“I’m Allergic to Everything but….”

Liza Halcomb, MD 10/23/15

Prescription Medication Overdoses : There is more than Vicodin and Percocet

Neuroleptics Haloperidol Risperidone Olanzapine

Clozapine Ziprasadone

Fluphenazine Thiothixine Quetiapine

Chlorpromazine Mirtazapine

Thioridazine Mesoridazine

Aripiprazole

Haldol ™ Risperidol ™ Zyprexa ™ Clozaril ™ Geodon ™` Prolixin ™ Navane ™ Seroquel ™ Thorazine ™ Remeron ™ Mellaril ™ Serentil ™ Abilify ™

Mechanism of Action

Mechanism of Action

Case # 1

• 30 year old prisoner admitted to the hospital for acute psychotic break.

• Started on haloperidol for agitation, 5-10 mg po PRN.

• On day 2 of hospitalization develops fever of 104, tachycardia.

• Altered mental status. • Marked rigidity.

Case # 1

• CBC – WCC 10, H&H 13/40, Plt 262 • Chem 7 – Nml • Coags – Nml • LFTs - Nml • CK -1218

Diagnosis

Neuroleptic Malignant Syndrome

NMS

• Hyperpyrexia due to hypothalamic dysregulation.

• Muscle rigidity leads to rhabdomyolysis. • Autonomic instability. • Altered mental status.

NMS Treatment

• Patient was started on 5 mg bromocriptine TID.

• Benzodiazepines PRN for agitation. • Aggressive cooling measures. • Treated for seven days then tapered. • Mental status, fever and rigidity

improved. • CK down to 149.

Shields,W. and Bray, F.: A Danger of Haloperidol Therapy in Children. Journal of Pediatrics 88, 301-303 1976.

Adverse Effects • Extrapyramidal

– Haloperidol, fluphenazine

Adverse Effects

Adverse Effects

• Deep sedation – Seen with

quetiapine and olanzapine

Adverse Effects

• Antimuscarinic – Olanzapine, clozapine, chlorpromazine

• Hypotension – alpha antagonism – Chlorpromazine, thioridazine,

mesoridazine • Agranulocytosis

– Clozapine, mirtazipine

Treatment

• Dystonia – Stop meds, IM/IV diphenhydramine 1 mg/kg.

Continue PO for 2-3 days. • Sedation

– Supportive care. • Hypotension

– Fluids, alpha-agonists. • Cardiotoxicity

– Treat like TCAs.

Case # 2

• 48 year old man with history of depression presents to ER c/o severe headache and chest pain.

• 2 hours prior to presentation ate beef stroganoff with red wine sauce.

Case # 2

• On arrival the patient is agitated, but A&O x 3 • BP 240/140, HR 85, RR 16, T 37 • CVS – RRR no M/R/G • Pulm – Clear • Abdo – Soft NT/ND • Neuro – Intact • HEENT – PERRLA, unable to visualize fundi

Case # 2

• Labs – Nml. • EKG – Nml. • Head CT – Nml. • Chest CT – Nml.

Diagnosis

MAOI Food Interaction

Diagnosis

• Patient was on isocarboxazid for refractory depression.

• Was unaware that sauce at dinner contained red wine.

• Developed hypertensive emergency.

MAOIs

Tranylcypromine

Phenelzine

Isocarboxazid

Selegeline (B)

=

=

=

=

Parnate ™

Nardil ™

Marplan ™

Deprenyl ™

Mechanism of Action

• Depression is thought to be caused by a deficiency of monoamines, particularly norepinephrine and serotonin.

• Depression can be alleviated by drugs that increase the availability of norepinephrine and serotonin.

Mechanism of Action

MAO MAO

inactivates monoamines

MAOI transported by NE reuptake

pump into neuron

MAOIs block enzymatic

breakdown of monoamines

Hypertensive Crisis

• MAO-A (gut) – Responsible for food interactions.

• MAO-B (brain) – Responsible for antidepressant effects.

• MAOI may be selective or non-selective.

• Reversible or irreversible. • Hydrazine or amphetamine like.

Overdose

• Symptoms often delayed for 12-24 hours. • Excess catecholamine release results in

hemodynamic instability. – Hypertension, myoclonus, agitation,

seizures • Followed by catastrophic cardiovascular

collapse. – Thought to be due to catecholamine

depletion

Serotonin Syndrome

• Occurs when MAOIs interact with agents that increase serotonin in the synapse.

• SSRIs are most commonly implicated. • A two week washout period should be

given before switching patients from SSRIs to MAOIs.

Treatment

• Hypertensive Reaction – Oral terazosin or

nifedipine in pts with normal baseline BP.

– Phentolamine. – Benzodiazepines.

Treatment

• Overdose – Admit patients to the hospital. – Aggressive supportive care.

• Decontaminate – Hyperthermia, agitation, seizures are

treated with cooling and benzodiazepines. – Hypotension is treated with fluids and

direct acting pressors such as norepinephrine.

Treatment

• Serotonin Syndrome – Sedate with a benzodiazepine. – Active cooling should be instituted. – Paralysis with EEG monitoring may be

necessary in cases of extreme rigidity.

Case # 3

• 53 year old woman presents to ED after overdose on her antidepressant medications 15 minutes ago

• Witnessed ingestion, brought in by husband.

• Initially awake and alert in triage, suddenly collapses.

Case # 3

• VS - 80/50, P-120, RR-16, T-99.8 • CVS - Tachycardia. • Pulm – Clear. • Abdo – Mild distension, decreased

bowel sounds. • Neuro – No gag, pupils 5 mm • Skin – Dry.

Case # 3

• Pt gets intubated, ventilated.

• IV, O2, monitor. • Fluids started. • EKG obtained.

Case # 3

Case # 3

• QRS narrowed with 1 mEq/kg of bicarbonate.

• Put on a bicarbonate gtt at 200ml/hr • Admitted to ICU. • Improved overnight. • Extubated 2 days later.

Case # 3

• Amitriptyline

Tricyclic Antidepressants

• Block reuptake of NE, DA and 5HT in central presynaptic terminals.

• May account for antidepressant efficacy.

TCA

• Anticholinergic effects – Red as a beet – Hot as a hare – Blind as a bat – Dry as a bone – Mad as a hatter

• Often not apparent in TCA OD

TCAs

• Cause sodium channel blockade

• Type 1A antidysrythmic – Prolonged QRS

• Antihistamine – Sedation

• GABA antagonism – Seizures

• Alpha-blockade – Hypotension

TCA Treatment

• Intubate and hyperventilate • Benzodiazepines for seizure • Sodium Bicarbonate

– QRS >100 ms – Repeat EKG to see if QRS has narrowed – May need bicarbonate gtt.

Case # 4

• 36 year-old female presents with palpitations, “shakiness” – Hx depression, multiple suicide

attempts • Started on a “safe” antidepressant

because of previous attempts. • 36 hours ago, ingested 50 tablets.

Case # 4

• Dizziness, blurry vision, dry mouth, difficulty urinating.

• Had a witnessed seizure (no evaluation).

• Sudden onset of palpitations 12 hours ago, getting worse.

Case # 4

• T 99 F, P 102-160, BP 84/44, RR 17, 99% RA

• Irregular tachycardia • Exam otherwise

normal except for marked anxiety.

Initial EKG

Case # 4

• Patient gets IV, oxygen, monitor. • Fluid bolus. • Airway intact – activated charcoal. • 2 g IV magnesium sulfate. • Patient required transvenous pacing

and aggressive supportive care. • 48 hours later symptoms resolved.

Case # 4

• Immediate and delayed toxicity

• Citalporam is anticholinergic

• Seizures • QT Prolongation,

dysrhythmias caused by metabolite

Case # 4

• Escitalopram (Lexapro™) – S-isomer of

citalopram • Newer agent, less

clinical experience. • Admit for 24 hours

with telemetry.

Names

Fluoxetine Paroxetine Sertraline

Venlafaxine Fluvoxamine Escitalopram

Citalopram

Prozac ™ Paxil ™ Zoloft ™ Effexor ™ Fluvox ™ Lexapro ™ Celexa ™

SSRIs

• Safer drugs than MAOIs and TCAs • Overdose generally benign.

– Sometimes cause nausea, vomiting and sedation.

– Rare cases of seizure activity. – Occasionally get hyponatremia.

• Supportive care +/- AC.

Mechanism of Action

SSRIs block re-uptake of

serotonin from the synapse

prolonging it action

Bupropion • Used in smoking

cessation and social anxiety.

• Inhibits NE and DA reuptake.

• Seizures very common even with therapeutic doses.

• Concern for delayed onset in sustained release form.

• Treat with benzodiazepines.

Case # 5

• 25 year old man presents with confusion, nausea, vomiting and tremor.

• PMHx: Bipolar disorder • Got into a fight with his girlfriend several

hours ago and took all of his medication.

Case # 5

• Drowsy, slightly slurred speech. • BP 145/85, P 115, RR 18, T 98.8 • CVS – Tachycardic, no M/R/G • Pulm - Clear • Neuro – PERRLA, tremor, ataxia,

hyperreflexia • Abdo - + bowel sounds • Skin – Nml

Case # 5

• CBC – WCC 17, otherwise nml • Li + - 5.67 mEq/L • Chem 7 –

1108.1

2723

1103.4

132

1108.1

2723

1103.4

132

Lithium

• Lithium is an alkali metal with a long history of medicinal uses.

• In the early 20th century, lithium chloride was used as a salt substitute in patients with congestive heart failure and other salt sensitive states.

Lithium • Significant toxicity and at least one fatality

occurred from this practice and the FDA banned its use in 1949.

• At this same time, Cade, an American neuroscientist, discovered the calming effect that lithium had on guinea pigs; further research was delayed by the FDA ban.

• Lithium carbonate (Li2CO3) was approved in 1970 for use in manic depressive illness

Lithium

• Of patients on chronic lithium therapy 75-90% are at risk for some sign or symptom of toxicity.

• Lithium toxicity does not occur from lithium batteries.

Mechanism of Action

• Antimanic effects remain undefined – May attenuate DA

and NE effects – Increases GABA

• Antidepressant effects – Increases turnover

and function of 5HT

Therapy

• Goal for acute mania: 0.7-1.2 mEq/L • Goal for maintenance: 0.5-0.8 mEq/L • Levels usually checked 12 hours after

last dose

Side Effects at Therapeutic Doses

• Fine tremor • Renal

– DI • Hypothyroidism • Weight gain • Rare cardiac

conduction abnormalities

• Teratogenicity • Hematologic

– leukocytosis

Overdose

• Must distinguish acute vs chronic vs acute on chronic

• Acute overdose, higher levels with less symptoms vs. chronic overdose, more symptoms with lower levels

• Acute on chronic overdose, intermediate findings

Overdose

• Mild – Apathy, lethargy, weakness, tremor, GI symptoms

• Moderate – Coarse tremor, slurred speech, ataxia,

drowsiness, confusion, hyperreflexia, clonus, non-specific ECG changes, DI, RTA, muscle fasciculations

• Severe – Seizures, coma, cardiovascular collapse, EPS,

generalized fasciculations

Treatment

• Whole bowel irrigation for sustained release preparations.

• Normal saline hydration, twice maintenance • Antiemetics for nausea and vomiting

Valproate

• Anticonvulsant approved in 1995 for mania (mood stabilizer)

• Increases GABA (inhibits degradation)

• Frequency dependent Na+ effects – Slows rate of recovery

from inactivation

Overdose

• GI – nausea, vomiting • CNS – sedation, respiratory depression,

ataxia, seizure, coma • Hyperammonemia, hypernatremia,

hypocalcemia, metabolic acidosis • Presentation can be delayed with

sustained-release products

Treatment

• MDAC • Naloxone (reverse sedation) • Supportive care • Carnitine

– Hyperammonemia and altered mental status – PO 12.5 mg/kg q 8 – Children max 2 g per day – IV 50 mg/kg bolus; 20 mg/kg q 4 – Maximum 10 g/day

Questions?