“i’m allergic to everything but….”
TRANSCRIPT
“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?