Medicines and Drugs

Pictured: Resident expert on this subject matter.

I. Pharmaceutical Products

List the effects of medicines and drugs on the functioning of the body

Drug- Any chemical that alters the physiological state (including consciousness, activity level, or coordination), alters incoming sensations, or alters mood/emotions

Medicine- Drugs used for therapeutic purposes

Drugs are designed to compliment or assist the body’s own natural healing processes

Placebo- A pill with no intended function designed to be used in control tests

Placebo Effect- A response by the body to a placebo during which the body begins to mimic the effects of those drugs

Outline the stages involved in the research, development, and testing of new pharmaceutical products

Stages Involved with Pharmaceutical Testing:

• Cell Tests (in Vitro)
• Animal Tests (3 non-human species)
• Test for effective + lethal dose
• Phase 1
• 50% given drug, 50% given placebo
• Test for safety, dose range, and side effects
• Phase 2
• Variables (response and investigator response) eliminated
• Test for positive effect (benefit > risk)
• Phase 3
• Extended human trials
• Application to Sell Drug in intended Country
• Sometimes, problems with a drug are not stopped. Example: Thalidomide was prescribed to treat morning sequence in pregnant women. Resulted in birth defects and absent/deformed limbs

Describe the different methods of administering drugs

Different methods of administering drugs (OPIR)

• Oral- Through the mouth.
• Pro- Convenient + absorbed through small intenstine
• Con- Rate of absorption relies on solubility, stomach contents
• Parenteral- Through a subcutaneous (beneath skin), intramuscular (into muscles) or intravenous (through the vein) injection.
• Pro- Safe for large doses and distributes quickly
• Con- No retrieval and abused by illegal drug-users
• Inhalation- Through the lungs
• Pro- Rapid absorption and effect on the brain
• Con- No retrieval
• Rectal- I’m not gonna explain this one…
• Pro- Stop nausea, pH sensitivity not an issue
• Con- Limited range of distribution

Discuss the terms therapeutic window, tolerance, and side-effects

Therapeutic window- Measure of how safe a drug is for a particular treatment in an average population. It’s a ratio of ED₅₀:LD₅₀ (effective dose for 50% of population to lethal dose for 50% of the population)

Tolerance- The body’s need for more drug to produce a physiological effect

Side-effect- Any undesired effect from a drug

II. Antacids

State and explain how excess acidity in the stomach can be reduced by the use of different bases

pH of Gastric Juices- 1.0-3.0

Purpose of acidic stomach contents- hydrolyze proteins à amino acids, inhibit bacteria growth

Heartburn- Stomach discomfort caused by excess gastric juice production

Antacid- Base used to neutralize stomach acid to the desired pH

Examples of bases used in antacids (and their respective equations)

• Magnesium oxide (Milk of Magnesia)

MgO + 2HCl à MgCl₂ + H₂O

• Magnesium hydroxide (Mealox/Milk of Magnesia)

Mg(OH)₂ + 2HCl à MgCl₂ + 2H₂O

• Aluminum hydroxide

Al(OH)₃ + 3HCl à AlCl₃ + 3H₂O

• Calcium carbonate

CaCO₃ + 2HCl à NaCl + 2H₂O + CO₂

Alginates- Compounds that produce a neutralizing layer, preventing acid from rising into the esophagus and causing heartburn

Dimethacone- Anti-foaming agent that reduce surface tension of gas bubbles

III. Analgesics

IV. Depressants

Describe the effects of depressants

Depressant- Substances that depress (relax) the central nervous system (CNS). Are dose dependent

            Low dosesà Little effect

            Moderate dosesà Soothing (reduced anxiety)

            High dosesà Induce sleep

            Very high dosesà DEATH!!!

Depressants are also called antidepressants

***DEPRESSANTS RELIEVE DEPRESSION. “Depress” refers to their effect on the nervous system

Tranquilizers- Reduce nervous tension and anxiety, but do not cause sleep in normal dose

Sedatives- Stronger than tranquilizers and produce same effect

Hypnotics- Sleep inducing

Discuss the social and physiological effects of the use and abuse of ethanol

Type of alcohol drank- Ethanol

Prolonged consumption leads to psychological and physiological dependence

Social effect of Alcoholism-  hospital care, lost productivity, crime, DUI’s (accidents, deaths)

Family effect of Alcoholism- violent behavior, loss of income

Short-term effects of alcohol- relaxation, confidence, increased warmth, impaired judgement, lengthened response time

Long-term effects of alcohol- liver disease, coronary heart disease, high blood pressure, miscarriage, fetal abnormalities

Describe and explain the techniques used for the detection of ethanol in blood, urine, and breath.

Ways to identify intoxication- Breathalyzer, Gas-Liquid Chromatography, Infra-Red Spectroscopy

How a Breathalyzer works: Concentration of ethanol vapor depends on the concentration of ethanol in the blood due to equilibrium. Both decrease over time as ethanol is metabolized. When a person breathes into a breathalyzer, a redox reaction occurs as acidified Potassium Dichromate (K₂Cr₂O₇) oxidizes any ethanol in the breath, causing a color change from orange to green. The transfer of electrons produces an electromagnetic field, which is sensed by the device to indicate BAC

How Gas Liquid Chromotography works: This is used to ID small samples of gas and volatile liquid (like ethanol) from blood, urine, or breath. The sample is injected into the system along with an inert carrier gas like N₂. Samples move through a series of columns with each sample moving at a unique speed. Computer then shows how much of each substance there is based off of speed and how much occurs at each time period

How IR Spectroscopy works: IR energy causes molecules to vibrate, with each vibration dependent on the bonds in each compound. Each bond absorbs a specific wavelength of IR energy. The device measures the intensity of IR absorbed by the wavelength for C-H and C-O bonds (but not O-H because those are also seen in water) and converts it to % transmittance to determine the level of intoxication.

Describe the synergistic effects of ethanol with other drugs

Synergetic effect- Ability of depressants (especially alcohol) to increase the effect of other drugs because the CNS is inhibited.

Alcohol can be fatal when mixed with benzodiazepines, narcotics, and barbiturates

Alcohol can also cause stomach bleeding when mixed with aspirin

Identify other commonly used depressants and describe their structures

Other important depressants to know…

Valium- Sedative. Inhibits nerve transmission by interacting with neurotransmitters.

            Structure- Phenyl group, Cl group on the fused benzene ring

Nitrazepam- Tranquilizer. Induces sleep, but also causes seizures and infant spasms.

            Structure- Phyenl group, NO₂ group on the fused benzene ring

Prozac- (Fluoxetine hydrochloride). Prevents neurons from re-absorbing serotonin, causing a build up that preserves a mellow effect

            Structure- Two benzene rings, trifluro-methyl group, amine group

V. Stimulants

Listh the physiological effects of stimulants

Stimulant- Drugs that stimulate the CNS by increasing alertness, wakefulness, and suppressed appetite. Examples include caffeine, nicotine, and amphetamine

Compare amphetamines and adrenaline

Epinephrine (adrenalin)- Natural stimulating hormone produced by the body

Amphetamine- Sympathomimetic drugs that mimic the effects of epinephrine. Like adrenalin, this is derived from the phenylethylamine structure.

Sympathiomimetic drugs- Stimulate the sympathetic nervous system by mimicing the effects of adrenaline

Discuss the short- and long-term effects of nicotine consumption

Short term effects of nicotine- increased blood pressure and heart rate, reduction in urine output, other stimulating effects

Long term effects of nicotine- increased risk of heart disease, coronary thrombosis, peptic ulcers

Nicotine addiction- is a problem as this chemical is extremely addictive. Produces a tolerance and psychological dependence. Withdrawals à weight gain, nausea, insomnia, irritabilty

Risks associated with smoking- cancer, heart/blood-vessel disease, emphysema, chronic bronchitis, air pollution, fires, stained fingers/teeth, halitosis

Describe the effects of caffeine and compare its structure with that of nicotine

Caffeine- respiratory stimulant that increases metabolism inside nerve cells. Enhances alterness, motivation, and concentration in moderate doses. High doses result in anxiety, irritability, and sleeplessness.

Diuretic- Stimulates the kidneys

Caffeine and nicotine structures both have a tertiary amine group

VI. Antibacterials

Antibacterial- Drugs that inhibit the growth of microorganisms responsible for causing disease

Outline the historical development of penicillins

History of Penicillin- Alexander Fleming first noticed that the mold penicillium notatum inhibited bacterial growth in 1928. Found it too difficult to isolate however. In 1940, Florey and Chain renewed research and isolated the desired compound. A London Police man received the drug in 1941. Made clinically available in 1943. Nobel Prize was won in 1945. PRODUCTION PUSHED ALONG BY WORLD WAR II.

Explain how penicillins work and discuss the effects of modifying the side-chain

Penicillin works by interfering with the chemicals that bacteria need to form cell walls. T

Modifying the side chain à penicillins that are more resistant to the penicillinase enzyme.

Discuss the importance of patient compliance and the effect of overprescription

Importance of patient compliance- The regiment of taking drugs must be strictly adhered to. Any violation à the profligation of bacteria resistant to the drugs. This is especially true with bacterial treatments for Tuberculosis.

Overpresciption also results in the formation of resistant-bacteria. This is especially true with the use of penicillins in animal feedstock.

VII. Antivirals

State how viruses differ from bacteria

How do bacteria and viruses differ?

• Bacteria have cells, viruses do not
• Bacteria can reproduce on their own, viruses must use a cell’s mechanisms
• Bacteria have metabolic pathways, viruses do not
• Bacteria can grow, viruses cannot
• Bacteria feed to survive, viruses do not
• Bacteria are much larger than viruses

(Seriously…if you can’t get this question after 4 years of Biotechnology hell, something is wrong with you)

Describe the different ways in which antiviral drugs work

How anti-virals work:

• Vaccines help to build up an immunity prior to infection (Innoculation)
• Altering the cell’s genetic material so that viruses cannot use them to multiply
• Blocking enzyme activity within the host cells to prevent replication
• Altering ribosomes to prevent their use for replication

Discuss the difficulties associated with solving the AIDS problem

Difficulties with solving the AIDS problem:

• Attacks specific white blood cells (decreasing body’s ability to fight)
• Hinders the body’s ability to fight infection
• Increased susceptibility of patient to weaker pathogens that the immune system normally fights off
• Undergoes metabolic reactions similar to the cell, so antivirals are hard to create
• Also, quick mutation slows ability to create antivirals
• High price of anti-retrovirals exacerbates problems
• Socio-cultural issues remain (due to associations with promiscuity and homosexuality)

X. Mind-Altering Drugs (It’s easier to cover these first before moving onto drug design)

Describe the effects of the following drugs:

GROOVATATIONAL MIND ALTERING TABLE OF DOOM!

Drug	Effects
Lysergic acid diethylamide (LSD)	Extreme hallucinations, magnified perception, decreased judgement, relaxation and/or tension (depending on the user), dilated pupils, increased heart rate, “bad trips,” flashbacks. Tolerance disappears and disappears rapidly. Addiction rare
Mescaline	Color hallucination (milder than LSD), decreased appetite, liver damage, 12 hour trips, increased damage w/ alcohol
Psilocybin	Mild hallucinations, magnified perception, relaxation, 4 hour trip Tolerance limited. Addiction not seen
Tetrahydrocannabinol (THC)	Low doses: silly + excited feeling. High doses: increased perception, very mild hallucinations, joy à anxiety, depression, panic, and fear. Decision making decreased No tolerance. Mild psychological dependence

Discuss the structural similarities and differences between LSD, mescaline, and psilocybin

Indole- Heterocyclic amine compound with N as part of the ring and fused to benzene

Drug	Indole Ring?	Other Features
LSD	Yes	Dietyl amine side chain Non-polar structure (à easy diffusion into brain and placenta)
Mescaline	No	Benzene ring (not fused like indole) Primary amine group
Psilocybin	Yes	Dimethylamine side chain Dihydrogen phosphate

Discuss arguments for and against the legalization of cannibas

Arguments for the Legalization of Cannabis

• Medical uses
• Relief pressure in eyeball for Glaucoma patients
• ↑ appetite in AIDS patients
• Relieve nausea from Chemotherapy patients (and ↑ appetite)
• Better quality control and fewer harmful impurities
• Dissociate cannabis from environments where “hard” drugs are available

Arguments against the Legalization of Cannabis

• Respiratory problems due to inhaling smoke
• Regular use à Suppressed immune system
• Decreased fertility in men
• Birth defects due to chromosomal abnormalities
• Cannabis users move on to “harder” drugs

VIII. Drug Action

Describe the importance of geometrical isomerism in drug action

Geometrical Isomerism- Two molecules “flipped” functional groups due a double bond restricting rotation. Have different physical properties (polarity, solubility, bp, mp)

Cisplatin- Heavy metal complex with two Cl and two NH­₃ ligants in the cis position

How cisplatin works:  Cisplatin is used in chemotherapy. The neutral complex exchanges Cl^- ions with H₂O in the body, forming a positively charged complex. This positively charged species becomes attracted to the negatively charged DNA, specifically 2 adjacent guanines. The H­₂O is released as the Pt binds to nitrogen, inhibiting the cell’s DNA repair process and à cell death. The trans isomers could not bind in this way.

Discuss the importance of chirality in drug action

Enantiomers- Two non super-imposable molecules constructed around a central (chiral) carbon

Racemic mixture- Mixture containing two enantiomers of a single compound

Importance of chirality: While biological processes will produce only one enantiomer of a compound, in vitro (laboratory) manufacturing à racemic mixture. While one enantiomer can be pharmacologically active, the other can have no effect or possibly even a negative one. It is important to make sure the patients are receiving positively functioning drugs to ensure both improvement of the patient and safety.

Thalidomide tragedy- Thalidomide was a compound prescribed to treat morning sickness in pregnant women and sold as a racemic mixture. While the R isomer was safe, the S isomer caused birth defects in the fetus. The drug was pulled from the market and it was discovered that the enantiomers inter convert (RàS and vice versa).

Review Organic Chem notes to ensure you can identify chiral carbons!

Discuss the importance of the beta-lactam ring in penicillin

Beta-lahctam- Ring composed of a Nitrogen and 3 Carbon atoms (one C=O) bonded in a square planar ring (90^o). This unnatural configuration à stress on bonds, so they generally will split between the N and C=O (i.e. within the amide group) and bind to peptides

Action of Penicillin- Beta-lactam ring breaks and binds to a specific enzyme that synthesizes bacterial cell walls. Without this enzyme, the cell will burst and die. Some bacterial enzymes protect against penicillin by severing the beta-lactam ring.

Changing the Penicillin Side Chain à derivatives that prevent the enzyme from binding to the ring

Explain the increased potency of diamorphine (heroin) compared to morphine

Dimorphine- Also known as heroin, this drug is similar to morphine, but contains two Ester groups instead of –OH groups

Compared to morphine, dimorphine is more potent

Why is morphine more potent?

The body is a very aqueous which makes soluble drugs easy to pass around the body. However, any drugs targeting the brain and CNS must past a non-polar membrane barrier surrounding the brain. While some morphine (polar) is able to pass through this layer, a large amount of heroin (non-polar, due to the esters) can penetrate the barrier. After passing the barrier, heroin re-converts back to morphine and is absorbed into the CNS. This makes it not only more powerful, but more addicting as well

IX. Drug Design

Discuss the use of a compound library in drug design

How drugs used to be discovered- Trial and error

Rational drug design- The action of designing drugs to specifically counter a target molecule in the body

Compound Libraries- Databases of compounds and related molecules (such as those with altered functional groups and geometries) kept by pharmaceutical companies. These are used to identify potential drugs that are similar to the lead compound but with greater potency and lesser side effects. Improves the efficiency of finding new drugs

Explain the use of combinational and parallel chemistry to synthesize new drugs

Combinational Chemistry- Technique in which machines are used to synthesize a large number of compounds and then screen them for biological activity, forming a “combinational library” of information

Solid-phase chemistry- Also called the “mix-and-split” technique. Resin beads with linking groups were placed into 3 separate vats of amino acids. They were then combined, mixed, and split again into 3 separate vats with another amino acid added to each. The process is then repeated until a series of unique polypeptides were created.

How the number of combinations can be found- Taking the number of amino acids used and then raising them to an exponent equal to the number of mix-and-splits

Example: If 3 amino acids were used to create 4 amino-acid chains, then there would be 3⁴ (or 81) different combinations.

Parallel Chemistry- A highly reactive intermediate is formed that is put in many vials with various reagents then added. An automated version of this process can create up to 144 different compounds, each in separate reaction tubes

Describe how computers are used in drug design

CAD (Computer-aided Design)- Software has been invented that allows scientists to construct 3-D representations of a compound and test to see how they would react against specific biological targets. Target sites can be identified using NMR and X-ray crystallography techniques. Compound libraries can be used to ID similar compounds

Discuss how the polarity of a molecule can be modified to increase its aqueous solubility and how this facilitates its distribution around the body

How polarity affects distribution- Polar molecules are generally more soluble, and therefore can be more easily distributed throughout the body.

How to make a substance more polar- Carboxylic acids (acidic) and amines (bases) can be easily converted into soluble ionic salts.

Soluble aspirin- The carboxylic acid is converted into a salt group, making it more effective at dissolving

Prozac- The amine is reacted with HCl to form a soluble salt

Describe the use of chiral auxiliaries to form the desired enantiomer

Chiral auxiliary is used to convert a non-chiral molecule into just the desired enantiomer, thus avoiding the need to separate enantiomers from a racemic mixture. It works by attaching itself to the non-chiral molecule to create the stereochemical conditions necessary to force the reaction to follow a certain path. Once the new molecule has been

formed, the auxiliary can be taken off (recycled) to leave the desired enantiomer. An example is the synthesis of Taxol, an anti-cancer drug.