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Flashcards in 27. Diuretics Deck (16)
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1
Q

Draw a nephron and indicate
where diuretic drugs exert their
effects.

A

fig 27.1

pg 129

2
Q

How does mannitol exert its

effects?

A

> Mannitol is a sugar alcohol solution,
which works as an osmotic diuretic.

> The drug has a molecular weight of
182 Daltons and so is freely filtered
by the glomerulus but not reabsorbed.

> It increases the osmolality of the
filtrate and so water
follows the drug to be excreted.

> Osmotic activity occurs mainly at
proximal convoluted tubule and loop of Henle.

3
Q

What is the major indication for

using mannitol?

A

Mannitol is used primarily in the treatment
of raised intracerebral pressure
(ICP). It reduces ICP by:

> Decreasing the formation of CSF.

> Decreasing plasma volume and
thereby encouraging water to move
out of the brain, reducing oedema.

Mannitol does not cross the intact
blood–brain barrier.

However, if the membrane is disrupted,
mannitol can cross it and worsen oedema
by drawing water with it.

Hence, unless a patient is actively coning,
it should only be used on
the advice of a neurosurgeon.

> It is free radical scavenger and
so may afford some additional neuroprotection

4
Q

Can mannitol be used repeatedly?

A

No, mannitol is used to ‘buy time’ until
raised ICP can be treated definitively.

The dose cannot be repeated indefinitely,
as it will cause an unacceptable
rise in serum osmolality
and circulatory overload.

With repeated dosing it will
eventually cross the
blood–brain barrier and cause a rise in ICP.

5
Q

How are diuretics used in renal failure?

A

Diuretics do not reverse renal failure,
but they can be used to control its
symptoms.

The use of diuretics,
particularly loop diuretics, reduces:

> Hypertension, mediated by
decreased sodium excretion
and water retention

> Congestive cardiac failure
caused by circulatory overload

> Oedema.
Large doses of the drugs may
be needed as their efficacy is decreased in
the face of low renal blood flow,
reducing delivery to their target organ.

It may be necessary to give the drugs by continuous infusion and to combine
various diuretics to achieve optimum results.

6
Q

FUROSEMIDE
(and also bumetanide)

MOA

ADME

USES

A

FUROSEMIDE
(and also bumetanide)
Loop diuretic

MOA

• Act mainly on thick ascending limb
loop of Henle,

and less so on early
distal convoluted tubule

• Inhibit reabsorption of
Na+ and Cl-

• This impairs counter-current multiplier system

• Medulla becomes less
hypertonic so less water
reabsorbed

METABOLISM
AND EXCRETION

• Excreted mostly
unchanged in urine

ABSORPTION/
DISTRIBUTION

• Both well absorbed
orally

• Bioavailability =
Frusemide – 65%
Bumetanide – 95%

• Protein binding >95%

USES

• CCF

• Peripheral and
pulmonary oedema

• To force diuresis in acute
and chronic renal failure

7
Q

Furosemide

Effects

A

EFFECTS

CVS

• Arteriolar vasodilation
causes ↓ SVR and ↓ preload

RENAL
• ↑ Renal blood flow
• ↑ GFR

BIOCHEMISTRY
• ↓ K+
• ↓ Cl–
• ↓ H+
• ↓ Na+
• ↓ Mg2+

• ↑ Ca2+
(less common than
thiazides)

• ↑ Uric acid causes gout
(less common than with
thiazides)

METABOLIC
• Hyperglycaemia
(less common than with
thiazides)

• ↑ Cholesterol and
triglycerides –
though they
return to baseline with
long-term treatment
OTHER
• Ototoxicity – 
rapid IV injection can cause
deafness, 
higher risk in
patients in renal failure or
on aminoglycosides

INTERACTIONS
• Raise serum lithium levels

8
Q

BENDROFLUMETHIAZIDE

prep

dose

MOA

ADME

USES

A

BENDROFLUMETHIAZIDE

Thiazide diuretics
• Tablets: 2.5/5 mg DOSE

• 2.5–5 mg od PO

MOA
• Act on early distal convoluted tubule

• Inhibit reabsorption of Na+ and Cl-

• ↑ Na+ and Cl- excretion
and =↑ H2O excretion

METABOLISM
AND EXCRETION
• Hepatic metabolism
to active compounds

• Metabolites and
unchanged drug
(30%) excreted in
urine

ABSORPTION/
DISTRIBUTION
• Well absorbed orally
• Effective in 90 min
• Lasts 18–24 hours

USES
• Hypertension
• Heart failure

9
Q

BENDROFLUMETHIAZIDE

Effects

A

EFFECTS
CVS
• ↓ BP as ↓ circulating vol

RENAL

  • ↓ Renal blood flow
  • ↓ GFR
BIOCHEMISTRY
• ↓ K+
• ↓ Cl-
• ↓ Na+
• ↓ Mg2+
• ↓ H+
• ↑ Ca2+
• ↑ Uric acid causing gout
METABOLIC
•  ↓Glycogenesis
• ↓ Insulin secretion
• ↑ Glycogenolysis
• ↑ Cholesterol and
triglycerides
So, use with caution in
diabetics
HAEMATOLOGY
• Blood dyscariasis including:
    • Anaemia – aplastic and
     haemolytic
    • Leucopenia
    • Agranulocytosis
     • Thrombocytopenia
OTHER
• Impotence
• Rash
• Photosensitivity
• Pancreatitis
INTERACTIONS
• Metolazone shows
synergism when used with
loop diuretics
• Effects antagonised by
NSAIDs
10
Q

AMILORIDE

A

AMILORIDE
K+ sparing diuretics

• Tablets: Co-amilofruse

(Amiloride/Frusemide
2.5 mg/20 mg or 5 mg/
40 mg)

DOSE
• 1–2 tablets per day

MOA
• Act at distal D convoluted tubule

• Blocks Na+/K+ exchange so less K+ lost in urine

METABOLISM
AND EXCRETION
• Not significantly metabolised

CHEMICAL PROPERTIES
• Nil

ABSORPTION/
DISTRIBUTION
• Poorly absorbed orally

• Minimal protein binding

USES
• In combination with loop
diuretic to decrease
hypokalaemia, e.g.
co-amilofruse

(frusemide + amiloride)

EFFECTS
METABOLIC
• Hyperkalaemia

11
Q

SPIRONOLACTONE

MOA

Dose

Chem

USES

A

SPIRONOLACTONE

Aldosterone antagonist
• Tablets: 25/50/100 mg

DOSE
• 100–400 mg/day

MOA
• Acts at distal convoluted
tubule and collecting
ducts

• Competitive antagonist of
aldosterone

• Aldosterone stimulates
reabsorption of
Na+
in exchange for

K+

• NB limited diuresis as 
Na+ reabsorbtion 
stimulated by
aldosterone only accounts
for 2% of total water
reabsorbed

CHEMICAL PROPERTIES
• Nil

USES
• Ascites
• Nephrotic syndrome
• Conn’s syndrome (primary
hyperaldosteronism)
12
Q

Spirinolactone

ADME

A
METABOLISM
AND EXCRETION
• Hepatic metabolism
• Excreted in urine
ABSORPTION/
DISTRIBUTION
• Oral bioavailability 70%
• Protein binding > 90%

EFFECTS
BIOCHEMISTRY
• ↑ K+
• ↑Na+

HORMONAL

• Gynaecomastia in men

• Irregular menstruation
due to anti-androgenic
effects

OTHER
• Nausea and vomiting
• ↓ Response to
vasopressors
• ↑ Response to
cardiovascular
depressants
13
Q

ACETAZOLAMIDE

A

ACETAZOLAMIDE

Carbonic anhydrase inhibitor

• Tablets: 250 mg

• Clear colourless solution:
500 mg/vial

DOSE
• Oral: 250 mg – 1 g/day in
divided doses orally

• IV: 250 mg – 1 g 4 hourly

MOA
• Acts at proximal convoluted tubule

• Non-competitive inhibitor
of carbonic anhydrase (CA)

• CA catalyses:
CO2+ H2O

H2CO3-

H+ and HCO3 -

• Affects Na+ exchange for
H+ in PCT so, fewer H+ ions
generated for excretion

• This causes alkaline urine &
mild metabolic acidosis which counteracts the respiratory alkalosis associated with
ascending to altitude

USES
• Weak diuretic
• Mountain sickness
(prophylaxis and treatment)
• Glaucoma
14
Q

ACETAZOLAMIDE

A
ABSORPTION/
DISTRIBUTION
• Oral bioavailability 100%
• Protein binding 70–90%
• t½ up to 6 hours

METABOLISM
AND EXCRETION
• Hepatic metabolism
• Excreted in urine

EFFECTS
RS
• ↑ RR in response to
↑ CO2

CNS
• ↓ Intra-ocular pressure
by ↓ rate of aqueous
humour production

• ↓ ICP by ↓ rate of CSF
production

GI
• ↓ Gastric secretions
• ↓ Pancreatic secretions

RENAL
• Mild diuresis
• ↓ Excretion of uric acid

OTHER
• Hyperchloraemic
metabolic acidosis and
alkaline urine as H+
excretion decreased and
bicarbonate not
reabsorbed
15
Q

MANNITOL

USE

DOSE

MOA

ADME

A

Osmotic diuretic

• 10–20% clear colourless
sugar alcohol solution

DOSE
• 0.5–1 g/kg bolus
over 20 min

MOA
• Freely filtered by glomerulus and not reabsorbed
(Mol weight 182 Da)

• Water follows mannitol
as osmolality of
filtrate
is increased

USES
• To reduce raised
intracranial pressure

• To force diuresis in major
vascular surgery (this is
no longer in vogue)

METABOLISM
AND EXCRETION

• Not significantly
metabolised

• Freely filtered at
glomerulus

ABSORPTION/
DISTRIBUTION
• Given IV

• t½ 100 min

16
Q

MANNITOL

Effects

A
EFFECTS
CVS
• Initial ↑ in circulating volume 
take care in patients with
CCF

RENAL
• ↑ Renal blood FLow

CNS
• ↓ ICP

• NB unable to cross intact BBB, but following head injury it may cross and then draw Fluid into the brain, worsening ICP.

So, give with caution, under
guidance of neurosurgeons
unless in life-threatening
situation

OTHER
• Allergy, though rare
• Free radical scavenger –
thought to be neuroprotective

• Dose cannot be repeated
indefinitely as causes rise in
serum osmolality, 
circulatory
overload, ultimately will cross
BBB and cause ↑ ICP