FUNDAMENTALS
OF
PHARMACOLOGY
4BBY1040
Toxicology & Drug Discovery,
Diuretic & Anaesthetic Drug
Mechanism
, LECTURE 19:
Poison – All substances are poisons; there is
none that is not a poison. The right dose
differentiates a poison from a remedy. (Dose
makes the poison)
- Effects of toxicants are proportional to
the exposure / dose
- There may be variable sensitivity to
toxicants between species and
population
- Acute and chronic toxic effects may
be different and mediated by different
mechanisms
LD50: Lethal Dose in 50% of test population
- Can vary within specie and route of administration (e.g. snake venom)
o E.g. LD50 of dioxin in guinea pig is 0.001 mg/kg and hamster is 1-
5mg/kg
Therapeutic Index: The Lethal or Toxic dose
in 50% divided by the effective dose in 50%
The larger the value, the greater is the
margin of safety between effective
pharmacological dose and the toxic dose,
but it does nor indicate the shape of the
dose response curve
- E.g. Comparison of toxicity
o A and B have the same LD50
but A is more hazardous than
B, emphasizing knowing the
dose-response curve
ADME: Absorption -> distribution ->
metabolism -> excretion
Alteration to any one of the ADME phases
can alter the efficacy and toxicity of a drug
Toxic substances:
- Toxin: a poison of plant or animal origin
- Toxicant: man-made poison or product introduced into the environment as
a result of human interaction
Alcohol
Acute toxicity – depression of CNS (drunkness) – visual impairment, muscular
incordination, slow reaction time, vomiting, hangover, unconsciousness
Chronic toxicity – liver cirrhosis,
brain damage, cancer (oral
cavity, pharynx, larynx,
oesophagus, liver, colorectum,
breast)
- Cardiovascular health
benefits at lower units of
alcohol
OF
PHARMACOLOGY
4BBY1040
Toxicology & Drug Discovery,
Diuretic & Anaesthetic Drug
Mechanism
, LECTURE 19:
Poison – All substances are poisons; there is
none that is not a poison. The right dose
differentiates a poison from a remedy. (Dose
makes the poison)
- Effects of toxicants are proportional to
the exposure / dose
- There may be variable sensitivity to
toxicants between species and
population
- Acute and chronic toxic effects may
be different and mediated by different
mechanisms
LD50: Lethal Dose in 50% of test population
- Can vary within specie and route of administration (e.g. snake venom)
o E.g. LD50 of dioxin in guinea pig is 0.001 mg/kg and hamster is 1-
5mg/kg
Therapeutic Index: The Lethal or Toxic dose
in 50% divided by the effective dose in 50%
The larger the value, the greater is the
margin of safety between effective
pharmacological dose and the toxic dose,
but it does nor indicate the shape of the
dose response curve
- E.g. Comparison of toxicity
o A and B have the same LD50
but A is more hazardous than
B, emphasizing knowing the
dose-response curve
ADME: Absorption -> distribution ->
metabolism -> excretion
Alteration to any one of the ADME phases
can alter the efficacy and toxicity of a drug
Toxic substances:
- Toxin: a poison of plant or animal origin
- Toxicant: man-made poison or product introduced into the environment as
a result of human interaction
Alcohol
Acute toxicity – depression of CNS (drunkness) – visual impairment, muscular
incordination, slow reaction time, vomiting, hangover, unconsciousness
Chronic toxicity – liver cirrhosis,
brain damage, cancer (oral
cavity, pharynx, larynx,
oesophagus, liver, colorectum,
breast)
- Cardiovascular health
benefits at lower units of
alcohol
