Toxicology

Front 1

What is the most common class of drug that causes poisoning?

Back 1

Analgesics at about 12% of all poisonings

Front 2

What substance is responsible for the most number of deaths?

Back 2

Sedatives/hypnotics/antipsychotics

Front 3

Think of the two main simple things to look for in patients thought to be exposed to a toxic substance....

Back 3

Oxygen and glucose

Note: 10-15 L/min of O2 via FACE MASK never exceed 5 L/min via nasal prongs

Front 4

Methemoglobin

Back 4

Hemoglobin with iron in oxidized state(Fe+3) that cannot pick up oxygen.

Front 5

Discuss toxicity of acetaminophen...

Back 5

Acetaminophen(NAPA) is metabolized to NAPQI which is an electrophile that is reduced by glutathione reductase. When glutathione is overwhelmed you get toxicity.

Front 6

What toxicity can INH/hydrazines have? What do you use to treat it? Why?

Back 6

It can cause lactic acid buildup due to inhibiting lactic acid dehydrogenase which can lead to acidosis and seizures.You use Pyridozine(Vit B6) to treat because it overrides the inhibition of pyridoxine phosphokinase by INH/hydrazines which is necessary for GABA synthesis from glutamate.

Front 7

Over 90% of all toxic effects on peripheral nerve are....

Back 7

Axonopathies

as opposed to neuronopathies or myelinopathies

Front 8

Which toxins cause seizures?

Back 8

Cyclic antidepressants, withdrawal from alcohol, camphor from Camphophenique, cocaine

IMPORTANT - withdrawal from alcohol

Front 9

Mechanism of seizures from toxins...

Back 9

Sodium channel poisoning, GABA chloride channel poisoning, NMDA receptor stimulation, or metabolic causes which are:
Hyponatremia
Hypoglycemia
Hypocalcemia
Hypomagnesemia
Hypophosphatemia

Front 10

Treatment for toxin induced seizures...

Back 10

Check A,B,C(airway breathing circulation)
Give Thiamine and Glucose
Check glucose, sodium, calcium, magnesium
Give benzodiazepines

Front 11

Diazepam(Valium) and Lorazepam(Ativan)

Back 11

For urgent treatment of any hyper-stimulated CNS state.
Little risk to pushing dose as high as necessary to treat seizures. Just make sure to rule out hypoglycemia

Front 12

Phenobarbitol(propofol)

Back 12

2nd line drug for seizures but make sure you give airway support if needed

Front 13

What does black widow spider toxins do?

Back 13

it is alpha latrotoxin and it stimulates release of acetylcholine.

Front 14

What are common things that cause acetylcholine inhibition?

Back 14

Crotalidae venoms, Elapidae venoms, Botulinum toxin

Front 15

Describe clinical manifestations of inhibition of acetylcholine.

Back 15

ptosis, weakness, cranial nerve palsies, respiratory failure

Front 16

What are the manifestations of dopamine imbalance?

Back 16

Dystonia and/or Neuroleptic Malignant Syndrome(NMS)
NMS involves
--hyperthermia
--altered mental status
--autonomic dysfunction
--muscular hypertonicity

Front 17

Neuroleptic Malignant Syndrome diagnostic Criteria

Back 17

Recent use of antipsychotic drug or other dopamine altering drug is ESSENTIAL criterion.
Muscle rigidity, elevated CK fever without other cause, and autonomic instability is major criterion.
Leukocytosis is a minor criterion

Front 18

Serotonin Toxicity

Back 18

You see confusion/disorientation, agitation, and coma in cognitive/behavioral category.

Diaphoresis, hyperthermia, sinus tachycardia, hypertension and tachypnea are manifestations of autonomic dysfunction.

Myoclonus, hyperreflexia, muscle rigidity and tremors are most common neuromuscular abnormalities.

Front 19

Which drugs can cause serotonin toxicity?

Back 19

SSRI + MAOI
SSRI + meperidine
SSRI + CAD/TCA
SSRI/SNRI

Front 20

Discuss generation of reactive electrophilic metabolites

Back 20

Cyt P450 creates these from acetaminophen or carbon tetrachloride
These electrophiles cause lipid membrane peroxidation chain reaction
They also cause centrilobular necrosis.

Front 21

Agents that increase observed incidence of cancer in liver

Back 21

Ethanol, Aflatoxin, and most common promotor(HBV) and vinyl chloride(angiosarcoma)

suspected: Comfrey tea(pyrrolizidine alkaloids), False sago palm(Cycasin), Safrole(Sassafras), Arsenic

Front 22

Classic renal toxins

Back 22

Aminoglycosides, amphotericin, Cisplatin, Iodinated radiocontrast, and analgesics(phenacetin, acetaminophen, NSAIDs)

Front 23

Which part of the kidney is most commonly injured?

Back 23

The proximal tubule is most commonly injured because it expresses P450.

Front 24

Common presentation for acute renal failure

Back 24

relatively abrupt decline in plasma filtering generally caused by acute tubular necrosis. Wide spectrum of "failure"

Commonly caused by CCl4, gentamycin, mercury, and acetaminophen overdoes.

Front 25

toxin induced acute renal injury...

Back 25

Tubulo-interstitial nephritis caused by orellanine in mushrooms that interrupts ATP production. Creates unremarkable glomeruli

Oxalate crystals product of ethylene glycol metabolism

myoglobin from muscle breakdown can be from neuroleptic malignant syndrome,

hemoglobin from IV hemolysis can be caused by arsine gas, chlorates.

Front 26

Chronic renal impairment

Back 26

slow decline of renal function, tends to be permanent.

Chronic exposure to Phenacetin, Cadmium, Toluene(glue sniffers, leads to distal renal tubular acidosis).

Front 27

Describe the epidemiology of terata exposure

Back 27

Very few terata are linked to exposures. Only 2% of births show terata, mostly minor and only 5% of the 2% can be linked to drug/toxin exposure.

Front 28

discuss developmental toxicity

Back 28

Critical period for terata is organogenesis which is week 2-8. Exposure must occur DURING, not before/after critical period to lead to structural damage.

Front 29

What do you watch out for in terms of toxicity in third trimester of pregnancy?

Back 29

pharmacologic or toxic activity in organ systems of fetus. Example: ACE inhibitors reduce placental blood pressure, drug addiction withdrawal in baby.

Front 30

Fertility toxicity

Back 30

alcohol, Di Bromo Chloro Propane(daddys birth control pills)

Front 31

What is the risk equation?

Back 31

Risk = Hazard X exposure
Hazard is the total spectrum of harmful potential while the risk is scenario specific.

TO change risk change exposure

examine dose-response relationship between amount of toxin and risk of toxic effect.

Front 32

What are landmarks on dose-response curve?

Back 32

NOEL - No observable effect level which is an actual test dose that did not produce an observable effect

LOEL - Lowest observable effect level which is the lowest actual test dose that did produce an observable effect

Threshold dose is a smidgen above NOEL which makes sense.

Front 33

Limitations of LD50...

Back 33

While you can COMPARE POTENCY of chemicals it is not good clinically because it does not contribute information about lethal effects, no information about organ systems affected/pathology, results vary by species/gender while testing is done on homogenous sample set.

Front 34

What is important about toxicokinetics of lethal doses?

Back 34

Kinetic profiles of toxic doses may differ from normal doses

Front 35

Utility of kinetics in poisonings...

Back 35

predict onset and duration of toxic effect, predict peak blood levels, monitor effectiveness of interventions, and serial blood levels validate kinetic projections

Front 36

Multi-tablet ingestions

Back 36

can lead to "concretions" which will prolongue peak blood levels due to decreased surface area but huge drug reservoir. Beware aspirin and meprobamate.

Front 37

Anticholinergic overdose

Back 37

If patient takes anticholinergic drug and slows GI motility can trap drug and let gut recover, then letting drug become absorbed more relapsing sickness.

Front 38

Modifed release overdose

Back 38

Peak concentration will plateau for very long time and can be delayed, sometimes even a day later. Must monitor blood levels until post absorptive state is assured.

Front 39

Effect of chewing on extended release dosage pills

Back 39

Some tablets that are chewed will convert to immediate release

Front 40

What are strange cells that store drugs?

Back 40

Renal proximal convoluted tubules store cadmium with half life of 20 years. Lead stays in cortical/trabecular bone.

Front 41

Discuss methods of enhancing clearance via renal excretion

Back 41

Maintain adequate or robust hydration. Ion trapping is another method...by manipulating pH of urine to make it so that drugs leave renal tubule into urine tubule.

Note: Forced diuresis is a NO NO NO NO NO.

Front 42

What can cause miosis?

Back 42

Cholinergic excess(organophosphate insecticides), Opiates, clonidine, nicotine

Front 43

What will hyperventilating do to blood pH?

Back 43

It will make it more alkaline

Front 44

What is an example of an analgesic?

Back 44

salicylates. It can cause ox phos to uncouple.

Front 45

What causes nail changes? What do you see?

Back 45

Mee's lines or white transverse growth arrest bands caused by heavy metals due to sulfhydryl group binding

Front 46

Cyanosis(pale skin color)

Back 46

methemoglobinemia(nitrates, aniline dyes, phenazopyridine, benzocaine)

Front 47

What can cause mydriasis(dilated pupils)

Back 47

Sympathomimetics, cocaine, amphetamines, anticholinergics, antihistamines

Front 48

Toxic Alopecia

Back 48

Exposure to thallium or radiation

Front 49

Tachypnea(fast breathing)

Back 49

toxins producing acid, toxins uncoupling ox phos, toxins resulting in hypoxemia, toxins stimulating patient(sympathomimetic, cocaine, PCP)

Front 50

bradypnea(slow breathing)

Back 50

opiates and many other toxins will lead to eventual apnea(absent breathing)

Front 51

Pulmonary edema

Back 51

heroin, salicylate

Front 52

Toxic Coma treatment

Back 52

four basic antidotes:
-- oxygen
-- naloxone
-- thiamine
-- dextrose
spells DONT

Front 53

Antidote for metheglobinemia

Back 53

Methylene blue is something that reduces methemoglobin. Glucose 6 phosphate also plays a role and this antidote is ineffective in patients with G6PD

Front 54

What does Digoxin do to cardiovascular system?

Back 54

it can cause a wide variety of arrhythmias in overdose(atrial and ventricular)

Front 55

What do TCAs do to CVS?

Back 55

They may result in a wider QRS wave on ECG or prolongued QT interval. This happens because they poison the Na channel which widens the QRS. THey also poison the K+ channel which prolongs QT. This can lead to tachyarrhythmias such as ventricular tachycardia or ventricular fibrillation.

Front 56

Tachycardia can be caused by....

Back 56

IMPORTANT - Cyclic antidepressants

amphetamines, antihistamines, anticholinergic, cocaine, withdrawal from sedatives, synthroid

Front 57

bradycardia can be caused by...?
how do you treat?

Back 57

IMPOTANT Calcium channel and Beta blockers(propranolol) which can be distinguished by....

antagonists(diltiazem), clonidine, cardiac glycosides(digoxin), opioids, organophosphates

treat calcium channel blockers with calcium chloride or calcium gluconate. Also to treat severe life threatening hypocalcemia caused by HF poisoning.

Treat beta blocker poisoning with Glucagon.(limited benefit in calcium channel blocker OD). Bypasses blocked beta receptor to switch on adenylyl cyclase. Side effects of glucagon is nausea/vomiting.

Front 58

GI exam test helps you differentiate what?

Back 58

between anticholinergic(stops stomach motility) and sympathomimetic(may have bowel sounds)

Front 59

Anticholinergic Toxidrome signs and treatment

Back 59

DRY as BONE(dry mouth/skin)
RED as a BEET(flushed skin)
BLIND as a BAT(dilated pupils and loss of accommodation)
MAD as a HATTER(central anticholinergic mania)
HOT as HADES(hot, dry skin less able to release heat)
FULL as a FLASK(urinary retention and full bladder)

Antidote is Physostigmine Salicylate which is a reversible acetylcholinesterase inhibitor which can cross BBB. Can treat atropine poisoning as well. NEVER USE WITH TCAS as can cause lethal arrhythmia.

Front 60

Cholinergic Toxidrome

Back 60

Diarrhea
Urination
Miosis
Bradycardia(IMPORTANT)
Bronchorrhea(IMPORTANT)
Bronchoconstriction(IMPORTANT)
Bradypnea(IMPORTANT)
Emesis
Lacrimation

Salivation
Lacrimation
Urination
Diarrhea
Gastric Upset
Emesis

Front 61

Can cause fluid loss from GI tract

Back 61

corrosives, cathartics, methylxnthines(caffeine, theophylline), cholinergic overdose

Front 62

can cause redistribution of volume

Back 62

iron, snake envenomation, vasodilators, vasodilating drugs(ethanols, nitrites, opiates)

Front 63

can cause electrolyte losses

Back 63

hyponatremia - diuretics, chronic lithium use

hypokalemia - beta adrenenergics, loop diuretics, salicylates, methylxanthine overdose

hypERkalemia - digoxin overdose, fluorides(also causes low Calcium which can be lethal)

hypocalcemia - EG, HF, NH4HF2

Front 64

Anion gap metabolic acidosis

Back 64

MUDPILES
M = methanol
U = Uremia
D = Diabetic Ketoacidosis(alcoholic)
P = Phenols
I = Iron, isoniazid, inborn errors, inhaled solvents(toluene)
L = Lactic acidosis (many causes, shock sepsis)
E = Ethylene glycol, ethanol
S = Salicylates

ALSO IMPORTANT TO KNOW
acetaminophen which will cause acidosis AND hepatic failure

Front 65

Anion gap equation. What is normal anion gap?

Back 65

Anion Gap = Na+ - (Cl- + HCO3-)

normal gap is less than 14

Front 66

Osmolar Gap equation.

Back 66

Calc osmolarity = 2 x Na + BUN/2.8 + BloodSugar/18
normal is 290 to 300 mOsm/kg

Osmolar Gap = Measured Osm - Calculated Osm

Estimated blood level of toxin(mg/dL) =
(Osmolar gap X MW)/10

Front 67

Describe mechanism of EMIT test

Back 67

Enzyme multiplied immunoassay test -- you have an enzyme locked up with antibodies. If drug present, competes for binding site and releases antibodies and then enzyme catalyzes colorimetric reaction.

Front 68

What gives cocaine false positives in UA?

Back 68

nothing

Front 69

What gives Cannabinoid false positives in UA?

Back 69

Efavirenz, an HIV treatment

Front 70

What gives false results in Amphetamine UA?

Back 70

false positives - variable, detection of other sympathomimetic amines

Front 71

What gives false results for Benzodiazepines in UA?

Back 71

No false positives listed

False negatives - Lorazepam, Alprazolam, Clonazepam

Front 72

What gives false results for Barbiturates in UA?

Back 72

false positive - Phenytoin

Front 73

What gives false results for Phencyclidine(PCP) in UA?

Back 73

False positives - DXM, Diphenhydramine, Ketamine

False negatives - PCP analogues

Front 74

What gives false results for Opiates in UA?

Back 74

all synthetic/semisynthetic opiods will give false negatives.

Front 75

What gives false results in tricyclic antidepressants?

Back 75

False positive - Many many things. FUck.

False negative - Amoxepine

Front 76

Radioimmunoassay(RIA)

Back 76

competition of known radioactive labeled drug mixed with known amounts of drug specific antibody and unknown drug in patient serum. Precipate is measured by radioactivity and if it is reduced then they have the drug.

Front 77

Atomic Absorption Spectrophotometry is used for...

Back 77

Used to assay metals like arsenic, mercury, iron, selenium, thallium, and cadmium

Front 78

Radioopacity of pharmaceutical substances

Back 78

CHIPS
Coated pills
Heavy metals
Illicit drugs(Iron pills)
Phenothiazines
Sustained Release

Front 79

Atropine

Back 79

Muscarinic antagonist and is used to treat symptomatic bradycardia due to any cause because it releases vagal influence on SA.

Front 80

Extrapyramidal Toxidrome

Back 80

leads to dystonia(abnormal twisting movements), oculogyric crisis, gyric tongue movements, choreoathetosis, torticollis

all sorts of crazy movements caused by dopamine imbalance

Front 81

Extrapyramidal Dystonia

Back 81

Pathophys is super complex involving multiple neurotransmitters and brain structures.
Neuroleptics selectively inhibit D2 allowing endogenous dopamine to stimulate D1 altering the balance.

Front 82

WHat is the antidote to Extrapyramidal toxidrome?

Back 82

Cogentin(Benztropine mesylate) and diphenhydramine works by reducing central acetylcholine activity. Very effective treatment. Diphenhydramine(benadryl) used in children.

Front 83

What is antidote for opiate toxidrome?

Back 83

Naloxone - pure opiate antagonist for reversal of opiate induced CNS/respiratory depression. Very common ER OD drug

Front 84

Ipecac

Back 84

natural product with reduced use in modern medicine. induces emesis

toxic effects:
dehydration, alkalosis, hypokalemia, myocarditis

Front 85

Gastric Lavage

Back 85

crazy. tube down throat != pull out pills! clinical benefit not shown. should never be used.

Front 86

Activated Charcoal

Back 86

Single dose generally given with NG tube. single dose AC should not be administered routinely. Most beneficial if given within an hour.

Front 87

Whole Bowel Irrigation

Back 87

uses a polyethylene glycol solution but has no control trials proving efficacy.
Reports suggest benefit from potentially toxic ingestion of packets of drugs.

Front 88

Which important biological metals are transition metals?

Back 88

Iron and copper, Zn, Mn, Cr. These are capable of several oxidation states and serve important roles as electron acceptors in redox reactions

Front 89

Iron overload

Back 89

cardiomyopathy, GI corrosion(IMPORTANT0, damages blood all pathology due to ROS

Front 90

Manganese overload

Back 90

causes basal ganglia damage and can cause parkinsons disease

Front 91

common allergenic metals

Back 91

chromium, nickel, cobalt

Front 92

Toxic Heavy metals

Back 92

Hg, Ti, Pb, As, Cd
mechanism is usually electrophilic interference with sulfhydryl groups in enzymes but some also create free radicals.

Toxicology is complex, can target different organs depending on inorganic/organic/elemental form.

Front 93

Lead toxicity mechanism and signs

Back 93

Heme synthesis is very sensitive to sulfhydryl group interference. Aminolevulinic acid dehydratase and ferrochetalase accumulate. Blood smear show basophilic stipping. Gingival lead lines cased by precipitated lead sulfide.

Front 94

lead toxicity CNS effects

Back 94

Acute effects are seizures, coma, headache, deadly encephalopathy.

Chronic effects in CNS are developmental impairment of IQ, hearing, growth and behavior.

Chronic adult CNS effect is peripheral MOTOR neuropathy. Leads to wrist drop or foot drop

Front 95

lead toxicity nephropathy

Back 95

Acute lead poisoning --> Fanconi syndrome, isolated proximal tubular defects, azotemia(increased BUN)

Chronic lead nephropathy --> slowly progressive tubulointerstitial nephritis. Saturnine gout occurs in 50% patients.

Epidemiological association with hypertension.

Front 96

Metaphyseal Lead Lines

Back 96

Most common cause is increased calcium deposition. Sometimes it can just be normal. It is rarely a side effect of lead poisoning.

Front 97

Common lead poisoning symptoms in children

Back 97

ABDCDE
Anorexia, Anemia, Apathy
Behavioral disturbances
Clumsiness
Developmental deterioration
Emesis and colic

Front 98

What is the antidote for lead poisoning?

Back 98

IV only
Ethylene Diamine Tetra Acetic Acid (EDTA) chelates lead. But shouldn't use with really high dose of poisoning because it can mobilize lead into bloodstream and cause bad things. In that case combine EDTA with dimercaprol(BAL).

adverse effects: renal toxicity

Oral
Dimercaptosuccinic acid, treat milder forms of lead poisoning, water soluble, and treats other heavy metal poisonings. Safer than other chelators

Front 99

What is an antidote used to treat heavy metal poisoning(Hg, Pb, Cd)?

Back 99

Oral
Penicillamine used to treat Hg, Pb or Cd poisoning. However DMSA is preferred because this drug has a crapton of horrible sideeffects

Front 100

Arsenic

Back 100

it is a metalloid and can form compounds with metals and C, N, and O. Can exist oxidized or reduced.
Natural contamination of well water.
Local airborne contamination by burning high arsenic coal.

it is used as a Dopant for silicon chips.

Front 101

Arsenic poisoning

Back 101

trivalent arsenic is more toxic than pentavalent(in shellfish)
explosive onset of severe gastroenteritis, rice water diarrhea, projectile vomiting and excruciating abdominal pain. Goes along with sudden drop in blood pressure and encephalopathy.

Also damage to multiple organs, delayed sequelae if patient lives(Mees lines, alopecia, sensomotory neuropathy)

Chronic arsenic poisoning - mild encephalopathy, peripheral neuropathy(muscle weakness/pain), hyperpigmentation/hyperkeratosis on hands, predisposed to skin cancer, lung and bladder cancer. Only systemic poison that increases skin cancer

Front 102

What is the antidote for arsenic poisoning?

Back 102

BAL(British anti-lewisite) 2,3 dimercaprol. Chelator that binds arsenic, Hg, gold and maybe for lead with EDTA if there is encephalopathy.

DOES NOT WORK for iron, cadmium or selenium

Front 103

Mercury

Back 103

elemental mercury - INHALATION hazard(pneumonitis) with acute exposure.

Chronic Hg exposure - renal impairment, ptyalism(excessive production of saliva), gingivitis, stomatitis, erethism(neuropsychiatric), Acrodynia("pink disease", bright pink painful hand rashes), peripheral neuropathy

Front 104

Toxicology of ingestion of mercury

Back 104

elemental - non toxic
mercuric salts - GI corrosion, renal failure
chronic ingestion of organic mercury - severe CNS impairment(fish in japan)

Front 105

Antidote to Mercury poisoning?

Back 105

Succimer, Penicillamine, BAL

Front 106

Thallium

Back 106

former rodenticide, can cause gastroenteritis, delayed neuropathy(sensorimotor), alopecia in second week(complete baldness characteristic)

Front 107

Antidote to Thallium poisoning

Back 107

Prussian Blue. Also treats radioactive Cesium(dirty bomb). It causes repetitive cycling through GI-blood-liver-GI-blood-liver pathway.

Front 108

Herbicide - 2,4-D; 2,4,5-T(agent orange, dioxin contamination).

Back 108

herbicide, weakly inhibits ox phos.(fever, tachycardic), striated muscle toxin(muscle pain), CNS toxin, peripheral neuropathy, can use HCO3 for ion trapping to alkalize urine for clearance.

Front 109

Glyphosate

Back 109

herbicide, interferes with chlorophyll, not particularly toxic, has GI problems

Front 110

Paraquat

Back 110

herbicide, highly toxic, causes chain reaction of oxygen radicals. Causes diffuse pulmonary fibrosis and there is absolutely NO treatment.

Front 111

Pyrethroids

Back 111

insecticide, RAID, mammals protected by esterases, delays closure of sodium channel.

paresthesias upon skin contact and you treat with topical Vitamin E.

Front 112

Organophosphates

Back 112

insecticides, nerve agents

inhibits acetylcholinesterases permanently, involves ALL cholinergic receptors

Front 113

Antidote for organophosphates

Back 113

Antidote is Atropine for muscarinic effects(give as much as needed), parlidoxime chloride aka 2-PAM(must give before a certain point where AChE binding to poison is permanent)

Front 114

carbamates

Back 114

similar to organophosphates but binding isn't permanent and symptoms will eventually resolve.

antidote - atropine

Front 115

Organochlorine

Back 115

Lindane is a notable one, used topically to treat for lice/mites
DDT was an insecticide.

They are CNS stimulants and can cause seizures. They deposit in body fat.

Front 116

rodenticides

Back 116

Monofluoracetate(krebs cycle poison), vacor(causes diabetes), most are now long acting anti-coagulants(superwarfarins, eg brodifacoum)

Front 117

Antidote for rodenticides

Back 117

frozen plasma if hemorrhaging to supply coagulation factors or vitamin K to competitively overcome inhibition of synthesis.

Front 118

Antidepressants are the ___ leading cause of death due to OD...

_____ are the #1 cause of death due to pharmaceutical injection

_____ are the most common ingestants.

Back 118

5th, sedative/hypnotic/antipsychotic, analgesic

Front 119

Salicylates(ASA)

Back 119

it is a weak acid, therefore non ionized and can utilize ion trapping. and it is easily dialyzable(low MW 148 dalton).

Front 120

A molecule is easily dialyzable if...

Back 120

it is less than 500 daltson and relatively low protein bound and has a low volume of distribution(less than 1L per kilo)

Front 121

Salicylate overdose....

Back 121

ASA half life may be 20 hrs at toxic doses. Elimination is normally first order but switched to Michaelis-Menten in OD. Salicylates interfere with Krebs Cycle limiting ATP production by uncoupling ox phos.
IMPORTANT - Salicylates also interferes with coag factors V, VII, X
Salicylate crosses placental membrane and may cause metabolic acidosis in newborn.

Front 122

Describe the pregnancy risk categories of drugs...

Back 122

"X" means contraindicated in pregnancy.

"A" means control studies have shown no risk. "D" is positive evidence of risk.

Front 123

What is the antidote for Salicylate(ASA)?

Back 123

Sodium Bicarbonate...bicarb is used to correct acidosis(ethylene glycol or high loads of acid). Can also improve wide-complex ventricular rhythms associated with tricyclic poisoning and other toxins blocking Na channels such as diphenhydramine. Sometimes also used to decrease crystallization of hemoglobin/myoglobin in renal tubules

Front 124

Acetaminophen

Back 124

Peak plasma levels of APAP may be delayed if coingested with another drug that slows GI motility. APAP is metabolized by glucuronidation, some of it will be turned into toxic metabolite NAPQI by Cyp2E1.

Front 125

NAPQI is detoxed by....

Back 125

glutathione and excreted as mercapturic acid and cysteine conjugates

Front 126

Antidote for NAPA OD?

Back 126

NAC(N-acetylcystein) which prevents NAPA induced hepatotoxicity when administered within 12 hours. NAC promotes glutathione synthesis and offers subtitute target for harmless binding of NAPQI. Reduces RISK of hepatocellular damage, not CERTAINTY of damage.

Front 127

NSAIDs

Back 127

divided into 6 categories, one of which is Propionic Acids(ibuprofen)

Front 128

Dose and Symptoms of OD on NSAID

Back 128

CNS depression, respiratory depression, metabolic acidosis, renal insufficiency

Ingestion of over 400 mg/kg is associated with significant risk for serious toxicity

Front 129

Antidepressants in OD lead to...

Back 129

excessive NE reuptake blockade, direct quinidine-like effect(heart block), and central plus peripheral anticholinergic effects

Front 130

TCAs/CADs effect on ion channels...

Back 130

direct inward fast sodium channel and potassium rectifier channel blockers and this causes certain calcium channels to open due to sustained hypopolarization.

Front 131

Treatment of TCA OD

Back 131

Alkalinization with NaHCO3 and hyperventilation, Na+ bolus to overcome sodium channel blockade.

Front 132

Iron overdose...treatment?

Back 132

metabolic acidosis via....
Tissue hypoperfusion and lactate formation,
hydration of ferric ion which makes 3 H+,
disruption of ox phos

treatment is chelator(deferoxamine)

Front 133

Chronic use of deferoxamine is associated with....

Back 133

yersinia sepsis and mucormycosis and high frequency hearing/visual loss.

Front 134

name common Anticonvulsants

Back 134

Carbamazepine(CBZ), Valproic Acid(VPA), phenobarbital and phenytoin.

Front 135

What is mechanism of CBZ and what is important about CBZ toxicity?

Back 135

CBZ is a Na+ channel blocker.
Carbamazepine can occur from drug drug interaction with erythromycin(Cyp3A4)

Front 136

Symptoms of CBZ overdose...

Back 136

CBZ crosses placenta, decreased GI motility which can delay peak concentration by 72 hours. Also causes respiratory depression. Major metabolite forms which can peak 24 hours later.

Front 137

Valproic acid mechanism and what happens in overdose...

Back 137

enchances GABA, in OD may consume carnitine and affect mitochondrial fatty acid oxidation

Front 138

Pheytoin mechanism

Back 138

phenytoin blocks Na+ channels

Front 139

Phenobarbital mechanism

Back 139

GABAergic

Front 140

Opiates and opioids

Back 140

natural opiates are morphine and codeine.

semisynthetics include heroine, oxycodone, hydrocodone

synthetics are propoxyphene, meperidine and methadone

homologues are fentanyl derivatives

Front 141

Heroine induces what side effect?

Back 141

Pulmonary edema. Recovery from OD is usually rapid(24 to 48 hours) from naloxone treatment and edema can show up later after patient is discharged.

Front 142

Naloxone

Back 142

Effects mu1, mu2, kappa and sigma receptors.
used for reversal of opiate induces respiratory/CNS depression. very frequently used in ER.

Front 143

Cocaine

Back 143

Potent CNS stimulant by blocking reuptake of NE and promotes release of NE.
IMPORTANT - It BLOCKS presynaptic monoamine transporters.

primarily metabolized by plasma cholinesterase. So some addicts take organophosphates to make their cocaine high last longer.

Front 144

Side effects of cocaine

Back 144

can cause CNS hemorrhage, myocardial infarction, pulmonary edema, pneumothorax, pneumomediastinum after smoking crack, seizures and rhabdomyolysis.

Front 145

Cocaine + ethanol results in..

Back 145

a unique metabolite: cocaethylene which is more toxic than individual drugs.

Front 146

What is an important factor to consider when monitoring a cocaine OD?

Back 146

Ratio of benzoylecgonine(BE) to cocaine is very important. A ratio of greater than 100:1 suggests use more than 10 hours prior.

Front 147

Psychostimulants

Back 147

cocaine, amphetamines and derivatives(MDMA), also methylphenidate.

IMPORTANT - Promote increase of catacholamines or block reuptake transporter.

Front 148

Amphetamines mechanism of action, structural significance and notable side effect.

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Dopamines placement of hydroxyl group allows it to be degraded. This is compared to methamphetamines which do not have these hydroxyl groups which allows them to last longer.

Mechanistic models of amphetamine actions:
-- induction of catecholamine release
-- blockade of transporters(DAT)

IMPORTANT Side effects: rhabdomyolysis

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What is important about amphetamine metabolism?

Back 149

It is metabolised by various P450 enzymes but the most important polymorphism is Cyp 2D6 because it has the most variation.

Front 150

SSRIs

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can lead to serotonin toxicity by various rules we have discussed.

Front 151

Sedative/Hyponotices

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Barbiturates result in increase GABA and CNS/respiratory depression. Benzodiazepine increase GABAergic tone.

Front 152

Antidote for sedative/hypnotics

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Flumazenil is competitive antagonist at GABA cloride channel BZD receptor.

However, this drug should NOT be used if there is a possibility for mixed OD with drugs or toxins that cause seizures such as TCAs, cocaine or unknown. Not used too often. A mixed drug OD can unknowingly lead to seizures due to a benzo just so happening to "treat" seizure activity of another drug.

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Antipsychotics

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Clozapine has caused the serious side effect of drug induced agranulocytosis.

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Aripiprazole

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one of the newest atypical antipsychotics has a stabilizing effect on DA levels. In overdose, adverse effects include somnolence, anxiety, ataxia, and dystonia. Cardiotoxicity and ECG changes are generally NOT seen

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Digoxin

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Cardiac glycosides in overdose poison the Na+/K+ ATPase pump and can cause (IMPORTANT) hyperkalemia.

Oleander can look like digoxin overdose.

Front 156

Antidote for Digoxin OD...

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Antibody fragments that are digoxin specific

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Beta Blockers

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are lipid soluble. This is important because it can have neurotoxicity before it has cardiotoxicity because it reaches the brain much quicker. It has side effects that include decreased contractility, bradycardia, hypoglycemia(via B2 blockade)

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The antidote for beta blocker poisoning

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Glucagon is given because it bypasses the beta receptor and switches on adenylyl cyclase. This treats hypoglycemia and myocardial contraction via calcium channel influx.

Front 159

treatment of OD on Anticoagulants

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treatment of overdose includes stopping anticoagulant and adminstering Vit K active form(phytonadione) and considering fresh frozen plasma.

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Ethanol

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Ethanol augments GABA mediated synaptic transmission and binds to GABA chloride channel leading to CNS depressant effects.

Causes hypoglycemia, especially in children and (IMPORTANT)can result in ketoacidosis.
Included in differential of high anion gap acidosis.

Front 161

What is the most common cause of seizures?

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Withdrawal from ethanol.

Front 162

What is the antidote to ethanol OD?

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Supportive care involves IV fluids, thiamine first and then glucose.

Its important to give thiamine FIRST as an acute glucose load may precipitate acute, severe cerebral thiamine deficiency(Wernickes).

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Discuss various alcoholic metabolic pathways...

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Methanol ---> Alcohol dehydrogenase ---> Formaldehyde ---> Formic acid

Ethanol ---> Alcohol dehydrogenase ---> acetaldehyde

Ethylene Glycol ---> alcohol dehydrogenase ---> Glycoaldehyde ---> glycolic acid and glyoxalate+calcium oxalate which can lead to kidney failure

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Methanol

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found in windshield washer fluid and is metabolized by ADH to formaldehyde, formic acid, CO2 and water.

Formate(formic acid) is the toxic agent.

Front 165

What is methanol antidote?

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4-methylpyrazole(Fomepizole) used succesfully to block ADH so the formation of toxic metabolites is prevented and the parent molecule is excreted unchanged via hemodialysis.

Another method of blocking ADH is giving ethanol to competitively inhibit ADH so that methanol isn't metabolized into toxic metabolites.

Ethanol and 4-methyl pyrazole should not BOTH be given because ethanol will not be metabolized. Fomepizole is preferred.

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Ethylene Glycol

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Found in radiator antifreeze, brake fluids.
Metabolized to glycolic acid, glyoxalate and oxalate with resultant anion gap metabolic acidosis.

Hypocalcemia results from oxalate complexing with tissue calcium.

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What two things like to bind to calcium?

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Oxalate and hydrofluoric acid.

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Isopropanol

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found in cleaners, perfumes, deicers, soaps and is absorbed oral, dermal or inhalation.

IMPORTANT
isopropanol does not cause acidosis but does cause ketosis.(there is no anion gap). Osmolar gap IS elevated.

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Hydrocarbons and solvens

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Aliphatic hydrocarbons(kerosene, gasoline, mineral seal oil, etc.) risk aspiration and chemical pneumonitis.
Halogenated hydrocarbons(trichloroethane, freons, keyboard cleaners, etc.) can sensitize myocardium --> arrhythmias

Front 170

Hydrocarbons and solvents

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Toluene(glue sniffing) may result in severe neurological deficits when used chronically.
Adverse effect include CNS depression, (IMPORTANT) distal renal tubular acidosis, hepatotoxicity. CNS effects are absolutely irreversible

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mechanism of injury for Carbon Monoxide inhalation

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Cellular hypoxia is primary mechanism. treatment is with hyperbaric oxygen

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mechanism of Cyanide Toxicity and treatment

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Cellular hypoxia is primary mechanism. Newer treatment is hydroxocobalamin which combines with cyanide to form cyanocobalamin(cobalamin = Vitamin B12). Older treatment is cyanide antidote kit to bind cyanide to methemoglobin and then convert with rhodanese.

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Envemonation - snakebites

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Snake venom is fucking complex.

pit viper neurotoxins and elapidae(coral snakes) beta neurotoxins prevent acetylcholine release.

Front 174

Snake venom antidote

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Antivenins which are antibodies isolated from equine or bovines exposed to actual venom. CroFab is commercial Fab

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Envenomation - arthropods

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brown recluse and black widow.

brown recluse venom is dermonecrotic

black widow venom(alpha latrotoxin) binds on presynaptic neuronal membranes opening Ca+2 channels causing release of Ach and NE and motor end plate ---> pain and rigidity

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Lionfish

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lionfish has a toxin that is heat labile. (pterois species)

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Stonefish(synaceja)

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stonefish(synaceja) heat labile toxin causing muscle paralysis

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Box jellyfish

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Box jellyfish(chironex fleckeri) is very toxic can cause hemolytic, lethal, myotoxic, and dermonecrotic effects.

Front 179

IMPORTANT
Certain fish can give you what kind of poisoning?

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IMPORTANT
Ciguatoxin poisoning which increases permeability of voltage sensitive Na+ channels(cold hot reversal, pain)

Front 180

Botanical toxins - mushrooms
95% of shroom toxicity caused by....

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Cyclopeptide(amanita) account for 95% of toxic mushrooms. Amanitin is cytotoxic.

IMPORTANT
It binds to RNA polymerase II thereby preventing mRNA, prevents transcription and ultimately protein synthesis. Histologically one can see hepatic steatosis, central zonal necrosis, centrilobular hemorrhage.(similar to Tylenol)

Front 181

Botanical toxins - mushrooms
Gyromitra mushrooms contain...

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Monomethylhydrazine which interferes with GABA metabolism which can lead to seizures(treat with Vit B6) just like isoniazid.

hydrazines bind to pyridozine and inhibit pyridoxine kinase which decreases pyridoxine 5-phosphate(PLP). PLP required for GABA synthesis.

Front 182

Veno-occlusive disease can be caused by...

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pyrrolizidine alkaloids

Front 183

Aristolachia fangchi

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Chinese herb that can cause nephropathy

Front 184

St. John's Wort

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Prozac substitute as a natural SSRI(MAOI interaction) can cause serotonin toxicity in combination with SSRI

Front 185

Food poisoning

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Increasingly recognized as a source of illness
--- staph, salmonella, campylobacter

Front 186

Botulinum Toxin

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inhibits release of Ach. descending paralysis. (IMPORTANT)Classic EMG finding of brief, small, abundant motor unit action potentials to repetitive stimulation