Dose Response

What is a poison? All substances are poisons;

there is none which is not a poison. The right
dose differentiates a poison and a remedy.

Paracelsus (15th century Swiss physician and alchemist)
Est i mat ed Toxi ci t y of Subst ances
LD
50
- Dose that represents the concentration of
chemical required to produce death in 50% of
animals exposed to it.

Exampl es of Acut e Or al LD
50
Substance LD
50
(mg/kg)
Ethyl alcohol 10,000
Sodium Chloride 4,000
DDT 100
Nicotine 1
Dioxin 0.001
Botulinus toxin 0.00001
Pr obl ems
o Clinical usefulness? (minimum toxic dose)
o Other patient parameters influencing toxicity
Age
Disease
Drugs
o Animals vs. humans

Hazar d i s det er mi ned by:
Toxic + significant exposure hazard.
Toxic + no serious exposure no hazard.
TOXICITY
EXPOSURE
and
For exampl e:
o SIGNIFICANT hazard:
Ingestion of a cup of antifreeze
A few drops of dimethylmercury on the skin
A victim soaked with parathion-containing liquid
o NOT a hazard:
Antifreeze applied to the skin
Handling an intact ant stake with arsenic trioxide

Dose i s det er mi ned by:
o Route of exposure
Amount
Duration
Admi ni st r at i on Of Phenyl ephr i ne By Ot her
Rout es
Heart
Esophagus
Mouth
Liver
Stomach
Small Intestine
Heart
Esophagus
Mouth
Liver
Stomach
Small Intestine
Farid et al. AJNR Am J Neuroradiol. (2011): 1-4
Brain Tissue Brain Tissue
Blood
Injection
Nerve & Mucosa Transport
Blood
Note:
1. Other routes
bypass liver
2. Higher blood
levels
3. More effect in
blood pressure
4. Disrupts brain
blood barrier, if
very high
pressures that
overwhelm
regulatory
process
Brain Tissue
Blood
Heart
Liver
Small Intestine
Heart
Liver
Small Intestine
Stomach
Esophagus
Mouth
Stomach
Esophagus
Mouth
Oral
Heart
Liver
Small Intestine
Stomach
Esophagus
Mouth
Nasal
Top Fi ve Li st NPDS
Subst ances i nvol ved i n Deat hs
1. Sedative-hypnotics
2. Opioids
3. Antidepressants
4. Cardiovascular agents
5. Acetaminophen combinations

Sudden Cat ast r ophi c Toxi c Event s Fr om
Poi soni ng
o Arrhythmias cardiac/heart failure
o Anoxia lack of oxygen
o Hemorrhage shock
o Seizures respiratory failure, accidents
o Metabolic (hypoglycemia, Hyperthermia)