | Clinical uses of osmotic diuretics
[Mannitol] | - Treatment of raised intercranial pressure (cerebral oedema)
- glaucoma (reduces intraoccular pressure)
- If given orally, can cause 'osmotic diarrhoea' - eliminates toxins
- May be useful for treatment of acute renal failure | | 41 |
| 2690030828 | Unwanted effects of osmotic diuretics
[Mannitol] | Presence in blood also exerts osmotic pressure
=> increased plasma volume...
==> can't be used in patients with hypertension | | 42 |
| 2690032180 | Water as a diuretic | - most simple of diuretics
- Under normal conditions, increased water intake leads to increase in volume of urine excreted
- Process is controlled by antidiuretic hormone (ADH) | | 43 |
| 2690032599 | Characteristics of ADH | - Most important hormone regulating water balance
- Normally some ADH is present in the circulation, maintaining urine volume at approximately 1.5 L/day
- However, this can be adjusted in various ways... | | 44 |
| 2690033198 | What happens in increased fluid intake? | reduction in plasma osmolality
==> reduced secretion of ADH from the posterior pituitary
===> Reduced expression of AP-2 receptors
on apical surface of DT and collecting duct
cells
====> more water excretion
[Note - there is no increased excretion of Na+
- the AP-2 channel moves water only] |  | 45 |
| 2690040576 | Give an example of an agent inhibiting ADH release
What is the consequence? | Alcohol
-> inhibits ADH release
=> increase urine excretion:
(although tolerance develops rapidly so diuresis not sustained) | | 46 |
| 2690042670 | What other agents increase diuresis?
How? | Xanthines
[caffeine, theophylline, theobromine]
- Commonly found in tea and coffee
- increase cardiac output
- Possibly also some vasodilatation of the glomerular afferent arteriole
==> Results in increased renal and glomerular blood flow which increases glomerular filtration rate and urine output
====> Produce a weak diuresis | | 47 |
| 2690043902 | Are Xanthines used clinically?
Why? | Rarely used clinically
due to gastric irritant effects
(but theophylline used clinically as a bronchodilator for asthma) | | 48 |
| 2690041653 | What agents increase ADH release?
What is the consequence? | Nicotine (anecdotal evidence)
Ether
Morphine
Barbiturates
->increase ADH release
=> reduce urine excretion | | 49 |
| 2690035971 | What are the two non-selective ADH antagonists developed as possible New Diuretics Agents? | Two nonselective agents (orally active)
- Lithium (Li+) and demeclocycline. | | 50 |
| 2690038417 | What are the problems of Lithium & demeclocycline? | Toxicity is a Problem
- Can cause diabetes insipidus
- Renal failure reported for both Li+ and demeclocycline
- Li+ can cause tremors, mental confusion, cardiotoxicity, thyroid dysfunction and leukocytosis
- Demeclocycline shouldn't be used in patients with liver disease | | 51 |
| 2690039278 | What drug is currently in fast track trial for the treatment of Polycystic Kidney Disease? | Tolvaptan (OPC-41061) - V2 receptor antagonist,
- approved in US for treatment of hyponatriuraemia.
- In fast track clinical trials for polycystic kidney disease | | 52 |