I m Allergic to Everything

Transcription

1 I m Allergic to Everything but. Prescription Medication Overdoses : There is more than Vicodin and Percocet Liza Halcomb, MD 10/23/15

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5 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

6 Mechanism of Action

7 Mechanism of Action

8 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.

9 Case # 1 CBC WCC 10, H&H 13/40, Plt 262 Chem 7 Nml Coags Nml LFTs - Nml CK -1218

10 Diagnosis Neuroleptic Malignant Syndrome

11 NMS Hyperpyrexia due to hypothalamic dysregulation. Muscle rigidity leads to rhabdomyolysis. Autonomic instability. Altered mental status.

12 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.

13 Adverse Effects Extrapyramidal Haloperidol, fluphenazine Shields,W. and Bray, F.: A Danger of Haloperidol Therapy in Children. Journal of Pediatrics 88,

14 Adverse Effects

15 Adverse Effects Deep sedation Seen with quetiapine and olanzapine

16 Adverse Effects Antimuscarinic Olanzapine, clozapine, chlorpromazine Hypotension alpha antagonism Chlorpromazine, thioridazine, mesoridazine Agranulocytosis Clozapine, mirtazipine

17 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.

18 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.

19 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

20 Case # 2 Labs Nml. EKG Nml. Head CT Nml. Chest CT Nml.

21 Diagnosis MAOI Food Interaction

22 Patient was on isocarboxazid for refractory depression. Was unaware that sauce at dinner contained red wine. Developed hypertensive emergency. Diagnosis

23 MAOIs Tranylcypromine Phenelzine Isocarboxazid Selegeline (B) = = = = Parnate Nardil Marplan Deprenyl

24 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.

25 Mechanism of Action MAO inactivates monoamines MAOIs block enzymatic breakdown of monoamines MAO MAOI transported by NE reuptake pump into neuron

26 Hypertensive Crisis MAO-A (gut) Responsible for food interactions. MAO-B (brain) Responsible for antidepressant effects. MAOI may be selective or nonselective. Reversible or irreversible. Hydrazine or amphetamine like.

27 Overdose Symptoms often delayed for hours. Excess catecholamine release results in hemodynamic instability. Hypertension, myoclonus, agitation, seizures Followed by catastrophic cardiovascular collapse. Thought to be due to catecholamine depletion

28 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.

29 Treatment Hypertensive Reaction Oral terazosin or nifedipine in pts with normal baseline BP. Phentolamine. Benzodiazepines.

30 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.

31 Treatment Serotonin Syndrome Sedate with a benzodiazepine. Active cooling should be instituted. Paralysis with EEG monitoring may be necessary in cases of extreme rigidity.

32 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.

33 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.

34 Case # 3 Pt gets intubated, ventilated. IV, O2, monitor. Fluids started. EKG obtained.

35 Case # 3

36 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.

37 Case # 3 Amitriptyline

38 Tricyclic Antidepressants Block reuptake of NE, DA and 5HT in central presynaptic terminals. May account for antidepressant efficacy.

39 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

40 TCAs Cause sodium channel blockade Type 1A antidysrythmic Prolonged QRS Antihistamine Sedation GABA antagonism Seizures Alpha-blockade Hypotension

41 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.

42 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.

43 Case # 4 Dizziness, blurry vision, dry mouth, difficulty urinating. Had a witnessed seizure (no evaluation). Sudden onset of palpitations 12 hours ago, getting worse.

44 Case # 4 T 99 F, P , BP 84/44, RR 17, 99% RA Irregular tachycardia Exam otherwise normal except for marked anxiety.

45 Initial EKG

46 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.

47 Case # 4 Immediate and delayed toxicity Citalporam is anticholinergic Seizures QT Prolongation, dysrhythmias caused by metabolite

48 Case # 4 Escitalopram (Lexapro ) S-isomer of citalopram Newer agent, less clinical experience. Admit for 24 hours with telemetry.

49 Names Fluoxetine Paroxetine Sertraline Venlafaxine Fluvoxamine Escitalopram Citalopram Prozac Paxil Zoloft Effexor Fluvox Lexapro Celexa

50 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.

51 SSRIs block reuptake of serotonin from the synapse prolonging it action Mechanism of Action

52 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.

53 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.

54 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

55 Case # 5 CBC WCC 17, otherwise nml Li meq/l Chem

56 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.

57 Lithium Significant toxicity and at least one fatality occurred from this practice and the FDA banned its use in 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 (Li 2 CO 3 ) was approved in 1970 for use in manic depressive illness

58 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.

59 Mechanism of Action Antimanic effects remain undefined May attenuate DA and NE effects Increases GABA Antidepressant effects Increases turnover and function of 5HT

60 Therapy Goal for acute mania: meq/l Goal for maintenance: meq/l Levels usually checked 12 hours after last dose

61 Side Effects at Therapeutic Fine tremor Renal DI Hypothyroidism Weight gain Rare cardiac conduction abnormalities Teratogenicity Hematologic leukocytosis Doses

62 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

63 Overdose Mild Apathy, lethargy, weakness, tremor, GI symptoms Moderate Coarse tremor, slurred speech, ataxia, drowsiness, confusion, hyperreflexia, clonus, nonspecific ECG changes, DI, RTA, muscle fasciculations Severe Seizures, coma, cardiovascular collapse, EPS, generalized fasciculations

64 Treatment Whole bowel irrigation for sustained release preparations. Normal saline hydration, twice maintenance Antiemetics for nausea and vomiting

65 Valproate Anticonvulsant approved in 1995 for mania (mood stabilizer) Increases GABA (inhibits degradation) Frequency dependent Na+ effects Slows rate of recovery from inactivation

66 Overdose GI nausea, vomiting CNS sedation, respiratory depression, ataxia, seizure, coma Hyperammonemia, hypernatremia, hypocalcemia, metabolic acidosis Presentation can be delayed with sustained-release products

67 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

68 Questions?