sedative hypno, psychotropics, a

pathophysiology of BZDs

enhance inhibitory neurotransmittion through:

1. GABA A receptor modulation

2. CNS depresssion

3. relative safety(unlike barbiturates due to ceiling effect)

BZDs acute toxicity vs chronic

acute : drowsy, ataxia, normal pupil, diplopia

chronic: coma, resp depression, hypotension, hypothermia, hyporeflexia

lab investigation for BZDs

urine drug test

blood glucose

ABGs

management of BZDs toxicity

ABCD

decontamination: GL (only 1 hr, after airway protection), AC(single dose 1-2 hrs)

enhanced elimination not effective due to large distribution volume

antidote: flumazenil

supportive care:IV fluids for hypotension, warming for hypothermia, oxygen for hypoxemia

flumazenil mechanism, indications and contraindications

comp bind to BZDs at GABA A receptor without activating

indications: select case of pure BZDs overdose with severe resp depression

CI:

1. coingestion with proconvulsant drugs(seizure)

2. BZD dependence (acute withdrawal symptoms(seizure))

barbiturates pathophysiology

1. GABA A receptor enhancement(bind to distinct site, increasing durability of chloride channel

2. direct mechanism effects: at toxic doses, directly inhibits neuronal excitability by affecting Sodium and potassium channel

3. CVS effect: direct myocardial depression, peripheral vasodilator and reduced symp tone → hypotension

4. resp depression: dose dependent depression of medullary response center

mild vs severe barbiturates toxicity

drowsiness, nystagmus, confusion

coma, shock, hypothermia, hyporeflexia, dilated or normal pupils, bullous skin lesion(pathognomonic), pulmonary edema

investigation for barbiturates

1. serum barbiturates level

2. ABG

3. serum electrolytes, glucose

4. blood urea nitrogen and creatinine

5. Liver function tests

6. kidney function tests

7. ECG

8. chest radiography(aspiration pneumonia)

management of barbiturates

ABCD

decontamination: GL(1 hr after securing airway), AC(1g/kg within 1-2 hours, max 50g), MDAC(phenobarbital)

Elimination:

1. urinary alkalinization(phenobarbital)

2. hemodialysis(severe poisoning unresponsive to care, phenobarbital 100-150mg/L+, refractory shock, prolonged coma, renal failure, removes long lasting barbiturates, less effective for lipophilic agents)

3. supportive care

TCA mechanism of action

1. inhibition of neurotransmitter reuptake(norepinephrine and serotonin)

2. receptor blockade: muscarinic cholinergic blockade, histamine blockade, peripheral a1 adrenergic blockade

3. CVS toxicity: sodium channel blockade quinidine like effect(wide QRS complex, prolonged QT), myocardial depression and hypotension

important manifestation of TCA toxicity

CNS excitation → CNS depression

multiple seizures = severe toxicity

anticholinergic syndrome

CVS manifestation: sinus tachycardia, hypotension, cardiac conduction abnormalities (QRS <100ms low risk but >100ms high risk), cardiac arrhythmia

mechanism of hypotension in TCA toxicity

1. direct myocardial inhibition

2. peripheral vasodilation(a1 blockade)

3. may progress to shock

investigations for TCA

ABG(lactic acidosis indicates severe poisoning)

ECG(immediate, continued monitoring, QRS>100ms → sodium bicarbonate therapy

electrolytes

renal function

glucose

liver function tests

urine drug screen

management for TCA toxicity

ABCD

decontamination:protect airway, GL(May be effective hours post ingestion dt anticholinergic induced delayed gastric emptying), AC(recommended 1-2 hrs or even 4), MDAC(TCA overdose(enterohepatic circ.)

specific therapy:

1. sodium bicarbonate(first line)

symptomatic treatment

1. hypotension: crystalloid fluids and sodium bicarb/ norepinephrine and epinephrine

2. ventricular dysrhythmias (sodium bicarb(1-2 mEq/kg bolus)/lidocaine

3. seizures: BZDs/phenobarbital, propofol

sodium bicarb Indications and mechanism in TCA toxicity

1. QRS> 100.ms

2. ventricular dysrhythmias

3. hypotension refractory to fluids

4. metabolic acidosis

mechanism: sodium loading overcoming sodium channel blockade

alkalinizatuon increasing protein binding to TCA, decreasing free drug

antipsychotics mechanisms

I. receptor blockade

1. dopamine receptor blockade

2. a1 receptor blockade

3. myscarinic blockade

4. histamine blockade

II. CVS toxicity :

1. hypotension(a1 blockade, depression of vasomotor center medulla and direct myocardial depression)

2. sodium channel blockade(quinidine like)

aodium channel blockade mechanism antipsychotic

impairs myocardial conduction

decrease cardiac contractility

prolonged QRS, QT AND PR INTERVALS

risk: ventricular dysrhythmias, torsades de pointes

imp manifestation of antipsychotic

resp depression, dystonia, parkinsonism, hypothermia, anticholinergic effect, orthostatic hypotension, sinus tachycardia, arrhythmia

miosis due to a1 blockade

mydriasis due to anticholinergic

mydriasis is more significant

neuroleptic malignant syndrome pathophysiology and 4 cardinal signs

1. hypothalamic D2 blockade → impaired. thermoregulation → hyperthermia

2. basal ganglia D2 blockade → severe muscular rigidity

3. autonomic dysfunction → CVS instability

signs:

1. hyperthermia

2. severe generalised ms rigidity

3. altered mental state

4. autonomic instability

lab findings characteristics to NMS

CK highly elevated

leukocytosis

myoglobinuria

elevated AST, ALT

metabolic acidosis

acute kidney injury

electrolyte abnormalities

investigations for antipsychotic drugs

ABG

CBC(leukocytosis=NMS or infection)

electrolytes

renal and liver function tests

glucose

CK(essential to detect rhabdomyolysis)

ECG

management of antipsychotic drugs

ABCD

Decontamination: GO(1 hr maybe more dt anticholinergic effect of delayed gastric emptying), AC

specific management:

1. hypotension (IV crystalloids/Vasopressor with a1 agonist(norepinephrine)

2. cardiac arrhythmia: QRS>100ms=sodium bicarbonate, ventricular tachycardia=sodium bicarb and lidocaine

3. acute dystonia(diphenhydramine, benztropine, diazepam)

4. parkinsonism anticholinergic agents(benztropine) and amantadine

5. serizure management: BZDs, phenobarbital, propofol

NMS management

requires ICU admission

1. discontinue all antipsychotic drugs

2. supportive care(ICU monitoring, aggressive IV hydration, prevent AKI from myoglobinuria

3. cooling measures

4. BZDs: diazepam

5. dantrolene(ms relaxant): inhibit calcium release from sarcoplasmic reticulum

6. bromocriptine(dopamine agonist): restores dopaminergic activity