Pharm-Toxicology

Describes the absorption, distribution,
metabolism, and excretion (ADME) of toxins,
toxic doses of therapeutic agents, and their
metabolites

Denotes the injurious effects of these
substances on vital functions

LD50

ED50

Non-Comulative Poison

Commulative Poison

zero-order kinetics

Exhibit dose-dependent elimination kinetics at
low doses
• See a first-order elimination process at higher
doses
• See a mixture of zero- and first-order elimination
at even higher doses
• Complete saturation may occur, leading to zero
-order kinetics

severe GI disorder that may progess to CNS abnormalities
Nots
Dx can be hard because it presents as sx of appenditicitis,peptic ulcer and pancreatitis

weakness,anorexia,nervousness,tremor, and weight loss

lead poisoning

measure blood lead
i.d of abnormalities of poryphyrin metabolism

Note
wrist drop is a characteristics of lead poisoning

caused by tetraethyl or tetramethyl lead in gasoline
sx: acute CNS disorder

FEP test: free erythrocyte protoporphyrin

• Prevent further exposure and provide supportive
measures
• Seizures (diazepam)
• Cerebral edema (mannitol and dexamethasone)
• Maintain fluid and electrolyte balance
• Initiate chelation therapy ( Dimercaperol-
EDTA
Penicillamine

mercury poisoning

• Mercuric ion reacts with sulfhydryls
• Very corrosive
• Precipitates proteins
• Inactivates sulfhydryl enzymes
• Methylmercury readily accumulates in cells and
tissues
• Concentrates as it moves up food chain

 Renal insufficiency
 Personality changes, irritability
 Hair analysis may indicate poisoning

• Usually diagnosed from information on exposure
• Remove exposure
• Chelation therapy with dimercaprol
• May use oral penicillamine
• Monitor removal

Arsenic poisoning

Arsenic competes with inorganic phosphate in the formation of ATP.

Pyruvate dehydrogenase is very sensitive to Arsenic poisoning. So look for a build up of pyruvate in blood

Chelation with Dimercaprol chased with penicillamine

cadmiun

1. Good water solubility
2. Resistance to metabolism
3. Ability to get to metal ions
4. Ready excretion of the chelate with little or no
dissociation
5. Ability to function at physiological pH
6. Complexes less toxic than free metal
7. Low affinity for Ca2+ and Zn2+
8. High affinity for metal
9. Minimal inherent toxicity
10. Absorbed via oral administration

1. Dimercaprol
2. Ethylenediaminetetraacetic acid (EDTA)
(CaNa2EDTA)
3. Penicillamine (Cuprimine)
4. Desferoximine Mesylate (Desferal)

 Arsenic
 Lead
 Mercury
 NOT FOR CADMIUM

Increased systolic and diastolic pressures
• Tachycardia
• Nausea and vomiting; abdominal cramps
• Headache; sweating forehead
• Painful or burning sensation in mouth, lips, throat
• Conjunctivitis, rhinorrhea, lacrimation, salivation
• Constrictions in throat and chest
• Anxiety and unrest
• Fever in children

EDTA

Beryllium
Cadmium
Cobalt
Copper
Iron
Lead
Manganese
Nickel
Zinc
*NOT MERCURY*

Penicillamine

chelates copper, Mercury, lead and iron.
It’s also used to treat Wilson’s Disease (you remember, Copper overload).
Chronic use of this drug can cause nephrotoxicity

deferoxamine

Arsenic poisoning
Treatment: Penicillamine or orally administered 2,3
-dimercaptosuccinic acid (DMSA

brain and heart tissues

headache, weakness, nausea and vomiting followed by loss of muscular control. collapse, unconsciousness and death

100% oxygen

Small doses cause:
 Giddiness
 Headache
 Palpitations
 Nausea and vomiting

At high doses ataxia, convulsions and coma result

onset of sx is abrupt
odor of bitter almonds on breath

Cyanide works by binding to the iron in the enzyme cytochrome oxidase. This enzyme is a part of the electron transport chain, which ultimately provides most of the energy for the cell. Normally, this enzyme facilitates the transformation of oxygen into water, a process which the cell uses to generate energy.

Because the toxicity is due to the binding of the iron in cytochrome, the treatment is aimed at disrupting this relationship.
Amyl nitrate and sodium nitrate are used an antidote.

The nitrites oxidize some of the hemoglobin's iron from the ferrous state to the ferric state, converting the hemoglobin into methemoglobin. (Treatment with nitrites is not innocuous. Methemoglobin cannot carry oxygen. The adult dose can cause a fatal methemoglobinemia in children or may cause profound hypotension. Treatment of children affected with cyanide intoxication must be individualized and is based upon their body weight and hemoglobin concentration.)

 Severe GI cramps and vomiting
 Dilated pupils, blurred vision
 Acidosis
 Cardiac depression
 Respiratory and circulatory failure.
 Blindness may be permanent if you survive. If not, death will also be permanent.

Formaldehyde damages the retinal cells and causes blindness.
Formic acid cause acidosis and cardiac depression