Pharmacology: Block 6: Toxicology

Front 1

Contraindications of vomiting induction

Back 1

unconsciousness, caustic and volitile susbstances, rapid poison

Front 2

Gastric lavage: risks

Back 2

esophageal perforation, aspiration

Front 3

Activated charcoal: uses

Back 3

adsorbs organic lipid-soluble compounds

Front 4

Alkalinization of urine: use what? for what?

Back 4

Use NaHCO3, acteazolamide

Increases excretion of acidic compounds (e.g. barbiturates, salicylates)

Front 5

Acidification of urine: use what? for what?

Back 5

Use NH4Cl

Use to increase excretion of basic compounds (e.g. amphetamines)

Front 6

Dialysis: clears substances with what characteristics?

Back 6

water-soluble, low MW, not protein bound

Front 7

4 components of the evaulation of the poisoned patient

Back 7

1. Identity of the poison.
2. Time of exposure
3. Route of exposure
4. Amount of exposure

Front 8

Opiod toxicity: antidote

Back 8

Pharmacological antagonist: Naloxone (Narcan)

Front 9

Beta-blocker overdose: antidote

Back 9

Give a physiological antagonist (beta-agonist)

Front 10

Acetaminophen overdose: antidote

Back 10

Give a chemical antidote (N-acetylcysteine)

Front 11

CO poisoning sx

Back 11

10%: mild HA, vasodil
20%: throbbing HA
30%: severe HA, dizziness, visual changes
40%: unconsciousness, inc HR, RR
50%: intermittent seizures
60%: hypotension, vent dep
70%: death

Front 12

Carbon monoxide: attributes

Back 12

Affinity for Hb > 200x that of O2
Displaces oxygen from binding to Hb
Shifts O2 dissociation curve to the LEFT
Binds to cytochrome oxidase

Front 13

CO poisoning: txt

Back 13

Eliminate source of CO
Give 100% O2
Consider mechanical vent, paralysis (?)
Consider hyperbaric therapy
Consider barbiturate coma (?)

Front 14

CO: half-life

Back 14

4-6 hr in room air
40-80 min in 100% oxygen
15-30 min in 100% oxygen at 3 atm

Front 15

Aspirin: CP of early and late OD

Back 15

Aspirin uncouples oxidative phosphorylation.

Initially: respiratory alkalosis, compensatory metabolic acidosis

Later: combined respiratory and metabolic acidosis

Lethal dose: 10-30 g

Front 16

Acetaminophen: management of OD

Back 16

Decrease absorption: vomiting, charcoal

Inc elimination: inc urinary pH (NaHCO3, acetazolamide)

Correct acid/base, consider mech vent, dialysis

Theraputic window for N-acetylcysteine (NAC) is about 36 hrs after ingestion

Acetaminophen metabolism:
Glucuronide (60%), Sulfate (35%), Mercapturic acid (5%)

Front 17

Cyanide sources, chemistry

Back 17

HCN gas use as pesticide, photography, ore extraction, fruit pits.

Binds tightly to Fe3+
Major target is cytochrome oxidase
Lactic acidosis
Lethal dose:
KCN, about 200 mg
HCN, about 50 mg

Front 18

Cyanide: detox chemistry

Back 18

CN(-) + S2O3(2-) --rhodanase--> SCN(-) + SO3(2-)

cyanide + thiosulfate --rhodanase--> thiocyanate + sulfate

Front 19

Cyanide: management of poisoning

Back 19

Intentional converstion of Hb(2+) to Hb(3+) via amyl nitrate (inhaled), sodium nitrate (IV)

Sodium thiosulfate IV: supply of S2O3(2-) is rate limiting

100% oxygen

Consider gastric lavage

Very often fatal.

Front 20

Steps of ethanol metabolism vs. steps of methanol metabolism

Back 20

Ethanol --alcohol dehydrogenase--> acetaldehyde --aldehyde dehydrogenase--> acetic acid (vinegar)

Methanol --alcohol dehydrogenase--> formaldehyde --aldehyde dehydrogenase--> formic acid

Front 21

Signs of methanol OD

Back 21

Severe metabolic acidosis
Formic acid toxic to the retina
15 mL causes blindness
100 mL is a fatal dose

txt: ehtanol or fomepizole prevents methanol conversion to formic acid (by inhibiting alcohol dehydrogenase) MECH?

Front 22

Pesticides: type, toxicity, management

Back 22

Types:
Organophosphates:
Malathion, Parathion, Diazinon

Carbamates:
Carbaryl, Baygon

Pesticide tox:
Inc muscarinic effects (N, V, inc pulmonary secr, sweating, salivation, miosis, bradycardia)

Inc nicotinic effects: (hypertension, muscle weakness, twitching)

CNS Effects:(anxiety, restlessness, sz, coma)

Management: Prevent additional absorption (skin-bathing, GI - gastric lavage, charcoal. Atropine to dry secretions. Pralidoxime.

Front 23

Lead: environmental sources, lead kinetics, lead toxicity in adults, lead tox in children, management

Back 23

Env sources: house dust (used in paint until 1978). in dirt (tetraethyllead was an additive in gasoline until 1970s), lead pipes, lead solder to join copper pipes, batteries, radiators, acidic fruits

Kinetics: after GI absorp circulates bound to hemoglobin, then redistributes to bone. Half life in circ = 2 months. Half life in bone = 30 years.

Lead tox in adults:
Vague GI effects (anorexia, constipation, metallic taste, later painful intestinal spasms)
Renal (proteinuria, hematuria, cell casts)
Hematopoietic (microcytic, hypochromic anemia)
Neuro (periph neuropathy, hypertension)

Lead tox in children:
CNS (HA, irritability, ataxia, lowered IQ, behavioral problems)
Abdominal pain, anemia
Screen routinely
[Pb] > 10 mcg/dL --> change environment
[Pb] > 25 mcg/dL --> chelation therapy

Management:

CaNa(2)EDTA:
Pb displaces Ca.
Must be given IV or IM
Causes proximal tubule damage.
Also chelates essential metals (Cu, Zn, Fe)

Dimercaprol:
Solution in peanut oil
Must be given IM
Used in combination with EDTA in Pb poisoning
Inc HR, BP
Requires an alkaline urine

Penicillamine
Metabolite of penicillin
Effective orally
Useful in long-term outpt txt of Pb poisoning
Also used in Wilson's dz
Tox: autoimmune phenomena

Succimer:
Effective orally
Less toxic than dimercaprol, penicillamine
Does not chelate essential heavy metals (Cu, Zn, Fe)
Only approved in Pb poisoning
Toxicity: chemical hepatitis

Front 24

Mercury: characteristics, tox, management

Back 24

Characteristics:
Elemental Hg is a vapor at room temp. Found in pressure meters, switches.

Hg salts:
Used in medicine through the 1970s, used in many industries, converted to methylmercury by bacteria

Methylmercury:
Poisons sulfhydryl enzymes, rises in the food chain.

Mercury poisoning:
Primarily CNS sx, visual and hearing loss, ataxia

Management:
Chelation therapy: dimercaprol, penicillamine, succimer (not approved, only for Pb)

CNS damage may not be reversible.

Front 25

Arsenic: characteristics, sources, management

Back 25

Characteristics:
As(5+): least toxic form, AsO4(3-) competes with PO4(3-). Converted in vivo to As(3+)

As(3+): inhibits sulfhydryl enzymes, esp Krebs cycle. Early signs are neurological (weakness, aching), late signs include hepatic cirrhosis. GaAs are used in LEDs

AsH3: denatures hemoglobin, used to make silicon chips

Sources:
usually ingested in drinking water.
Natural constituent of ground water (esp that contaminated with agricultural runoff)
Very occasionally used in medications (e.g. Trypanosomiasis)

Management:
Dimercaprol initially
Chronic therapy: penicillamine, succimer (not approved, only for Pb)

Front 26

Cadmium: sources, tox, management

Back 26

Common uses:
NiCd batteries, many alloys, paint (cadmium yellow)

Routes of exposure:
foods (esp grains), tobacco smoke, inhalation of dust

Inhalation:
acute: pneumonitis
chronic: emphysema, fibrosis

Ingestion:
renal damage (tubule and glomerulus)
carcinogen

Management:
Acute: chelation therapy, drug of choice unknown
Chronic: half-life is 10-30 years, ? effectiveness.

Front 27

Which gov org monitors public water supplies, private wells, and air?

Back 27

The EPA (Environmental Protection Agency)

Front 28

Which gov org monitors the safety of the workplace?

Back 28

OSHA (occupational safety and health administration)

Front 29

What are some of the parameters used to monitor drinking water?

Back 29

Maximum containment level goal (MCLG)

Maximum containment level (MCL)

MCLG < or = to MCL

Front 30

What are some of the parameters for monitoring workplace exposure?

Back 30

Permisible exposure lmits (PEL): time-weighted average (TWA), acceptable ceiling, maximum peak.

PEL's not established for most organics.

a CIH (certified industrial hygenist) determines if workplaces are "safe"

Front 31

Tricholorethylene (TCE)

Back 31

Used for: volatile anesthetic until 1977, industrial drycleaning solvent, decaffinating coffee

Metabolism:
Via the glutathione-S-transferase pathway, then beta-lyase

TCE in drinking water:
MCLG = 0
MCL = 5 ppb
Removing TCE from water: aeration, activated charcoal filtration

Industrial exposure to TCE:
TWA (8 hr day) = 100 ppm
Acceptable ceiling = 200 ppm
Max peak = 300 ppm, 5 min

Tox:
Acute: anesthetic effect (MAC = about 1% = 10,000 ppm)
drowsiness, ataxia, dizziness

Chronic: carcinogenic kidney, liver, esophagus, leukemia, NHL

Front 32

Benzene

Back 32

Sources:
present in most fuels, common industrial solvent, used to separate out foods in making veggie burgers

Tox:
bone marrow supression, carcinogen

Metabolism: via CYP to an epoxide

Benzene in drinking water:
MCLG = 0
MCL = 5 ppb
Removing benzene from water: aeration, activated charcoal filtration

Industrial exposure to benzene:
TWA (8 hr day) = 10 ppm
Acceptable ceiling = 25 ppm
Max peak = 50 ppm, 10 min

Front 33

TCDD (Dioxin)

Back 33

Sources:
from burning organic matter
low volatility, high lipid solubility
persists in the env
conc rises in the food chain

Kinetics:
binds to AChR?
Induces CYP1A1
metabolizes PAH
not metabolized itself
half-life is about 8 years

Tox:
Acute: chloracne
Chronic:
diabetes mellitus
inc female births (60-62%)
CNS, PNS damage
endometriosis
hypothyroidism
immunosuppression

Front 34

Polychlorinated biphenyl (PCB)

Back 34

Characteristics:
Many isomers
Insulators in transformers, capacitators
Low volatility, high lipid sol
Almost inert
Conc rise in the food chain

Acute: chloracne
Chronic:
Cancer: melanoma, non-Hodgkin lymphoma, brain, liver, gall-bladder, bile duct

Neuro: Parkinson's disease, ALS