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Allan Tang
Medicine and drugs: Option D
D.1 Pharmaceutical products
Lines of defense
First line of defense: barriers to prevent entry
Skin
Mucous membranes
Closures and secretions of natural openings such as lips, eyelids, ear wax etc.
Second line of defense: attack invaders
White blood cells engulf invaders (phagocytosis)
Blood clotting to prevent loss of blood and further invasions.
The inflammatory response
Third line of defense: immune system
White blood cells produce specific proteins called antibodies to recognize and destroy the
invaders
Memory cells enable the body to fight a repeat invasion of the same organism more effectively
Medicines vs. Drugs
Drug: a chemical that affects how the body works. This includes changes for the better and for the
worse. The term is sometimes associated with substances which are illegal in many countries, such as
cocaine, ecstasy and heroin.
The effects on the body of drugs include:
Alteration of the physiological state, including consciousness, activity level and coordination
Alteration of incoming sensory sensations
Alteration of mood or emotions
Medicine: a substance that improves health. Medicines, which may be natural or synthetic, therefore
contain beneficial drugs. Synthetic medicines also contain other ingredients, which are non-active but
help in the presentation and administration of the drug. The beneficial effect of a medicine is known as
its therapeutic effect.
The Placebo effect: Patients that receive therapeutic and healing effects from medicines that are
pharmacologically inert, when they believe they are taking an effective drug.
Methods of administering drugs:
Oral: taken by mouth: tablets, capsules, pills, liquids.
Inhalation: vapor breathed in; smoking: medications for respiratory conditions such as asthma.
Skin patches: absorbed directly from the skin into the blood: some hormone treatments like estrogen or
nicotine.
Suppositories: inserted into the rectum: treatment of digestive illnesses, hemorrhoids.
Eye or ear drops: liquids delivered directly to the opening: treatments of infections of the eye or ear.



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Parenteral by injection:
Intramuscular drug is injected into a muscle many vaccines
Intravenous fastest method of injection drug if injected directly into the bloodstream local
anesthetics
Subcutaneous drug is injected directly under the surface of the skin dental injections
Therapeutic effect the intended physiological effect
Side-effect unintended physiological effects
Sometimes side-effects can be beneficial: aspirin, taken for pain relief, helps prevent against
heart disease
Can be relatively benign: causing drowsiness, nausea or constipation.
Dosing Regimen the amount of drug used for each does and the frequency of administration.
Many variables used to determine dosing regimen age, sex, weight, diet, and environment.
Ideally, the dosage should result in constant levels of the drug in the blood, but it is almost
impossible without an intravenous drip.
Therapeutic Window - The range of a drugs concentration in the blood between its therapeutic level
and its toxic level. Concentration in the bloodstream must remain within a certain range: above this
range, unacceptable side-effects may occur. Below this range there may not be effective therapeutic
outcomes.
Tolerance when a person is given repeated doses of a drug, and they have a reduced response to the
drug. Higher doses are needed to produce the same effect.
Dependence or addiction when a patient becomes dependent on the drug in order to feel normal and
suffers from withdrawal symptoms if the drug is not taken.
Discovery research
First stage in drug development involves identifying and extracting compounds that have been shown to
have biological activity and are known as lead compounds. Usually derived from plants, often have low
levels of activity. Microorganisms have rich sources of lead compounds.
Next, effectiveness of the lead compound is optimized by making and testing chemically related
compounds called analogues. Using combinatorial chemistry and high-throughput screening, scientists
test vast numbers of candidate medicines in a short time. Potential medicines then tested on animals.
Development research
Three Phases of human trial, each subsequent human trial involving more patients. In the Phase III, the
effectiveness of the drug is judged by the relative improvement in the patients who have received real
medications compared with those on a placebo.
D.2 Antacids
The stomach produces hydrochloric acid from the linings of the walls that kill bacteria and provide an
optimum environment for digestive enzymes. Some factors, such as excess alcohol, smoking, stress and
anti-inflammatory drugs can cause excess produce of acidic secretion known as gastric juice. This leads
to:
Acid indigestion: a feeling of discomfort from too much acid in the stomach


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Heartburn: acid from the stomach rising into the esophagus often called acid reflux.
Ulcer: damage to the lining of the stomach wall, resulting in loss of tissue and inflammation.
Antacids
Weak bases which neutralize excess acid.
Work by neutralizing the hydrochloric acid, hence reliving the symptoms.
Antacids are usually weakly basic compounds (often metal oxides or hydroxides, carbonates or
hydrogencarbonates) that react with the acid to produce salt and water.
Examples: Aluminum hydroxide and Magnesium hydroxide.
Magnesium salt tends to act faster and acts as a laxative. Aluminum dissolves more slowly to
provide longer lasting relief.
Other antacids contain metal carbonates and hydrogencarbonates which react with the acid to
produce salt, water and carbon dioxide, which can cause bloating and flatulence.
o Using antifoaming agents can help avert this problem.
Some antacids contain alginates which float to the top of the stomach, which acts as a barrier to
prevent reflux into the esophagus.
D.3 Analgesics
Pain is only a symptom of a bigger problem such as an injury or disease, so long-term relief is dependent
on treating the underlying cause, while analgesics are only there to soothe the pain.
Pain receptors Detect pain sensations and send nerve messages to the brain.
Prostaglandins chemicals that stimulate pain receptors, which are released from cells damaged by
thermal, mechanical or chemical energy. Once released prostaglandins also mediate the inflammatory
response by causing the dilation (widening) of blood vessels near the site of injury. This can lead to
swelling and increased pain. Also may cause increased body temperature or fever.
Painkillers must intercept or block this pathway somewhere between the pain receptors and the
perception in the brain.
Mild analgesics
Including aspirin and non-steroidal anti-inflammatory drugs such as ibuprofen.
Act by preventing stimulation of the nerve endings at the site of pain.
They inhibit the release of prostaglandins from the site of injury and give relief to inflammation
and fever as well as pain.
They do not interfere with the functioning of the brain, so they are non-narcotics.
Aspirin
The active ingredient in willow bark that gave it the pain relieving ability was salicin, which is
converted to salicylic acid in the body.
1890, Bayer Company in Germany made an ester derivative of salicylic acid which was more
palatable and less irritating to the stomach, called aspirin.
o Today it continues to hold its place as most widely used drug in the world.
o Used to treat headaches, toothaches, and sore throat.
o Effective in reducing fever and inflammation.


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Aspirin reduces the ability of the blood to clot and this mkes it useful in the treatment of
patients at risk from heart attack and strokes.
o But, can be dangerous if taken by a person whose blood does not blot easily or before
surgery.
Negative side-effects: irritation and ulceration of the stomach, lead to bleeding. May become
more acute when ingested with ethanol. Also linked to Reyes syndrome, rare and potentially
fatal liver and brain disorder.
Paracetamol
Acts by reducing the production of prostaglandins in the brain, but does not affect the
prostaglandin production in the rest of the body. So, not effective in reducing inflammation.
Safest of analgesics when taken correctly.
o Does not irritate the stomach and rare allergic reactions
But, overdoes or chronic use of paracetamol can cause severe and possibly fatal damage to
kidneys, liver and brain. Used with ethanol, it has toxic effects as well.
Strong analgesics
Including drugs related to morphine, known as opioids.
Bind to the so-called opioid receptors in the brain, which then blocks the transmission of pain
signals between brain cells and so alters the perception of pain.
They cause drowsiness and possible changes in behavior and mood, so are called narcotics.
Most effective pain killers for severe pain, but since they have side-effects and potential
problems with dependence, their usage must be monitored.
Opium
Opioids also known as narcotics, derived from the extract of poppy seeds.
Narcotic drugs derived from opium are primarily morphine and its derivatives.
We are considering three of these: codeine, morphine and diamorphine, known as heroin.
o These are powerful analgesics, acting on the central nervous system to block the
perception of pain.
o Adverse side-effects include:
Causing constipation
Suppressing the cough reflex
Causing constriction of the pupil in the eye.
Narcotic effects
The three drugs have increasing effect as analgesics, increasing narcotic effects and increasing
side-effects in the order: codeine morphine heroin
Codeine, morphine, and heroin have a common basic structure that accounts for their similar
properties, as well as some different functional groups.
o Benzene ring
o Ether
o Alkene



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Codeine
Therapeutic uses:
o Sometimes used in preparation with a non-narcotic drug such as aspirin or paracetamol
in the second stage of pain management ladder.
o Also used in cough medications and in the short-term treatment of diarrhea.
Structure contains: benzene ring, ether(2), alkene, alcohol (1), tertiary amine
Morphine
Therapeutic uses:
o Used in the management of severe pain, such as in advanced cancer
o Can be habit forming and can lead to dependence, so use must be regulated by a
medical professional.
Structure contains: benzene ring, ether, alkene, alcohol (2), tertiary amine
Diamorphine/Heroin
Therapeutic uses:
o Used medically only in a few countries legally for the relief of severe pain.
o The most rapidly acting and the most abused narcotic.
o Initially produces euphoric effects, but very high potential for causing addiction and
increasing tolerance.
o Dependence leads to withdrawal symptoms and many associated problems.
Structure contains: benzene ring, ether, alkene, ester-ethanoate (2), tertiary amine
The conversion of morphine into heroin involves an esterification reaction in which both its OH
groups are converted into ethanoate (ester) groups by reaction with ethanoic acid. The loss of
two polar OH groups means that heroin is less polar and so more lipid-soluble than morphine.
This enables it to cross the blood-brain barrier quickly, which is why it is faster acting than the
other opioid drugs. In the brain, it is hydrolyzed to morphine by reversing the esterification
reaction.
World Health Organization (WHO) Three step analgesic ladder.
1. Use mild analgesics.
2. Add a weak opioid such as codeine or tramadol.
3. In severe intractable pain, use strong opioids such as morphine, fentanyl or methadone.
Narcotic effects
In the short term, heroin induces a feeling of well-being and contentment, as it causes a dulling of pain
and lessening of fear and tension.
Long-term regular use leads to constipation, reduced libido, loss of appetite and poor nutrition.
Heroin users start to show dependence relatively quickly, so they cannot function properly without it,
and will start to suffer withdrawal symptoms.
Helping heroin addicts to break their dependence is slow and difficult.
Sometimes an alternative analgesic methadone is administered. This can reduce drug craving and
prevent symptoms of withdrawal.



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D.4 Depressants
Depressants
Drugs that act on the brain and spinal cord (Central Nervous System or CNS).
Changes the communication between the brain cells by altering the concentration or the activity
of chemicals called neurotransmitters.
Cause a decrease in brain activity that in turn influences the functioning of other parts of the
body such as the heart and the mechanisms determining breathing rate.
They include drugs also classified as tranquilizers, sedatives and hypnotics.
Dosage effect: Low to moderate dose:
Calmness
Relief from anxiety
Very relaxed muscles
High dose:
Slurred speech
Staggering gait
Altered perception
Sleep induced
Extremely high
doses/lethal dose:
Respiratory depression
Coma/death
Description: Tranquilizer Sedative Hypnotic

Increasing dosage
Ethanol
Present in beer, wine, and hard liquor
Most widely used psychoactive drug and is legal in most countries.
Has antiseptic properties so can be used on skin before an injection or to clean a small wound.
o Rubbed into feet to prevent blistering
In low doses, it can help to create a mild excitement and users become more talkative, confident
and relaxed.
o Evidence that low doses of ethanol might have a beneficial effect on the circulation and
diminish cardio-vascular diseases. Has some mild anti-clotting effects.
Being a CNS depressant, ethanol changes behavior and adverse effects increase as dose
increases.
Short-term effects of ethanol abuse Long-term effects of ethanol abuse
Loss of self-restraint; memory, concentration
and insight are impaired.
Loss of balance and judgement
Violent behavior
Dangerous risk-taking behavior
Dehydration
Vomiting, loss of consciousness, coma and
death.
Dependence known as alcoholism,
associated with withdrawal symptoms
Liver disease, cirrhosis, liver cancer
Coronary heart disease
High blood pressure
Fetal alcohol syndrome
Permanent brain damage

The polar OH group enables ethanol to form hydrogen bonds with water, making it readily
soluble in aqueous solution.
o Also dissolves in lipids, which allows it to cross cell membranes easily.


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Following ingestion, ethanol passes quickly from the gut into the blood through stomach wall,
and then circulates to all tissues of the body.
90% of the ethanol load is broken down in the liver. Easily passes across the placenta to fetus.
Ethanol has the potential to increase the activity of other drugs when taken at the same time.
The effect is known as synergy.
o Synergistic effects can lead to very serious, even fatal, results.
o Some examples are:
With aspirin, ethanol can cause increased bleeding of the stomach lining and
increase risk of ulcers.
With other depressants such as barbiturates and sleeping pills, ethanol can
induce heavy sedation, possibly coma.
With tobacco, ethanol appears to increase the incidence of cancers, particularly
of the intestines and liver.
With many other drugs, ethanol can interfere with their metabolism by the liver,
which can cause greater and more prolonged drug effects.
Ethanol is a volatile compound and at body temperature in the lungs it establishes equilibrium
between being dissolved in the blood and released into the air in exhaled breath.
o The equilibrium constant Kc for this reaction has a fixed value at a particular
temperature so measurement of the ethanol in the breath can be used to assess the
blood alcohol concentration.
o A breathalyzer that contains crystals of potassium dichromate(vi), are orange, but
become green chromium(iii) ions as they oxidize the ethanol to ethanal and ethanoic
acid.
The extent of the color change is measure with a photocell to determine
ethanol concentration.
o More accurate technique infrared spectroscopy using an intoximeter.
Ethanol has absorption band at 2950 cm-1.
The size of the peak can be used to measure ethanol concentration when
compared to ambient air.
o Gas-liquid chromatography
Blood or urine is vaporized, injected into stream of inert gas. The ethanol gas
and other vapors move at different rates depending on boiling point and
relative solubility in the two phases. Each leaves the column holding the liquid
phase after a specific interval of time called retention time. A peak at retention
time that corresponds to ethanol can be used to confirm its presence.
Benzodiazepines
A major group of depressants that depress activity in the part of the brain that controls emotion
and used as tranquilizers in the treatment of anxiety disorders and related insomnia.
Used as sleeping pill and muscle relaxant.
Little side-effects other than dependence. Used for short term treatments.
Some example drugs are: diazepam (Valium) and nitrazepam (Mogadom)


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o Benzodiazepine implies, they contain both benzene rings and the diazepine structure,
which is a seven-membered heterocyclic ring containing carbon and two nitrogen
atoms.
Widely used anti-depressant drug is fluoxetine hydrochloride, or Prozac. It decreases levels of
serotonin, an important neurotransmitter in the brain. Used to treat depression and eating and panic
disorders.

D.5 Stimulants
Stimulants
A different class of drugs that affect the central nervous system
Function largely opposite to that of depressants. Increase the activity of the brain and the
persons mental alertness.
o Used to prevent excessive drowsiness and allow greater concentration.
o They can help facilitate breathing by causing relaxation of the air passages.
o They may reduce appetite and so have been used as part of treatment for obesity
o They may cause palpitations or tremors to occur.
o When used in excess, they can cause extreme restlessness, sleeplessness, fits, and
delusions and hallucinations.
They alter the levels of neurotransmitters, chemicals that act as messengers in the nervous
system.
Adrenaline
The hormone that is released in times of stress and enables the body to cope with sudden
demands such as those imposed by pain, shock, fear, and cold.
The response, sometimes called the fight or flight reaction stimulates the pathways that:
o Increase the heart rate and blood pressure
o Increase the blood flow to the brain and muscles
o Increase the air flow to the lungs
o Increase mental awareness.
Similar in both its structure and physiological effects to a neurotransmitter called noradrenaline
which is responsible for communication in the part of the nervous system known as the
sympathetic nervous system.
Amphetamines
One major group of similar drugs that act to mimic and enhance the effects of adrenaline and
nonadrenaline.
Have a structure quite similar to that of adrenaline and noradrenaline.
Both adrenaline and amphetamine molecules are derivatives of the phenyl ethyl amine
structures.
Because of their role in stimulating the sympathetic nervous sytem, the amphetamines are
called sympathomimetic drugs.
In small doses: it increases mental alertness and physical energy.


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Side effects: dilation of pupils, decreased appetite, blurred vision, dizziness.
Regular use leads to tolerance and dependence, depression, and reduced resistance to
infections.
Modifications to amphetamine structure produce designer drugs, which are powerful and
addictive stimulants.
o Methamphetamine (speed or crystal meth) and ecstasy.
Nicotine
One of the most widespread and abused stimulants.
Obtained from tobacco plants.
Inhaled as smoke from cigarettes and cigars, but can be chewed as well.
Lipid-soluble molecule, nicotine able to cross blood-brain barrier, bringing rapid effects to brain
activity.
o Increases level of adrenaline, alters concentration of certain neurotransmitters.
Short-term effects of nicotine consumption Long-term effects of nicotine consumption
Increases concentration
Relieves tension and boredom
Helps to counter fatigue
Increases heart rate and blood pressure
Decreases urine output
High blood pressure
Increases risk of heart disease including
angina
Coronary thrombosis
Increases the level of fatty acids in the blood
which can lead to atherosclerosis and stroke
Over-stimulation of stomach acids which can
lead to increased risk of peptic ulcers.
Nicotine is habit-forming, quickly leads to dependence or addiction.
Users will suffer withdrawal symptoms: nausea, weight gain, drowsiness, lack of concentration.
Caffeine
Present in coffee, tea, chocolate and colas.
Legal and unregulated, consumed by 90% of American adults.
Reduces physical fatigue and restores mental alertness.
Caffeine, like nicotine, contains heterocyclic rings (containing both carbon and nitrogen) and a
tertiary amine group. Also has two amide groups.
Acts as a respiratory stimulant increasing the rate of energy release within cells.
o Intensifies and prolongs the effects of adrenaline.
Consumption of caffeine in small amounts Consumption of caffeine in large amounts
Enhancement of mental energy, alertness
and ability to concentrate
Acts as a diuretic, increasing the volume of
urine; can cause dehydration
Can cause anxiety, irritability and insomnia
Can cause dependence; side-effects on
withdrawal include headaches and nausea.
Helps absorb some analgesics and is often included in the formulation of headache pills and
other medications.




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D.6 Antibacterial
First example of a chimerical used to kill pathogens came from observations that certain dyes
used in the dyestuffs industry were able to kill some microorganisms.
1891, this led to the treatment of malaria using methylene blue.
Paul Ehrlich introduced concept of a magic bullet, chemical designed to kill specific disease but
not touch the host cells, successfully treated syphilis patients with arsenical drug.
Sulfonamide drugs like Prontosil in 1933, seemed to cure septicemia.
Penicillin
Chemicals, usually produced by microorganisms, which act against other microorganisms.
Alexander Fleming in 1928 worked on bacteria cultures.
o Noticed fungus or mold known as Penicillium notatum had contaminated some of his
cultures, so he was going to throw them away.
o But, he noticed that the mold had generated a clear region where no bacterial colonies
were growing.
Concluded that the mold produced something that specifically inhibited the
bacterial growth.
1940, Howard Florey and Ernst Chain successfully isolated penicillin as the antibacterial agent in
the mold.
o Used in human trials in 1941, helped during WWII, saved thousands of lives and they
won the Nobel Prize with Fleming.
Research moves to the United States, isolation and development of penicillin occurred.
Dorothy Hodgkin in 1945 using X-ray crystallography determined the structure of penicillin G,
the major constituent of the mold extract.
o Core structure is four-membered ring consisting of one nitrogen and three carbon
atoms and known as beta-lactam. This part of the molecule is known to be responsible
for its antibacterial properties.
By acting as an irreversible inhibitor of an enzyme, it prevents the development of cross-links in
bacterial cell walls, so weakening the walls and causing the bacteria to rupture and die during
their reproductive phase.
o Its action is effective against a wide range of bacteria responsible for infections in the
ear, nose, throat, and mouth, and wounds.
Penicillin G can be broken down by stomach acid and has to be injected directly into the blood.
o Different forms of penicillin have been developed by modifying the side chain (the part
denoted as R in the structure) and these enable the drug to retain activity when
ingested in pill form.
Bacterial resistance
A major problem with the use of penicillin and other antibiotics.
Penicillin started to prove ineffective against some populations of bacteria.
o Now its known that theses resistance bacteria produce an enzyme, penicillinase, which
can open penicillins beta-lactam ring and render it inactive.


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Antibiotic resistance arises by genetic mutation in bacteria that would normally account for a
very small population.
o But the number of resistant organisms increases dramatically when antibiotic exposure
increases.
o Widespread resistant strains of bacteria threaten usefulness of antibiotics.
o Superbugs are bacteria which carry several resistant genes.
Resistance problem increasing because of its wide use of penicillin used in animals feeds to
lower disease in stock.
o This causes antibiotics to enter the human food chain, hence increasing the resistant
bacteria population.
Response to the challenge of antibiotic resistance include:
o Developing different forms of penicillin, with modified side chains able to withstand the
action of penicillinase.
o Controlling and restricting the use of antibiotics by legislation to make them
prescription-only drugs; also encouraging doctors not to over-prescribe.
o Education and encouragement of patients in the importance of completely the full
course of treatment with antibiotic, referred to as patient compliance; this is essential
to prevent resistant bacteria prolonging the disease or spreading into the community.
D.7 Antiviral
Virus
Small and simple structure
Contain only two components: Protein and nucleic acid(either RNA or DNA)
Has no cellular structure and are only capable of reproducing inside another living cell.
They take over the functioning of another cell (the host cell) and use it to carry out their own
reproduction.
o Host cells components are used in the assembly of new viral particles and the cell
eventually dies, releasing thousands of viral particles.
Treating viral infections is a challenge because they live within cells, so its hard to target them.
o Lacking cell structure of bacteria, they are not affected by antibiotics.
o They can multiply and spread throughout the body rapidly before symptoms arise.
o Viruses can mutate rapidly (making small changes in their genetic material) and this
changes their susceptibility to drugs.
Fighting against Viruses
Successful vaccination programs enable the body to prepare specific antibodies against a virus,
have reduced incidence of diseases such as cholera, polio and measles.
Some antivirals work by altering the cells genetic material (DNA) so that the virus cannot use it
to multiply.
Others clock enzyme activity within the host cell, which prevents the virus from reproducing.
o Progression of the disease will be halted and there will be relief from symptoms, but the
virus will not be completely eradicated. Symptoms can flare up.


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Amantadine
Antiviral drug that causes changes in the cell membrane that prevent the entry of virus into the
cells.
Best used as prophylactic (preventative) before the infection has spread widely, most effective
way to treat influenza.
AIDS
Cause by the human immunodeficiency virus (HIV).
Characterized by a failure of the immune system, so the body falls prey to life-threatening
infections like pneumonia and cancer.
Spread throughout the world, 40 million HIV positive.
HIV
Primarily infects vital white blood cells in the immune system. These cells are called CD4
+
T cells.
The virus binds to specific receptor proteins on the cell surface and penetrates the cell.
HIV is a retrovirus (its genetic material is in the form of RNA, not DNA). It releases its RNA into
the cell and the enzyme reverse transcriptase controls the synthesis of viral DNA from the RNA.
o The viral DNA integrates into the cells own DNA and replicates when it divides.
o The virus is replicated inside the host cell and released in large numbers when it dies.
Three main reasons HIV is hard to defeat
o The virus destroys T-helper cells, the very cells in the immune system that should be
defending the body against the virus.
o The virus mutates rapidly, with more variations in HIV in a single patient than in
influenza virus worldwide in a year. Variations mean it escapes the immune response.
o Virus often lies dormant within host cell, so immune system doesnt respond to it.
Antiretroviral drugs
Drugs to help fight against HIV.
Act at different stages in HIV lifecycle:
o One is to inhibit the enzyme reverse transcriptase, so it only affects the virus.
o The drug AZT or zidovudine works this way and was approved for AIDS treatment.
Effective in delaying progression.
Blocks transmission of HIV to fetus during pregnancy.
Other antiretroviral drugs:
o Block the binding of HIV to cell membranes
o Inhibit the assembly of new viral particles in the cell.
The variable nature of the virus within cells and the fact that immune response seems to act too
slowly in the HIV infection is the main problem.