Fludrocortisone

Chemical

Synthetic mineralcorticoid

Use

Postural hypotension

Adrenocortical insufficiency

Adrenogenital syndrome

Presentation

Tablets

Dose

Initially: 0.05-0.1mg od

Maintenance: 0.05-0.2mg od

Variable schedule from bd to thrice weekly

Route

PO

Onset

Variable

DoA

1-2 days

MoA

Replaces endogenous aldosterone

Binds mineralcorticoid receptors in kidneys

Alters gene transcription

­↑Na channels on apical side of renal tubule cells & ­↑Na/K/ATPase channels on basolateral side

Overall:  ­↑Na reabsorption & ↓K excretion

Also acts on glucocorticoid receptors but with a much lower affinity

PD

RENAL: sodium and water reabsorption, K excretion

PK

A

Rapid & complete

D

80-85L

70-80% PPB

M

Liver to inactive glucuronide and sulfate metabolites

CYP3A

E

Renally (active – majority, inactive metabolites)

Small amounts excreted in feces

T1/2β 3 hrs

Adverse Effects

CVS: HF, cardiomegaly, oedema, HTN

CNS: delirium, depression, glaycoma

Endo: hypokalaemic alkalosis, hypokalaemia, hyperglycaemia, HPA-axis suppression, cushing’s syndrome, DM, glycycosuria, growth suppression, hirtutism

GI:  abdominal distention, gastric & oesophageal ulcers, pancreatitis

Haem:  petechia, purpura, bruising

MSK: osteoporosis, myopathy, osteonecrosis,

Derm: acne vulgaris, striae, erythema, hyperpigmentation, maculopapular rash

Multiple drug interactions