CNS

Question 1

Discuss non sedating antihistamines including risk assessment (Ceturuzubem fexofenadine, loratadine)

Answer 1

Produce mild CNS depression in overdose. They are notable for their associated with QT prolongation in both therapeutic and supratherapeutic doses

Mild sedation or anticholinergic effects are anticiupated following OD
QT prlongation following OD of currently available agents is reported but rare more common in massive OD or with coingestion with another agent that prolongs the QTc

Question 2

Discuss TK and TM of non sedating antihistamines

Answer 2

Mildy lipohilic and less able to cross the BBB than sedating antihistamines. They are slective, competitively reversible inhibitors of peripheral H1. They have lower affinity for central H1 M1 adrenergic and serotonergic receptors compared to sedating antihistamines. In OD selectivity is lost and some anticholinergic, sedation and hypotension may be seen. QT prolongation is secondary to cardiac potassium blockade

TK
Well absorbed reach peak in 1-3 horus and have VD of less than 1.5L/KG.Hepatic metabolism is minor and hlaf lives are variable ranging from 8-24 hours

Question 3

Discuss clinical features of non sedating antihistamines

Answer 3

Minor sedation nasuea and ataxia
Mild anticholinergic sytmpoms
Symptoms develop wihtin 4-6 horus of infestion and resovle wihtin 12 hours

Question 4

Discuss management of non sedating antihistamines

Answer 4

Resus
ABCD
-Anticholinergic delirium
-Severe QTC prolongation with torsades is a theoretical risk. Treatment should it occur includes correction of hypoxia, hypokalaemia, hypomagnesaemia and hypocalcaemia.
If heart rate less than 100BPM consider isoprenaline infusion (1-10 mic.min or 0.05-2.0 mic/kg/min) or overdrive pacing to maintain heart rate at 100-120 BPM

D: nil
e: nil
A: physostigmine administration is considered in patient wtih severe anticholinergic delirum not controlled with benzo
D: Continous cardiac monitroing and 12 lead ECG every 4 hours until ther eis clear evidence of clinical improvement
-Can be discharged if clinically well, ambulant, passing urine eating and drinking

Question 5

Discuss sedating antihistamines

Answer 5

Characterised by dose dependent sedation and anticholinergic effects. CVS toxicity is associated with massive ingestion

Risk

• Dose dependent sedation anticholinergic effects and orthostatic hypotension occur
• all agents lower seizure threshold but seizures are infrequent
• Massive overdose may result in cardiac conduciton abnormaltiies (QRS and QT) and hypotension requiring inotropes

Question 6

Discuss TM and TK of sedating antihistamines

Answer 6

TM: Act by competitive inhibition of histamine receptors. Side effects and toxicity are due to antagonism at M1 A1 and serotenogeric receptors. Some agents lower seizure threshold through unclear mechanisms
Cardiac Na and K blocakde is reported in massive ingestion

TK
Antihistamines are well absorbed orally reaching peak leveles in 2-3 horus. They are lipid soluble have large columes of distrubtion and are metabolised in the liver

Question 7

Discuss clinical features of antihistamines

Answer 7

• Dose dependent CNS dpression
• Anticholinergic syndrome
• Seizures, hyperthermia and rhabdo rare complaitions
• Significant hypotension and arrythmia secondary to fast sodium channle blockade occur after massive OD

Question 8

Discuss management of sedating antihistamiesn

Answer 8

Resus
ABCD
-Anticholinergic delrium
-Toxic seizrues
-Hypotension usually reponds to fluid if not a1 adreneric agnosit is second line
-In the rare event of QRS prolongation complicated by ventricular dysrythmias, intaube hyperventilate and given IV bolus sodium bicarb

D: Charcoal generally not indicated becuase the onset of sedation occurs in the first few hours and simple supportive care ensure a good outocome
E: nil
A: phyostigmine
D: Observation.

Question 9

Discuss risk assessment of benztropine

Answer 9

Frequently presribed to patients on antipsychotics to ameliorate dyskinaesia this a potent anticholinergic agent in overdose.

Any overdose is likley to precipitate anticholinergic symptoms and require medical care.

TK and TM little known

Question 10

Discuss management fo benztropine overdose

Answer 10

Clinical features are those of anticholinergic syndrome

ABCD

• Supportive and consistes of sedation with benzo, IVF and insertion of IDC
• control of delirium can be challenging and physical restraint may be necessary

D: can be useful if within 2 hours and GCS okay
E: nil
A: phyostigmine is considered in cases wher ethe delirium is not easily controlled
D: once delirium controlled admission to high dependnacy area with one to one nursing