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1.    A 77-year-old woman who is a nursing home resident has been taking desmopressin for the treatment of enuresis (involuntary urination). She is receiving oral desmopressin each night before sleep. The nursing staff at this centre encourages all patients to drink plenty of fluids, especially during the warmer summer months. The next morning, she has a seizure and is brought to the Emergency Department with increased confusion. Her serum sodium level is 109 mmol/L (136 – 145 mmol/L).

(a)  Why does the patient develop seizure?

(b)  How to prevent the same neurological problems to occur in patient taking desmopressin?

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1.    A 50-year-old male patient of liver cirrhosis with ascites and pedal oedema was treated with furosemide 80 mg twice a day. He started passing larger quantity of urine and the ascites and oedema started regressing. After a week, he was brought with incoherent talking, drowsiness, tremor and ataxia. His wife informed that for the past 2 days he was no longer passing the increased amount of urine as at the start of medication. His serum potassium measurement was 2.8 mmol/L (3.5 – 5.0 mmol/L).

(Hint: Liver cirrhosis is associated with raised aldosterone and low plasma potassium levels.)

(a)  What is the cause of the neurological symptoms and decreased diuretic response to furosemide?

(b)  How should the patient be managed at the present stage?

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a)  Thiazide inhibits NaCl transport in the DCT
b) potassium sparring diuretics prevent potassium ion secretion by antagonizing the effects of aldosterone in collecting tubules.
c)  For patients with HF, intravenous conivaptan cannot be used
a & b - true
c - false
Because it has been found that the blockage of V1a receptors by this drug leads to decreased peripheral vascular resistance & increase CO

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2T1L

1) Acetamizole can be use to treat galucoma

2) Loop diuretics can cause hyperuricemia

3) Thiazide acts primary/predominant on PCT

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1.Carbonic anhydrase inhibitor used in glaucoma and acute mountain sickness
2.Ethacrynic acid enhance uric acid reabsorption at proximal convoluted tubule
3.Thiazide diuretics cause kidney stones

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TTL

1) Side effects of loop diuretics:
A) ototoxicity
B) metabolic acidosis
C) hyperurecemia

By inhibiting salt reabsorption in the TAL, loop diuretics increase Na +    delivery  to  the  collecting  duct.  Increased  delivery  leads  to  increased secretion of K +  and H +  by the duct, causing hypokalemic metabolic alkalosis (page 260)

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a) All thiazides are secreted by the organic acid secretory enzyme in the proximal tubule and compete with the secretion of uric acid by that system.
b) By inhibiting H+ secretion in parallel with K+ secretion, the K+ sparing diuretics can cause acidosis similar to that seen with with type IV renal tubular acidosis.
c) Carbonic Anhydrase Inhibitors are contraindicated in Glaucoma
ANSWER: TTF
F-The reduction of aqueous humor formation by carbonic anhydrase inhibitors decreases the intraocular pressure. This effect is valuable in the management of glaucoma, making it the most common indication for use of carbonic anhydrase inhibitors.

REFERENCE: Katzung

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a) Bumetanide are used in the treatment of hyperkalemia and acute renal failure

b) Thiazide decrease the reabsorption of Na+ by inhibition of epithelial Na+ channel (ENac)

c) In the kidney, vasopressin binds to the V2 receptor to increase water permeability and reabsorption in the collecting tubules

Answer:
TLT
Explanation:
Thiazide decrease the reabsorption of Na+ by inhibition of Na+/Cl− cotransporter (Reference: Lippincott page 663)

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TTL

a)      Acetazolamide acts primarily on the luminal membrane of Proximal convoluted tubule

b)     Ethacrynic acid is used to treat hyperuricemia.

c)      Tolvaptan is used to treat Syndrome of Inappropriate Antidiuresis (SIAD)
TTL

a)      Acetazolamide acts primarily on the luminal membrane of Proximal convoluted tubule

b)     Ethacrynic acid is used to treat hyperuricemia.

c)      Spironolactone is used to treat hyperaldosteronism

Ans:

·        a and c – true

·        b – false: because ethacrynic acid (loop diuretic) can cause hyperuricemia and precipitate attacks of gout. This is caused by hypovolaemia-asscociated enhancement of uric acid reabsorption in the Proximal convoluted tubule. (Page 260; Basic and Clinical Pharmacology 12th edition Bertram Katzung)

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2 truths 1 lie

L - Mannitol is given orally to increase its bioavailability.
T - K+ sparing diuretic can be administered together with loop diuretics and thiazide.
T - Anti-diuretic hormone antagonist is used to treat congestive heart failure.

Explanation
Mannitol is given intravenously instead as it is poorly absorbed by the GI tract and cause osmotic diarrhea instead of diuresis. (Katzung - Page 263)

To treat hypokalemia commonly happened when using thiazide and loop diuretics. (Katzung - Page 262)

CHF causes increase in ADH secretion due to decrease renal perfusion to compensate the diminish CO thus can cause oedema and hyponatremia. (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4470207/#__sec6title)
(Katzung - Page 264)

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1. Mannitol is contraindicated in patients with congestive heart failure. T
2. Site of action of tolvaptan is Distal Convoluted Tubule. L
3. Hypokalemia develops in patient taking Thiazides. T

Site of action of tolvaptan is collecting tubule.

Reference : Katzung page 264 - "Antidiuretic hormone antagonists inhibit the effects of ADH in the collecting tubule."

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1. Vasopressin is a treatment of choice for diabetes insipidus

2. V1 receptors are found on on renal tubule cells

3. Vasopressin increase the expression of aquaporin (water channel) thus increase the reabsorption of water
(TFT)

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A. Vasopressin is indicated in patients with coronary artery disease.

B. Hydrochlorothiazide inhibits Na/Cl transporter in the distal convoluted tubule.

C. Mannitol toxicity causes water extraction from cells and subsequently, hyponatremia.

Answer A- False
B & C - True
Explanation: Vasopressin is contraindicated in patients with coronary artery disease as it causes vasoconstriction of vascular smooth muscles further exacerbating coronary artery disease.

(Reference: Katzung page 675 - ‘Vasopressin (but not desmopressin) can cause vasoconstriction and should be used cautiously in patients with coronary artery disease.’).

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a. Acetazolamide reduces the reabsorption of bicarbonate ion in the proximal convoluted tubule.

b.  One of the toxicity effects of spironolactone is hyperchloremic metabolic acidosis.

c.  Vasopressin acts on V1 receptors on renal tubule cells to increase water reabsorption.

Answers:
Truth – a & b

Lie – c

Explanation:

a) Katzung page 257

‘Inhibition of carbonic anhydrase activity profoundly depresses HCO3− reabsorption in the PCT.’

b) Katzung page 263

‘By inhibiting H+ secretion in parallel with K+ secretion, the K+-sparing diuretics can cause acidosis similar to that seen with type IV renal tubular acidosis.’

a) Katzung page 674

‘Vasopressin activates two subtypes of G protein-coupled receptors (see Chapter 17). V1 receptors are found on vascular smooth muscle cells and mediate vasoconstriction via the coupling protein Gq. V2 receptors are found on renal tubule cells and reduce diuresis through increased water permeability and water resorption in the collecting tubules via Gs.’

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1. Mannitol must be used cautiously in patients with even mild renal insufficiency.

2. Tolvaptan are selectively active against the V2 receptor.

3. Thiazides stimulates NaCl reabsorption from the luminal side of epithelial cells in the DCT

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1. Hydrochlorothiazide inhbits Na/Cl transporter in distal convoluted tubule
2. Ethacrynic acid  can cause hypersensitivity reaction
3. Indamapide is contraindicated in gout patient

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TTL:

A. Loop diuretics can cause hypercalcemia.

B. Thiazides inhibit NaCl reabsorption from luminal side of epithelial cells in the distal convoluted tubule by blocking the Na+/Cl- transporter.

C.  Concomitant use of K+ sparing diuretics and agents that blunt the renin-angiotensin-aldosterone system increases risk of hyperkalemia.

Answer:

Truths – b & c

Lie – a

Explanation:

Loop diuretics causes hypocalcemia. (Reference: Katzung page 260 – ‘Loop agents can cause hypercalciuria, which can lead to mild hypocalcemia and secondary hyperparathyroidism.’)

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NURUL HIDAYAH BT ISMAIL FAROOK AMEERALI 200760

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NURUL HIDAYAH BT ISMAIL FAROOK AMEERALI 200760

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1. Conivaptan and tolvaptan are direct ADH receptor antagonist
2.  Thiazide acts at the thick ascending loop of henle
3. Loop diuretic cause hyperurcemia

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A. Acetazolamide are contraindicated in patient with cirrhosis.

b. thiazide act predominantly in the distal convoluted tubule.

c. vasopressin act on V2 receptor at the smooth muscles cells and mediate vasoconstriction.

answer: TTL
explanation:
V2 are found in renal tubules and reduce diuresis through increase water permeability and water reabsorption.
reference Katzung page 674.