Medicinal Chemistry

Terms in this set (88)

Any substance that, when taken into a living organism, brings about change in biological function through its chemical action

1) Crude preparations derived from plant or animal materials
2) Pure compounds isolated from natural sources
3) Semi-synthetic compounds produced from the chemical modification of pure compounds
4) Synthetic compounds

A drug that treats, prevents or alleviates the symptoms of the disease and has a therapeutic action

Medicine Components

1) Active drug
2) Non-active drug
Ex: Effective drug that needs to improve its taste

Drug or Medicine Effects on Body

1) Alters the psychological state
2) Alters incoming sensory sensations
3) Alters mood

Neural Communication

1) Electrical impulses (action potentials) travel from one neuron to another across the synapse (tiny junction)
2) When an action potential reaches an axon terminal it stimulates the release of neurotransmitter molecules from vesicles (sacs)
3) The molecules cross the synaptic gap and bind onto receptor sites
4) The sending neuron will reabsorb excess neurotransmitter molecules, this is called reuptake

Neurotransmitters

Chemical messengers released at the axon terminal through the synapse

Types of Neurotransmitters

1) Adrenaline
2) Noradrenaline
3) Dopamine
4) Serotonin
5) Gaba
6) Acetylcholine
7) Glutamate
8) Endorphines

Calming neurotransmitter. It blocks the production of dopamine.

Target molecule

What a drug interacts with to produce an effect. When a drug binds to it, the drug will either stop it from functioning or stimulate it. This can be therapeutic or toxic. It is typically an enzyme or a receptor

A biochemical catalyst that catalyses nearly all of the chemical reactions that occur in the body

Proteins found on the surface of cells or inside cells that bring about a response in the cell when molecules bind to them

Normal Population

A type of enzyme action, where the substrate and the enzyme react due to an induced fit model

The enzyme that breaks down lactose to glucose and galactose

A medication that supplies the lactase enzyme

A drug whose target receptors are dense in the limbic system (part of the brain that is involved in emotions)

A pleasure neurotransmitter.

Effect of Opiods on Dopamine Production

Upon activation of opioid receptors in certain neurons, dopamine is released in other neurons. The result is an intense high and sense of happiness, which may lead to dependence

Morphine's Process

1) Morphine activates the opioid (Mu) receptor in the neurons of the nucleus accumbens
2) As a result, it stops the release of the GABA neurotransmitter
3) The drop of GABA production causes an influx in the production of dopamine
4) In turn, this elicits the euphoria associated with opioids

Nucleus Accumbens

The area of the brain where neurons release the dopamine neurotransmitter

Competitive Inhibitor

A substance that reduces the activity of an enzyme by entering the active site in place of the substrate whose structure it mimics

Noncompetitive inhibitor

A substance that alters the conformation of an enzyme so that its active site is no longer fully functional

Methods of Administering Drugs

1) Orally
2)Rectally
3) Pulmonary (Inhalation)
4) Topical
5) Injection

Oral Administration

The effect will vary due to the absorption being affected by the stomach. It will be absorbed in the primary intestine. It is the most convenient method

Rectal Administration

Drugs are inserted through the anus into the rectum. Occurs when a drug cannot be taken orally or is pH sensitive

Pulmonary Administration

Rapid due to the blood vessels in the lungs (respiratory system)

Topical Administration

Applying drug to skin for local effects

Injection Administration

Can be: Subcutaneous (beneath the skin & slow absorption), Intra-muscular (skeletal muscle, large volumes & slow response), and Intravenous (instantaneous response & not affected by stomach)

Fat-soluble drugs

Drugs that are more easily absorbed

Blood-Brain Barrier

This brain structure prevents the diffusion of many substances into the brain

Kidneys and Liver

Organs that break down drugs

The time it takes for half of the drug to be eliminated

Therapeutic Effect

A desirable and beneficial effect

An unintended secondary effect. It is usually undesirable. Ex: nausea

Experimental results caused by human expectation alone

The dose (in PPM) that is lethal to 50% of laboratory animals tested. The lower the lethal dose, the more toxic the drug.

The dose (in PPM) that is toxic to 50% of the laboratory animals tested and results in any toxic side effect. The lower the toxic dose, the more toxic the drug.

The dose (in PPM) required to produce a therapeutic effect in 50% of the animals tested. The lower the dose, the better.

Therapeutic Index

The ratio of toxic dose to a therapeutic dose. It relates to the dose of a drug required to produce a desired therapeutic effect to that required to produce a toxic effect

Therapeutic Window

The range of doses that gives safe, effective therapy

Drug Bioavailability

The fraction of an administered dose of a drug that reaches the systemic circulation. When a drug is administered intravenously, its bioavailability is 100%

Drug Development

It is very expensive and takes a long time since this process is controlled by the government

Stages of Drug Development

1) Identification of lead compounds
2) Toxicity animal testing
3) Clinical trials

Identification of Lead Compounds

AKA new chemical entity. Biological testing of compounds is obtained through many sources. They have a desired biological effect

Lead Optimization

Chemically modifying a lead compound to find more active and less toxic compounds to be further developed

Toxicity Testing in Animals

Using studies to looks for different types of toxicities over a period of time

Clinical Trials

This stage occurs after the drug has been proven safe for animals. Occurs in three phases

Clinical Trials Phase 1

It idendifies the dose range of the drug that gives a therapeutic effect and will identify side effects on healthy volunteers

Clinical Trials Phase 2

Trials continue on volunteers with the disease to establish effectiveness and side effects

Clinical Trials Phase 3

Trials continue on a larger group and compares its activity with other drugs

1960s drug used for morning sickness but caused major birth defects. This was caused by an isomer. Optical isomer.

Due to repeated use the drug, the body will adapt by increasing its metabolism of the drug. Over time, an individual will need an increased amount to achieve the same effect.

Pain relievers that act by interfering pain receptors

Mild Analgesics

Block the production of prostaglandins by inhibiting the COX enzyme. Ex: aspirin

Synthesized in damaged cells which bind to receptors, thus stimulating sensory nerves at the site of the injury. The nerves send signals to the brain which are interpreted as pain. It allows for swelling by increasing the permeability of capillaries

An analgesic formed from salicylic acid and an acetyl group, which lowers acidity

Prevents or reduces fever. Ex: salicylic acid

Disadvantages of aspirin

1) Can cause an upset stomach
2) Risk of gastrointestinal bleeding following alcohol consumption
3) Small risk of allergy
4) Accidental infant poisoning and correlation to Reye's syndrome in children

Addition-elimination

Type of reaction that characterizes the synthesis of aspirin

Increasing the Bioavailability of Aspirin

The drug must become more soluble. This is done by reacting the carboxyl group of the drug with a strong alkali (base) to form an ionized salt.

Prozac Synthesis

The amine group of this drug is basic, so it will react with a strong acid to form an ionized salt

A competitive inhibitor for the opioid receptor. It is administered to reduce opioid dependence.

Neutralize acidity in the stomach

Erosion of a part of the gut lining that is caused by the penetration of the gut lining by the acid. Aspirin can sometimes cause this.

Neutralizing Reactions

1) Al(OH)3(s) + 3HCl(aq) -> AlCl3(aq) + H2O(l)
2) CaCO3(s) + 2HCl(aq) -> CaCl2(aq) + H2O(l)
3) NaHCO3(s) + HCl(aq) -> NaCl(aq) + H2O(l)

Additional compounds added in drugs to prevent heartburn by producing a neutralizing layer on top of stomach contents. This prevents acid from rising into the esophagus.

Anti-Foaming Agents

Additional compound added in drugs to reduce bloating by reducing CO2 production. Ex: dimethicone

H2 Receptor Antagonists

Drugs that prevent histamine from binding onto the H2 receptor (that will produce HCl) therefore inhibiting acid production

Proton Pump Inhibitors

Prevent the acid from being secreted into the stomach by blocking the enzymes ATPase, which provides the energy necessary to transport H+ ions against the proton gradient into the stomach.

Active Metabolite

An active form of a drug that has been administered inactively. Ex: Aspirin

Strong Analgesics

1) Codine
2) Morphine
3) Diamorphine (Heroin)

Similarities between Strong Analgesics

Basic amine group and the benzene ring

AKA heroin, this drug is synthesized from morphine via simple acetylation. It is able to cross the blood-brain barrier

Types of Dependance

1) Psychological
2) Physical

Psychological Dependance

When the drug taker craves the drug

Physical Dependance

When the drug taker's body cannot function without the drug

Selective drugs that can attack infectious bacteria rather than human cells. They are ineffective against viruses

Types of Antibacterials

1. Bacteriostatic
2. Bacteriocidal

Inhibition of bacterial cell division

Directly killing bacteria

An antibacterial drug

Components of Penicillin

1) Amide
2) B-Lactam Ring
3) Carbolic Acid
4) R-Group

Beta Lactam Ring

The portion of the chemical structure of penicillin that is responsible for its antibacterial properties. They function by interfering with the cross-links that connect the separate layers of the bacterial cell wall, by inhibiting the enzyme tripeptase. As a result, the bacterial cell wall is weakened and the cell bursts, killing the bacteria.

The Reason Why Human Cells are Unaffected by Penicillins

The human cell does not have a cell wall

Overprescription of Penicillin

Results in the destruction of harmless bacteria in the body and my lead to genetic resistance over time.

Broad Spectrum Antibiotics

Effective against a wide variety of bacteria

Narrow Spectrum Antibiotics

Effective against only certain type of bacteria. Ex: penicillin

The enzyme produced by bacteria as a result of bacterial resistance against penicillin. This enzyme opens the beta lactase ring of penicillin, thus making it inactive

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