Pharmacopeia

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Field MANNITOL
Renal · Renal · Level 3
SPIRONOLACTONE
Renal · Renal · Level 3
Mechanism of action

Freely filtered at the glomerulus and not reabsorbed. It increases tubular-fluid osmolality and urine volume. Because it does not cross an intact blood-brain barrier, it also draws extracellular water from brain into plasma and reduces CSF volume and pressure.


osmotic agent. inc plasma osmolality and draws water out of the CSF and vitreous body. Freely fi¬ltered at the glomerulus but poorly reabsorbed. Because
the PCT is involved in the reabsorption of 60-70% of the -filtered load
this is the most important site of action


• increases the osmolarity of the glomerular
filtrate -> increasing urinary volume
• decreases CSF volume & pressure by
(1) decreasing rate of CSF production
(2) withdrawing brain extracellular water across
the BBB into plasma

Acts in the DCT.
It is a competitive antagonist of aldosterone at the receptors in the DCT.
Decreased Na reabsorption and increased K reabsorption
= Increased Na loss and Diuresis.

Physiological effects

↓ICP/IOP

Sedation and muscle weakness (due to electrolyte abnm)
Antihypertensive,
Diuresis (in 3-4 days)
Potassium retention
Anti-androgenic effect- inhbn of ovarian androgen secretion
↑renal Ca excr, ↑plasma urea
Reversible hyperchloraemic MA

Absorption

IV only.

PO - BA 70%, extensive 1st pass metb. Onset 3-4hrs, dur upto 3 days

Distribution

Biphasic – plasma and ECF.
Does not cross BBB

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Protein binding —

90%

Volume of distribution

0.47 L/kg

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Metabolism

Not metabolised to a clinically significant extent. Excreted unchanged in urine.


Minimally hepatic to glycogen


Unmetabolized

Hepatic: Rapidly and extensively metabolised by deacetylation and dethiolation. Active metab: canrenone and 7-alpha-spirolactone

Excretion

Urine (~55% to 87% as unchanged drug)

Urine and faeces

Half-life

Term half life: 4.7 hrs

1-2hours, metab upto 24hrs

Adverse Effects Toxicity

Usually rare and idosyncratic. It may cause symptoms of pulmonary hypertension.

↑K+(esp in renal failure). N/V and GI disturbances
Menstr irreg, Gynaecomastia
↑digoxin conc.
↓pressor response
↑effects of CVS depressants

Class Group

Osmotic Diuretic


Diuretic - Osmotic

Diuretic – Aldosterone antagonist

Indications Uses

Used to reduce CSF pressure and volume, for short-term management of acute glaucoma, as an osmotic diuretic in selected renal indications, for bowel preparation and in rhabdomyolysis.


osmotic diuretic
(to ↓intracranial pressure or introccular pressure).
Used to test for airway hyperresponsiveness


1. reduce CSF volume -> reduce ICP
2. preserve renal function during perioperative
period in jaundice patients under going major
vascular surgery.
3. acute management of glaucoma
4. bowel prep
5. initiate diuresis in transplanted kidney
6. treatment for rhabdomyolysis

Oedema – CHF, cirrhosis with ascites, refractory. HTN, Nephrotic syndrome. With loop/thiazide to conserve K+, diagn of Conn's syndr

Introduction

Mannitol is a low-molecular-weight polyol (molecular weight 182) used as an osmotic agent.


polyhydric alcohol MW 200, synthesized by redn of mannose


an alcohol derived from Dahila tubers (6 carbon
sugar)

decrease ICP: 0.25g/kg over 15min to 1g/kg

PROS & CONS – See BELOW

A synthetic steroid

Legacy Cicm Level

Level 3

Level 3

Presentation

Sterile 10% and 20% aqueous solutions. Crystallisation may occur at low temperatures.


1-% or 20% (100gm in 1000ml or 500ml)
Crystallizes at ↓temp


sterile solution
10-20% in water

25/100mg tablets

Route And Dose

1-2gm/kg IV

PO. 25-200mg/day

Special Points

Osm (20%) 1100

ADVANTAGES:
Still fairly cheap
• Rapid effect (onset – minutes, duration – 3
hrs)
• Seems to have some sort of rheological
benefit (increases red cell deformability)
• Acts as a transient volume expander
• May have a better effect on cerebral blood
flow for a given reduction in ICP.

DISADVANTAGES:
Unstable in storage: at low temperatures
and at altitude, it precipitates.
• Medium for bacteria and fungus.
• Causes a brief state of volume overload
• Causes torrential diuresis and hypovolemia
• Causes hyponatremia while in the serum,
and hypernatremia after the inevitable
diuresis
• washes out medullary interstitial gradient -
> decreased ability to concentrate urine
• Endpoint is serum osmolality(320), which is
cumbersome to measure
• May cause ICP to "rebound" after
prolonged use
• should be discontinued if Na+ > 160 or
osmolarity > 320mosmol/kg

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