Option D - Medicinal Chemistry Flashcards
List the possible ways of administration of drugs and examples of medicines for each.
- oral - mouth - tablets
- inhalation - breathed in - asthma medications (bronchodilators).
- skin patches - absorbed from skin into the blood - hormone treatments.
- suppositories - inserted into the rectum - digestive illnesses treatments
- eye/ear drops - come on - eye/ear infections (who would’ve expected).
List the types of injections with the corresponding level of tissue the substance is injected into.
- intramuscular - muscle (wow)
- subcutaneous - subcutaneous tissue
- intravenous - veins
- intradermal - epidermis
Define bioavailability of a drug and state its significance.
Amount of a drug that reaches the bloodstream.
(higher in intravenous)
Important to consider in choosing dosage.
Define the first-pass effect.
Initial metabolism/alteration of a (orally ingested usually) drug that occurs in the liver after it is absorbed from the gastrointestinal tract and before it enters the systemic circulation.
(reduction in the amount of active drug entering the bloodstream)
State the advantages for drug solubility of both water and lipid solubility.
- water solubility: crucial for circulation in the aqueous solution in the blood.
- lipid solubility: helps in the passage of drug through membrane.
Define and thus distinguish tolerance and addiction.
Tolerance - a person given a repeated dose of a drug responds with a reduced response to the drug of the same dose.
Addiction - occurs when a patient requires a drug to feel normal and suffers from withdrawal symptoms if the drug is not taken.
Define the therapeutic index (TI) of a drug and list its formula.
Ratio comparing the dose of a drug required to produce a therapeutic response (ED50) to the dose that causes toxicity (TD50)
TI = TD50 / ED50
State the correlation between the TI of a drug and its safety.
Higher TI -> safer drug.
Define the ED50.
Effective dose 50%
Dose of a drug required to produce a therapeutic effect in 50% of the population/experimental subjects.
Define LD50.
Lethal dose 50%
Dose of a drug lethal/ causing death in 50% of the population/experimental subjects.
Define TD50.
Toxic dose 50%
Dose of a drug required to produce a toxic effect in 50% of the population/experimental subjects.
Distinguish the TI testing in animals vs in human subjects.
TI (animals) = LD50/ED50
TI (humans) =TD50/ED50
List the stages of drug development.
- Identify target molecule within the body.
- Find lead compound with desired pharmaceutical activity.
- Optimize the lead compound by synthesizing and testing chemically related analogues.
- Combinatorial chemistry to produce and test candidate medicines.
- Laboratory testing
- Animal testing
- Determine TI
- Human trials (three phases)
- Evaluate drug effectiveness based on real medication vs placebo in phase III.
- Post-marketing surveillance programs.
- Adverse reaction monitoring.
Define the prostaglandins.
Chemical stimulating the pain receptors, released from damaged cells, which mediate the inflammatory response.
State the principle of functioning of prostaglandins.
Causing blood vessel dilatation near the injury site, leading to swelling and increased pain
impact body temperature regulation potentially causing fever.
Define the major principle of painkiller action mechanism.
Interception or blockage of the pathway between the source of pain and the receptors in the brain, disrupting the transmission of pain signals.
State the category of drugs aspirin belongs.
non-steroidal anti-inflammatory drugs (NSAIDs)
mild analgesics
State the bulk of aspirin mechanism of action.
Prevention of the stimulation of the nerve endings at the site of pain and inhibition of the release of prostaglandins from the site of injury.
Gives relief to inflammation and fever as well as pain.
State why mild analgesics are known as non-narcotics.
Because they do not interfere with the functioning of the brain
(as strong analgesics do).
State the historical predecessor of aspirin and the active ingredient in it.
chewing willow bark
active: salicin
State the current active ingredient in aspirin and what changed.
Ester derivative of salicylic acid
(by Bayer).
Changed alcohol group into an ether which made it more palatable and less irritating substance.
State the name of the property of a drug reducing fever.
Antipyretic
State the process of synthesis of aspirin.
Salicylic acid (2-hydroxybenzoic acid) esterificated in a condensation reaction with usually ethanoic anhydride to form aspirin.
State the current use of aspirin.
anticoagulant - heart
attacks/strokes
antipyretic - mild analgesic
State and describe the production process of aspirin.
- Concentrated sulfuric/phosphoric acid is added to the reactants.
- Gentle warming of the mixture.
- Isolation and purification of aspirin from the mixture.
- Cooling to induce crystal formation (crystallization), followed by suction filtration and washing with chilled water which helps remove soluble acids without losing the (not
very soluble) aspirin. - Recrystallisation - impure crystals are dissolved in a minimal volume of hot ethanol, which is a better solvent for impurities than for aspirin, creating a saturated aspirin solution.
- Crystallization of aspiring first through slowly cooling and filtration of the impurities and unreacted salicylic acid in the solution.
Describe how is the purity of aspirin determined.
Through melting point determination
as pure substances exhibit well-defined melting points which would be altered by the presence of impurities.
State the melting point of pure aspirin vs salicylic acid.
aspirin 138-140 degrees
salicylic acid 159 degrees
State the purpose of IR.
Infrared spectroscopy.
Aids in identifying the functional groups within a molecule through the absorption of specific wavenumbers of infrared radiation.
State the possible potential risk of aspirin.
- dangerous for individuals with difficulty clotting blood or post surgery when clotting is necessary.
- stomach and duodenal irritation, possible bleeding.
- allergic reactions especially in those prone to asthma.
- not for kids under 12 (Reye’s syndrome).
State and define the effect of consuming aspirin with ethanol.
Synergistic
Means the physiological effects intensify when taken with ethanol
which means it may increase bleeding of the stomach lining elevating the risk of ulcers.
Define, state another name and list the practical use of soluble aspirin.
Formulations containing the salt of the acid, formulations containing various coating and buffering components.
For example: reacting aspirin with an alkali to form an ionic salt (NaOH for example).
Dispersible aspirin.
Delay of its activity until its in the small intestine to help alleviate some of its side-effect or because it has low solubility in water (is largely a non-polar molecule) increasing its solubility and thus bioavailability.
Describe the basics about the discovery of penicillin and its consequence.
Alexander Fleming (in only 1928)
observed that fungus Penicilium notatum inhibited bacterial growth.
Birth of antibiotics and in 1940s an isolation of penicillin as an antibacterial agents by Florey and Chain.
Describe the structure of penicillin.
Dipeptide formed from two amino acids: cysteine and valine.
Nucleus thiazolidine (a five-membered ring containing a sulfur atom) attached to a beta-lactam (four-membered ring containing a cyclin amide group).
State the role of the beta-lactam ring in penicillin.
Responsible for its antibacterial properties because by specifically inhibiting (acetylating irreversibly) the transpeptidase that catalyzes the final step in cell wall biosynthesis, the cross-linking of peptidoglycan.
State the chemical structure of the beta-lactam ring and its consequence.
Bond angles reduced to about 90 degrees, despite that because of the sp2 and sp3 hybridized atomic orbitals the atoms would seek to form bonds with angles 120 and 109.5 respectively.
Puts a strain on the bonds - weakening them -> the ring will easily break.
State the biological mechanism behind the bacterial resistance to penicillin problem.
Resistant bacteria produce an enzyme - penicillinase (or beta-lactamase) opening penicillin’s four-membered ring and making it inactive.
State a possible strategy to combat antibiotic resistance on the example of penicillin.
Synthesis of different penicillin forms resistant to penicillinase (like oxacillin replacing methicillin) which retain the beta-lactam ring but have different side chains protecting against enzyme binding.
State a disadvantage of penicillin.
Its broken down by the stomach acid and thus has to be administered intravenously
(but that’s dealt with by the modifications of the side chains).
Also allergic response to it.
Describe the mechanism of action of penicillin.
Disruption of the formation of bacterial cell wall by inhibition of the key enzyme in that process - transpeptidase.
The high reactivity of the amide group in the ring causes it to bind irreversibly near the active site of the enzyme as the ring breaks thus inactivating the enzyme as it prevents polypeptide cross-links from forming between the mucopeptide chains.
The cell wall is unable to support the bacterium and thus it bursts and dies.
Define opiates and its origin.
Strong analgesics derived from unripe seed pods of opium poppy.
State the principles on which opiates work.
They cross the blood-brai barrier by binding temporarily to the opioid receptors in the brain which will block the transmission of impulses between brain cells that would signal pain.
State the correlated to their function structural feature of the opiates.
Phenylamine chemical moiety.
Gives molecule rigidity and allows it to interact strongly with the opioid receptors.
List the most popular drugs derived from opium.
- morphine
- codeine
- diamorphine (heroine)
State the utilization of morphine.
- powerful analgesic
- narcotic - sleep inducing
- used in cough mixtures
- narcotic - sleep inducing
- less powerful than morphine analgesic
State how morphine and codeine are interconvertible.
morphine -> codeine
by replacing -OH by and ether group -OCH3 (methoxy)
achieved by reacting morphine with CH3I in KOH
State the utilization of heroin (diamorphine).
Metabolized in the brain rapidly into morphine and binds to the opioid receptor and thus its effects but much more powerful.
State why is heroine more powerful than morphine.
The acetylation of morphine substitutes the both hydroxyl group with ester groups reducing the polarity of the molecule.
Thus increases lipophilicity and its ability to cross the blood-brain barrier.
State the reaction of formation of heroin.
morphine + ethanoic anhydride in an acetylation reaction.
State the reactions in which morphine can be converted into codeine and diamorphine.
Morphine -> Codeine is achieved through methylation.
Morphine -> Diamorphine is achieved through esterification.
State the possible side effects of using morphine and its derivatives.
- constipation
- suppression of the cough reflex
- constriction of the pupil in the eye
- narcotic effects.
List the narcotic effects od morphine and its derivatives.
- induces a sense of euphoria
- depresses nervous system - sedation
- vasodilation
- high dosages - coma or death by suffocation
- quickly growing dependence and withdrawal symptoms
State the utilization of methadone.
Reduces drug cravings and prevents symptoms of withdrawal.
Effective treatment for opioid dependence.
State how the human body combats viruses.
Producing specific antibodies as an immune response and developing immunity in case of repeated infections.
State the ability of viruses that makes them hard to treat.
Ability to alter their genetic material and thus fool the antibodies.
Define prophylactic treatment of viruses.
Vaccine treatment stimulating the human body to create antibodies.
State the use of antiviral medication to fight of viruses.
Interference in some way with the viral life cycle so as to prevent the release of new viral particles from the cell.
State the ways in which the antivirals work.
- altering cell DNA do that the virus cannot multiply.
- blocking of the enzyme activity within the host cell to prevent the virus from reproducing.
State an example of an antiviral drug and its mechanism of working.
Amantadine.
Cage-like structure causes changes in the cell membrane to prevent the entry of virus into the host cell.