Week 6: Toxicology Part II Flashcards

Question

Bath Salts

Answer 1

synthetic cathinones ex: cathinone, methcathinone, mephedrome, methylone, MDPV SS: agitation, tachycardia, insomnia, paranoia, seizures, violen unpredictable behavior Management: supportive care

Answer 2

have similar chemicalstructure to epinephrine or amphetamines, so when overdosed, can exibit sympathomimetic toxidromes

Answer 3

clinical effects: benzos airway protection: intubation hyperthermia: ice packs, cool fluids, antipyretics, benzos dysrhythmias: sodium bicarb, lidocaine rhabdomyolysis: fluids

Answer 4

aspirin methyl salicylate (oil of wintergreen) topical salicylates bismuth subsalicylate (peptobismol) 1ml=8.7 mg of Salicylic acid

Answer 5

ranked first amoung pharmaceuticals most frequently reported in human exposure

Answer 6

A: rapidly bsorped in non ionized form due to acidic ph D: small Vd (-0.2L/kg) and highly protein bound M: metabolized by liver. hydrolized to salicylic acid E: excretes renally t1/2 at low doses (antiplatelet effects)=2-3 hrs t1/2 at high doses (anti-inflammatory)= 12 hours

Answer 7

delayed absorption due to pylorospasm and bezoar formation in the stomach (immediate release stomach) peak ocnc may not be seen until 24-36 hrs after ingestion w. enteric coated products decreased protein binding and larger vd *higher conc and low pH *larger amounts of free drugs reach the tissue prolonges t1/2 due to hepatic metabolism saturation saturation *elmimnatino changes from irstorder kinetics tozero order kinetics

Answer 8

serum ph faks and SA acid shifts to a nonioned state than can readily cross lipid bilayers and cell membranes effecting s variety of organs krebs cycle inhibition impairs cellular respiration and uncoupling of oxidative phosphorylation leading to accumulation of pyurivc and lactic acid release of energy as heat Acid base disturbances *depend on time from exposure *anion gap metabolic acidosis from presence of SA, production of lactate, ketones, and inorganic acids neurologic; neuronal dysfunction causing cerebral edema *discordance btw serum and cfs glucose ototoxicity and tinnitus hematologic *plaelet dysfunction and hypoprothombinemia pulmonary *stimualte resp. driving causing hyperpnea and tachypnea *acutre resp. distress syndrome (ARDS) GI *N/V Renal *prerenal AKi due to volume losses 8excrete large quantities of bicard, Na, and K

Answer 9

n/v gi irritation tinnitus tachypnea,hyperpnea resp alkalosis or resp acidosiss metabolic acidosis(anion gap or non-anion gap) altered mental status/halucinations coma seizures hyperglycemia or hypoglycemia (neuroglycopenia) pulmonary edema hepatic injury HUGE CONSEQUENCES *coagulopathy *cerebral edema *acure resp distress syndrome (ARDS) *hyperthermia

Answer 10

early: primary resp alkalosis, alkalemia, alkauria intermediate: mixed resp alkalosis and anion gap metabolic acidosis, alkalemia, and aciduria late: metabolic acidosis w. either a resp alkalosis or resp acidossi, acidemia, and aciduria

Answer 11

non specific and often misiagnosed severe toxicity is associated w. serum conc.>60 mg/dl, altered mental sttaus, and acid base disturbances cerbral edema and acutelung injury may be present

Answer 12

acute: *younger *intentional *early dx *suicial ideation *severely elevated serum conc *death is uncommen chornic *older *Iatrogenic/unintentional *underrecognized as a dx *intermediate elevation in serum conc *death is more common due to delayed recognition

Answer 13

1. serum salicylate level *toxiicty associated w. conc >30 mg/dL *THEREPEUTIC RANGE (INFLAMMATORY CONDITIONS(15-30g/dL) *therepeutic range for analgesia (5-10 mg/dL) acute toxicity *mild symptoms seen in 150-200 mg/kg or 6.5 g of spirin *severe symptoms>300-500 mg/kg chronic toxicity>100 mg/kg/day for several days 2. blood gas and anion gapto classify acid-base disorder

Answer 14

no true antidote: tratment based on supportive therapies 1. GI decontamination 2. IV fluids 3. glucose amdinisistration

Answer 15

1. multiple-dose activated charcoal(MDAC) *prevents absoprtion of salicyates, can consider if pharmcobezoar or XR preparation suspected 2.hypovolemia should be corrected w. iv crystalloids 3.0.5-1g/kg of dextrose followed by additional bolus doses or continuous infusion for severe salicylate toxicity

Answer 16

cornerstone of management for ASA toxicity. shifts ASA out of brain and intro the serum to promote renal elimination ion trapping of salicylate into serum and urine by alkalination. promotes excretion once ionized. iv sodium bicarb is recommended for all symptomatic pts *bolus dose: 1-2mEq/kg continuous in fusion: 150mEq sodium biacrb in 1000mL of 5% dextrose at a rate of 1.5-2x maintenance rate *goal urine pH 7.5-8 maintain normal K+ levels (due to shifts of K+ into intracellular space by admin of sodium bicarb)

Answer 17

can be considerd in severe toxicity and is recommended in the following ocnditions *serum salicylate level >100 mg/dL *serum salicylate level>90 w. impaired renal function OR failure of supportive therapies serum salicylate level >80 w. imapired renal function AND failure of supportive therapies supplemental o2 required due to altered mental status form hypoxemia d/c HD when serum salicylate level is <19 mg/dL and pt is clinically improving

Answer 18

serum salicylate conc q2-4 hrs until pt is improving clinically urine pH serum pH more frequent monitoring may be needed in critically ill patients

Answer 19

methanol containing consumer products *windshield wiper fuid (>60% of cases) ethylene glycol *engine coolant (antifreeze) in car radiators. it has sweet taste, but bittering agents have been added isopropanol *rubbing alcohol *solvent used in household products, cosmetics, and topical pharmaceuticals

Answer 20

primary alcohols *methanol *ethylene glycol secondary alcohols *isopropanol

Answer 21

A: ingestion: rapidly absorpbed. F=92-100% inhalation: occupational or intentional inhalation of methanol (huffing) athylene glycol inhalation does not cause poisoning transdermal: isopropanol and methanol penetrate skin better than EG D: rapidly to total body water 0.5-0.77L/kg Metab and elminiation: (alcohol dehydrogenous and/or aledhyde dehydgrogenase (ALDH) couples to the reduction of NAD+ to NADH *EG is eliminated via kidney unchanged *methanol eliminated as vapor in expired air

Answer 22

methanol: formic acid formed by conversion by alcohol dehydrogenase and then aldehyde dehydrogenase *formic acid causes metabolic acidosis w. minimally elevated latate EG: metabolized by alcohol and then aldehyde dehygrognse. toxic metab is glyoxilic acid Isopropanol: acetone is toxic metabolite whihc is formed by alcohol dehydrogenase

Answer 23

cns *iINEBRIATION is dependenton dose and mlecular-weight *absense of inebriation doe snot include ingestion metabolic acidosis *toxic alcohols are metabolized to toxic organic acids [methanol->formic acid; EG->glycolic acid] which cause high anion gap metabolic acidosis *exception: isopropanol's metabolite acetone does not cause metabolic acidoses. it causes ketosis w.o an acidosis

Answer 24

retinl toxicity *blurry vision to complete blindness which can be asymptomatic neurotixicity *basal ganglia lesions bilaterally which can lead to parkinsonism AKI pancreatitis

Answer 25

neurotoxicity *oxalic acid+calcium=calcium oxalate monohydrate crystals which deposit renal tubules *this precipitation can cause hypocalcemia

Answer 26

hemorrhagic gastritis

Answer 27

serum conc. *results may not e availbale in timely manner *prolonged time from ingestion?formate levels may be helpful serum and urine oxalate conc are usually not clinically relevant handle samples w. care (put in airtight container to prevent evaporation (isopropanol and ethanol) toxic conc of methanol and eg>25 mg/dL obtain electrolytes, Ca, BUN, Cr, UA, VBG or ABG, lactate, measured serum osmolality and serum ethanol concentration

Answer 28

! ANION GAP AND OSMOL GAP CAN BE USED TO INITIATE TREATMENT WHILE AWAITING RESULTS ON SERUM CONCENTRATION! high anin gap metabolkic acidosis of unkown etiology *lack of high anion gap metabolic acidosis can be seen with recent ingestion of toxic alcohol extrememly elevated osmal gap (>50 mOsm/L) *normal osmol gap ranges from -14+10 mOsm/L **a baseline osm gap is needed to compare current value as results maybe within normal range, but abnormal for the pt (i,e osmol gap=12, currentlyosmol gap=+6) serum ethanol conc can prevent metbaolism to the organic acid and is consider protective elevated lactate leves can be seen wih methanol and ethylene glycol poisoning

Answer 29

resucitation inhibition of ADH: cornerstone of therpy *indicated for methanol and EG toxicity 1)IV ETOH10%continous infusion (rarely used in US) *serum conc *many complication s including hypotension, respiratory depression, cns depression and inebriation, flushing, hypoglycemia, hyponatreia, pancreatitis and gastrititis 2)fomepizole *competitive inhibition of ADH *intial boud: 15mg/kg IV piggyback over 30 in *maintnenance dose: 10mg/kg iv piggyback q12 hours x4 doses hours then increase dose to 15mg/kg iv piggyback q 12 hours(induced its own metabolism after ~48hrs) *continue until serum toxic alcohol conc is <20mg/dL+ asymptomatic w. normal serum pH AE: hypotension and bradycardia hemodyalisys preffered over renal replacement therapy

Answer 30

methanol: folic acid: enhances formate elmination *methylprednisolone 1 g(high dose) q24 hrs for 3 days may improve the amount o vision loss experienced *sodium bicarb continuous infusion: shifts formic acid to formate and causes ion trapping in the urine Goal serum pH:>7.2

Answer 31

thiamine: promotes coversion of EG to ketodipate pyridoxine: promotes conversion of glycine to hippuric acid sodium bicarb continuous infusion can be administered in pts w. ph <7.15

Answer 32

imipramine (1st approved) desipramine amitriptalyine nortriptyline doxepine trimipramine protriptyline

Answer 33

higher incidence of hospitalization and fatality in comparison to SSRI's

Answer 34

classified at tertiary or secondary amines inhibit reutake of NE and seretonin, incrasing amount at cns receptors competitive antags of muscuranic ach receptots peripheral a1 receptor antsgonists inhibit periheral and central postsynaptic histaminr receptos interfere w. chloride conductance

Answer 35

A: completely and rapidly absorbed i gi tract d: 10-40L/kg and variable lipophillic rapidly distribute to other organs M:demtyhlat E: 7-58 hrs

Answer 36

delayed absoprtion due to decreased gastric motility severe overdoses leas to low blood ph increasing amount of free drug saturable metabolisms prolong t1/2 clinicaltoxiicty is rapid and unpredictale: therepeutic dose: 2-4 mg/kg/day; conc. 50-300 ng/mL NARROW therepeutic index Acute ingestino causing cardiotoxicity and cns toxicity dose: 10-20 mg/kg; conc 300-1000ng/mL

Answer 37

EEG findings *prolonged qrs complex *ight bundle branch bloc pattern Sinus bradycardia *antimuscarinic, vasodilatory, and sympathomimetic effects Hypotnsino *dirct myocardial depression from alterations in sodium channels *alpha 1 blockade cuasing peripheral vaso dilation binding to na channels occurs in ionized state *tcas weak bases and become increasingly ionized in acidic environment agitation, delerium, and depressed sensorium seizures *increases conc of monoamines, muscarinic antagonism, na channel alterations, and gaba inhibiton

Answer 38

cv *hypotension and ventricular dysrythmias *prolonges pr interval, qrs and qt interval cns *delerium, agitatoin, psychotic behaviors w. hallucinations, seizures lethargy, and ocma other *anticholinergic: dilated pupils minimally responseive to light, dry moutg, drug flushed skin, urinary retention and ileus *ARDS aspiration oneumonitis, and multisympton organ fialure

Answer 39

not life threatening sedation and sinus tachycardia

Answer 40

ECG TCA conc : limited utility early after ingestion electrolytes glucose venous or arrterial blood gas

Answer 41

GI decom. *actiated charcoal given to pts within 2 hrs and pt must have normal mental status and protected airway serum alkanalization: membrane stbailization effect *sodium stabilizing effect control arrthmias, hypotension and seizures IV lipid emulsion (ILE) salavge therapy when cv therapy is refractory standard therapues *only effective for lipophillic drugs (amitriptylie and clopiramine 8AE: ARDS and pancreatitis

Answer 42

in presence of tcas na channel is altered slowing the rate of rise of action potentioal increase in sodium gradient 9by giving sodium bicarb) speeds rate of rise of action potential drug induced effects are counteracted increasing ph removes tcas from binding to sodium channels

Answer 43

effective for wide comples dysrthrimas (qrs compex duraion>100ms) w. ocnduction delays and hypotenion sodium bicarb preffered *BOLUS OR RPAID INFUSION OVER SEVERAL MINUTE 1-2 MEQ/KG *ADDITIONAL BOLUSES Q 3-5 MIN UNTIL QRS DURATION NARROWS AND HYPOTENSION IMPROVES, THEN consider initiatinf continuous infusion to maintain ph target ph: 7.5-7.55 monitor K and ionized calcium alternative: hypertonic saline 1-2 meq/kg bolus only used with alkanization when sodium bicarb admin is not possible or ci

Answer 44

if pt not responsive to sodium bicarb therapy Lidocaine: *Class 1b *for pts who not responsive to sodium bicarb therapy Magnesium sulfate: consider after alkalinzation, sodium loading and trial of lidocaine fails

Answer 45

class 1a: (procainamide-similar pharm action to tcas class 1c: (flecainide-similar pharm action to tcas) class III: amiodarone and sotalo prolongn qtc

Answer 46

*0.9% NaCl or sodium bicarab bolus doses if hyotension continues dispite volume resucitation *norepinephrine vasopression Extracorporeal membrane oxygenation

Answer 47

first line: benzos second line:propofol or barbiturate

Answer 48

phenytoin *fails to temrinate seizures *enhances cv toxicity flumezanil *induces seizures physostigmine *induces seizures

Answer 49

indictated when exposed to digoxin or digitoxins including cardioacive steroids ex: lilly of the valley

Answer 50

causes most cases of pharm induced cardioacctive steroid toxicity (CAS) more ocmmonly seen in pts at extremes of age or with ckd

Answer 51

onset of action *po: 1.5-6 hrs IV: 5-30 min max effect: po:4-6 hrs iv: 1.5-3 hrs intestinal absorption : 40-90% plasma protein binding: 25% Vd: *adults:5-7 days *4-5 route of elimination :60-80% w. limited hepatic metabolism enterohepatic circulation: 7%

Answer 52

elevated serum conc result in greater renal cl before distribution to tissues , dec. t1/2 hypokalemia and hypomagnesemia enhances efffects on myocardim leading to toxicity at lower serum conc tox can be seen w. changes in liver, kidney, or heart function, aong w. drgu-drug interactions including quinidine, verapamil,carvedilol, amiodarone and spirinolactone

Answer 53

in presence of dgoxin, sodium-K ATP-ASE is inhibited, causing increase in intracellular sodium conc, preventing antiporter calcium and enhanced inotropy excessive elevations in calcium inc resting potential, leading to dysrhtmias

Answer 54

increase excitability increase automaticity decrease conduction velocity decrease refractory time toxiciy causes increased dysryhtmias and mocardial irritability

Answer 55

asymptomatic period of min -sev hours n/v, abdominal pain, lethargy, confusion , and weakness

Answer 56

difficult to dx loss of appetite, weakness, anoriexia, n/v abdominal pain, weightloss, delerium, confusion, drowsiness, headache, visual disturbances, andrarely seizures

Answer 57

electrolyte abnormalities (hyperkaemia) cardiac abnormalities includuing ventricular tachy dys. or brady dys , a flutter, a fib w. av block, etc.

Answer 58

gi decomtam: AC 1g/kg q2-4 hrs up to 4 doses electrolyte therapy (hypo/hyperkalemi) *do not admin calcium, could exagerate cardiac effects hypomag: *mg sulfate 2g iv over 20 min followed by 1-2 grams/hrs if needed dig-specific antibody fragments CORNERSTONE

Answer 59

lifethreatenning dysrthmias regardless of digoxin serum conc K+ more than 5meq in setting of acute digoxin tocitiy chornic levls of serum dig w. dysrhtmias, gi symptoms, and ams serum digoxin conc at anytime:>15 6hrs after injestion>10 acute ingestion of 10mg of digoxin in an adult

Answer 60

antigen binding fragments binds to free digoxin in iv and interstitial space *movement of free intracellular and dissociated digoxin into II or IV space due to concentration gradient which is established immediate decl.ien in free digoxin massive increase in serum dig conc(clinically unimportant) increases renal cl dec serum potassium conc

Answer 61

emperic if dig serum conc unknown: give 3-6 vials for chrnoic toxicity give 10 vials for acute " dig-secific fab dosing *if serum conc known [serum dig conc (ng/mL)x pt weight (kg)]/100=# of vials *known amount ingested [amount ingested mg/0.5 mg/vial]x 80% bioavailability=# of vials ROUND U TO A WHOLE VIAL

Answer 62

atropine:early bradydysryhtmias 05 mg iv push q5min phenytoin and lidocaine:ventricular tachydysrythmias pacemaker cardioverison

Answer 63

hypotension bradyardia dysryhtmias hypoglycemia seizures resp depression and apnea coma

Answer 64

halmark SS:hypotension and bradycardia lack of perfusion to cns can cause fatigue, dizziness, lighthededness hyperglycemia severe overdose can cause syncope, coma, sudden death, ARDS

Answer 65

ecg cardiac and hemodynamic miint=oting chest xray and o2 sat digoxin level thyroid function cardiac enyzymes lactate

Answer 66

gi decom: ac!!, mdac, whole bowel irrigation hypotensive: crystalloid fluid bradycardia: atropine 0.5-1mg IV titrate in severe posioning, wont respond to above therapies, need to move on to these next therapies calcium: calcium chloride 10% : increase extracellular calcium and leading to improvements in hypotensino and reverses impairs inotropy and conduction glucagon *3-5 mg iv over 1-2 min; may repeat with 4-10 mg after 1-2 minutes; may repeat with 4-10 mg after 5 min w. no improvement in hemodynamics (glucagon has ionotrpoic and chronotropic effects bypassing adrenergic receptors) IN CCB overdose: calcium should be given beforegglucagon BB overdose: glucagon before calcium REMEMBER: do not use calcium if digoxin tox is suspected or confirmed due to stone heart phenomena IV lipid emulsion-salvage therapy. only done if above therapies failed

Answer 67

trt of choice HDI impairs sodium calcium antiporter resulting in an increase of intracellular calcium which increases calcium in sarcoplasmic reticulum increasing cardiac contractility delayed onset of action 15-40 min bolus: 1 u/kg iv push w. 0.5g/kg of dextrose infusion at 0.5 /kg/hr continuous infusion 1u/kg/hr titrated to effect in combo w. dextrose infusion at 0.5g/kg/hr monitor bg q 30 min for the first 4 hours and then every hr monitor more frequently of bloog glucose if pt has renal failure adverse reactions" hypoglycemia and kyopkalemia

Answer 68

inotropes and vasopressors cardiac pacing intraaortic balloon pump extracorpeal membrane oxygenation