Introduction to Syllabus

Presented by :
Ms. Jagruti Marathe
 Pharmacology

• Pharmacology is the science of drugs (Greek pharmakos,

medicine or drug; and logos, study
• Originating in the 19th century,

• The discipline makes drug development possible

• Pharmacology is one of the cornerstones of the drug

discovery process
• Pharmacology studies the effects of drugs and how they
exert their effects
• Pharmacology

• Pharmacology is the science of drugs (Greek:

Pharmacon--d.rug; logos-discourse in) .
• In a broad sense, it deals with interaction of
exogenously administered chemical molecules (drugs)
with living systems.
• It encompasses all aspects of knowledge about drugs,
but most importantly those that are relevant to
effective and safe use for medicinal purposes
• The two main divisions of pharmacology are pharmacodynamics
and pharmacokinetics.

• Pharmacodynamics (Greek: dynamis-power) What the drug does

to the body.

• This includes physiological and biochemical effects of drugs and

their mechanism of action at organ system/ subcellular I
macromolecular levels,

• e.g.- Adrenalin…… interaction with adrenoceptors……. G-protein

mediated stimulation of cell membrane bound adenylyl
cyclase…………. Increased intracellular cyclic 3',5' AMP……… cardiac
stimulation, hepatic glycogenolysis and hyperglycaemia, etc
• Pharmacokinetics (Greek: Kinesis-movement) - What the
body does to the drug. (ADME Studies)

• This refers to movement of the drug in and alteration of

the drug by the body; includes absorption, distribution,
binding/localization/ storage, biotransformation and
excretion of the drug

• Eg : Paracetarnol is rapidly and almost completely absorbed

orally attaining peak blood levels at 30-60 min; 25% bound
to plasma proteins, widely and almost uniformly
distributed in the body (volume of distribution - lL/kg);
extensively
• Thus, Amoxicillin cures a strep throat, and
• Cimetidine promotes the healing of
duodenal ulcers. Pharmacology asks “How”?

• The main tasks of pharmacologists are

• Screening for desired activity,

• Determining mode of action, and

• Quantifying drug activity

 Toxicology
• Definitions
• Toxicological studies
• Dose-response correlations
• Threshold limit values
• Examples
 Hazardous
• Denotes the probability of injury or illness
from contact or use
• Industrial Hazards
– Toxicity
– Explosivity
– Ignitability
– Reactivity
 Toxicology
• Toxicology is the scientific study of adverse effects
that occur in living organisms due to chemicals. ...

• The substances that are assessed by toxicologists

includes environmental agents and chemical
compounds found in nature, as well as
pharmaceutical compounds that are synthesized for
medical use by humans.
 Toxic Substance
• Capacity of a substance to produce injury or
illness
• Acute Effects
– Short term, appear shortly after exposure. Can be
from single exposure
• Chronic Effects
– There is a latency, long period of time before you
see effect
 Three Types of Toxic Hazardous Materials
(Soures of toxicity)
• Chemical Agents (Poisons)

• Physical Agents (Dusts, fibers, heat, noise,

corrosive)

• Biological Agents (Pathogens)

1. Animals : Venom, fungi, bacteria, shellfish
toxin, fish etc.

2. Vegetables : Aconite, strychnine, Insulin

(Sugar)etc.

3. Chemicals : Drugs, HCN, Ethanol, Chloroform,

Lead, Argon etc.
 Definitions
• Toxicology is the quantitative and qualitative
study of the adverse effects of toxicants on
biological organisms

• Toxicant is a chemical or physical agent that

produces adverse effects on biological
organisms.
 So Toxicology is the study of:
• How toxicants enter the organism

• How toxicants effect the organism

• How toxicants are eliminated from (leave) the organism

All substances are toxic if taken in the wrong quantities

 How toxicants enter organism
• Inhalation (mouth or nose to lungs) then into
blood(+*)

• Ingestion (mouth to stomach) then into blood(+)

• Injection (cuts, punctures in skin) into blood

• Dermal absorption (through skin) into

blood(+*)
+ Involve membrane transport
* Greatest threats in industry
 Effects of Toxicants
Irreversible Effects
• Carcinogen - causes cancer
• Mutagen - causes chromosome damage
• Reproductive hazard - damage to reproductive
system
• Teratogen - causes birth defects
 Effects of Toxicants
May or may not be reversible
• Dermatotoxic – affects skin
• Hemotoxic – affects blood
• Hepatotoxic – affects liver
• Nephrotoxic – affects kidneys
• Neurotoxic – affects nervous system
• Pulmonotoxic – affects lungs
 Definitions
Pharmacology :The branch of medicine concerned with the
uses, effects, and modes of action of drugs
• Pharmacokinetics – the absorption, distribution, metabolism
and excretion (ADME) of chemicals through the (human)
system.
• Pharmacodynamics :is the study of how a drug affects an
organism,
• Bioaccumulation – things such as lead, mercury, PCBs, carbon
tetrachloride that build up in organs and have low excretion
rate.
 Elimination of toxins
• Excretion through kidneys, liver and lungs

• Detoxification is the biotransformation of

chemicals into something less harmful
 Toxicological Studies
• Aim:
• LD50 = Lethal dose 50 (Dose of drug at which 50 % Population
shows mortality)
• ED 50 = Effctive dose 50 (Dose of drug at which 50 %
Population shows pharmacological effect)
• To determine the therapeutic index, i.e. ratio between the
lethal dose and the pharmacologically effective dose in the
same strain and species (LD50/ED50).
• The greater the index, safer is the compound.
• The LD50 dose thus found was administered to guinea pigs,
rabbits, cats or dogs on weight basis (on basis of relative
surface area gives better results).
• To determine the absolute dose for a species
 Pharmacological testing

A. Preclinical studies ….Animal studies

B. Clinical studies ……Human studies
 A. Preclinical
Criteria for evaluation of preclinical toxicological studies
(Acute, subacute & chronic toxicity studies)

Sr. No. Acute Subacute Chronic

01 Species Species Species

Rats preferred for oral and
inhalation tests;
rabbits preferred for dermal
tests
Rodents (usually rats) preferred for Two species recommended;
oral and inhalation studies; rodent and non rodent (rats
Rabbits--- for dermal studies; & dog)
non rodents (Usually dogs)
recommended as a second
species for oral tests.

02 Age : Young adult Age : Young adult Age : Young adult

03 Number of animal :5 of 10 of each sex for rodents, 20 of each sex for rodents,
each sex (M/F) per dose 4 of each sex for non rodents 4 of each sex for non
level per dose level rodents per dose level
Sr. No. Acute Subacute Chronic

04 Dosage : Three dose levels Dosage : Three dose levels plus Dosage : Three dose levels
recommended; exposures a control group; include a toxic recommended; include a
are single doses or dose level plus toxic dose level and NOAEL;
NOAEL; exposure are 90 days exposures
fractionated doses up generally for 12 months;
to 24 hours for oral and FDA requests 24 months for
dermal studies; and 4 hour food chemicals
exposure for inhalation
studies

05 Observation period Observation period Observation period

14 days 90 days (same as treatment 12-24 months

period)
 Application of LD50
• It provides a measure of relative toxicities of chemical under
similar or identical conditions.

• Thus the major application of the LD50 is comparative,

allowing for semi quantitative toxic evaluation of compounds

• This test provides a screening method for toxic evaluation,

particularly useful for new unclassified substances.
• Dermal LD50
• Skin
• Eyes
• Mucosal surface
• Inhalation LD50
 Dose Limit Values

• EDf – Effective dose for f

percent of population.
Reversible response
• TDf – Toxic dose for f
percent of population.
Undesirable response that
is irreversible
• LDf – Lethal dose for f
percent of population.
 Definitions
• Therapeutic Margin
– TM = LD50% - ED50%
• Margin of Safety
– MOS = LD5% - ED95%
• Safety Index
– SI = LD5%/ED95%
• Therapeutic Index
– TI = LD50%/ED50%
 Relative Toxicity Classification

Classification Human Oral LD50

Extremely Toxic Taste (1 grain)
Highly Toxic 1 tsp
Moderately Toxic 1 oz
Slightly Toxic 1 pt
Practically nontoxic 1 qt
Relatively harmless > 1 qt
 Poison & Poisoning
A poison is any substance that is harmful to your body
Human poisoning could be suicidal, homicidal, stupefying
(shocking) or accidental.
Let us see each case in detail
a) Poison generally used for suicidal purpose are : potassium
cyanide, oxalic acid, hydrocyanic acid, opium, barbiturates,
organophosphorus compound & arsenic
b) Poison used for homicidal purposes are : Arsenic, antimony,
aconite, organophosphorus compounds, strychnine & Oleander
c) The poison used for stupefying purposes are: (Used to feel
properly) Dhatuta, Belladonna, Hyoscyamus, cannabis indicia
& cigarette containing arsenic.
d) Accidental poisoning commonly occurs as a result of
carelessness with the poisonous & non-poisonous material
are stored together.
A number of case of accidental poisoning have been reported from the
greater use chemicals in industry & for household purposes.

Classification of poisons:
Poisons are classified according to their mode of action. Accordingly
poisons are classified in to three main groups viz:
1) Corrosive
2) Irritants
3) Neurotics
A. Corrosive : A corrosive poison is simply a highly active irritants
& not only produce irritation but also acute ulceration of tissue
Eg: a) Strong acid like sulphuric acid, nitric acid, hydrochloric acid
b) Organic acid like oxalic acid, carbolic acid
c) Conc. Alkalies like caustic soda, caustic potash & carbonates of
sodium, calcium & potassium.
2. Irritants: Irritants poisons produce symptom of pain in the
abdomen, vomiting & purging.
Corrosive in dilute solutions acts as irritants, example of irritant
are:
a) Inorganic: Non – metallic & metallic compounds
The non metallic poison are phosphorus, chlorine, bromine, iodine
& boron .
The metallic poisons consist of arsenic , antimony, mercury, silver,
iron, copper, bismuth lead.
b) Organic : The organic poison can be divided in to two types;
i) VEGETABLE poison &
ii) Animal poisons
Vegetable Poison Animal poison
Castor oil, castor seeds, croton oil,, colocynth, snakes, venom, scopions
ergot, marking nut & aloes venom & poisononous insect .

c) Mechanical : This group include powdered glass, chopped

hair, sponge & diamond dust
3. Neuroleptics : These poisons primarily act on the CNS. The chief
symptoms of this type of poisoning includes hedache, drowsiness,
gidiness, delirium, stupor, coma & sometimes paralysis
The poisons in this group are classified as:

a) Poisons having specific action on cerebrum :

These poison may have a somniferous, inebriant or deliriant effect.

The somniferous poison include opium & its alkaloids.

The inebriant (intoxication) include alcohol, anasthetics, (ether,

chloroform) sedative & hypnotics (Chloral hydrate &
barbiturates) & insecticides (organophosphorus compound,
coal tar insecticide & naphthalene)

The deliriant (hallucinogen) ones include dhatura, belladona, &

cocaine.
b) Poisons acting peripherally: The poison acting on peripheral
nerves include conium & curare
C) Poisons acting on specifically spinal cord : This category include
nux vomica, & its alkaloids & gelsemium
Poisoning in the living could be divided in to:
a) Acute poisoning : Symptoms appear suddenly soon after
consumption of poison. The symptoms rapidly increases in
severity & are followed by death or recovery.
Poison can be detected in the ingested food, medicine of fluid or
vomit, urine or stool of the victim

C) Chronic poisoning : Symptoms develop more gradually. There is

an aggrevations of symptoms after the suspected food , medicines
or fluid is administered.
There is remission or even complete disappearance of symptoms
on the removal of patient from his usual surroundings.
The main symptoms in chronic poisoning are usually malaise,
chronic ill health & increasing cachexia (condition of abnormal
low body weight, weakness & general bodily decline).
Repeated attack of undiagnosed gastrointestinal irritation
should arouse suspicion of homicidal poisoning.
General Treatment of Poisoning

The main aim of treatment is to help the patient to stay alive

by attention to respiration & circulation while he is encouraged
to get rid of his by metabolism or excretion.

The step involved in treatment of a case of poisoning are:

1) Removal of unabsorbed poison from the system
2) Use of antidote
3) Elimination of absorbed poison
4) Treatment of general symptoms &
5) Maintenance of the patients general condition
1. Removal of the unabsorbed poison from the system
a) For inhaled poisons: When a poison like carbon monoxide are or
a gas from septic tank is inhaled by patient,
*he must be immediately removed to fresh air.
*Artificial respiration must be given

b) For injected poisons: If a poison has been injected torniquets

must be applied proximal to the point of application. Unabsorbed
poison can be removed by means of incision & suction.

c) Contact poison : If poison is split & sprayed on skin,eye, or

wound,or be inserted to vagina , rectum or bladder ,
It must be washed with plain water.
If specific antidote is known, it can be neutralised with it.

d) Ingested poison : The most important thing is to remove the

ingested poison . It can be through about by vomiting &/or by
washing the stomach (Gastric lavage)
Emetics can be used to bring about vomiting .
Simple means; such as copious draughts of warm water,
Mustard powder (2-3 teaspoonful) or
Salt (3 level teaspoonful) in a glass full of water can be used.
Ipecac 1-2 g or sulphate 1-2 g in 200 ml of water or
Ammonium carbonate 1-2 g dissolved in water can also be used.
Apomorphine in dose of 6 mg given subcutaneously causes prompt
vomiting.
It must not be used frequently as it is a respiratory depressant.

Vomiting is contraindicated in cases of acid or alkali

poisoning as it may cause rupture of the stomach in cases of coma
as in this case there is a risk of the poisoning entering the bronchial
tree.
Gastric lavage is the best method for it can be undertaken about 4 to
6 hrs after the ingestion of poison.
 GASTRIC LAVAGE : The method to perform this is : the
patient should be prone or semiprone on his side with hips
higher than his head, as this will aid respiratory drainage . The
stomach tube must be passed inside though the mouth.

After checking that the tube is not in the trachea, most of the stomach content
should be removed first by mechanical suction if available.

After this first washing of the stomach is done with warm

water. The process is repeated either with warm water or the
antidote until the returning fluid clear

When the poison has been removed , some of the

antidote or either suitable solution may be left in the stomach.
(The useful solutions for this purpose are magnesium sulphate or sodium sulphate to
ensure purgation of any poison that has passed the intestine activated charcoal to
absorb alkaloid & liquid paraffin as a demulcent fluid)
Antidote :
An antidote is a substance that can counteract a form of

poisoning.

Antidote are classified as:

1) Mechanical

2) Chemical

3) Systemic
1) Mechanical antidote : These are the substance which hinder the
absorption of poison by their mere presence
Eg: a) Fats, oils, egg, albumin.
These act by forming coat cover over mucous membrane of stomach
b) Charcoal is specifically useful in absorbing alkaloidal poisons

2) Chemical antidote : These substance react with poison to form non –

toxic substances Eg:
a) Magnessium oxide calcium oxide neutralizes acids.
b) Tannis forms insoluble complexes with most of the alkaloids.

3) Systemic antidote: They produce the action which are opposite to

that of poison
Eg: Chloroform for strychnine
Caffeine for morphine etc.

*Demerits : The antagonism is not always complete & the remedy

may itself produce most undesirable effect.
Certain chelating agents are widely used as specific antidotes against
some heavy metals.
These compound forms stable, soluble non toxic complexes with
heavy metals.
Eg: BAL, EDTA & Versenate (Calcium diethyl tetra acetate) for
arsenic EDTA &
Versenate for mercury & lead ,
N-penicillamine for lead, mercury & copper &
desferroxamine – B (D-F- M)- for iron.
BAL : (Dimercaprol): (British Anti-lewisite)
Most of the enzyme in the body have –SH groups, which are essential for
their activity.

Many heavy metals like arsenic & mercury have great affinity for these
groups.
Thus, after combining with these –SH groups these compounds reactivate
them.

BAL has many-SH groups, which combine with these heavy metals.
 Leaving the –SH group of enzyme of body free.

The compound formed by the heavy metal & the di-thiol, dimercaprol
is relatively stable & is excreted without causing damage to the
excreting mechanism (Kidney, liver etc.)
BAL is given IM as 5 % solution in arachis oil with benzyl benzoate.

In severe poisoning a dose of 3mg/kg is administered at 4 hourly

interval for the first 2 days , at 6 hourly intervals there after for
about 10 days.
Sodium calcium EDTA: It has great affinity for lead.
Therefore, it is now used in poisoning caused by inorganic lead &
tetraethyl lead.
Short causes of treatment are advised in order to minimize the danger of
depleting the body of metallic ions essential for metabolism. The usual
dose is 1g twice daily for periods up to 5days. After an interval of 2
days this course of treatment may be repeated.
EDTA can also be used in poisoning by arsenic & mercury
Universal antidote:
It is used as an antidote in cases of where the nature of the poison
is not known or a combination of poison are administered.
It consist of

Sr.No Ingredient Quantity Uses

1 Powdered charcoal 2 parts Adsorb alkaloids
2 Magnessium oxide 1 parts Neutralises acids
3 Tannic acid 1 parts Precipitates alkaloids

The mixture is administered in the doses of

tablespoonful , repeated once or twice.
5) Elimination of absorbed poison: Elimination by catharsis
(removal) may be encouraged.
A) Forced diuresis
B) Peritoneal dialysis
C) Hemodialysis

 A) Forced diuresis using IV (Intravenously)

 Chlorthiazides or mannitol infusion is useful in

Barbiturate poisoning.

 B) Peritoneal dialysis (Peritoneal dialysis (PD) is a treatment

that uses the lining of your abdomen (belly area), called
your peritoneum, and a cleaning solution called dialysate to
clean your blood. Dialysate )

 is useful in salicylate poisoning.

C) Haemodyalysis (Haemodialysis is a way of cleansing the blood
of toxins, extra salt and fluids through a dialysis machine)

has been employed for removing barbitutes, boric acid, bromides,

glutethimide, salicylates etc.

6) Treatment of general symptoms: Morphine (Centrally acting

analgesic, opioid analgesic, steroidal antinflamatory drug) should
be given for pain,
Oxygen for respiratory failure,
Cardiac stimulant failing particular symptomatic effect of the poison.

7) Maintenance of patients general condition: The patient should

be kept warm & comfortable. In cases of poisoning especially in
elderly (Geriatric) patient there is a possibility of upper respiratory
tract infections. To avoid this prophylactic administration of
antibiotics in all cases is desirable.
Thank you.