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BASIC PHARMACOTOXICOLOGY
Eman SutrisnaDepartement of Pharmacology and Therapy
Medical School Unsoed
LEARNING OBJECTIVES
Student able to explain : Definition and field of
pharmacotoxicology Various of Pollutant, Toxic agents
and resourcers Application of the principles of
toxicology examination in drug development.
Assessment of Substant sefety in food
TOXICOLOGY
The study of poisoning and the harmful effect of chemicals on the living organism
THE FIELD OF TOXICOLOGY
Descriptive or experimental toxicology
Forensic toxicology Enviromental toxicology Occupational toxicology Clinical toxicology Ect…
THE CLASIFICATION OF TOXICOLOGY(The kind of Agents and the incidence time)
The toxicology of the drug The toxicology of the food The toxicology of the pesticide The toxicology of the industry The toxicology of the environment The toxicology of the accident The toxicology of the war The toxicology of the radiation
THE CLASIFICATION OF TOXICOLOGY(The type of Agents)
Metallic Pollutant Heavy metals Non Metallic Pollutant Air
Pollutant
VARIOUS TOXICANTS
Chemical Industrial Household
Agricultural Pesticides Natural toxicants
Mushrooms Plant toxin Snake/insect toxin Marine toxin
Heavy metal Pb Mercury Arsen Cadmium Iron
VARIOUS TOXICANTS
Drugs OTC free drugs Illegal Prescription
The drug which can cause harmdeath : Antihistamine Acetaminophene Carbon-monoxide Psychotropic : Barbiturates, chloral hydrate,
major tranquillizer, anti depressant tricyclic , karbamazepine
Teophilline Verapamil, digoxyne Narcotic : opiat ect
TOXICOLOGY EXAMINATION
Pharmacokinetic test Pharmacodynamic test The assessment of substance sefety
PRE CLINICAL TRIAL
Animal study Laboratory based To evaluate :
Active compound Performing pharmacological Toxicology Safety testing
CLINICAL TRIAL
Human study Phase I
Small number of subject (≤30) Healthy volunteer By clinical pharmacologist Determine metabolism of the drug in
human A safe dosage Extremly toxic effect in human
Phase II
Patient who have a target disease 100-200 subject By clinical pharmacologist Determine pharmacokinetic of the drug Additional toxic effect Preliminary information on the efficacy Dosage regiment
Phase III
Large number of patient (several hundred-thousands)
By clinical researcher To verifies phase I and II To make sure and proves that the
drug is more effective than previously available drugs
Phase IV
Post marketing surveillance. Conducted once the drug is
approved To gather information a long term
outcome Long term toxic reaction Neoplastic effect Terratogenic effect
SUBSTANCE SEFETY
IMPORTANT in toxicology NEL (No effect Level)/NOEL (No Observe
Effect level) the concentration of substance or drugs found in research that have no effect to cause dysfunction or damage of organ or death.
ADI (acceptable Daily Intake) the maximal concentration (mg/kgbw/d) of the substance can be daily in-taken for a long time and predicted no influent to human body
SUBSTANCE SEFETY
100 = safety factor 10 = the difference between animal and
human 10 = the difference among the human
ADI use to measure the additive or contaminant substance
MPC (maximal permissible concentration) the maximal concentration of the substance permitted in the foods
ADI= (NEL/100) mg/kgbw/d
SUBSTANCE SAFETY
Food factor = the average of food consumption every person (kg/person/d)
MPC= ADI x BW (kg) food factor (kg)
LEAD TOXICITY
HEAVY METALS
Heavy metals are natural constituents of the Earth's crust and are present in varying concentrations in all ecosystems
Metals differ from other toxic substances in that they are neither created nor destroyed by humans. Therefore, they tend to accumulate in the soils, seawater, freshwater, and sediments.
HEAVY METALS
Mercury is a contaminant of our water ways. Humans are exposed to mercury in the fish they eat as well as in the amalgam fillings in their teeth.
Arsenic is found naturally in high concentration in drinking water in various parts of the world.
Cadmium has been classified as a known human carcinogen.
Sources of Lead - environmental
Combustion of tetramethyl in gasoline Persistent lead-based paint (children with
Pica) Improperly glazed earthenware Lead piping (acid rain) Solder in food containers Automobile battery casing
Mercury
MAJOR PHYSICAL AND CHEMICAL FORMS OF MERCURY
INORGANIC Hg, Hg2++ Hg++ Metallic Mercurous Mercuric
ORGANIC C6H5Hg+, CH3Hg+, Phenyl Mercuric Methyl Mercuric
Human Exposure
Mercury Vapor Environmental - unimportant
Occupational - main source Electrical equipment, paints,
thermometers, laboratory Dental
Amalgam fillings - main source of background exposure
ORGANIC
Methylmercury important Environmental - main source is fish
Biomethylation - Hg (all forms) --> Hg++ --> CH3Hg and CH3HgCH3
Bioaccumulation in aquatic food chains Industrial, agricultural
By-product of plastic industry Fungicide in seed grain (also ethylHg) Misuse of treated grain (developing countries)
Cadmium
Cadmium is a natural element in the earth's crust. It is usually found as a mineral combined with other elements such as oxygen (cadmium oxide), chlorine (cadmium chloride), or sulfur (cadmium sulfate, cadmium sulfide).
All soils and rocks, including coal and mineral fertilizers, contain some cadmium. Most cadmium used is extracted during the production of other metals like zinc, lead, and copper.
Cadmium does not corrode easily and has many uses, including batteries, pigments, metal coatings, and plastics.
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