*
Jan 3, 2010

Pharmaceutical products

Antacids

Analgesics

Depressants

Stimulants

Antibacterials

Antivirals

Drug action (HL)

Drug design (HL)

Mind altering
drugs (HL)
1
*
*
Jan 3, 2010
A substance that alters one or more
of the following:

Incoming sensory sensations

Mood or emotions

Physiological state

Consciousness

Activity level

Co-ordination
2
*

Infection fighters




Affecting metabolism



Hormones
Vitamins
Affecting central nervous system



Jan 3, 2010
Antiseptics
Antibiotics
Antivirals

Stimulants
Depressants
Analgesics
3
Anaesthetics
*
Jan 3, 2010

Inert substance but effective

Used as control substance

Power of suggestion

Body’s natural healing
4
*Placebo effect:
*A pharmacologically inert substance (often a
sugar pill) produces a significant reaction
because the patient expects, desires, or was told
it would happen
*Used as a control in clinical trials
*Highlights the body’s natural healing powers
*Research and Development:
*Development of a new drug is a very costly, lengthy process
controlled by the government:
*In 1970, 3620 drugs were tested.
16 came
on the market at an average cost of $20
million
*Only 1 in 2000 drugs eventually make it to
the market
*Phase I: Initial clinical trials on volunteers
after the drug has proven safe when given to
animals
*Phase II: Thorough clinical investigation to
eliminate investigator bias
*Phase III: Extended clinical evaluation
•Early 1960’s given to
pregnant women to
treat morning sickness
•Later found to cause
major birth defects
•One isomer controls
morning sickness, the other
leads to birth defects
(optical isomers)
*
*
*
Tests on animals
*
Clinical trial (phase 1)
*
Clinical trial (phase 2)
*
Clinical trial (phase 3)
*
*
*
Jan 3, 2010
Dose, side effects
Safety, dose range
Response, investigator bias, statistics
Extended evaluation
> 16/3620 medicines into the market in 1970
> Thalidomide: for morning sickness but deformed
babies
8
*

Oral
convenient, absorbed at small intestines

*

Rectal
when not able from mouth or destroyed by
acids
Inhalation
rapid, anaesthesia

Parenteral / Injection



Jan 3, 2010
Subcutaneous (dental, slow)
Intramuscular (vaccinations, large V)
Intravenous (fast, practical)
9
*
*
= the dose of a substance in mg per Kg of body
mass, that kills 50% of sample
*
*
*
The smaller the LD50,
the more toxic the substance
Examples:
aspirin
*
*
Jan 3, 2010
10
rat: 200
rabbit: 1000
nicotine
rat: 50
ethanol
rat: 9000
*
*
= the dose of a substance in mg per Kg of body
mass, that is effective to 50% of sample
*
*
*
*
Jan 3, 2010
The smaller the ED50,
the more effective the substance
Examples:
aspirin
11
55
*
*
= the ratio of LD50 over ED50
*
*
*
Examples:
The wider the window,
the safer the substance
aspirin
therapeutic window = 200/55
*
Jan 3, 2010
12
*

Main effect (desired)

Side effects (unwanted responses)
*
*
*
*
Jan 3, 2010
Drug effects are relative!!
Morphine:
For pain relief, constipation is side effect
For diarrhoea, pain relief is side effect
13
*
*

Increase of hazards (larger amounts)

No tolerance to side effects

Jan 3, 2010
Over time and with regular use, the
user requires larger dose of the drug to
achieve the effect originally obtained
by smaller dose
If drug not taken for long time >
decrease of tolerance >
overdose
14
And now a short
presentation of the rest of
the topics of this option...
Jan 3, 2010
15
*
Jan 3, 2010

Why is stomach acidic?

How can we neutralize it?

What are the most common antacids?

What are the neutralizing reactions?

With what can the antacids be combined?
16
*

What are soft and strong analgesics?

How do they prevent pain?

Aspirin versus paracetamol?

Jan 3, 2010
Morphine versus heroin/codeine?
Advantages – disadvantages?
17
*
Jan 3, 2010

What is their effect?

How is effect dependant on dose?

Tranquilizers

Sedatives

Hypnotics

Anaesthetics

Ethanol (effects, detection)

Most common depressants?
18
*

What is their effect?

Adrenaline versus amphetamines

Nicotine

Jan 3, 2010

Short-term effects

Long-term effects
Caffeine

Effects

Comparison to nicotine
19
*
Jan 3, 2010

The discovery of penicillin

How penicillin works

Modifications of penicillin

Use and overprescription

Broad versus narrow spectrum antibiotics
20
*
Jan 3, 2010

Viruses versus bacteria

How do antiviral drugs work?

What is HIV and what AIDS?

Why is it difficult to fight HIV?

(AIDS prevention methods?)
21
*






Jan 3, 2010
Geometrical isomers can have different
pharmacological effects
Examples: CISplatin – Thalidomide
Optical isomers can have different
pharmacological effects
Examples: Thalidomide
How structural features affect the
pharmacological effect
Examples: Penicillin, heroin
22
*
Jan 3, 2010

Compound library

Combinatorial and parallel chemistry

Computer aided drug design

Polarity modification

Chirality modification
23
*
Jan 3, 2010

LSD, Mescaline, Psilocybin, THC

Effects similarities, differences

Legalization of cannabis
24
D.3 Analgesics
What is pain?

An unpleasant sensory and emotional
experience associated with actual or
potential tissue damage.
What are pain receptors and their functions.
 Pain
receptors in our bodies are nerves
that transmit pain. These are free nerve
endings located in various body tissues
that respond to thermal, mechanical and
chemical stimuli.
 When stimulated, these pain receptors
generate an impulse. The pain results of
various impulses arriving at the spinal cord
and the brain.
 When tissues become injured, they
release chemicals called prostaglandins
and leukotrienes that make the pain
Definition of analgesics and categories
 Analgesics
are drugs that relieve pain.
These are:
 Mild analgesics: used for relief of mild
pain.
(aspirin, acetaminophen)
 Strong analgesics: used for relief of vary
severe pain.(morphine, heroin, codeine)
 Local anesthetics: used as pain killers in
localized areas.(lidocaine, procaine)
Mild analgesics

They work by blocking the enzymecontrolled synthesis of prostaglandins.
The main effects prostaglandins are:
The constriction of blood vessels, which
helps increase the body temperature.
Direct effect on the body’s heat regulating
centre, hypothalamus, which produces
fever.

Natural painkillers
 They
are produced naturally in the body.
 Endorphins and enkephalins are the
natural opiates found in the part of the
brain and the spinal cord that transmit pain
impulses. They are able to bind to neuroreceptors in the brain and produce relief
from pain.
 The temporary loss of pain immediately
after an injury is associated with the
production of these chemicals.
Salicylic acid-Aspirin





Salicylic acid was widely used as a fever reducer
However, it is relatively strong acid so it was unpleasant
to take orally and it damaged the membranes lining the
mouth, esophagus and stomach.
Sodium salicylate (its salt) was used but it was also
highly irritating to the stomach.
Its ester called Acetyl Salicylic Acid (ASA) named
aspirin retains the beneficial properties of salicylic acid
but is less irritating to the stomach.
ASA is relatively tasteless so it can be taken orally.
Uses of derivatives of salicylic acid
mild analgesic for minor aches and
pains.
 As an antipyretic.
 As an anti-inflammatory agent when
there is swelling from injuries.
 As an anti-clotting agent in the
prevention of abnormal blood clotting and
as an anti clotting agent after heart
 As
Disadvantages of Aspirin
Aspirin can cause stomach upset and internal bleeding
due to its acidic nature.
 There is a risk of developing severe gastrointestinal
bleeding following use of alcohol.
 0,5% are allergic to aspirin leading to skin rashes,
respiratory difficulty and even shock
 Aspirin is one of the most frequent causes of accidental
poisoning in infants.
 The taking of aspirin by children under twelve has been
linked to Reye’s disease (a fatal liver and brain disorder
with the symptoms of vomiting, lethargy, irritability and
confusion.)

Aspirin substitutes (Acetaminophen)
Acetaminophen is the metabolic byproduct of
phenacetin and is active ingredient of many over-thecounter drugs (OTC)
 It is like aspirin as it is an anti-pyretic.
 It is an analgesic to reduce mild pain.
 It does not upset the stomach or cause bleeding.
 It is not an effective anti inflammatory drug.
 It is a safe drug when it is used in the correct dose BUT
can rarely cause side effect such as blood disorders and
kidney damage.
 In great dose (>20 tablets) can cause serious liver
damage, brain damage, coma and even death.

Phenacetin
Aspirin substitutes(Ibuprofen)
 Ibuprofen
has many of the same effects as
aspirin but seems to cause fewer stomach
problems.
 It is an anti-inflammatory drug.
 It is effective in low doses and has a wide
margin of safety.
 In great dose has similar side effects as
ASA.
Strong analgesics
They temporarily bind to the opiate
receptor sites in the brain preventing
the transition of pain impulses
-The opium alkaloids:
Opiate: it is a natural or synthetic drug that
exerts actions on the body similar to those
induced by morphine.
Narcotic: is a term generally used for drugs
that have both a narcotic and analgesic
morphine, heroin and codeine
 Morphine
is the principal alkaloid and
makes up about 10% by mass of raw
opium.
 Codeine makes up about 0.5% by mass
of raw opium.
 Heroin is usually synthesized from
morphine and thus is a semi-synthetic
drug and it is obtained by relatively simple
structural modification of morphine or
Opium plant
Morphine
Advantages and disadvantages of
opiates.
Pharmacological effects:
Opiates exert major effects on:



The central nervous system.
The eye
The gastrointestinal tract (the digestive system)
The prime medical uses of opiates are:
As strong analgesic in the relief of severe pain caused
by injury and chronic disease.
 In the treatment of diarrhea by producing a
constipating effect.
 To relieve coughing by suppressing the “cough centre”
situated in the brain system.

Advantages and disadvantages of
opiates.
Physiological effects of opiates:
Opiate produce:
 Analgesia
 Drowsiness
 Mood changes
 Medical clouding
Some individuals experience:
Tolerance
 Tolerance
appears due to the induction of
drug metabolizing enzymes in the liver
and also to the adaptation of neurons in
the brain to the presence of the drug.
 The users that became tolerant to one
opiate will also exhibit a tolerance to all
other opiates.
Dependence

Physical dependence is the state in which people
do not function properly without a drug.
Symptoms:
 Restlessness
 Sweating
 Fever
 Chills
 Vomiting
 Increase rate of respiration
 Cramping
 Diarrhea
 Unbearable aches
Dependence
Depends on:
 The dose
 Frequency of drug administration
 The duration of the drug dependence
 The opiate used
The opiates (in general)
 They
are extremely potent and valuable
drugs for the treatment of pain
 They have the capacity of inducing a state
of euphoria and relief from
physiological pain
 The opiates induce profound tolerance
and physiological dependence
 They are important both medically and
sociologically as the user is difficult to treat
and must frequently resort to crime to
support the habit and reach a source of
Summary of the effects of opiates
Short term effects
 Sedation and
stupor
 Euphoria
 Reduced tension,
worry and fear
 Reduced coughing
reflex
 Occasional death
from overdose





Long term effects
Loss of appetite
Sterility
Withdrawal illness,
loss of job, crime
Diversion of energy
and money
Risk of dangerous
infections due to
shared needles.
D4: Depressants
Jan 3, 2010
What are the depressants?
Substances that calm and relax (depress)
the central nervous system by interfering
with nerve impulse transmission.




Jan 3, 2010
They slow down brain activity
They slow down heart activity
They reduce breathing rate
They dull emotional responses
51
What are the
anti-depressants?
Depressants are also called antidepressants because they
relive depression.
Jan 3, 2010
52
Categories of doses

Low doses


Moderate doses




Little or no effect
Sedation
Soothing
Reduction of anxiety
High doses
– Sleep

Extremely high doses


Jan 3, 2010
Comma
Death
53
Tranquilizers



Jan 3, 2010
Mild action
Relieve anxiety and tension
Ethanol & Valium
54
Sedatives



Jan 3, 2010
Soothing of distress
Not producing sleep at normal
doses
Barbiturates
55
Use and abuse of ethanol
Doses




Jan 3, 2010
30-50mg /100ml of blood
Euphoria
100mg / 100ml of blood
Slurred speech, staggering,
aggressive behavior
200mg / 100ml of blood
Difficult movement and vision
400mg / 100ml of blood
Comma, death
56
Use and abuse of ethanol
Social effects
Sickness, death
- Cost of treatment
- Lost productivity




Jan 3, 2010
Violent crimes
Car accidents
Alcoholism, family problems
57
Use and abuse of ethanol
Physiological effects

Jan 3, 2010
Short-term effects
euphoria
sociability
relaxation
decreased inhibitions
loss of judgement
impairment of perception/memory
increased reaction time
violent behavior
dizziness
loss of balance
58
nausea, vomitting
Use and abuse of ethanol
Physiological effects

Long-term effects
cirrhosis of liver
liver cancer
coronary heart disease
high blood pressure
strokes
gastritis
peptic ulcers
anxiety/depression
fetal abnormalities
physical dependence/tolerance
Jan 3, 2010
59
Use and abuse of ethanol
Synergistic effects
Jan 3, 2010

Alcohol + aspirin
risk of stomach bleeding

Alcohol + sedatives
heavy sedation
comma, death

Alcohol + cocaine
high blood pressure
irregular heart beat
60
Detection of ethanol
Breathalyzer






Jan 3, 2010
Road-side test
Ethanol in breath
Oxidation of ethanol to ethanoic
acid
Use of acidified K2Cr2O7
Orange to green color
Transfer of electrons > current >
voltage measured
61
Jan 3, 2010
62
Detection of ethanol
Chromatography (GLC)






Jan 3, 2010
Ethanol in breath, blood and urine
Inert gas through liquid or solid
Compounds separated by b.p.
Different retention times recorded
Amount = area under peak
Other drugs can be detected, too
63
Jan 3, 2010
64
Jan 3, 2010
65
Detection of ethanol
Intoximeter
(infra-red spectroscopy)
Ethanol in breath
 Transmittance versus wavenumber
=IR spectrum
 Characteristic peak of -OH @
3340cm-1
 Comparison of sample and reference
 Amount = size of peak

Jan 3, 2010
66
Jan 3, 2010
67
Other depressants
Diazepan (Valium)

Jan 3, 2010
Sedative
68
Other depressants
Nitrazepan (Mogadon)

Jan 3, 2010
Sleeping pill
69
Other depressants
Fluoxetin hydrochloride (Prozac)


Jan 3, 2010
Anti-depressant
Amine+HCl=hydrochloride:
water soluble
70
Comparison
Jan 3, 2010
71
D.5 STIMULANTS
Stimulants are drugs that
> stimulate the brain and the central
nervous system
> increase the state of mental alertness
> decrease appetite
A) Amphetamines
B) Caffeine
C) Nicotine
Adrenaline (epinephrine)
is a natural stimulant produced in the
adrenal gland.
> it is released when in stress or fear
> it controls
- heart/breathing rate
- pupil dilation
- sweating
AMPHETAMINES
•
•
Amphetamines are chemically related to adrenaline.
They both derive from phenylethylamine.
They are sympathomimetic drugs which mimic the
effect of stimulation on the nervous system by increasing
the levels of dopamine.
•
Amphetamines were initially used to treat narcolepsy and in
WW II were used by soldiers to combat fatigue.
• Later during the 50’s and 60’s they were used as slimming
pills.
• Regular use can lead to both tolerance & dependence.
•
Short-term effects:
- increase in heart rate and breathing
- insomnia
- dilation of the pupils
- decrease in appetite
- possible fatigue and depression
•
Long-term effects:
- weight loss
- constipation
- emotional instability
- dependence
•
Phenylethylamine
(love molecule)
- “high” feeling of lovers
- also found in chocolate
Dopamine
Transmits to neurons
signals of
- joy
- happiness
- excitement
Amphetamine
- stimulant
- suppresses appetite
- treats narcolepsy and attention deficit
hyperactivity disorder (ADHD)
Methamphetamine (“speed”)
- potent stimulant
- very addictive
- severe withdrawal symptoms
- “meth mouth”
Ecstasy
- potent stimulant
- designer drug
- can be fatal
- neurotoxic
CAFFEINE
•
It is the most widely used stimulant in the world.
It is present in coffee, tea, chocolate and cola drinks and
is also found in some pain killers or other medicines.
•
People that consuming 400 mg of caffeine a day may
have dependence & physical side effects.
•
Like nicotine, morphine, codeine and cocaine, caffeine is
also an alkaloid.
•
Alkaloids are nitrogen-containing compounds of plant
origin containing heterocyclic rings and a tertiary amine
group.
•
Theobromine has a similar structure to caffeine, which is
also found in chocolate. (It does not contain bromine!)
•
caffeine
theobromine
Effects at low doses:
- respiratory stimulant
- weak diuretic
- enhances concentration and alertness
- reduces migraines (constriction of blood vessels)
•
Effects at high doses:
- anxiety
- irritability
- sleeplessness
•
NICOTINE
One third of the world’s population is addicted to
smoking because tobacco contains nicotine
•
Nicotine produces psychological and/or physical
dependence
•
•
Nicotine builds up tolerance
Stopping smoking can produce temporary symptoms
like a craving for tobacco, nausea, weight gain, insomnia,
irritability and depression
•
Short-term effects:
- stimulates nervous system
- increases heart rate and blood pressure
- increases concentration
- constricts blood vessels
- stresses heart
- reduces urine output
•
Long-term effects:
- increases risk of heart disease coronary thrombosis
- inhibits ability of blood to carry oxygen (CO)
- excess acidity > peptic ulcers
- mouth/lung cancer
- adverse effects on pregnancy
Both compounds are heterocyclic with one or
more carbon atoms in the ring replaced by
nitrogen atoms.
They both contain a tertiary amine group
caffeine
nicotine
D.6 Antibacterials
Antibacterials/Antibiotics
= Drugs that prevent the growth of, or kill, microorganisms that cause
infectious diseases.
These drugs are selective, they are ineffective against normal body
cells.
Microorganisms = single celled life forms capable of independent life if
given a required amount of nutrients.
Infectious diseases = Occur when the body’s natural defenses are
ineffective due to 1) lack of natural immune system against infection.
2) too many microorganisms for the body’s immune
system to overcome.
3) rapid growth of the microorganisms.
Infectious Agents
There are two types of infectious agents:
•
Bacteria
•
Viruses
Antibiotics are ineffective against viruses since they incapable of combating
normal body cells.
Antibiotics aid white blood cells by
1. Preventing bacteria from multiplying
2. Preventing cell division (bacteriostatic drugs)
3. Directly killing Bacteria (bacteriocidal drugs)
Examples of bacterial infections: tetanus, tuberculosis (TB), cholera, etc.
Examples of Viral infections: influenza, common cold, hepatitis, etc.
History of Penicillins
1890s: Found out that certain fungi
killed bacteria.
1928: Alexander Fleming finds out
that the mold penicillium notatum
prevented the growth of the bacteria
staphylococcus aureus.
1940: Florey and Chain used
penicillin on mice.
1941: Penicillin used for the first time
on a human being.
1943: Penicillin available clinically.
1945: Fleming, Florey and Chain
receive Nobel prize.
Alexander Fleming, a
bacteriologist
Florey and Chain
renewed Fleming’s
research
Structure of Penicillin
Penicillin G (first penicillin used): deactivated
by 1) stomach acid
injected into body.
2) Penicillinase, an enzyme created by
bacteria
Penicillin V: acid resistant penicillin created
by modifying side chains.
Active penicillin: Aminopenicillanic acid, 6
APA, (common in all penicillins) and a
sidechain:
• C6H5-CH2: benzyl penicillin or penicillin G
• C6H5-CH2-CH2-:penicillin V
• Cloxacillin, effective against pencillinase
and acid.
Penicillin G
Spectrum of Antibiotics
Broad spectrum antibiotics = one that is effective against a wide variety of
bacteria. Examples:
• Ampicillin
• Tetracyclines such as Aureomycin and Terramycin. ‘Mycin’ is the suffix
used for antibiotics obtained from soil fungi.
Repeated use:
1) wipes out harmless bacteria
2) wipes out helpful bacteria such as those in the Oesophagus, stomach and
large intestines.
3) destroyed bacteria may be replaced by harmful ones.
Narrow spectrum Antibiotics
= the antibiotics effective against only certain types of bacteria.
Most penicillins (and sulfa drugs) are narrow spectrum
antibiotics.
Treatment of infection:
Ideally bacterium should be identified before prescribing
antibiotic. But this takes time so first a broad spectrum antibiotic
is given and then a narrow spectrum one.
Bacteriocidal Drugs
Bacteria have cell walls mainly composed by polysaccharides that protects
their cell structure and inside components. These cell walls are strong due
to the chemical cross-links.
How does it work?:
1. Penicillins interfere with cell wall construction of bacteria.
2. The cross links are destroyed, hence weakening the cell walls.
3. Bacteria is unable to hold its size and shape.
4. Water enters by osmosis, the cell expands and bursts
5. Bacteria is killed by this.
Bacterial cell walls
Disadvantages of Penicillin Use
1. Small percentage of the population (10%) experience allergic reactions and
other side effects such as body rash.
2. If used repeatedly, it may wipe out harmless or helpful bacteria. In addition
these bacteria that are wiped out may be replaced by harmful bacteria.
3. Genetic resistance of bacteria. If antibiotics are used extensively some
bacteria survive and pass on their immunity to next generations. Such
examples are Typhoid, Gonorrhoea and Malaria.
A microorganism may become resistant as a result of mutation. A mutated
bacteria may produce an enzyme that makes antibiotics ineffective.
Result of these mutations: Need for constant renewal of antibiotics.
Hence, antibiotics should only be used when no other treatment is effective.
Use of Antibiotics
Antibiotics are used to control animal diseases and to increase the rate of
their growth (increase production).
This is done by adding antibiotics to the animal feedstock which can
contain animal pathogens which are dangerous to animals and humans.
As before mentioned, if bacteria are extensively exposed to antibiotics they
can develop an immune system that allows them to spread and reproduce
quickly. Such are Salmonella and E.Colli that are not killed in animal
feedstock
Hence, is it wise to use routine addition of antibiotics to animal livestock?
D.7
Antivirals
What is HIV?
• Human Immunodeficiency
Virus. HIV attacks the immune
system - the part of our body
that protects us from infections
and illnesses. It takes about 3 6 months for HIV to appear
after infection.
What is AIDS?
• AIDS, the Acquired Immune Deficiency,
is a disease caused by HIV. Once
infected with HIV, it typically takes 10
years to develop AIDS (although in
some, this time may be shorter).
People with AIDS cannot fight common
diseases, and therefore become very ill
and die. A person can be infected with
HIV and not have AIDS.
HIV/AIDS Infection:
How do you get it?
• Unprotected sexual intercourse anal,vaginal, oral
• Sharing drug needles and syringes
• Sharing unsanitary piercing
instruments
• From mother to child
• Blood contact
HIV is NOT spread via…
• Kissing
• Biting
• Blood sucking insects
Who can get HIV?
• ANYONE…Man, Woman, Gay,
Straight, Christian, Jew, Black,
White, Asian, Latino, Canadian,
Young, Old …ANYONE.
»That includes you!
Can I tell if my partner is
sick?
• People who are infected can
have the virus in their body for
years before getting sick.
During this time, they look and
feel healthy. If they have sex
with anyone, there is the
chance that they will spread the
virus to their sex partner.
The College Facts
• One in every 500 American college
students is infected with HIV
• The rate of HIV infection in the general
American population is one in 250
• 4 factors that put college students at
increasing risk: peer pressure, lack of
maturity, increase in alcohol/drug use,
and growing incidence of date rape