060514 Pharmacology of drugs in Emergency casesdr.Datten Bangun,MSc,SpFKDept.Farmakologi & TherapeutikFak.Kedokteran UHNMEDAN

What is Emergency Medicine

International Federation for Emergency Medicine in 1991: = A field of practice based on the knowledge and skills required for the prevention, diagnosis and management of acute and urgent aspects of illness and injury affecting patients of all age groups with a full spectrum of undifferentiated physical and behavioural disorders.

Acute asthmaDystonic reactionsHyperthermiaHypertensive crisisForeign body aspirationDiabetic hypoglycemiaAddisonian crisisObstetrical concernsMandibular dislocationMedical Emergencies in the OfficeAllergic reactions / anaphylaxisOversedation / vomitingSyncopeSevere hyperventilationBleeding disordersAcute chest painSeizuresStrokes (CVA's)

1.Allergic Reactions / AnaphylaxisDefinition :Anaphylaxis = acute systemic allergic reaction that occurs after antigen-antibody interaction causing release of chemical mediators Mediator Substances Causing AnaphylaxisMost released by mast cells & basophils :Histamine - BradykininsLeukotrienes - ProstaglandinsThromboxanePlatelet aggregating factorMiscellaneous

Major Effects of Anaphylactic MediatorsVasodilationSmooth muscle spasmIncreased vascular permeabilityEdema formationCauses of Death from AnaphylaxisUpper airway edema : 70 % of deathsCirculatory collapse : 20 %Both : 10 %

2. RespiratoryThroat "tightness""Lump in throat"HoarsenessStridorDysphagiaRhinorrheaBrochospasm : wheezing, cough, dyspnea, chest tightness Clinical Manifestations of Anaphylaxis1. CutaneousPruritisFlushingUrticariaAngioedema

3. CardiovascularWeaknessHypotensionLightheadednessShock (inadequate perfusion)Loss of consciousness4. GastrointestinalCrampsNauseaVomitingDiarrhea5. MiscellaneousSense of impending doomMetallic tasteUterine contractions Clinical Manifestations of Anaphylaxis

Anaphylaxis : CausesAntibiotics : most commonLocal anestheticsLatexShould question all patients about latex allergy ; If allergic, use plastic or nitrile gloves, nozzles, etc.FoodInsect bite

General Treatment of Allergic Reactions1. Remove offending agent if possibleStop drug being administeredWipe off area if topicalConsider PO activated charcoal (if drug given PO)2. If only local reaction (only localized redness, pruritis, swelling) :Often no treatment neededOr PO antihistamineBenadryl 1/2 mg/Kg Chlortrimeton

General Treatment of Allergic Reaction (cont.)3. If systemic (diffuse pruritis, hives, any throat or chest symptoms) :Place IV or heplockAssess vital signsIf vital signs OK, treatment : SQ epi, PO or IV antihistamine, PO or IV steroid, Observe one hourEmergent treatment if VS not OK

Emergent Treatment of Systemic Allergic ReactionStart this sequence if VS not OK (increased HR, decreased BP, or any throat tightness, SOB or wheezing) :1. Place patient recumbent / supine (to prevent empty ventricle syndrome) & start FMO22. SQ epi 0.3 mg (0.01 mg / Kg) ; rub area ; If hypotensive : dilute epi (1:10,000) & give 0.1 to 0.2 mg IV slowly (never more than 0.1 mg IV at a time)3. IV diphenhydramine or hydroxyzine 1 mg / Kg (50 mg in adults)4. IV steroids (100 mg hydrocortisone)

Emergent Treatment of Systemic Allergic Reaction (cont.)5. IV fluid bolus (LR or NS 1 liter or 20 cc / Kg)6. Metaproteronol or albuterol aerosol if wheezing (0.2 to 0.5 cc in 3 cc NS)7. Consider IV ranitidine or cimetidine8. Atropine if bradycardic Dopamine if hypotensive despite IV fluids Racemic epi aerosol if throat swelling Early intubation if airway compromise

2. HypoglycemiaUsually IDDM patientDecrease PO intakeIncrease activity (exercise)Also in NIDDM patientOral hypoglycemic drugs cause longer duration hypoglycemia than does insulin excess-patient on OAD,when consuming NSAIDs,then NSAIDs will displace OAD from protein binding ----->OAD intoxication------hypoglicemia

HypoglycemiaCan occur in non-diabetic patient :ETOH ingestionToxic salicylate ingestionMalnourished statesInsulin-producing tumors

Patients on beta blockers susceptible ==== -blocker is contraindicated in DM

Hypoglycemia : Symptoms (any of these may be present)AnxietySleepinessLethargyCold, clammy skinWeaknessDizzinessLightheadednessHeadacheAny focal neuro signMay have seizure or comaFatigueConfusionPalpitationsTremulousnessSweatingHungerCombativeness

Hypoglycemia : DiagnosisConfirm with fingerstick glucose (ChemStrip)Additional serum verification by lab not always required

Hypoglycemia : Treatment1. If reasonably alert and able to manage own airway, then give glucose-containing gel or fluid PO2. Otherwise start IV (draw red top or green top tube of blood if possible also so that diagnosis can be confirmed later in lab) and give 1 amp (50 cc) of 50 % dextrose in water (for child give 1 gm / kg IV of 25 % dextrose in water)3. May need to repeat dose once4. If unable to start IV : consider glucagon 1 mg IM (only works if glycogen stores OK in liver)5. Call EMS if patient not a known diabetic or if no rapid response to initial treatment with sugarImportant to diagnose and treat quickly to prevent hypoglycemic neuronal damage

3. Hypertension EmergenciesHypertensive crisis (emergency) :Severe elevation in blood pressure with rapid or progressive CNS, cardiac, renal, or hematologic deteriorationHypertensive " urgency " :Elevated BP but no symptoms of end-organ damageBP reduction over 24 to 48 hrs. recommended

Hypertension : Treat, Refer, or Ignore ?Level of BP requiring acute treatment in the asymptomatic patient is controversial among M.D.'sUsually however does not need STAT RxBe sure to repeat BP in both arms and after patient has relaxed for 15 minutes before considering referralRemember BP will increase in non-hypertensive patient due to pain, stress, anxiety, etc.Probably should document patient advised of increased BP if checked in office

Specific Criteria for Hypertensive Crisis (Presence of Listed Item and BP)Start treatment and transfer to ED to admitEncephalopathy (altered mental status)Vomiting : protractedSeizuresCVA / intracranial hemorrhageAngina / MI / pulmonary edemaAortic dissectionEclampsia (toxemia)? ARF? grade III / IV retinopathy? hemolytic anemia / DIC? epistaxis

Conditions That May Mimic Hypertensive CrisesAcute left ventricular failureUremia from any cause, particularly with volume overloadCerebral vascular accidentSubarachnoid hemorrhageBrain tumorHead injuryEpilepsy (postictal)

Causes of Hypertensive CrisesAccelerated hypertensionHypertensive encephalopathy (malignant hypertension)Uncontrolled primary hypertensionRenal vascular diseaseToxemia of pregnancyPheochromocytomaIntake of catecholamine precursors in patients taking monoamine oxidase inhibitorsHead injuriesSevere burns or traumaRebound hypertension after withdrawal of antihypertensive drugs

Causes of Hypertensive Crises (cont.)Severe to moderate hypertension accompanying :Acute left ventricular failureIntracranial hemorrhageDissecting aortic aneurysmPostoperative bleedingSevere epistaxis

Blood pressureDiastolic usually greater than 130 mm HgFunduscopic findingsHemorrhagesExudatesPapilledemaRenal symptomsOliguriaAzotemiaGastrointestinal symptomsNauseaVomiting Signs and Symptoms of Hypertensive Crises

Treatment of Hypertensive Crisis in the OfficeHigh flow O2Call EMSConsider placing IV / heplockConsider IV narcotic or benzodiazepineConsider SL TNG to decrease BP acutely (0.4 mg)Recheck BP frequently till EMS arrives

Specific BP Levels For Emergent TreatmentHypertensive encephalopathyCerebral infarctionIntracerebral hemorrhage >200/130Subarachnoid hemorrhage

Eclampsia >140/90

MI / CHF / Aortic dissection >130 to 140 / 90 to 100

Options for Office Treatment of Hypertensive EmergencyOral / SL Nifedipine 10 to 20 mgClonidine 0.1 mg to 0.2 mg POLabetolol 100 mg PO or 20 to 40 mg IV+ IV furosemide 20 to 80 mgTNG ointment 1/2" to 1"MgSO4 2 gms IV if eclampticMorphine 2 to 4 mg IV (if CHF)

Drug Induced Hypertensive CrisisCocaineAmphetaminesPhencyclidine (PCP)Diet pillsOTC sympathomimeticsMAO Inhibitors / Tyramine

4.Antihypertensive Meds for EclampsiaDrugs of choice : Hydralazine, LabetololInhibit uterine contractions : Diazoxide, Calcium antagonistsUse only if refractory to other agents : nitroprussideContraindicated : Trimethaphan (meconium ileus), "Pure" beta blocker agents ( decreased uterine blood flow), Diuretics (patient already volume depleted)Don't forget magnesium--------MgSO4

Treatment of Drug Induced Hypertensive CrisisLabetalol : preferredNitroprussideNifedipine / VerapamilPhentolamineSince duration of HBP often brief, may not need treatmentNote : Pure Beta blockers may cause increased BP (from unopposed alpha effect)

Medical Therapy in5. Acute Myocard Infarction

MONA + BAHMorphine (class I, level C)AnalgesiaReduce pain/anxietydecrease sympathetic tone, systemic vascular resistance and oxygen demandCareful with hypotension, hypovolemia, respiratory depression

Oxygen (2-4 liters/minute) (class I, level C)Up to 70% of ACS patient demonstrate hypoxemiaMay limit ischemic myocardial damage by increasing oxygen delivery/reduce ST elevation

Nitroglycerin (class I, level B)Analgesiatitrate infusion to keep patient pain freeDilates coronary vesselsincrease blood flowReduces systemic vascular resistance and preloadCareful with recent ED meds, hypotension, bradycardia, tachycardia, RV infarction

Aspirin (160-325mg chewed & swallowed) (class I, level A)Irreversible inhibition of platelet aggregationStabilize plaque and arrest thrombusReduce mortality in patients with STEMICareful with active PUD, hypersensitivity, bleeding disorders

Beta-Blockers (class I, level A)14% reduction in mortality risk at 7 days at 23% long term mortality reduction in STEMIApproximate 13% reduction in risk of progression to MI in patients with threatening or evolving MI symptomsBe aware of contraindications (CHF, Heart block, Hypotension)Reassess for therapy as contraindications resolve

ACE-Inhibitors / ARB (class I, level A)Start in patients with anterior MI, pulmonary congestion, LVEF < 40% in absence of contraindication/hypotensionStart in first 24 hoursARB as substitute for patients unable to use ACE-I

Heparin (class I, level C to class IIa, level C)LMWH or UFH (max 4000u bolus, 1000u/hr)Indirect inhibitor of thrombin less supporting evidence of benefit in era of reperfusionAdjunct to surgical revascularization and thrombolytic / PCI reperfusion24-48 hours of treatmentCoordinate with PCI team (UFH preferred)Used in combo with aspirin and/or other platelet inhibitorsChanging from one to the other not recommended

Additional medication therapyClopidodrel (class I, level B)Irreversible inhibition of platelet aggregationUsed in support of cath / PCI intervention or if unable to take aspirin3 to 12 month duration depending on scenario

Glycoprotein IIb/IIIa inhibitors (class IIa, level B)Inhibition of platelet aggregation at final common pathwayIn support of PCI intervention as early as possible prior to PCI

MANNITOLOsmotic diuretic for cerebral edema may inc ICP initial dose 0.5-1g/kg IV of 25% solutionNote: highly irritating to the veins forms crystals

9.Alcohol Withdrawal(Delirium Tremens)

Approximately 5% of patients withdrawing from alcohol will experience delirium tremens characterized by:

HallucinationsDisorientationTachycardiaHypertensionLow grade feverAgitationDiaphoresis

Alcohol WithdrawalTime scaleMinor withdrawal symptoms = 6-12 hoursAlcoholic hallucinations = 12-24 hoursWithdrawal seizures = 24-48 hoursDelirium Tremens = 48-72 hours

Risk factors for DTs includeHistory of sustained drinkingHistory of previous DTsAge>30>2 days since the last drink

*Our patient= 17 HIGH!3400050050Minimal to mild= 15

Withdrawal Severity: 0(not present) to 6/7 (extreme); Higher = >risk8-10 Mild Supportive, no Meds (i.e. Social Detox)10-15 Moderate - Some meds (BZP) (i.e. Medically Supported Detox)15/> Severe - DT Risk (i.e.. Hospitalization)N.B. May also be used to monitor recovery and medication management

Treatment**Benzodiazepines-

The preferred agents for treating the symptoms of alcohol withdrawal syndrome.

Diazepam and Chlordiazepoxide are long acting agents. The long half life makes withdrawal symptoms and rebound from the Benzos less likely to occur.Ex: Diazepam 5mg IV (2.5mg/min). If initial dose is not effective, repeat in 5-10minutes. If the second dose is not effective, use 10mg for 3rd and 4th doses every 5-10 minutes. If not effective, use 20mg for the 5th and subsequent doses until sedation is achieved,. Use 5-20mg/hour as needed to maintain light somnolence (5)

With appropriate treatment, mortality rate from DTs is

Alcohol withdrawal treatmentShort acting benzos like lorazepam may be better for pts who are elderly or have substantial liver disease and prolonged sedation is a risk.

Diazepam, Lorazepam may be administered parenterally when oral dosing is impossible.

Fixed Dose or Loading dose vs. symptomatic therapyFixed dose allows stable control of symptoms followed by a 4-7 day taperSymptomatic- Pts use less benzodiazepines but must have trained/available nurses to administer

Choice of a BZD Long half-life (chlordiazepoxide, diazepam): Seizures: ~ 58% Distress (smoother detox)

Shorter half-life (lorazepam, oxazepam) Oversedation Safer in elderly / liver impairment

Alcohol withdrawal treatmentB-Blockers in conjunction with benzos to control persistent HTN and tachycardia. There is no evidence these improve outcome.

Carbamazepine can be used to treat the seizures, this is done more in Europe than in the US.

Haloperidol can be used to treat agitation and hallucinationsNutrition support: Thiamine to avoid Wernicke-Korskoff, Mg supplementation, folate if needed.

Acamprosate, disulfiram appropriate for abstinence therapy NOT withdrawal

Carbamazepine and Valproate Effective in: Mild to moderate AW / protracted AW distress and faster return to work No abuse potential / alcohol interactions No toxicity in 7-day trials

Limitations: Not better than BZDs Side effects Cost Limited data in AW seizures/delirium

Nonpharmacological Treatment Quiet environmentNutrition and hydration:Oral thiamine (prevents Wernicke-Korsakoff) / folic acidOral fluids / electrolytesOrientation to realityBrief interventions / motivate to changeReferral to AA / relapse prevention tx.

ASTHMAPatients with asthma (both adults and children) may have an attack whilst at the surgery. Most attacks will respond to a few activations of the patients own short-acting beta2-adrenoceptor stimulant inhaler such as salbutamol (100 micrograms/actuation). Repeat doses may be necessary.

If the patient is unable to use the inhaler effectively, additional doses should be given through a large-volume spacer device.

ASTHMASymptoms and SignsClinical features of acute severe asthma in adults include: Inability to complete sentences in one breath. Respiratory rate > 25 per minute. Tachycardia (heart rate > 110 per minute).Clinical features of life threatening asthma in adults include: Cyanosis or respiratory rate < 8 per minute. Bradycardia (heart rate < 50 per minute). Exhaustion, confusion, decreased conscious level.

ACUTE SEVERE ASTHMA MANAGEMENTIf the reponse is unsatisfactory and a nebuliser is unavailable, 46 activations from the salbutamol inhaler should be given using a large-volume spacer device and repeated every 10 minutes if necessary until an ambulance arrives.If the a nebuliser is available, give salbutamol 2.5mg-5mg via a nebuliser, and oral prednisolone, 30mg stat.If the response remains unsatisfactory and the patient develops tachycardia, becomes distressed or cyanosed, arrangements must be made to transfer the patient urgently to hospital.

Recommended Minimal Emergency Drugs / Equipment for the OfficeOxygen masks / nasal prongsReliable O2 tank supplySuction catheters : flexible and YankauerIV catheters : 20 g, 18 g (22 g if children treated)500 cc or 1000 cc bags of NSIV tubing setsEpinephrine 1 : 1000 vials (1 mg per cc)

Optional Meds for Office EmergenciesAntihistamines ampsAlupent or albuterol solution for aerosols or MDI'sHydrocortisone 100 mg ampsGlucagon 1 mg amps

Office EmergenciesLecture SummaryBe prepared and educate the office staff about management of emergenciesCheck office emergency equipment and meds regularlyKnow how to access local EMS for help

Medical Emergencies When you prepare for emergencies, they cease to exist!MalamedYou have to have seen it to recognize it.Greens Rule

************