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

Diuresis
Reversible, non-competitive inhibitor of carbonic anhydrase
PCT: ↓H+ and HCO3- prodn
↓ cytosol H+ → ↓Na+ reabs in PCT→ ↑H2O loss
↓cytosol HCO3→↑luminal HCO3→ H2O diffusion with HCO3 ,Na, K to urine
Eye: ↓Na pump, ↓AH formation

Diuresis
Inhibition of active chloride ion reabsorption in PCT and ascending limb of LoH
↓ reabsorption of NaCl → ↓ tonicity in the renal medulla → ↓water reabsorption and diuresis.
Other effects are mediated by the induction of the COX-2 enzyme which assists in synthesis of prostaglandins.

inhibit Na+ reabsorption in the early portion of the distal tubule by
blocking the Na+.Cl- symporter in the apical membrane of these cells. Naturesis
occurs with thiazide diuretics is 5-10% of the filtered load

↓ICP/IOP

Metabolic: Acidosis via ↑ excretion of bicarb (and reabsorption of Cl)
Resp: ↑MV → comp resp alk
CNS: anticonvulsant properties, ↓ CSF and IOP by ↓d formation GIT: ↓ Pancreatic and gastric
GU: mild diuresis, Na retention

Pulmonary and systemic vasodilation
Diuresis ↑ RBF and ↑ corticomedullary blood flow
↓O₂ demand in the LoH (ischaemic
protection)

Anti-HTN: (↓TPR, ↓plasma volume)
↓RBF → ↓GFR
↓K+,Na+,Mg.
Hyperchloremic MA
↑Ca++ (↓excretion)
↑Glu: (↓glycogenolysis, ↓insulin)

IV only.

IV/PO
PO BA = 100%

PO/IV/SL/IM. PO BA 50% Onset PO/SL 30-60mins, IV 5 mins .
Dur PO/SL 6-8hrs, IV 2hrs

PO- BA ~50-80%. Onset 2hrs Dur 6-12hrs.

Biphasic – plasma and ECF.
Does not cross BBB

Lip sol: crosses BBB

70-90%

91-99% (Albumin)

68%

0.47 L/kg

0.1L/kg

3.6-7.8L/kg

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

Minimally hepatic to glycogen

Unmetabolized

Not metabolised

Renal to glucuronide
Minimal hepatic

Not metabolized

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

Unchanged in urine

80% unchanged in urine

Urine (unchanged)

Term half life: 4.7 hrs

6-9hrs

0.5-2hrs. ESRF: 9hrs

5.6-14.8hrs

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

metabolic acidosis, urinary alkalinisation, parathesias, fatigue,
hypokalaemia, N+V, abdo pain

Tox: Rashes, renal stones

↓ K+/Na+/Cl-/Ca++, Hyper- urea/glu/chol, Metabolic alkalosis
Tox: Deafness, Pancreatitis
BM depression
Interstitial nephritis (worse with aminoglycoside)

↓K+/Na+/Mg++, ↑Ca++/urea/glu/chol.
indiosyncratic blood
dyscrasias. Rash, photsensitivity. Interactions may prolong action of NDMBs. NSAIDs antagonise the action

Osmotic Diuretic

Diuretic - Osmotic

Diuretic – Carbonic Anhydrase Inhibitor

Diuretic - Loop

Diuretic - Thiazide

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

Glaucoma
Miniere’s disease
Altitude sickness
Adjunct in epilepsy

Oedema of cardiac, renal or hepatic origin, Renal insufficency
Hypertension
Raised ICP
Hypercalcaemia

heart failure and hypertension. Used in combination. mostly bound to plasma prot, and gain access to the tubule via secretion in the PCT.

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

Sulfonamide

Sulfonamide derivative

related to the sulphonamides

Level 3

Level 3

Level 1

Level 3

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

250mg white tablets
500mg vials for reconstitution

Photosensitive solution 10mg/ml
20/40/500mg tabs, Syrup

orange scored tablets of 25mg and combos

1-2gm/kg IV

250-1000mg q6hrly
IV/PO

20-2000mg daily
PO/IV/SL/IM.

PO. 12.5-200mg/day

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