Option D –
Medicine and Drugs
IB Chemistry
Outline of this option
Pharmaceutical products ( definitions, categories,
placebo effect, body's defenses, research,
Thalidomide, administration of drugs, toxicity,
tolerance)
Antacids
Analgesics ( mild - aspirin, acetaminophen,
ibuprofen
strong (opiates) - morphine, codeine, heroin)
Depressants ( tranquilizers - alcohol, "other")
Stimulants (adrenaline (epinephrine)
amphetamines - ecstasy, pheylethylamine,
dopamine, "speed")
Antibacterials (penicillin)
Antivirals (AIDS)
What is a medicine or drug?
·
A substance that alters one or
more of the following:
·Incoming sensory sensations
·Mood or emotions
·Physiological state
·Consciousness
·Activity level
·Co-ordination
D.1 Pharmaceutical Products
A drug or medicine is any chemical
which:
Alters sensory sensations
Alters mood or emotions
Alters physiological state
(consciousness, activity level, or
coordination)
Drugs: chemicals that affect how
the body works. Used to describe
substances both legal and illegal.
Medicines: substances that
improve health. Can be natural or
synthetic. The beneficial effects of
medicines are known as the
therapeutic effect.
Categories of medicines
·Infection fighters
·Antiseptics
·Antibiotics
·Antivirals
·Affecting metabolism
·Hormones
·Vitamins
·Affecting central nervous system
·Stimulants
·Depressants
·Analgesics
·Anaesthetics
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 and power of suggestion
·
Body’s Lines of Defense
First line defense:
·Skin, mucous membranes, closures and
secretions (lips, eyelids, ear wax, etc.)
·Second line defense:
·White blood cells, blood clotting,
inflammatory response
·Third line defense:
·Antibodies, memory cells
·
Research on new products
1. Tests on animals
·Dose, side effects
·2. Clinical trial (phase 1)
·Safety, dose range
·3. Clinical trial (phase 2)
·Response, investigator bias, statistics
·4. Clinical trial (phase 3)
·Extended evaluation
·
D.1.2 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
Thalidomide
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
isomer)
Administration of drugs
Oral
·convenient, effect varies because absorption is
affected by stomach content and drug
concentration
·absorbed at small intestines
·Rectal
·Effective if a drug cannot be taken orally or if a
drug is pH sensitive
·when not able by mouth or destroyed by acids
·Inhalation
·rapid due to extensive network of blood
vessels in lungs
·anaesthesia
·Parenteral / Injection
·Subcutaneous (dental, slow)
·Intramuscular (vaccinations, large V)
·Intravenous (fast, practical)
·
·Parenteral
(injection)
·Subcutaneous
·Beneath the skin
·Slow absorption
·Intra-muscular
·Used when immediate
response is not required
·Used for large volumes of
drug injection
·Intravenous
·Near instantaneous effect
·Concentration not affected
by stomach content
·More
about drugs
·Fat-soluble drugs are more easily
absorbed, since blood vessels
contain a fatty layer
·Capillaries of brain are denser and
prevent diffusion of many
substances into the brain (bloodbrain barrier)
·Drugs are broken down by the
kidneys and liver
·Half-life is the time required for half
of the drug to be eliminated
·Toxicity
·LD50 is the dose (in mg of substance per kg of
body mass) that is lethal to 50% of laboratory
animals
·The lower the LD50, the more toxic the
substance
·Lowest LD50 rating known as of yet: botulism
toxin (BoTox) – most toxic substance known
LD50 of roughly 0.005-0.05 µg/kg
·ED50 – the effective dose where 50% of the
population shows a noticeable effect.
Examples: aspirin 55
The smaller the ED50,
the more effective the
substance
Examples:
aspirin
nicotine
ethanol
(mg/kg)
rat: 200
rabbit: 1000
rat: 50
rat: 9000
Therapeutic window
= the ratio of LD50 over ED50
The wider the window, the safer the substance
Examples:
aspirin therapeutic window = 200/55
D.1.4 Terms to Know
Therapeutic window: physiological effects that
are intended when prescribed. It is also the
concentration in the blood where the drug
becomes effective but below the level where it
would be toxic.
·
·Side effects: physiological effects which are
not intended. They can vary greatly from drug
to drug.
·Tolerance: what occurs when a drug
becomes less effective over time. Higher
doses are then needed to have the desired
effect.
Drug effect
Main effect (desired)
·Side effects (unwanted responses)
·
·Drug effects are relative!!
·Morphine:
·For pain relief, constipation is side
effect
·For diarrhoea, pain relief is side effect
Tolerance and Dependence
Drugs may result in physical or psychological dependence
Tolerance means that over time, an
individual requires an increased amount
of the drug to achieve the same
physiological effect
ANTACIDS
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?
·
D.2 Antacids
Bases (metal oxides, metal hydroxides,
metal carbonates, or metal hydrogen
carbonates) that react with excess stomach
acid to adjust pH
·
·Often combined with alginates and antifoaming agents to prevent reflux
·Consumption of too much antacid results in
alkalosis (basic stomach)
·Stomach acid (gastric juice) is secreted
from gastric glands which line the stomach.
The acid (HCl) helps suppress growth of
harmful bacteria and aids in digestion by
creating a better environment for certain
enzymes to work.
The following antacids produce a salt, water
and carbon dioxide. This can lead to bloating
and flatulence.
·
·Anti-foaming agents (e.g. dimethicone) are
added to help reduce this.
CaCO3(s)+ 2HCl(aq)-->H2O(l) +CO2(g) +CaCl2 (aq)
NaHCO3(s) +HCl(aq) -->H2O(l) + CO2(g) +NaCl (aq)
·Some antacids also contain alginates. They
float on top of the stomach contents, creating
a barrier, preventing reflux into the
esophagus.
Neutralization Reactions
Aluminum hydroxide and magnesium
hydroxide react with the acid to produce a
salt and water.
·Reactions:
·Al(OH)3(s) + 3 HCl(aq) -->AlCl3(aq) + 3H2O(l)
·
·Mg(OH)2(s) + 2 HCl(aq) -->MgCl2(aq) + 2H2O(l)
ANALGESICS
What are soft and strong analgesics?
·How do they prevent pain?
·Aspirin versus paracetamol?
·Morphine versus heroin/codeine?
·Advantages – disadvantages?
·
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 very severe
pain.
(morphine, heroin, codeine)
Local anesthetics: used as pain killers in localized
areas.
(lidocaine, procaine)
General anesthetics
D.3 Analgesics
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 receptors more
sensitive and thus causing pain.
·
D.3.1 Analgesics
Pain relievers act by interfering with pain
receptors
·The brain sends nerve impulses through pain
receptors and nerve pathways.
·Mild analgesics work by interfering with the
pain stimulus at the source. One way is by
blocking the production of prostaglandins.
These are released when cells are damaged
by thermal, mechanical, or chemical energy.
·
·Prostaglandins:
·Constrict blood vessels
·Affect hypothalamus (region of brain controls
heat regulation and hence fever can result)
·Increase permeability of capillaries to allow for
swelling (inflammatory response)
Mild analgesics
They work by blocking the enzyme-controlled
synthesis of prostaglandins.
The main effects prostaglandins are:
1) The constriction of blood vessels, which helps
increase the body temperature.
2) Direct effect on the body’s heat regulating
centre, hypothalamus, which produces fever.
3) Increase of the permeability of capillaries
which allows water to pass to the tissue and
cause pain and swelling.
D.3.2 Mild analgesics
·Aspirin (acetyl salicylic acid or ASA)
produced from salicylic acid (relatively
strong acid, difficult to take)
·
·Addition of acetyl group lowers acidity
– less irritating to stomach
·ASA is called a prodrug: a less active
form that is converted to the active form
after administration
·ASA can also be used to produce alkaseltzer and other drugs by further
modification
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.
Uses of salicylic acid and its derivatives:·
·Relief from minor aches and pains
·Fever reduction (antipyretic)
·Anti-inflammatory agent
·Anti-clotting agent
·
As 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 surgery.
Disadvantages of aspirin:
Can cause upset stomach and ulceration
·Risk of severe gastrointestinal bleeding
following alcohol consumption
·Small risk of allergy (.5% of population)
·Accidental infant poisoning; small correlation
to Reye’s syndrome in children (a fatal liver
and brain disorder with the symptoms of
vomiting, lethargy, irritability and confusion.)
·
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.
·D.3.2 Aspirin substitutes
·Acetaminophen ( paracetemol)
·Does not upset stomach or cause
bleeding
·NOT an anti-inflammatory
·Safe in correct dose, but overdose
( >20 tablets) can cause serious liver
damage, brain damage, and death)
·Ibuprofen
·Many of the same effects as aspirin but
fewer stomach problems
·It is an anti-inflammatory drug.
D.3.3
Strong analgesics work by binding to
receptors in the brain
·Prevents transmission of pain impulses
without depressing the central nervous
system
·
·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
action.
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 codeine.
Opium plant
Morphine
·Strong analgesics
·Opiates (narcotics)
·Opium alkaloids (morphine, heroin,
codeine)
·Belong to “opiate” class (drug that
exerts actions on the body similar to
morphine) or “narcotics” (drug that
produces a narcotic (sleep-inducing)
effect as well as an analgesic (pain
relieving) effect) Morphine is principal
alkaloid, making up about 10% by mass
of raw opium
·Codeine is about .5% of raw opium
·Heroin (diamorphine)is synthesized
from morphine (semi-synthetic drug)
via a simple acetylation
Note: All three share the following functional
groups; benzene ring, ether, alkene, amine
(tertiary).
·Codeine and morphine also have a hydroxyl
group while heroin has ester functional groups.
·
Structures
D.3.3 Advantages of Opiates:
·Pharmacological effects
·Major effects on:
·Nervous system
·The eye
·GI tract gastrointestinal tract (the digestive
system)
·Uses:
·Strong analgesic for relieving severe pain
·Treatment of diarrhea (produces
constipation)
·Cough suppressant
·Constriction of the pupil
·Narcotic effects
·
·Disadvantages:
·Psychological effects
·Drowsiness, mood change, mental
fogginess, nausea and vomiting
·Anxiety, fear, lethargy, sedation, lack of
concern, inability to concentrate
·Effects increase from codeine to
morphine to heroin (highest)
·Tolerance and Dependence
·Cross-tolerance can occur (users
tolerant to one opiate will be tolerant to
other opiates)
·Users may not function properly without
the drug, experience withdrawal
symptoms (addiction)
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.
Narcotic Effects
·Short-Term:
·Feelings of well-being and contentment
·Dulling of pain and lessens fear and tension
·Euphoria
·Long-Term:
·Constipation and reduced libido
·Loss of appetite and poor nutrition
·Dependence, Tolerance and Withdrawal
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.
·
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 supply.
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
DEPRESSANTS
What is their effect?
·How is effect dependant on dose?
·Tranquilizers
·Sedatives
·Hypnotics
·Anaesthetics
·Ethanol (effects, detection)
·Most common depressants?
·
D.4 Depressants (anti-depressants)
·Drugs
that calm and relax (depress) the central
nervous system
·They alter the activity of neurotransmitters.
·They slow down brain activity
·They slow down heart activity
·They reduce breathing rate
·They dull emotional responses
·The effect depends upon the dosage as well.
Low doses have little or no noticeable effects.
The progression of dosage effects is as
follows:
·Low doses
·Little or no effect
·Moderate doses
·Sedation
·Soothing
·Reduction of anxiety
·High doses
·Sleep
·Extremely high doses
·Comma
·Death
Tranquilizers
Mild action
n Relieve anxiety and tension
·Alcohol, valium, librium (Reduce distress but
do not produce sleep)
·Sedatives
·Barbiturates (Reduce distress but do not
produce sleep, stronger than tranquilizers)
·Hypnotics
·Chloral hydrate (produces sleep in larger
doses)
·Lethal Dose
·Drugs used to treat clinical depression are
often called “antidepressants” because they
relieve depression.
Sedatives
Soothing of distress
Not producing sleep at normal doses
Barbiturates
·D.4.2 Alcohol
Small, fat-soluble organic molecule – readily
penetrates cell membrane and is easily absorbed
from the GI tract
·Social effects:
·Costs
·Sickness and death associated with abuse
·Crime and traffic costs
·Adverse effects to families due to abuse
·Physiological effects
·Short term:
·Reduces anxiety and inhibitions
·Impairs attention, judgment, and control
·Violent or aggressive behavior
·Loss of motor function
·Effect depends on body mass and concentration
of alcohol in the blood
·Dehydration, vomiting, loss of consciousness,
death (high amounts)
·
·Long-term
·Alcoholism is caused by an inability to
reduce alcohol intake
·Withdrawal symptoms (nausea,
sweating, anxiety, hypertension
·Tolerance
·Cirrhosis (scarring) and cancer of the
liver (the major detoxification organ)
·Heart disease
·Hypertension
·Strokes, brain damage
·Gastritis
·Ulcers
·Depression
·Birth defects (fetal alcohol syndrome)
D.4.4 Use and abuse of ethanol
Synergistic effects
·Alcohol + aspirin - risk of stomach bleeding
·Alcohol + sedatives - heavy sedation, comma,
death
·Alcohol + cocaine - high blood pressure,
irregular heart beat
Doses
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
·
Alcohol interacts with other drugs
(Synergistic effects)
·Can produce coma or death when combined
with sleeping pills or barbiturates
·Can cause stomach bleeding with aspirin
·Can inhibit breakdown of other drugs by the liver
·May increase the risk of cancer when used with
tobacco
·Measuring blood alcohol concentration
(BAC)
3
·Mass (g) of ethanol per 100 cm of blood 3
·.08% is legal limit in US (.080 g per 100 cm of
blood)
·Ethanol is easily absorbed from the stomach to
the blood, where it is exhaled by the lungs
(ethanol is fairly volatile)
·
C2H5OH(l) C2H5OH(g)
·The alcohol vapor can be detected by a number
of methods
·
D.4.3 Breathalyzer test
·Subject breathes into an analyzer
containing an oxidizing agent
(potassium dichromate (K2Cr2O7)) and a
detector
·Oxidizes ethanol to ethanoic acid
·This is an oxidation-reduction reaction
that involves an electron transfer
·This electron transfer generates an
electric current which can be detected
by the machine or produces a color
change (orange to green) detected by a
photocell
·Unreliable in legal cases
·
Detection of ethanol
Chromatography (GLC)
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
·
Gas Liquid Chromatography
·More precise than breathalyzer
·Uses a stationary phase (non-volatile liquid or
solid support) and a mobile phase (inert gas, like
N 2)
·Breath components (CO2, H2O, and alcohol vapor)
are injected into the machine and partitioned
(divided) between the stationary and mobile phases
·Or blood or urine components are vaporized,
mixed with inert gases and injected into the
machine over the surface of a non-volatile liquid
·Components exit at different intervals (each
substance has a different affinity and bond
strength for the two phases, and thus move
through at different rates)
·Components are detected
·Retention time for each component is measured
(time taken for each component to pass through
the column)
·Blood alcohol’s retention time is compared to the
retention time for a standard ethanol sample
Detection of ethanol
Intoximeter
(infra-red spectroscopy)
Ethanol in breath
Transmittance versus wavenumber
=IR spectrum
-1
Characteristic peak of -OH @ 3340cm
Comparison of sample and reference
Amount = size of peak
·Infra-Red Spectroscopy
·IR light does not promote electrons to higher levels,
but does provide enough energy to make molecules
“vibrate”
·Vibrational motion depends on the mass of the
molecule and the types of bonds present
·IR spectrum therefore depends on types of molecules
present (“molecular fingerprint”)
·Scale is based on wavenumber (1/wavelength)
·Police use intoximeter (IR spectrometer) to confirm
breathalyzer test
·IR radiation is passed through breath sample
·C-H group in alcohol absorbs a certain frequency of IR
light
·% transmittance of the C-H frequency is determined,
indicating amount of alcohol present
·A different version of the intoximeter uses a fuel cell
which oxidizes the ethanol, and a detectable amount of
electrical voltage is detected. (Quite accurate)
·D.4.5 Other Depressants
Diazepam (Valium) is a tranquilizer used to
relieve anxiety and tension
·Nitrazepam (Mogadon) – sleeping pills, is a
hypnotic drug used to induce sleep
·Fluoxetine hydrochloride (Prozac) –
antidepressant, is used to treat mental
depression by increasing activity of
serotonin (a neurotransmitter)
·Be familiar with the general structures of
these three molecules. See Data Booklet,
Section 20.
·
Structures
STIMULANTS
What is their effect?
·Adrenaline versus
amphetamines
·Nicotine
·Short-term effects
·Long-term effects
·Caffeine
·Effects
·Comparison to nicotine
·
D.5 Stimulants
Stimulate brain and central nervous system
·Alters the levels of neurotransmitters
·Effects:
·helps facilitate breathing by relaxing air
passages
·Cause increased alertness and awareness
·Reduces appetite
·Can cause palpitations and/or tremors
·Can cause restlessness, sleeplessness,
fits, delusions, and hallucinations
·
·Include amphetamines, nicotine, and
caffeine
D.5.2 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
Have structures similar to
adrenaline (epinephrine)
Both are derived from
Phenylethylamine
Mimic the actions of
adrenaline
(sympathomimetic)
Constrict arteries,
increase sweat
production, increase
heart rate, blood
pressure, respiration
Amphetamine
stimulant
·Suppresses appetite
·Treats narcolepsy and attention deficit
hyperactivity disorder (ADHD)
·
• 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
Ecstasy
potent stimulant
designer drug
can be fatal
neurotoxic
Phenylethylamine
(love molecule)
“high” feeling of lovers also
found in chocolate
Dopamine
Transmits to neurons
signals of joy,
happiness,
excitement
Methamphetamine (“speed”)
potent stimulant
very addictive
severe withdrawal symptoms
“meth mouth”
D.5.3 Nicotine
·Initial stimulant effect, followed by
depression, which encourages frequent use
·Short term effects:
·Increased heart rate and blood pressure,
putting stress on the heart
·Reduces urine output
·Long term effects
·Increased risk of heart disease and blood
clot (thrombosis)
·Inhibits oxygen-carrying capacity of blood
·Increased risk of peptic ulcers
·
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
Smoking can also lead to
·Lung cancer
·Cancer of the larynx and mouth
·Heart and blood vessel disease
·Empyhsema
·Chronic bronchitis
·Air pollution
·Fires!!
·Stained fingers and teeth
·Bad breath
·Very easy to develop dependence on
nicotine compared to alcohol or barbiturates
·Withdrawal symptoms: weight gain,
nausea, insomnia, irritability, fatigue,
depression, and inability to concentrate
·
D.5.4 Caffeine
·Increases rate of cellular metabolism and
therefore respiration
·In low doses, enhances wellbeing,
alertness, energy, and motivation
·In large amounts, physical coordination and
timing are affected, and sleeplessness may
also result.
·Weak diuretic (increases urine flow)
·Tolerance occurs, but no physical
dependence
·Vasoconstrictor (blood vessel constriction),
so can help in treating migraines
·Can help newborn babies to breathe as it
increases respiration
·
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.
·
Caffeine, like nicotine, contains a tertiary
amine group (nitrogen atom attached to three
organic [i.e. carbon-containing] substituents):
·
• 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!)
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
ANTIBACTERIALS
·The discovery of penicillin
·How penicillin works
·Modifications of penicillin
·Use and overprescription
·Broad versus narrow spectrum
antibiotics
Drugs that prevent the growth of, or kill,
microorganisms that cause
infectious diseases.
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.
D.6 Antibacterials
Antibacterials are selective: they attack
infectious bacteria rather than human cells
·These drugs are selective, they are
ineffective against normal body cells.
·Can be
·Bacteriostatic (inhibit bacterial cell division)
or
·Bacteriocidal (directly kill bacteria)
·Normally ineffective against viruses
because viruses live within host cell, which
are unaffected by most antibiotics
·The most well known antibacterials are
penicillins. The discovery was by accident,
sometimes called a serendipitous event.
·
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.
·
D.6.1 Penicillins:
·Produced from fungi (penicillium genus)
·Accidentally discovered by Alexander Fleming,
who noticed that bacteria did not grow around a
spot of penicillium notatum mold on a culture
plate
·Fleming could not isolate the “penicillin,” and
later gave up the research
·Florey and Chain, at Oxford, renewed the
research and started administering the drug to
humans
·Awarded the Nobel Prize
·Thousands of lives were saved during WWII
·
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.
D.6.2 Structure
Penicillins all have a certain structural feature in
common, the 6-APA group (6-aminopenicillic acid)
Structure has no effect on bacterial growth, but
when an extra side chain is added to the amino
(NH2) group, it becomes “active”
Side chain varies between different types of
penicillin:
Penicillin G, the first type created, is not acidresistant, and must be injected to bypass the
stomach
Penicillin V is acid-resistant
Cloxacillin is acid and penicillinase (bacteriaproduced enzyme that breaks down penicillin)
resistant
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.
·
Penicillins differ only in their type of side
chain
·Altering the side-chain makes them more
resistant to the penicillinase enzyme.
·
Penicillins function by interfering with the
cross-links (chemicals) that connect separate
layers of the bacterial cell wall
·Cell wall is weakened and the bacterial cell
bursts, killing the bacteria
·
·Humans' cells do not have cell walls and are
thus unaffected by penicillins
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.
·
Disadvantages of penicillins
·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.
·
D.6.3 Side effects Antibiotics
Side effects include fever, body rash, shock,
and death
·Over prescription can result in destruction
of harmless bacteria in the digestive tract,
allowing harmful bacteria to colonize
·Over prescription leads to genetics
resistance over time, rendering the antibiotic
eventually useless
·Superbugs, such as antibiotic resistant TB
(tuberculosis), are becoming increasingly
common. A combination of several drugs are
sometimes required in these cases.
·
·Thus, antibiotics should only be prescribed
when there is no other option that can
reduce suffering or save a life
Broad vs. Narrow Spectrum Antibiotics:
·Broad spectrum
·Effective against a wide variety of bacteria
·Tetracyclines (Aureomycin, Terramycin),‘Mycin’ is the
suffix used for antibiotics obtained from soil fungi.
·Ampicillin
·Repeated use may wipe out harmless or helpful
bacteria in the digestive tract, which may be replaced
by harmful strains
·Narrow spectrum
·Effective against only certain types of bacteria
·Penicillins (and sulfa drugs)
·
·Typically, a broad spectrum is initially prescribed until
the bacteria can be identified, at which point a narrow
spectrum is prescribed
·Humans also have an important role. Patient
compliance is also required to help with the resistance
issue. Patients should take the full course of the
antibiotic as prescribed to them.
·Antibiotics
in animal feed
·Antibiotics are added to animal feed to
prevent the spread of infection throughout
livestock
·However, this can encourage the
development of drug-resistant bacteria that
humans will eventually be exposed to
ANTIVIRALS
Viruses versus bacteria
·How do antiviral drugs work?
·What is HIV and what AIDS?
·Why is it difficult to fight HIV?
·(AIDS prevention methods?)
·
D.7 Antivirals
Viruses are submicroscopic, non-cellular
infectious particles that can only reproduce
inside a living host cell
·Unlike bacteria, which have a cellular
structure, viruses have no nucleus,
cytoplasm, or cell membrane
·This limits the effectiveness of antibacterial
drugs on viruses
·
·D.7.2 Controlling viruses
·Antibacterials may be effective if they
block the transfer of genetic information,
although few do
·Vaccination is primary method of
prevention
·Patient is exposed to weakened or inert
viral particles to stimulate immune system
·Immune system produces antibodies,
crucial in the immune response, specific to
that virus
·Future exposure to active viral particles is
more easily controlled because antibodies
have already been produced against it
·Ex: measles, meningitis, polio, AIDS, avian
flu
Many antiviral drugs work to inhibit the
function of replication-specific enzymes.
·Some alter the cell’s DNA so that the virus
can not use it to multiply.
·Progression of the disease is halted but
the virus is not completely eradicated from
the body. Ex: cold sores from herpes
infections
·
·Latent viruses are viruses that inject their
genetic material into a host cell, but the
material is not expressed until a later date
·Herpes simplex virus, certain types of
cancer
D.7.3 AIDS virus
The HIV virus is the that leads to the condition
we call AIDS.
·
·Attacks immune system by binding to a
receptor glycoprotein (CD4) on T4 immune
(white blood) cells
·Difficult to fight because of:
·its ability to mutate (thus rendering a previous
treatment ineffective)
·Its metabolism is similar to human cells
·Virus mutates rapidly
·It may lay dormant for a period of time,
making it difficult for the immune system to
fight.
·As of now, effective vaccines, antiviral, and
anti-retroviral drugs have not yet been
developed.
·Access to these very expensive treatments
become increasingly difficult for the hardest
hit areas of the World mainly due to socioeconomic conditions
AIDS/HIV
·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
·
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