IB Chemistry Option D: Medicinal Chemistry (SL)

D.1 What is drug development?

Direct research and development based on traditional leads for medicines or drugs

D.1.1 Outline the main stages (in order) of the development of a new drug.

Identification of need, determination of structure, synthesization, extraction, measurement of percent yield, testing

Dynthesis of new drugs

1. Discovery - natural source is identified and compounds are extracted
2. Pre-clinical animal trials test about 250 compounds
3. Passing compounds are used in clinical trials w increasing number of volunteers
4. The final compound is selected, approved, and manufactured to produce a new drug.

Means of drug administration

Inhalation, ingestion, rectal suppositories, injections (into blood, muscle, or under skin), absorption

One advantage of oral drug administration.

Oral administration is easy and preferable to patients

One disadvantage of oral drug administration.

Drugs that are administered orally may take longer to be absorbed into the body and absorption can be unpredictable due to degradation by stomach acids and enzymes

Describe how drugs function?

Target specific cells called target sites, and bind with them to inhibit or promote certain effects.

Explain the meaning of the term "tolerance."

The body's adaptation to a drug, which causes a need for a higher dosage in order to achieve the original effect

Define bioavailability

The amount of the administered dosage which reaches the target site - varies based on structure, means of administration, dosage of the drug.

What role does structure play in drug efficiency?

- They need to be absorbed into the body and cells
- Polar groups allow blood absorption (Ex. hydroxl, carboxyl, amino groups)
- Nonpolar to pass through cell membranes (Ex. esters, ether, phenyl rings)

What is the therapeutic window and index?

window - The range between the toxic dose and minimum effective dose of a drug

TI = TD50/LD50

What is the significance of the TI value?

Low TI = little difference between effective and toxic dose = MORE DANGEROUS

High TI = large difference between ED and TD = LESS DANGEROUS

Explain the meaning of the term "LD50."

The lethal dose; a sample dosage of a drug that kills 50% of tested lab rats

Explain the meaning of the term "TD50."

The toxic dose; a sample dosage of a drug that is toxic to 50% of humans

Explain the meaning of the term "ED50."

The effective dose; a sample dosage of a drug that has the desired effect on 50% of test subjects

State an effect, other than the alteration of physiological state, of medicines and drugs on the body.

Alteration of mood/emotion OR alteration of sensory perception

Explain the meaning of the term "therapeutic window."

The range of doses between the minimum effective dosage and the dosage that brings about undesirable effects; a wide range is desirable

What is a weak analgesic?

Derivatives of opium, called opiodes, that relieve pain by intercepting stimulus at the source, by stopping prostaglandin production
Ex. Aspirin

How can these drugs be taken

Local ingestion via oral consumption

Describe the reaction used to synthesis aspirin (w reagant + condition)

salicylic acid + acetic anhydride --> Acetylsalicylic acid + acetic acid

Reagents: H2SO4
conditions: heat

Process of Aspirin purification

Recrystallisation

Used to removed remaining impurities to make a more effective drug

Steps in the purification of aspirin

1. Add solvent (i.e. ethanol) and heat to dissolve
2. Set in ice bath to lower temperature to allow crystallisation
3. Collect solid product through filtration of impurities

Methods of test purity (name + describe)

Testing melting point range
- Pure aspirin has MP of 136
- More impure = lower or more different MP

Infrared Spectroscopy (IR)
- Identify number of bonds present

Explain how aspirin's interference with the production of prostaglandins produces an analgesic effect.

The prevention of prostaglandin synthesis produces an analgesic effect because prostaglandins are the molecules that cause pain, swelling, and inflammation.

Define prophylactic.

intended to prevent disease

State one important use for aspirin other than the relief of pain and fever.

Aspirin is also prophylactic, working as an anticoagulant to prevent strokes and heart attack

D.2.1 Describe the side effects of aspirin

Stomach ulcers, tinnitus, bleeding of the stomach lining, risk of hemorrages

D.2.1 State one advantage of the use of paracetamol instead of aspirin.

Paracetamol has less pronounced side effects than aspirin

D.2.1 State one disadvantage of the use of paracetamol instead of aspirin.

Paracetamol has a more narrow therapeutic window

D.2.2 State the type of reaction between salicylic acid and ethanoic anhydride.

Esterification

D.2.2 Deduce the equation of the reaction of salicylic acid with ethanoic anhydride.

salicylic acid + ethanoic anhydride ---> acetylsalicylic acid (aspirin) + ethanoic acid

D.2.2 How can aspirin be made more bioavailable?

- Can be reacted to form SODIUM ACETYLSALICYLATE which is more soluble
- Consumption with alcohol has a synergistic effect

D.2.2. Identify the functional group present in aspirin which allows it to be converted into a salt.

The carboxyl group

D.2.2 Suggest a reagent to be used in order to convert aspirin into a salt.

Sodium hydroxide

D.2.3 What are the uses of penicillin?

This drug is used to treat bacterial infections

D.2.3 Describe the side effects of penicillin

Diarrhea, nausia, fever, rashes

D.2.4 Describe what happens to bacteria when they come into contact with penicillin.

Penicillin will bind to the enzyme that bacteria use to synthesize their cell walls, blocking the active site. The cell wall then breaks, allowing water to enter the cell and causing the cell to burst.

D.2.4 Explain why the beta-lactam ring is important in the mechanism of the action of penicillin.

It's bond angles make it highly strained, allowing it to break/open up.

D.2.4 Explain antibiotic resistance.

Bacteria has evolved to become resistant to antibiotics because resistant mutants survive through treatment and are able to reproduce, creating offspring that are also resistant to specific antibiotic treatments.

D.2.4 Name a bacteria which is resistant to Penicillin + Describe its resistance

Penicillinase is able to break the beta-lactam ring and inhibit the function of the molecule

D.3.4 What are strong analgesics?

Opiates which bind with opioid receptors in the brain to inhibit the central nervous system

D.3 Identify two functional groups that are all present in morphine, codeine, and diamorphine (heroin).

All 3 compounds have a phenyl group and a tertiary amino group (amine).

D.3.4 Compare structure of morphine + derivatives

Morphine - two hydroxyl groups
Codeine - one hydroxyl replaced w alkyl group
Diamorphine - esterification replaces both -OH groups with esters

D.3.4 List opiates in order of strength

Codeine < Morphine < Diamorphine

Why?
Codeine is the least soluble, but has more bioavailability
Morphine is more polar but less bioavailability
Diamorphine has the greatest effect

D.3 State the type of chemical reaction that is used to convert morphine to diamorphine.

Esterification

D.3 Discuss two advantages of using opiates for pain relief.

Strong analgesics (opiates) are fast-acting and more effective.

D.3 Discuss two disadvantages of using opiates for pain relief.

Addiction is potential when using strong analgesics (opiates), and the development of social problems (theft, prostitution) may occur, as well as the development of health problems (AIDS, constipation).

D.3 Explain why heroin (diamorphine) is a more potent drug than morphine.

Heroin is less polar, making it soluble in lipids. This allows it to cross the blood-brain barrier, metabolize into morphine, and bind directly to opiod receptors.

D.3 State the name of a functional group, other than the phenyl group, that is common to aspirin and diamorphine (heroin).

Acetoxy group (OC(=O)CH3)

D.3 Suggest a reagent that could be used to convert morphine into diamorphine.

Ethanoic anhydride

D.3 Suggest how the bioavailability of diamorphine will be affected by its conversion into an ionic salt.

The bioavailability will increase because the compound becomes more soluble.

D.3 Suggest which (of diamorphine, morphine, and codeine) will be the most soluble in water.

Codeine

D.3 Suggest which (of diamorphine, morphine, and codeine) will be the most soluble in lipids.

Diamorphine

D.3.4 What is methadone?

An opiate derivative which can be used to treat addiction without the euphoric effects

D.4.1 What are antacids?

Drugs taken orally to relieve symptoms of strong stomach acid (i.e. heart burn, indigestion, acid reflux)

D.4.1 What is an alignate

An agent added to create a neutralising layer to stop reflux

D.4.1 What is an antifoaming agent + example?

An agent which stops the foaming of mucus caused by increased gas production.
Ex. dimethicone

D.4.1 Side effects of Antacids

Kidney stones, blood pH too low, renal failure, increased bloating/flatulence, hypertension

D.4.1 State the equation for the reaction between aluminum hydroxide and hydrochloric acid.

Al(OH)3 + 3 HCl ---> 3H2O + AlCl3

D.4.1 State the equation for the reaction between magnesium carbonate and hydrochloric acid.

MgCO3 + 2HCl ---> MgCl2 + H2CO3

D.4.1 State which compound (aluminum hydroxide or magnesium carbonate) will neutralize the most acid.

Aluminum hydroxide

D.4.2 Buffering action of the stomach

Stomach is able to regulate is pH using a buffer of carbonic acid and hydrogen carbonate

D.4.2 How do you calculate the pH of a buffer solution?

Henderson-Hasselbalch equation

pH = pKa + log ([A-]/[HA]

A- = conjugate base
HA = weak acid

D.4.2 What are methods of reducing secretion of stomach acid

1) inhibiting acid synthesis
2) inhibiting acid secretion
--> Caused be interfering with key receptors in the process

D.4.2 Name different receptors in acid production cells

Histamine
Gastrin
Acetylcholine

D.4.2 Describe the function of a H2 Receptor Antagonist

-Binds with histamine receptor to stop production of acid.

D.4.2 Give example of one such antgonist + structure

Ranitidine/Zantog
- ionic charges make it soluble
- 40-80% bioavailability
- Must be turned into active metabolite

D.4.2 Describe function of Proton Pump Inhibitor

- Restrict acid release by binding with H+ pumps in the cell membranes
- More effective than H2 receptor antagonist

D.4.2 Example of PPI + structure

- Omeprazole
- higher bioavailability - lasts 1-3 days
- Must be turned into active metabolite

D.5.1 State differences between viruses and bacteria.

- Viruses have a protein coating while bacteria have cell walls/membranes.
- Virus need host to metabolise, bacteria metabolise themselves
- Virus much smaller / Bacteria bigger

D.5.1 Describe steps of virus reproduction

1. Virus attaches to host cell
2. Viral DNA injected into cell
3. Viral DNA replicated using metabolic processes of host
4. New protein coats for viruses are made
5. Mature virions assembled in cell
6. Cell ruptures and releases mature viruses

D.5.1 How the body fights viruses

- Helper T-Cells must recognise viral/abnormal cells before new viruses are released
- A secondary viral infection is fought by memory B-cells releasing antibodies to mark viruses

D.5.1 Immunity via vaccines

- Fight virus before infection
A weakened form is injected and causes an immune response without the infection = body ready to fight if actual virus enters

D.5.1 Use of antiviral medicines

- Fight virus after infection
- Target different steps in the viral process
- Ex. block entrance, interfering w/ replication or release from cells

D.5.2 What is influenza?

- The flu
- Causes: headache, fever, runny nose, sore throat, etc.

D.5.2 Name two antiviral drugs for influenza

Oseltamivir /Tamiflu and Zanamivir/Relenza

D.5.2 Describe their function

Block rupturing of cell to release new virus by binding to neuraminidase

D.5.2 Compare structure

Oseltamivir: ester, carbonyl group
Zanamivir: alcohol, carboxyl
Bother: ether

D.5.3 What is HIV?

A retro virus that attacks the bodies T-cell that compromises the body's immune system, leading to AIDS

D.5.3 What is a retrovirus?

Contains viral RNA not DNA - therefor is more subject to mutation

D.5.3 What is the ART cocktail?
What does it do?

- A mixture of drugs which target various stages in the viruses cycle
- Decrease the rate of transmission of the virus, but do not stop HIV

D.5.3 What is antigenic drift mutation?

Small mutations in viral reproduction make new strains

D.5.3 What is antigenic shift mutation?

Two strains of virus resulting in a new variation

D.6.1 What is medical waste?

The leftovers created by the product and use of medicine which can have negative effects on the environment

D.6.1 What are leftover solvents?

Drug synthesis often uses solvents; these are majority of waste
Ex. water, alcohols, alkanes, benzenes

D.6.1 What are the dangers of nonpolar solvent waste (Name three)?

- Benzene = carcinogenic
- Hexane = numbness in limbs and stunted plant growth
- Ethers = dizziness in mammals vs. dehydration in plants

D.6.1 What creates antibiotic waste?

Incorrect disposal or incomplete use of perscription

D.6.1 Impacts of antiobiotic waste?

- Increased antiobiotic resistance
- Harmful to bacteria in ecosystems
- Influence in food systems (water/food sources) spreads resistance in humans
= Reduced efficiency

D.6.2 What is nuclear medical waste?

Waste produced by use of radioactive substances (i.e. radioisotopes)

D.6.2 Difference between high-level waste and low-level waste

High-level waste account for 4% of waster
- Very radioactive
- Stored in wet storage so it can decay and be shielded
Low-level waste accounts for 90%
- Protective clothing, tools, etc.
- Can be disposed in dry storage

D.6.3 Impacts of incorrect disposal

- Radiation exposure can have bad impacts
- Radiation sickness
- DNA mutation leading to disabilities
- Cancer, infertility, death

D.6.4 What is green chemistry?

A branch of science attempting to reduce waste and energy consumption related to production

D.6.4 Solutions to solvent waste

- Fraction distillation allows for recycling of solvents
- Biodegradation breaks down solvents (i.e benzene) using bacteria and organic compounds

D.6.4 Alternative synthesis methods ex. Tamiflu

Biosynthesis demands less from natural sources and produces less waste and energy.

Extra: Calculate experimental yield using starting mass and molar mass of reactant and mass and molar mass of product, and

Theoretical yield (g) = moles of reactant (mols) x mass of product (g)

Percent yield (%) = actual yield / theoretical yield