Communication on Labor and Delivery

Chasing the Dragon-How to Manage Your Patients When They Are Acutely IntoxicatedSurgical Grand RoundOctober 3, 2012University of Tennessee Health Science CenterObjectivesIdentify the signs and symptoms associated with acute intoxication from illicit substancesReview the appropriate management of acute intoxication by the substances covered in this presentationIdentify professionalism issues associated with the management of acutely intoxicated patientsMost common drug encountered will be ethanolCH3CH2OHFocus of this talk will be on other illicit drugsMarijuana

MarijuanaPsychoactive properties due to delta-9-tetrahydrocannabinol (THC)THC content has increased from 1-5% in the 1960s to 10-15% today.Typically causes euphoria with decrease in anxiety, alertness, depression and tension. Can cause anxiety, dysphoria and panicPerceptual changes such as colors being brighter and music more vidDistorted time and spatial perceptionCan cause hallucinationsMystical thinking, increased self consciousness, depersonalization, transient grandiosity, paranoia and other signs of psychosis can occurMarijuanaDecreases reaction time, impairs attention, concentration, short term memory and risk assessment.Impaired motor coordination and interferes with complex tasks that require divided attention.Impairment of cognition, coordination and judgment lasts much longer. Psychomotor impairment last for 12-24 hoursMarijuanaPhysiologic signsTachycardiaHypertensionTachypneaConjunctival injectionDry mouthIncreased appetite

Cocaine

CocaineBenzoylmethylecogninemethyl (1R,2R,3S,5S)-3-(benxoyloxy)-8-methyl-8-azabicyclo [3.2.1] octane-2-carboxylateCoca from the coca plant and the alkaloid suffix-aineCrystalline tropane alkaloidStimulant, appetite suppressant and local anesthetic CocaineFound in leaves of Erytholoxum coca plantPeople have been chewing the leaves of the coca plant for 2000 years with little risk of abuse1860-Cocaine isolated by Albert NiemannCoca-Cola contained 0.75 mg of cocaine/ounce until 1903.Cocaine still available as a 4% or 10% solution for use as a local anestheticCocaine14 millions users worldwide, 6.4 million in North AmericaUsage in UK and Spain has reached the same level as that of the USVery little cocaine usage in Africa, Asia, Eastern Europe and OceaniaMost common illicit drug associated with emergency room visits (31% or 450,000 visits)

CocaineSerotonin-norepinephrine-dopamine reuptake inhibitor or triple reuptake inhibitor (TRI)Has hydrophilic and lipophilic portions of the molecule. This allows it to cross the blood-brain barrier easilyHighly addictive due to effects on mesolimbic reward pathwayAlso blocks membrane voltage-gated sodium channelsCocaineTwo forms-base and saltCocaine base-crack or free base. Low melting point (98C) so it is easy to smoke. Water insoluble so cant be used for injectionCocaine salt-High melting point (195) so cannot be smoked. Water soluble so easy to inject and insufflate (snort).Rapidly taken up by most organs including liver, heart, kidney and adrenal gland.Found in blood, urine, hair, sweat, saliva, breast milk and meconium after usageCocaineOnset-inhaled or iv-seconds. Intranasal-20-30 min and GI-90 min. 95% is metabolized by hydrolysis of ester bonds. Carboxyesterases in liver hydrolyze it to benzoylecgonine. Butyrylcholinesterase throughout the body hydrolyzes cocaine to ecgonine methylester5% n-demethylated to norcaine by P450 systemEliminated in the urine, largely as benzoylecgonine. This is what is tested for in UDSCocaineTypical doses-12-15 gm orally (coca leaves), 20-100 mg intranasally, 10-50 mg iv or 50-200 mg inhaledIntended effects-increased energy, alertness and sociability; elation or euphoria; and decreased fatigue, need for sleep and appetiteAdverse effects-dysphoric mood (anxiety or irritability), panic attacks, paranoia, grandiosity, impaired judgment, psychotic symptoms such as hallucinations and delusionsCocaine40% of cocaine users suffer from sleep disturbance, weight loss, paranoia or hallucinations.Restlessness, agitation, tremor, dyskinesia, repetitive or stereotyped behaviors such as picking at the skin can also occur.Sensitization and tolerance can occur with chronic use of cocaine.Chronic cocaine abuse associated with cognitive impairment including visuo-motor performance, attention, verbal memory and risk-reward decision-making. It is also associated with suicide ideation and attempts CocaineWhen combined with ethanol, cocaine forms benzoylmethylecgonine or ethyl cocaine via transesterification.Ethyl cocaine half-life is 13 hours and is vasoconstrictive, cardiotoxic, dysrhythmogenic and neurotoxic.Inhibits dopamine reuptake as potently as cocaine24% of cocaine is converted to ethyl cocaine when taken iv, 18% when insufflated.

CocaineMonoamine reuptake inhibitorNa-channel blockadeExcitatory amino acid stimulationCocaineIndirect sympathomimetic agentStimulates -1, -2, -1, and -2 adrenergic receptors largely mediated by increases in norepinephrine and to a lesser extent epinephrinePreferential effects on the cardiac and peripheral vasculature. Additional cardiac effects via agonismBlocks the dopamine transporter protein, which pumps dopamine out of the synaptic cleft and into the presynaptic neuronResults in enhanced and prolonged dopaminergic effects on the postsynaptic neuron

CocaineEuphoria associated with serotonin reuptake inhibition in CNSSlows or block nerve conduction by blocking membrane voltage-gate Na channels in nerves.In high doses, affects Na channels in the heart with prolonged QRS and negative inotropy.Increases concentrations of the excitatory amino acids glutamate and aspartate in CNS, particularly in Nucleus accumbens. Glutamate is main excitatory amino acid in the CNS.CocaineAcute IntoxicationAgitationDilated PupilsEuphoriaTachycardia and HypertensionFeverCocaineCauses arterial vasoconstriction and enhanced thrombus formationCauses tachycardia, hypertension, increased myocardial oxygen demand and increase vascular shearing forcesCauses coronary vasoconstriction and 5% of patients who seek care in ED have myocardial ischemiaHigh doses can lead to decrease LV function and heart failure.Can cause supraventricular and ventricular dysrhythmiasAortic dissection and rupture occur rarelyCocaineCause psychomotor agitation, seizures, coma, headache, intracranial hemorrhage and focal neurologic symptomsPsychomotor agitation can cause hyperthermia when peripheral vasoconstriction prevents the body from dissipating head. Mortality can be as high as 33% when hyperthermia develops.Seizures occur in 3-4% of cocaine-related ED visitsCan get angioedema and pharyngeal burns during inhalation Cocaine uses have a high incidence of perforated ulcersCan cause ischemic colitis, intestinal infarction and metabolic acidosis.Intestinal obstruction-consider body-packing

CocaineDifferential Diagnosis includesAmphetamine AbusePhencyclidine AbuseHypoglycemiaHypoxiaAlcohol and sedative-hypnotic withdrawalNeuroleptic malignant syndromeSerotonin syndromeHeat-related illnessThyroid stormSubarachnoid HemorrhageCNS InfectionsSeizuresPsychiatric diseasesCocaineTreatmentABCs-Avoid succinylcholine for RSICooling if hyperthermia presentBenzodiazepinePhentolamine (only if hypertension refractory to benzodiazepine)IV fluidsNo -BlockersHeroin

HeroinOpium is crude substance isolated from opium poppyOpium has been used by humans since 4000 BC1804-Friederick Sertrner isolated morphine 1874-Heroin (diacetylmorhine or morphine diacetate) synthesized by C.R. Alder White. Added two methyl groups to morphine isolated from opium

HeroinOpioids activate specific transmembrane neurotransmitter receptors (,,) that couple G proteins.Activation of endogenous opioid receptors results in effects of reward, withdrawal and analgesia.2.4 million people in US have used Heroin.Heroin has a half-life of 30 min.Duration of action 4-5 hours, due to active metabolites including morphineHeroin is metabolized to 6-monoacetylmorphine (6-MAM) which is detectable on urine testing

HeroinSymptomsDepressed mental statusDecreased respiratory rateDecreased tidal volumeDecreased bowel soundsMiotic (constricted) pupilsHeroinTreatmentABCs-Particular attention to airway and breathingNaloxone-0.2-1 mg depending on symptoms. 2 mg if cardiopulmonary arrest.Supportive carePCP

PCPPhencyclidine or1-(1-phenylcyclohexyl)piperidine.1926-first synthesized1952-patented by Parke-Davis and marketed as Sernyl. It is a dissociative anaestheticPeak abuse was in the late 1970s. 710 reported cases of PCP intoxication in the US in 2010.Early 1970s-ketamine was isolated as a derivative of PCP. It is 5-10% as potent as PCPPCPThree primary sites of action in CNSN-methyl-D-aspartate (NMDA) receptor complex. Dopamine, norepinephrine and serotonin reuptake complexSigma receptor complexPCPPCP binds to NMDA receptor complexes in the hippocampus, neocortex, basal ganglia and limbic system. NMDA antagonism at these sites produces acute psychosis which mimics schizophrenia. It also leads to excess excitatory neurotransmitter release (glutamate, aspartate and glycine) which can cause agitation and seizures.Inhibits reuptake of dopamine, norepinephrine and serotonin in neurons.These actions contribute to adrenergic and dopaminergic effects of acute intoxicationSigma receptor effects may explain psychotic, anticholinergic and movement abnormalities seen with acute intoxication

PCPPCP can be injected, insufflated, smoked and ingestedPCP displays first order pharmacokinetics. Half-life of 7-26 hours.Primarily eliminated by liverPresenting symptoms are very variable. Adrenergic stimulation is typical but patients may have CNS stimulation or depression. Patients can progress to coma unexpectedly.Tachycardia and hypertension are common.PCPPatients can be hyperthermic or hypothermic.Psychomotor agitation is common as is violence.Associated withRhabdomyolysisSeizuresHypoglycemiaProlonged comatose statePCPTreatmentABCsBenzodiazepinesDroperidol or Haloperidol for refractory psychosisBarbiturate or Propofol for severe refractory psychomotor agitation or status epilepticusSupportive care for associated symptoms i.e. rhabdomyolysisLSD

LSDLysergic acid diethylamine1938-synthesized by Albert HofmannOriginally marketed as anesthetic agent and adjunct for psychoanalysisCauses altered thinking processes, closed and open eye visuals, synesthesia, an altered sense of time and spiritual experiences.LSDUsually ingested, although can be injectedDose is usually 20-30 mcgNo documented deaths from intoxicationMay temporarily impair judgment and understanding of common dangers, making the user more susceptible to accidentsCan cause dissociative fugue state with certain medications including lithium and tricyclic antidepressantsLSDTreatmentPlace patient in calm, safe environmentMay use benzodiazepinesAvoid neuroleptics because they may worsen hallucinations and delusionsRarely, other supportive careMethamphetamine

MethamphetamineSympathomimetic amine and is a phenethylamine1893-First synthesized1923-Pharmaceutical formulations used to treat nasal congestion and asthmaUsed in World War II to increase alertness and decrease fatigueAfter cannabis, most widely abused drug in the worldMethamphetamineDextromethamphetamine is a stimulant. It is FDA-approved for treatment of ADHD and obesity. Trade name is Desoxyn. Levomethamphetamine is CNS-inactive and used as non-prescription over-the-counter nasal decongestantMethamphetamine has an additional methyl group compared to amphetamine which increases the lipophilicity and CNS activity of methamphetamineMethamphetamineIt is an indirect neurotransmitter and lacks direct adrenergic effectsIncorporated into cytoplasmic vesicles where it displaces epinephrine, norepinephrine, dopamine and serotonin into the cytosol.These neurotransmitters diffuse out of the neuron and into the synapse where they activate postsynaptic receptorsIt also inactivates neurotransmitter reuptake transporter systemsMethamphetamineThese processes result in adrenergic stimulation.The lone modulator of these effects is degradation by catechol o-methyl transferase (COMT)Methamphetamine can be smoked, injected, insufflated, or ingestedMethamphetamine is eliminated by cytochrome CYP2D6 in the liver, other hepatic pathways and by the kidneyMethamphetamineSignsDiaphoresisHypertensionTachycardiaSevere agitationPsychosisMethamphetaminePatients may appear malnourished, agitated and disheveledViolence is associated with intoxicationCan see hypervigilance and akathisiaSevere intoxication can lead to sudden cardiovascular collapse, seizures, altered mental status requiring intubation, rhabdomyolysis, cardiac ischemia, MI, cardiomyopathy and deathMethamphetamineTreatmentABCsBenzodiazepinesAntipsychotics (ziprasidone, droperidol, haloperidol)Neuromuscular blockade with nondepolarizing agents for severe hyperthermia. No succinylcholine.Other supportive care i.e. sodium bicarbonate, IV fluids, ACLS for cardiopulmonary arrestMDMA

MDMA3,4-methylenedioxy-N-methylamphetamineEcstasyMember of the phenethylamines1912-synthesized by Anton Kllisch at MerckLegal and unregulated in US until 198510-25 millions users worldwide similar to cocaine, amphetamine and opioidsAssociated with electronic dance music, raves, dance clubs and dance partiesInduces euphoria, a sense of intimacy with others and diminished anxietyMDMAUsually ingestedDosage is 50-200 mgSympathomimetic amphetamine that increases release of norepinephrine and dopamine and blocks their reuptakeStructurally similar to serotoninIn addition to hypertension, tachycardia, hyperthermia, CNS stimulation, MDMA can cause serotonin syndrome and SIADHPrimarily excreted in urine and metabolized by CYP2D6MDMAMDMA increases alertness, reduces fatigue, leads to feelings of increased physical and mental powers and euphoriaCan also cause agitation, nausea, bruxism, ataxia, diaphoresis, blurry vision, tachycardia and hypertensionRarely causes hypertensive emergencies, intracranial hemorrhage, MI, aortic dissection and dysrhythmiasMDMATreatmentABCsMost effects are self-limited over 4-6 hoursDo not fluid resuscitate until sure the patient is not hyponatremicOther supportive careBath Salts

Not These

These

Bath SaltsUsually refers to designer drugs which are similar to cathinone. An example is mephedrone.Cathinone is found in Catha edulis or khatThe chemical composition of these substances is very variable but usually contain a cathinone such as methyenedioxypyrovalerone (MDPV), methylone or mephedroneVery little is understood about how they interact with the brain or their metabolismBath SaltsBehave similarly to amphetamine by increasing dopamine, serotonin and norepinephrineLess able to cross blood-brain barrier due to the presence of a beta-keto groupCan be inhaled, insufflated, injected or ingestedUsers can experience headache, heart palpitations, nausea and cold fingersHallucinations, paranoia, panic attacks, violence, MI and kidney failure can occurSymptoms include dilated pupils, involuntary muscle movement, tachycardia and hypertensionBath SaltsTreatmentLargely unknownSmiles

Smiles2C-I or 2,5-dimethoxy-4-iodophenethylamineMember of the phenethylamine familySynthesized by Alexander ShulginUsually ingestedEffects usually occur within two hours and last 4-12 hoursHallucinogenic and Entactogenic effectsCan cause muscle tension, nausea and vomitingSymptoms include dilated pupils, tachycardia and hypertensionProfessionalismProfessional competence is the habitual and judicious use of communication, knowledge, technical skills, clinical reasoning, emotions, values and reflection in daily practice for the benefit of the individual and community being servedEpstein RM and Hundert EM. Defining and Assessing Professional Competence. JAMA. 2002; 287:226-235My ThoughtsPatient doesnt have to earn the right to careTreat patient with dignityProtect yourself and staff from those who are violentUse law enforcement when necessaryDuty to societyPhysicians at increased risk for substance abuse