Option D: Medicinal Chemistry SL Flashcards
Define a drug.
A substance that affects bodily processes.
Define medicines.
Pharmaceutical drugs that are used for the treatment or prevention of a disease.
What is a drug or medicine?
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)
Define a placebo.
An inert substance given to patients for its probable beneficial effects. Suggests at the importance of the body’s natural healing process.
Give the methods of drug administration.
- 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).
Describe parenteral drug administration.
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.
What is the activity of drugs determined by?
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.
Define bioavailability of drugs.
The fraction of the administered dosage of a drug that enters the bloodstream, thereby accessing the site of action.
What is the bioavailability of drugs affected by?
- 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.
What are the main steps in the development of synthetic drugs?
- Identification of the need- Identification of the structure of the drug- Possible methods of synthesis- Extraction and yieldIt is then subjected to thorough laboratory and clinical pharmacological studies.
Define therapeutic window.
A measure of the relative margin of safety of a drug.
Give a quantitative description of the therapeutic window.
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.
Explain wide and narrow therapeutic windows.
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.
What does tolerance towards a drug mean?
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.
Define analgesics.
Drugs that relieve pain without causing loss of consciousness. Can be mild (eg. aspirin) or strong (eg. opioids).
Describe the synthesis of aspirin.
Salicylic acid + ethanoic anhydride -> aspirin + ethanoic acidConc. 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.
Describe how the purity of aspirin can be determined.
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.
How does aspirin work?
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.
Why does converting aspirin to an ionic salt not increase its bioavailability?
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.
What are the uses of aspirin?
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.
What are the disadvantages of aspirin use?
- 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.
Define synergistic effect/synergy.
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.
Define antibacterials/antibiotics.
Drugs that inhibit the growth of, or kill, microorganisms that cause infectious diseases. They are selective.
Describe the historical development of penicillin.
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.
How does penicillin work?
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.
