(Slu Curriculum) Pharmacology: Toxicology

Front 1

Environmental risks of Lead in patients

Back 1

1) Lead in gasoline (banned in US in 1981)
2) Lead-based paint in residences older than 1970, even if repainted
3) Lead more easily absorbed if around divalent cations (iron, zinc or calcium)

Front 2

Toxic mechanisms of Lead

Back 2

1) Interferes with sulfhydryl groups of many enzymes
2) Inhibit heme synthesis resulting in anemia
3) Blood smear shows basophilic stippling (blue-purple staining granules that are precipitated ribosomal protein common to any hemoglobin synthesis impairment)

Front 3

Lead Poisoning Symptoms

Back 3

GI Symptoms
- Vomiting, colicky abdominal pain, constipation
- Gingival "lead lines"

Bone Marrow
- Reduced hemoglobin synthesis and frank microcytic anemia

Nervous System
- Acute: headache, irritability then lethargy, seizure, coma then encephalopathy
- Chronic: Lower IQ, hearing and growth, behavioral problems
- Peripheral motor neuropathy

Kidney
- Chronic nephropathy
- "Fanconi syndrome" - isolated proximal tubule absorption defects
- "saturnine gout"
- Hypertension

Reproductive
- Male infertility

Long Bones
- "Lead Lines" in knee/elbow, resulting from increased Ca+2 deposition, NOT Lead deposition

Front 4

Lead Poisoning Symptoms Acronym

Back 4

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

Front 5

Arsenic Risk Areas

Back 5

1) Well water contamination - Bangladesh, Taiwan, New England, Great Lakes, Texas panhandle, Desert Southwest
2) Airborne contamination from coal burning, Southern Kentucky

Front 6

Arsenic Uses

Back 6

1) Dopant in semiconductors
2) Wood preservative (with chromium and copper)
3) Insecticides, fungicides, herbicides
4) Homeopathic/traditional medication
5) Arsenic trioxide used to treat acute promyelocytic leukemia

Front 7

Types of Arsenic and their relative toxicity

Back 7

Toxicity: Trivalent (arsenite) > Pentavalent (arsenate) > Organic arsenic

Front 8

Chelator for Arsenic poisoning

Back 8

BAL

Front 9

Arsenic Poisoning Symptoms

Back 9

Rapid onset of severe gastroenteritis
- Burning lips
- Intense thirst
- Dysphagia (difficulty swallowing)
- Projectile vomiting
- "Rice-water-like" diarrhea
- Excruciating abdominal pain

Other Acute Symptoms
- Sudden drop in blood pressure
- Encephalopathy or coma
- Muscle cramps, facial edema, bronchitis, dyspnea and chest pain

Later symptoms
- Rhabdomyolysis
- Cardiomyopathy
- Renal failure
- Hepatic injury
- Bone marrow depression of all cell lines

Long term effects
- Sensory-motor peripheral neuropathy
- Skin eruptions
- Alopecia
- Mee's lines

Front 10

Mees' lines

Back 10

1) Transverse bands on the nails
2) Show up 5-6 weeks after poisoning
3) Caused by Arsenic and Thallium poisoning

Front 11

Chronic Arsenic Poisoning Symptoms

Back 11

Non-specific Symptoms
- Weakness, malaise, anorexia, GI complaints
- Mild encephalopathy, tremors, ataxia, lack of coordination, confusion
- Peripheral neuropathy, painful paresthesias, muscle weakness and pain
- Hyper pigmentation, palmar/plantar hyperkeratosis, peripheral edema and squamous cell carcinoma of the skin
- Cancers of the skin, lung and bladder
- Chelation is not effective in chronic poisoning

Front 12

Elemental Mercury (Exposure risks, symptoms)

Back 12

Exposure risks
- Found in thermometers, dental amalgam, electronics
- Broken objects can leak elemental Hg

Symptoms
- Acute: pneumonitis after inhalation, ingestion is non-toxic
- Chronic: Renal failure, gingivitis, stomatitis, ptyalism (excessive saliva production), psychiatric abnormalities - "erethrism" - personality changes, Acrodynia: "pink disease"

Front 13

Acrodynia: "Pink Disease"

Back 13

Symptoms
- Painful, bright pink desquamating rash on hands and feet
- Peripheral neuropathy
- Excessive catecholamines in blood
- Hyper-adrenergic response
- Possibly hypersensitivity reaction to Hg

Cause
- Chronic Hg exposure

Front 14

Inorganic Mercury Salts (Symptoms)

Back 14

Symptoms
- GI tract corrosion, shock, acute renal failure

Front 15

Organic Mercury Poisoning (Historical example, symptoms)

Back 15

Historical Example
- Minimata Bay, Japan wide spread cerebral palsy

Symptoms
- Severe CNS dysfunction

Front 16

Sources of Mercury Exposure

Back 16

1) Fish
2) Thimersol to preserve vaccines
3) Dental amalgams

Front 17

Chelators for Mercury Poisoning

Back 17

Succimer, penicillamine or BAL

Front 18

Thallium Poisoning Symptoms

Back 18

Symptoms
- Severe acute gastroenteritis
- several days/week later, sensorimotor polyneuropathy and CNS abnormalities
- Complete baldness (alopecia)

Front 19

Thallium Chelator

Back 19

Prussian Blue

Front 20

2,4-D (and other chlorophenoxys) (Trade name, symptoms, how to facilitate excretion)

Back 20

Trade Name: Weed be gone

Symptoms
- Weak inhibitor of Ox Phos --> fever, tachypnea, tachycardia, flushing, sweating, metabolic acidosis
- Muscle weakness, rhabdomyolysis
- Lethargy, confusion, ataxia
- peripheral neuropathy after long exposure
- Weak organic acid, urinary alkalinization for enhanced excretion

Front 21

Glyphosate (Trade name, symptoms, MOA)

Back 21

Trade Name: Roundup
Symptoms
- NOT toxic, mixed with surfactant which is
- Severe GI irritation, hypotension, pulmonary edema

MOA
Inhibits chlorophyll synthesis

Front 22

Paraquat (Symptoms, MOA)

Back 22

Symptoms
- Diffuse pulmonary fibrosis from constant inflammation
- No therapy, even lung transplant fails

MOA
- Initiates an oxygen superoxide radical attack on cell membrane lipids

Front 23

Pyrethrins and Pyrethroids (Symptoms, MOA, Method of inactivation)

Back 23

Symptoms
- Paresthesias (altered cutaneous sensations) - Treat with Vitamin E topically, bronchospasm, oculo-rhinitis

MOA
- Delays closure of sodium channels causing prolonged after-depolarization

Method of inactivation
- Near-instantaneous hydrolysis and inactivation in humans

Front 24

Carbamates (Symptoms, MOA)

Back 24

Symptoms
- Excess muscarinic symptoms

MOA
- Temporarily block AChE

Treatment
- Atropine

Front 25

Organochlorines (Site of accumulation, Symptoms and Uses)

Back 25

Site of accumulation
- Fat

Symptoms
- Nausea, vomiting, headache, dizziness
- Agitation, confusion tremor, seizures

Uses
- Lindane used topically for lice treatment
- DDT used as pesticide

Front 26

Salicylate (OD Symptoms)

Back 26

OD Symptoms
- Nausea, vomiting, epigastric pain
- Decreased factor V, VII, X, Hypoprothrombinaemia
- Increased capillary fragility
- Decreased platelet adhesiveness, thrombocytopenia

Front 27

Salicylate (MW and meaning, pKa and absorption, Vd, protein binding, therapeutic level, normal half-life, OD half-life)

Back 27

MW: 138 Daltons (easily dialyzable)
pKa: 3.5, rapid absorption in stomach
Vd: 0.2 to 0.3 (stays in blood)
Protein binding: 90% bound
Normal half-life: 2-4 hours
OD half-life: Possibly over 20 hours

Front 28

Salicylate (MOA)

Back 28

MOA
- Interferes with Krebs cycle
- Elevates anion-gap
- Elevates lipid metabolism (elevated ketones)
- Uncouples Ox Phos --> HR, Oxygen consumption, CO2 formation and heat production all go up

Front 29

Salicylate treatment

Back 29

Sodium bicarbonate, alkalinization of urine

Front 30

Acetaminophen OD (MOA)

Back 30

MOA
- 4% Acetaminophen metabolized by CYP2E1 to NAPQI (Toxic)
- NAPQI conjugated with glutathione and excreted
- If glutathione reserves are depleted, NAPQI binds to hepatic macromolecules causing damage
- May also damage renal cells that also have high levels of CYP2E1

Front 31

Nonsteroidal anti-inflammatory drugs safety level

Back 31

1 pill per kg
200mg/kg

Front 32

Nonsteroidal anti-inflammatory drug treatment

Back 32

Over 200mg/kg ingestion use gastric emptying and administration of activated charcoal

Front 33

Cyclic Antidepressant Side Effects

Back 33

1) Anticholinergic effects
2) Excessive block of norepinephrine reuptake
3) Quinidine-like effects on myocardium

Front 34

Cyclic Antidepressant Poisoning Symptoms

Back 34

Symptoms
- Dry mouth, decreased GI motility
- Tachycardia, hypertension, ventricular dysrhythmias
- Increased QRS duration, increased QT interval, increased PR interval

Front 35

Cyclic Antidepressant MOA

Back 35

MOA
- Blocks Sodium ion channel
- Blocks Chloride ion channel of the GABAA Receptor

Front 36

Iron OD MOA

Back 36

MOA
- Catalyze redox reactions leading to lipid peroxidation and free radical formation

Front 37

Iron OD Symptoms

Back 37

Local Symptoms
- mucosal irritation, corrosive effect --> perforation
- mucosal congestion, venous thrombosis, infarction, mucosal ulceration and petechial hemorrhage

Systemic Symptoms
- Venodilation
- Increased capillary membrane permeability
- Increased clot time
- Metabolic acidosis
- Disruption of Ox Phos

Front 38

Anticonvulsant OD Symptoms

Back 38

Symptoms
- Nystagmus (involuntary eye movement), ataxia, depressed sensorium, blurred vision, convulsions and coma

Front 39

Carbamazepine (Type of Drug, side effects)

Back 39

Type of Drug
- Anticonvulsant

Symptoms
- Nystagmus (involuntary eye movement), ataxia, depressed sensorium, blurred vision, convulsions and coma
- Crosses placenta, causes asymmetric growth retardation, spina bifida

Front 40

Opiate/Opioid OD Symptoms

Back 40

Symptoms
- Respiratory compromise
- Coma
- Loss of corneal and deep tendon reflex
- Bilateral miosis (pinpoint pupils)
- Seizures from meperidine

Front 41

Cocaine OD Symptoms

Back 41

Symptoms
- Seizures in children
- Pulmonary edema
- CNS, cardiovascular and respiratory symptoms

Front 42

Cocaine MOA

Back 42

MOA
- Blocks reuptake of NE in the CNS
- Blocks reuptake of dopamine

Front 43

Amphetamines MOA

Back 43

MOA
- Disrupt vesicle pH gradients allowing vesicular DA to redistribute into cytoplasm
- DA exits neuron via reverse transport or channel-like activity

Front 44

Amphetamine OD Symptoms

Back 44

Symptoms
- Tachycardia
- Hypertension
- Hyperthermia
- Agitation
- Seizures
- CNS hemorrhage
- Rhabdomyolysis

Front 45

Phencyclindine (PCP) Symptoms

Back 45

Symptoms
- Dissociation, agitation and violent behavior
- Tachycardia
- Hypertension

Front 46

Phencyclindine (PCP) MOA

Back 46

MOA
- Antagonizes the effect of glutamate at the NMDA receptor by binding within the ion channel and blocking Ca++ influx

Front 47

Antipsychotic OD Symptoms

Back 47

Symptoms
- Somnolence
- Coma
- Agitation
- Insomnia
- Difficulty concentrating
- Hypotension
- Tachycardia
- Prolonged QT
- Widened QRS
- Neuroleptic Malignant Syndrome

Front 48

Aripiprazole MOA

Back 48

MOA
- Stabilizes Dopamine levels

Front 49

Digoxin OD Symptoms

Back 49

Symptoms
- Bradycardia/arrhythmias
- Vomiting is common
- Altered color vision
- Hyperkalemia

Front 50

Digoxin OD MOA

Back 50

MOA
- Poisons the NA+/K+ ATPase pump

Front 51

Digoxin OD Treatment

Back 51

Treatment
- Correction of electrolytes and Fab antibodies

Front 52

Warfarin OD Symptoms

Back 52

Symptoms
- Vitamin K problems

Front 53

Warfarin OD Treatment

Back 53

Treatment
- Stop Warfarin
- Administer Vitamin K active form

Front 54

Ethanol OD Symptoms

Back 54

Symptoms
- Ataxia
- Lethargy
- Coma
- Seizures
- Loss of deep tendon reflexes
- Hypothermia
- Hypoglycemia leading to convulsions

Front 55

Known causes of hepato-carcinogenesis

Back 55

Viral hepatitis
Ethanol
Aflatoxin (Aspergillus flavus mycotoxin from infected grain and legumes)
Vinyl Chloride

Front 56

Renal Toxins (Therapeutic agents and Chemicals)

Back 56

Therapeutic agents
- Antimicrobials
- Antineoplastics
- Iodinated radiocontrast agents
- Analgesics

Chemicals
- Metals (Hg, Cd, Pb)
- solvents (CCl4, toluene)
- aniline dyes
- Diquat herbicide
- Ethylene glycol

Front 57

Proximal convoluted tubule toxins

Back 57

High CYP450 -> free radical damage

CCl4, acetominophen

Front 58

Distal renal tubule toxins

Back 58

Chronic toluene

Front 59

Interstitial nephritis

Back 59

Analgesics

Front 60

Glomerular toxins

Back 60

Gold