Option D Medicinal Chemistry SL Flashcards

1
Q

Define a drug.

A

A substance that affects bodily processes.

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2
Q

Define medicines.

A

Pharmaceutical drugs that are used for the treatment or prevention of a disease.

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3
Q

What is a drug or medicine?

A

A chemical that does one or more of the following:
- alters incoming sensations
- alters mood or emotions
- alters physiological state (including consciousness, activity level or co-ordination)

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4
Q

Define a placebo.

A

An inert substance given to patients for its probable beneficial effects. Suggests at the importance of the body’s natural healing process.

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5
Q

Give the methods of drug administration.

A
  • Oral. Taken by mouth. Eg. tablets.
  • Inhalation. Vapour breathed in. Eg. asthma medication, nicotine.
  • Skin patches. Absorbed directly from the skin into the blood. Eg. hormone treatments, nicotine patches.
  • Suppositories. Inserted into the rectum. Treatments for digestive illnesses.
  • Eye or ear drops. Delivered directly to the opening. Treatments for eye/ear infections.
  • Parenteral (by injection).
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6
Q

Describe parenteral drug administration.

A

Parenteral refers to injection. There are three types.
1) Intramuscular (into the muscle). Used for many vaccines.
2) Intravenous (into the blood). The fastest method of injection. Used for local anaesthetics.
3) Subcutaneous (under the skin). Used for dental injections.

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7
Q

What is the activity of drugs determined by?

A

Their ability to bind to a specific receptor in the body. The binding of a drug to a receptor prevents or inhibits the normal biological activity and so interrupts the development of the disease.

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8
Q

Define bioavailability of drugs.

A

The fraction of the administered dosage of a drug that enters the bloodstream, thereby accessing the site of action.

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9
Q

What is the bioavailability of drugs affected by?

A
  • The method of administration.
    Intravenous drugs have a bioavailability of 100% as they are delivered directly to the bloodstream. Drugs taken orally are often broken down during digestion before reaching the bloodstream, so their dosage needs to be about 4 times higher than intravenous drugs.
  • The polarity (solubility of the drug).
    Water solubility is important for circulation in the blood but lipid solubility is important to help the passage of the drug across cell membranes. So very hydrophilic (polar) drugs are poorly absorbed because of their inability to pass through cell membranes and very hydrophobic (non-polar) drugs are poorly absorbed because of their insolubility in aqueous bodily fluids.
  • The type of functional groups present in the drug.
    Drugs that contain an acidic or basic group can be chemically modified to form an ionic salt thus increasing their bioavailability. This is because ionic salts are more soluble as they form stronger ion-dipole interactions with water.
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10
Q

What are the main steps in the development of synthetic drugs?

A
  • Identification of the need
  • Identification of the structure of the drug
  • Possible methods of synthesis
  • Extraction and yield

It is then subjected to thorough laboratory and clinical pharmacological studies.

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11
Q

Define therapeutic window.

A

A measure of the relative margin of safety of a drug.

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12
Q

Give a quantitative description of the therapeutic window.

A

The therapeutic index. (The ratio between the dosage of the drug that causes a toxic effect and the dosage that causes a therapeutic effect).

In humans, therapeutic index = TD₅₀/ ED₅₀.
In animals, therapeutic index = LD₅₀/ ED₅₀.
*The lethal dose cannot be determined in humans, so a toxic dose is used instead.

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13
Q

Explain wide and narrow therapeutic windows.

A

A wide therapeutic window means that there is a large margin between the effective and toxic dose. The drug is safer.

A narrow therapeutic window means that there is a higher risk of an overdose. Only a small increase in the dose may produce toxic effects as there is a small margin between the effective and toxic dose.

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14
Q

What does tolerance towards a drug mean?

A

Over time, and with regular use, a user needs increasing amounts of a drug to achieve the original biological effect. Tolerance towards a drug increases the risk of fatal overdose because higher doses are used, which increases the chances of toxic side-effects.

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15
Q

Define analgesics.

A

Drugs that relieve pain without causing loss of consciousness. Can be mild (eg. aspirin) or strong (eg. opioids).

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16
Q

Describe the synthesis of aspirin.

A

Salicylic acid + ethanoic anhydride -> aspirin + ethanoic acid

Conc. H₂SO₄ (or H₃PO₄) is added to the reaction mixture which is warmed gently. An esterification reaction occurs. The product is cooled to form crystals which are then suction filtered and washed with cold water. Aspirin has low solubility in cold water so this process removes the soluble acids, not the aspirin. The aspirin is then purified in a process called recrystallisation. The impure crystals are dissolved in hot ethanol. Water is then added and the solution is cooled slowly. The aspirin will recrystallise and the unreacted salicyclic acid will remain dissolved in the solution.

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17
Q

Describe how the purity of aspirin can be determined.

A

By its melting point. Pure substances have well defined melting points. Pure aspirin has a melting point of 128-140°C. Impure aspirin would have a lower and less well defined melting point.

Secondly, through infra-red spectroscopy. The functional groups that are specific to salicylic acid and aspirin can be identified.

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18
Q

How does aspirin work?

A

Aspirin works by preventing the enzyme prostaglandin synthase from being formed at the site of injury/pain. Prostaglandin synthase is responsible for the synthesis of prostaglandins, which produce swelling, cause fevers and transmit pain to the brain. By reducing the concentration of prostaglandins, aspirin reduces inflammation, fever and pain.

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19
Q

Why does converting aspirin to an ionic salt not increase its bioavailability?

A

Ionic salts of aspirin are more soluble because they form stronger ion-dipole interactions with water. However, the ionic salt is converted back into the unionised form in the acidic environment of the stomach. So converting aspirin to an ionic salt does not affect its bioavailability.

*The bioavailability can be increased by administering aspirin intravenously.

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20
Q

What are the uses of aspirin?

A

As a mild analgesic (painkiller) and an anticoagulant (prevents blood clots that can cause heart attacks or strokes). Its anti-inflammatory properties also mean that it can be taken for arthritis and rheumatism.

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21
Q

What are the disadvantages of aspirin use?

A
  • Bleeding of the stomach lining. This disadvantage is increased by drinking alcohol (called a synergistic effect).
  • Accidental poisoning in infants. Additionally, in children under 12yrs, it has been linked to the development of Reye’s disease.
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22
Q

Define synergistic effect/synergy.

A

The interaction between two or more drugs taken at the same time when their combined effect is greater than the sum of their separate effects.

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23
Q

Define antibacterials/antibiotics.

A

Drugs that inhibit the growth of, or kill, microorganisms that cause infectious diseases. They are selective.

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24
Q

Describe the historical development of penicillin.

A

In 1928, Alexander Fleming noticed that mould growing on a petri dish of cultured bacteria generated a clear region around it where no bacteria colonies grew. He concluded that the mould produced something which inhibited bacteria growth.

In the 1940’s, Florey and Chain successfully isolated penicillin. It was used during World War II and saved thousands of lives.

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25
Q

How does penicillin work?

A

The molecule penicillin contains a beta-lactam ring. This is responsible for penicillin’s antibacterial properties.

The beta-lactam ring interferes with the formation of bacterial cell walls by inhibiting the enzymes responsible for creating cross links in the cell wall (transpeptidase). It is sterically strained so breaks easily and binds irreversibly to transpeptidase. This inactivates the enzyme and prevents cross links from forming. Thus the cell wall is weaker and water is able to enter. This increases the osmotic pressure and causes the cell to burst and die.

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26
Q

What are the disadvantages of penicillin?

A
  • Penicillin G is broken down by stomach acid so has to be injected directly into the blood.
  • Its use is limited as many people are allergic.
27
Q

Describe antibacterial resistance to penicillin.

A

Penicillin resistant bacteria produce an enzyme called penicillinase. This deactivates penicillin G.

However, different forms of penicillin that are able to withstand penicillinase are able to be synthesised by modifying the side chain. The side chain can also be modified to give increased resistance to breakdown by stomach acid, so some forms of penicillin can be taken orally.

28
Q

Give three causes of antibiotic resistance.

A

1) Overprescription of antibiotics eg. used as treatment for a common cold.
2) Misuse. Not completing the given course of antibiotics.
3) The use of antibiotics in animal feed-stocks. The antibiotics are passed through the meat and dairy products to humans.

29
Q

What is the response to antibiotic resistance?

A

The control and restriction of the use of antibiotics (prescription only drugs).

30
Q

How do opiates work?

A

Opiates bind temporarily to opioid receptors in the brain. This prevents the transmission of pain impulses without depressing the central nervous system.

31
Q

Give the advantages and disadvantages of opiates.

A

Advantages:
- They provide relief for severe or acute pain.
- They can improve the quality of life.
- They are administered intravenously so the drug has an almost instantaneous effect.

Disadvantages:
- Regular usage can cause dependency/addiction (for this reason they are only available by prescription and their usage must be monitored with medical supervision).
- Users feel euphoria, a lack of self control and can indulge in dangerous behaviour.
- Users build up tolerance to the drug, increasing the risk of overdose upon prolonged use.

32
Q

What is the blood brain barrier?

A

The blood brain barrier is a layer of tightly packed cells that protect the brain by restricting the passage of substances from the bloodstream into the brain. It is largely composed of lipids, which are non-polar and hydrophobic molecules. Therefore, for a substance to pass through the barrier it must be non-polar and lipid soluble.

33
Q

Give the therapeutic uses of codeine, morphine and diamorphine.

A

Codeine:
- Cough medications.
- Short term treatment of diarrhoea.

Morphine:
- Used to treat severe pain eg. advanced cancer.

Diamorphine (heroin):
- Only legal in a few countries for the relief of severe pain. The most rapidly acting and most abused narcotic.

34
Q

Describe the polarity of morphine.

A

Morphine has two hydroxyl groups which makes it a polar molecule. This means it has a limited ability to cross the blood brain barrier.

35
Q

How is diamorphine produced?

A

Diamorphine is produced from morphine in an esterification reaction. The two hydroxyl (OH) groups in morphine are converted into ester (COO) groups.

Morphine + acetic anhydride -> Diamorphine + ethanoic acid

Diamorphine is a less polar molecule than morphine so is more lipid soluble. This means it is able to cross the blood brain barrier more rapidly and in higher concentrations than morphine.

36
Q

How is codeine produced?

A

Codeine is produced from morphine in a methylation reaction. A hydroxyl (OH) group is converted into a methoxy group (OCH₃).

Codeine is a less polar molecule than morphine so is more lipid soluble. This means it is able to cross the blood brain barrier more rapidly than morphine. However, this reaction also reduces the ability of codeine to bind to opioid receptors in the brain, making it a weaker analgesic than morphine.

37
Q

Describe the effectiveness of codeine, morphine and diamorphine.

A

In order of increasing strength as analgesics, increasing narcotic effects and increasing side effects;
Codeine -> morphine -> diamorphine (heroin)

38
Q

Describe the side effects of analgesics.

A
  • Constipation.
  • Suppression of the cough reflex.
  • Constriction of the pupil in the eye.
  • Narcotic effects (eg. euphoria, feeling of contentment, lessening of fear/anxiety and withdrawal symptoms).
39
Q

Describe the acidity of the stomach.

A

The stomach releases hydrochloric acid from parietal cells in the gastric glands. This kills bacteria which has been ingested and provides the optimum environment (pH) for the digestive enzymes.

40
Q

What are the consequences of gastric juice?

A

Acid indigestion (feelings of discomfort from excess acid in the stomach).
Heartburn (acid from the stomach rising into the oesophagus - often called acid reflux).
Ulceration (damage to the lining of the gut wall, resulting in tissue loss and inflammation).

41
Q

Give the medical treatment for dyspepsia.

A

Antacids
H₂ receptor antagonists
Proton pump inhibitors

42
Q

What are antacids and how do they work?

A

Antacids are weakly basic compounds which are used to reduce excess stomach acid (known as gastric juice). They work by neutralising the excess hydrochloric acid in neutralisation reactions.

43
Q

Why can strong bases not be used as antacids?

A

Because they can damage the stomach.

44
Q

What are two additional agents often added to antacids to reduce side effects?

A

1) Alginates. These produce a neutralising layer which prevents acid in the stomach from rising into the oesophagus causing heartburn.
2) Antifoaming agents (eg. dimethicone) to prevent bloating and flatulence caused by the production of carbon dioxide.

45
Q

Give the equations with hydrochloric acid for:
Calcium hydroxide
Magnesium hydroxide
Aluminium hydroxide

A

Ca(OH)₂ + 2HCl -> CaCl₂ + 2H₂O
Mg(OH)₂ + 2HCl -> MgCl₂ + 2H₂O
Al(OH)₃ + 3HCl -> AlCl₃ + 3H₂O

46
Q

Give the equations with hydrochloric acid for:
Sodium hydrogencarbonate
Sodium carbonate

A

NaHCO₃ + HCl -> NaCl + H₂O + CO₂
Na₂CO₃ + 2HCl -> 2NaCl + H₂O + CO₂

47
Q

How can acidic or basic buffer solutions be prepared?

A

By mixing a weak acid/base with its salt.

48
Q

Give two types of stomach acid inhibitors and give an example of each.

A

H₂-receptor antagonists (Ranitidine).
Proton pump inhibitors (Omeprazole).

49
Q

Describe the action of H₂-receptor antagonists and proton pump inhibitors.

A

H₂-receptor antagonists work by blocking the H₂ receptors in the stomach. Histamine binds to H₂ receptors and initiates a sequence of events which leads to the release of acid into the stomach. The H₂-receptor antagonists compete with histamine for binding, therefore reducing the amount of acid produced.

The gastric proton pump pumps protons (H+ ions) into the stomach. Proton pump inhibitors inhibit the proton pump which prevents the release of H+ into the stomach. They have a longer lasting effect (up to 3 days).

50
Q

Why can antibiotics not be used to treat viral infections?

A

Antibiotics work by disrupting the formation of the cell wall however viruses do not have a cell wall so antibiotics are ineffective against them.

51
Q

Why are viruses more difficult to treat than bacteria?

A
  • Viruses mutate quickly so adapt to drugs
  • Bacteria are more complex so can be targeted in more ways. Viruses lack subunits that can be targeted by antibacterials.
  • Bacteria can be killed by simple chemical agents but viruses must be targeted on a genetic level.
52
Q

How do antivirals work?

A

Antivirals work by preventing or hindering the release of viruses from the cell.

53
Q

Describe the role of hemagglutinin and neuraminidase in the flu viruses.

A

Hemagglutini is a glycoprotein that enables the virus to dock with the host cell before it enters. (Helps the virus to enter the cell).

Neuraminidase is an enzyme which catalyses a cleavage reaction that allows the newly produced viral particles to escape from the host cell and spread infection. It does this by ‘snipping’ off a sugar molecule from the glycoproteins on the surface of the host cell membrane. (Helps the virus to exit the cell).

54
Q

Describe how the antivirals oseltamivir and zanamivir work.

A

Both oseltamivir and zanamivir work by inhibiting the enzyme neuraminidase by binding to its active site. Neuraminidase is an enzyme found on the surface of the influenza virus which enables the virus to be released from the host cell. By inhibiting this enzyme, the virus is prevented from leaving the host cell and spreading the infection.

55
Q

What are the difficulties associated with treating HIV?

A
  • HIV destroys helper T cells (the cells that defend the body against viruses).
  • It can mutate rapidly.
  • High price of antiretroviral drugs.
56
Q

Factors relating to the AIDS problem.

A
  • Availability and cost of condoms.
  • Social stigma, ignorance and misinformation.
  • Illegal activities (drug use, prostitution).
  • Availability of medical services and the cost of antiretrovirals.
57
Q

What is the treatment for HIV infection?

A

Antiretroviral drugs (ARVs). These do not provide a cure but they can give lasting suppression of HIV infection and when used during pregnancy can prevent transmission of the disease from mother to child. However, they are very expensive.

58
Q

Discuss solvent waste.

A

The synthesis and extraction of most drugs involves multiple steps. In this process, organic solvents are used. These may be toxic and are often left over at the end of the process, resulting in issues of disposal. Disposal often involves incineration, which can release toxins into the environment.

59
Q

How are the suitability of solvents assessed?

A

1) Toxicity to workers - if the solvent is carcinogenic or associated with other health issues.
2) The safety of the process - whether the solvent is highly flammable, explosive or produces toxic byproducts.
3) Harm to the environment - whether the solvent will contaminate soil and ground water, cause ozone depletion or contribute to the formation of greenhouse gases.

60
Q

Explain high-level and low-level waste.

A

High-level waste gives off large amounts of ionizing radiation for a long time. The isotopes have long half-lives. eg. Cs-137

Low-level waste gives off small amounts of ionizing radiation for a short time. The isotopes have short half-lives. eg. protective clothing, gowns, gloves etc.

61
Q

How is low-level and high-level waste disposed of?

A

Low-level waste (eg. protective clothing) is stored in sealed containers until the isotopes have decayed. It is then disposed of by conventional means.

High-level waste is first stored under water in reinforced cooling ponds for 5-10 years and then transferred to dry storage in heavily shielded structures, often underground.

62
Q

How are antibiotics released into the environment?

A

1) The use of antibiotics in animal feeds. Healthy animals are given antibiotics to prevent livestock diseases. These pass through the animal waste into the soil and water and enter the human food chain.
2) Improper disposal of antibiotic medicines by hospitals and households.
3) Antibiotics excreted by humans in urine. Low concentrations of antibiotics then end up in the sewage system, which ends up in the drinking water supply.

63
Q

What are the issues with the sythesis of oseltamivir?

A

The synthesis of oseltamivir requires shikimic acid, which is extracted from the pods of star anise. Extracting shikimic acid is a complex, ten-step process which takes 6-8 months. It also has a low yield. For 30kg of star anise only 1 kg of shikimic acid is produced.

In 2005 there was a worldwide shortage of oseltamivir because of limited supply of star anise.

64
Q

Give some applications of Green Chemistry that help with the production of oseltamivir.

A

1) The production of shikimate from fermentation reactions of genetically engineered bacteria.
2) The harvesting of shikimate from the needles of several varieties of pine trees. Although this gives a low yield, the needles represent a plentiful resource.