Download tca overdose

TCA OVERDOSE
DANGEROUS DRUGS
Tricyclics
Amitriptyline
Desipramine
Imipramine
Nortriptyline
Doxepin
Clomipramine
Tetracyclics
Mirtazapine
Mianserin
Trazodone
Amoxapine
Setiptiline
Maprotiline
PHARMACOLOGIC CONSIDERATIONS
“Dirty Drugs”
Block many receptors
Serotonin/NA reuptake
H1&H2 – sedation
Alpha1&2 – hypotension
GABA-A – seizures
Muscarinic – anticholoinergic
Na+ channels – arrhythmias (class Ia)
K+ channels
Rapid incomplete absorption (decreased by anti-Ach effect – decr gastric emptying&
SR preparations)
LARGE Vd:
Plasma conc incr rapidly – affects heart/brain quickly (before it’s redistributed to fat)
PROTEIN BINDING:
10% free, 90% bound
Binding decreased by ACIDOSIS, increased by ALKALOSIS
(Important in treatment)
Increased FREE drug = greater effects,
ie ALKALOSIS = LESS FREE DRUG = LESS EFFECT
METABOLISM
T1/2 Prolonged by:
Hepatic metab (overwhelmed in OD)
Enterohepatic circulation
Active metabolites
Minimal renal excretion
SYMPTOMS/TOXIDROME
“TRI”-cyclics = 3 MAIN EFFECTS
1) CNS
2) ANTICHOLOINERGIC
3) CARDIOVASCULAR
1) CNS
Sedation – coma (can be rapid & precede CVS signs)
Seizures – treat as per normal
2)ANTICHOLINERGIC
(opposite of DUMBELS)
Mydriasis (dilated pupils)
Dry mouth/skin
Tachycardia
Urine retention
Ileus
Delirium
3) CARDIOVASCULAR
a) ECG
Can’t rule in or rule out TCA OD
“Suggestive” changes
Can have SERIOUS OD WITH NORMAL ECG
a) STRONGLY SUGGESTIVE of TCA OD
i) aVR: terminal 40msec >3mm
ii) Deep S in I and aVL
b) PREDICTORS
i) QRS > 100msec = PREDICTS “Serious Toxicity”
-  RISK:
Seizures
Arrhythmias
Hypotension
Coma/Intubation
ii) QRS > 160msec = PREDICTS VT
- No VT with QRS < 160msec
b)HYPOTENSION
i) direct myocardial depression
ii) vasodilation (alpha block)
Treat with fluid
INOTROPES OK AS LONG AS ADEQUATE BICARB GIVEN
4) OTHER:
Pulmonary – APO/ARDS (direct effect on pulmonary vessels)
Hyperthermia
Rhabdomyolysis
COMPLICATIONS
ACIDOSIS – mixed metabolic & resp
Respiratory depression – Incr CO2
Metabolic – seizures
BAD BECAUSE:
1) pKa 8.5
pKa – pH = (protonated/unprotonated)
RNH3+
<==> RNH2 + H+
Protonated
Unprotonated
Ionised
Non-ionised
<----- Acidic pH
Alkaline pH ------>
ACIDOSIS Bad because acidosis encourages drug to be in
IONISED/PROTONATED FORM
Alkalinisation pushes pH closer to pKa = more drug in non-ionised form
NON-IONISED DRUG
Less affinity for Na+ channels
Increased lipid solubility = redistributes to fat
2) ACIDOSIS – increases FREE drug
Alkalinisation – increases protein binding
SPECIFIC INVESTIGATIONS/LEVELS
TCA Levels do not correlate with severity
DECONTAMINATION
Activated charcoal if < 1hr
ANTIDOTE = BICARBONATE
INDICATIONS FOR NaHCO3i) ACIDAEMIC: pH < 7.35
ii) QRS > 100msec
iii) aVR R wave > 3mm
iv) WIDE COMPLEX TACHYCARDIA
ABNORMAL ECG (as above)
Defib unlikely to work
2nd line: lignocaine 1.5mg/kg (once pH >7.5)
CPR: may need PROLONGED CPR (hours)
ALSO: Intubate & HYPERVENTILATE
NB: Ia drugs Contraindicated (Amiodarone/B-blockers/Procainamide)
Hypotension
Crystalloid
Bicarb
Inotropes: NA/Adr infusion OK as long as
“adequate bicarb given” (ie pH > 7.50)
Seizures/coma
Not clearly an indication for HCO3Usually treat as for normal seizure (BZD’s)
Dose:
2 mEq/kg IV
Repeat every 1-2 mins until restoration of perfusing rhythm
Or pH > 7.5
Once pH > 7.5 can try Lignocaine if still in VT
SPECIFIC TREATMENT
ALKALINISATION
1) HCO32) Hyperventilate
Aim for pH 7.50-7.55
pCO2 30mmHg
SEIZURES:
TREAT WITH BENZODIAZEPINES
DIALYSIS HELPFUL?
No – Large Vd
NB CARDIAC ARREST:
= INDICATION FOR
PROLONGED CPR
INTUBATE & HYPERVENTILATE
BICARB
To pH > 7.50
GOOD OUTCOME IS POSSIBLE WITH THESE MEASURES
TAKE HOME POINTS:
Normal ECG does not exclude serious toxicity
DON’T GIVE AMIODARONE/B-BLOCKERS TO WIDE COMPLEX
TACHY IF TCA OD SUSPECTED