- Metabolized to cysteine → Regeneration of sulphydril groups and glutathione
- acting as an alternate substrate for conjugation
- reduces disulfide bonds in mucoproteins

Binds excess digoxin or digitoxin molecules circulating in the blood
- Fab fragment-digoxin complex excreted by kidney - Net shifts the equilibrium away from binding of digoxin to receptors

Reversal of MoP receptor effects such as sedation, hypotension, respiratory depression, and the dysphoric effects of partial agonists
Will precipitate acute withdrawal symptoms in opiate addicts

- Reduces hepatotoxicity
- mucolytic

- CVS: > 0.3 mg/kg → ↑MAP
- RESP: nil
- CNS: Drowsiness at high dose, Decreased pain tolerance
- OTHER: Sphincter of oddi spasm

PO: BA low

-

91% absorption but Oral BA 2% due to extensive first-pass metabolism

66-97%
Albumin

-

46%

0.5 L/kg

0.3 L/kg [DigiFab]
0.4 L/kg [Digibind]

2 L/kg
Highly lipid soluble

Liver
Deacetylated to cysteine -> normal metabolism (Rapid)

Nil

Liver
via glucuronidation to naloxone-3-glucouronide

Unchanged: 40% urine, 3% feces

Urine

25 ml/min/kg

5.5 hrs

Unbound: 11 hrs
Bound: 15-20 hrs

0.5-1.5 hrs

usually in 1st hr:
- rash around infusion site
- angiooedema
- bronchospasm
- hypo/hyper tension

Mx: stop, give antihistamine, then restart at slowest infusion rate

Anaphylaxis – rare
Digoxin Withdrawal: AF, heart failure, hypokalemia

Rapid onset of withdrawal symptoms in opioid drug addiction
At High Doses:
- Hypertension
- Tachycardia
- Arrhythmias

Synthetic derivative of cysteine

Monoclonal antibody (mAB) FAB (Fragment antigen-binding) fragment from sheep immunized with digoxin derivative

substituted oxymorphone derivative.
pKa = 8.0

Antidote

Antidote

Antidote

- paracetamol overdose
- non-paracetamol induced fulminant hepatic failure
- prevention of contrast nephropathy
- mucolytic therapy

- For treatment of acute and chronic digoxin overdose
- Treatment of toxicities of other cardiac glycosides: oleander, bufotoxin (cane toad), Chinese medicines

- the reversal of respiratory depression due to opioids
- the diagnosis of suspected opioid overdose and has been used in the
treatment of.
- clonidine overdose

Level 3

Level 3

Level 3

antioxidant and glutathione inducer

Binds Digoxin Molecules

competitive antagonist at mu-, delta-,
kappa-, and sigma-opioid receptors

Duration: short

Onset: 0-60min
Peak: 30-360min

Onset: 1-3 mins
Peak effect: 15 mins
Duration: 30 mins
> Less than the effect site time of most opioids → requirement for repeat dosing or infusion.

IV or oral formulation
200mg/mL
compatible with 5% dextrose

powder
contains 38-40mg of digoxin-specific Fab fragments (which binds approx. 0.5mg Digoxin)
reconstitute with sterile water

clear solution for injection containing 0.02/0.4 mg/ml of naloxone hydrochloride

IV, PO, Neb (inhaled)

IV:
1st : 150mg/kg in 200ml dextrose over 15mins
2nd : 50mg/kg in 500ml over 4hrs
3rd : 100mg/kg in 1l over 16hrs

IV

Empiric: 10vials of Fab fragments

Known dose, no level:
Total body load = Dose (in mg) x 0.8 (BA of digoxin)
Number of vials = TBL x 2

Known concentration:
No of vials = [(serum digoxin concentration in ng/mL) x (patient's weight in kg)]/ 100

IV/IM

- Reversal of post-operative respiratory depression and coma: 20-40mcg IV PRN
- For opioid overdose reversal 0.4-2 mg IM/IV → Via infusion a 5mcg/kg/hr
- Reversal of S/Es of opioids: 1-4 mcg/kg
- Increased cardiac contractility in septic shock at doses 1mg/kg IV

effective in alleviating the pruritus, nausea,
and respiratory depression associated with the epidural or spinal administration of opioids.