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APPENDIX 1 GLOSSARY OF TERMS

Acetylcholine Adrenergic

A neurotransmitter in the human nervous system Refers to nerves, receptors, or actions that involve the release of epinephrine or norepinephrine. Most postganglionic sympathetic nerve fibres are adrenergic. A drug that stimulates a receptor to produce a pharmacological effect An alkaline, nitrogen-containing chemical obtained from a plant. Many alkaloids are useful drugs Adrenergic drug receptor site that responds to norepinephrine and to blocking agents such as phentolamine Metabolism (body functioning) in which tissues or chemicals are built up from simpler substances Pain-relieving Male sex hormones or any masculinising substance Appetite suppressant drugs used in weight control; also termed anorexics A drug that binds to a receptor, producing no action of its own and blocking the action of the agonist A drug produced by a microorganism that has the ability to inhibit the growth of or kill other microorganisms Specific protein molecules synthesised by the immune response system as a defence against invading antigens A drug that blocks the action of acetylcholine; examples are atropine and nicotine A drug used to prevent or control vomiting A toxic, foreign protein, or microorganism that invades the body and induces the production of defence antibodies A drug with a structure so similar to that of a natural metabolite that it can inhibit or block the utilisation of the natural metabolite by preferentially occupying the receptor site A drug used to reduce fever

Agonist Alkaloid Alpha receptor Anabolism Analgesic Androgens Anorectics Antagonist Antibiotic Antibodies Anticholinergic Antiemetic Antigen

Antihypertensive A drug used to lower high blood pressure Antimetabolite

Antipyretic

Aphrodisiac Atrophy Autism

Any substance that arouses the sexual instinct To shrink, shrivel up, or waste away A mentally introverted, self-centred condition in which reality is excluded. Autistic children have little affect; they show either no emotional response or a very inappropriate response A unique chemical class of drugs used for their sedative and sleepinducing properties Not harmful

Barbiturate Benign

Benzodiazepines Minor tranquilisers such as Valium that have a characteristic sevenmembered ring with two nitrogen atoms Beta blocker Beta receptor Bioavailability Biomarkers A drug capable of competing with beta-adrenergic receptorstimulating agents for available receptor sites Adrenergic drug receptor that responds to epinephrine and to blocking agents such as propranolol The degree to which a drug becomes available to its target tissue after administration Substances found in the human body, such as proteins, enzymes, genetic material, and possibly hundreds of other blood constituents, whose presence can help in the diagnosis and treatment of disease Basal metabolic rate; a measure of the extent of body metabolism at complete rest and under the influence of no drugs A combination of drugs (e.g morphine plus cocaine) used to relieve pain in terminal cancer patients without drugging them into unconsciousness The space between the inside of the cheek and the teeth; a good area for drug absorption A mechanism by which a virus leaves the host cell without killing that cell. It provides the virus with a membrane whose lipid components are identical to those of the host. This allows the virus to penetrate new host cells without activating the hosts immune systems A drug or factor that can cause cancer Neurotransmitters in the body having the dihydroxyphenethylamine chemical structure; examples are epinephrine, norepinephrine and dopamine

BMR Bromptom Cocktail Buccal cavity Budding

Carcinogen Catecholamines

Cholinergic

Refers to nerves that use acetylcholine as their synaptic transmitter

Circadian rhythm Physiological process (or neural clocks) that operate on a 24-hour cycle, influenced by daily cycles of dark and light, temperature, meal times, exercise and stress Coenzyme Cofactor Combinatorial synthesis CNS CSF A cofactor that is organic and loosely bounded to a protein enzyme via ionic or other non-covalent bonding A non-protein chemical bounded to a protein to help it work as an enzyme; sometimes refer to inorganic substances such as Zn2+ A method of synthesising large quantities of compounds in small scale using automated or semi-automated processes. Normally carried out as solid phase synthesis The central nervous system; that is, the brain and spinal cord Cerebrospinal fluid; the fluid that bathes and cushions nerves in the CNS. In a spinal tap, CSF is withdrawn A drug or substance that increases the formation of urine Deoxyribonucleic acid; found in the nucleus of the cell, contains the genetic code or blueprint for the construction of all the cells proteins (double helix form) Vomitting An energy-using process, by which cells absorb molecules (such as proteins) by engulfing them. It is used by all cells of the body because most substances important to them are large polar molecules that cannot pass through the hydrophobic plasma or cell membrane. Coming from within An organelle that forms an interconnected network of membrane vesicles. There are two types, rough endopasmic reticulum (RER) and smooth endoplasmic recticulum (SER). The RER is studded with ribosomes which deals with protein synthesis. The SER is a smooth network without ribosomes. It deals with lipid and carbohydrate metabolism and detoxification in the cell Covered with a substance that prevents the medication from dissolving until it reaches the small intestine

Diuretic DNA

Emesis Endocytosis

Endocrine system All of the glands that secrete hormones

Endogenous Endoplasmic recticulum

Enteric coated

Enzyme

A biological chemical, a protein, produced by living cells, that can influence the rate of body processes. Enzymes can act independently of the cells that produce them. A female sex hormone A drug sold only on prescription Animal cell, with nucleus, cytoplasm and cell membrane One that has its source outside the body Follicle-stimulating hormone Gamma-amino butyric acid The gastrointestinal tract, consisting of the stomach and the intestines A plant product consisting of an organic molecule combined with a sugar. Some very important drugs are glycosides (e.g. cardiac glycosides) Organelles which package and process proteins for use and secretion A sex gland, that is, an ovary or testis

Estrogen Ethical drug Eukaryotic cell Exogenous drug FSH GABA GI tract Glycoside

Golgi bodies Gonad

Hormone Hypodermic Inflammation In vitro In vivo

A potent chemical secreted by a ductless gland directly into the bloodstream and having a specific action on a specific target organ Under or inserted under the skin, as in hypodermic injection A defence body process characterised by redness, heat, pain, and swelling and caused by injury to tissue Experimentation done in a controlled environment e.g. test tube or petri dish Experimentation using a whole living organism e.g. using animal and human testing Secretion and discharge of tears A fat or fat-like substance

Lacrimation Lipid

Metabolism (of drugs) Metabolite Mitochondrion Mitochondria(pl) Monoamine oxidase (MAO) Monoclonal antibodies Morbidity

All of the chemical and physical reactions the body carries out to prepare a drug for excretion Any substance produced by the body as a result of normal functioning, including breakdown products of drugs An organelle which generates most of the cells supply of adenosine triphosphate (ATP) used as a source of chemical energy. Also called cellular power plant One of a group of body enzymes that speed up the bodys biotransformation of amines such a norepinephrine, dopamine, serotonin, and drugs containing aminoid nitrogen Antibodies that have been cloned from one particular B lymphocyte to help fight infection Characterised by disease; state of being physically or mentally diseased

Morning-after pill A drug taken shortly after sexual intercourse to prevent implantation of any fertilized ovum and thus prevent pregnancy Mutagen An agent that causes mutations, that is, permanent changes in genetic material A substance that produces insensibility or stupor Norepinephrine Major tranquilising drugs used to treat psychotic episodes

Narcotic NE Neuroleptics

Neurotransmitter A chemical released from the end of one nerve to carry the nerve impulse across the synapse to the next nerve NRIs Noradrenaline re-uptake inhibitors. Action of stimulants such as amphetamines to act by inhibiting the re-absorption of the nerve transmitter noradrenaline into the presynaptic nerve cells, thus creating a high Nonsteroidal anti-inflammatory drug such as aspirin Any remedy derived from opium Any synthetic narcotic analgesic that has opiate-like pharmacology but is not derived directly from opium Specialised subunit within a cell that has a specific function and is usually separately enclosed within its own lipid bilayer; small organ Those drugs used in the treatment of rare diseases. Companies are reluctant to produce such drugs because they are not profitable

NSAID Opiate Opioid Organelles Orphan drugs

OTC Parenteral Pathogen Peristalsis Pituitary gland Placebo

Over-the-counter; legally purchasable without a prescription Administered by any route of injection A microorganism such as virus, bacterium or fungus that causes disease to the host The wave-like contractions of the GI tract by means of which the contents are propelled along The hypophysis, the master gland of the body; situated at the base of the brain, it secretes many important hormones A pharmacologically inactive substance given to satisfy a patients demand or used as a control to test the true effectiveness of an experimental drug Blood from which the formed elements (red blood cells, white blood cells and platelets) have been removed Normal constituents of the blood, smaller than red cells and essential to the process of blood clotting A molecule that is inactive in itself, but which is converted to the active drug in the body, normally by enzymatic reaction. Cell belonging to simpler organisms such as bacteria, no nucleus, DNA distributed within cytoplasm and it has a cell wall A large and diverse group of fatty acids made in the body that contain 20 carbon atoms and have an effect variously on blood pressure, uterine contraction, peristalsis, body temperature, inflammation, perception of pain and many other body processes. Aspirin apparently works by inhibiting the bodys synthesis of prostaglandins

Plasma Platelets Prodrug Prokaryotic cell Prostaglandins

Prosthetic group A cofactor that is tightly bounded to a protein enzyme via covalent bonds Proteins A class of substances found in all areas of nature that are composed of amino acids bound together in peptide linkages A chemical or drug, used in research, bearing a radioactive atom (tag) that permits a researcher to follow its behavior and ultimate fate in the body A response sometimes seen when a drug is discontinued, in which the suppressed body function returns as strong as or stronger than before, necessitating another round of drug administration

Radioactive tag

Rebound effect

Receptor site Rhinitis Ribosome RNA

Specialised cells in a body tissue to which a drug or chemical attaches to exert its pharmacological effect Inflammation of the mucous membranes of the nose An organelle which synthesise proteins for the cell Ribonucleic acid; crucial to the process by which protein synthesis takes place (not double helix) A neurotransmitter that causes a broad range of effects on perception, movement, and our emotions by modulating the actions of other neurotransmitters in most parts of the brain A fat-like substance containing a unique fused four ring carbon system (termed cyclopentanoperhydrophenanthrene) like that found in cholesterol Under the skin Under the tongue

Serotonin

Steroid

Subcutaneous Sublingual

Sympathomimetic A drug whose actions are similar to those seen upon stimulation of postsynaptic nerves of the sympathetic division of the autonomic nervous system. See Adrenergic. Target tissue THC Tincture Topical Transgenic Animals The glands or cells in the body to which a drug binds and thus exerts its pharmacological effect Tetrahydrocannabinol; the active, mind-altering chemical in marijuana A liquid medication in which the solvent is predominantly alcohol Pertaining to a surface, as on the skin Animals whose genetic code have been altered, e.g. mice with some mouse genes replaced by human genes. They will produce more human-like receptors or enzymes for in vivo testing against drug targets. A drug or agent that can cause a blood vessel to reduce its inner diameter (i.e. constrict its opening) Opposite of vasoconstrictor A virus particle

Vasoconstrictor Vasodilator Virion

APPENDIX 2 PROTEIN FUNCTIONS 1 Structural Proteins Structural proteins do not normally act a drug targets, except tubulin. Tubulin molecules polymerise to form small tubes called microtubules in the cells cytoplasm. These microtubules maintain the shape of cells, release of neurotransmitters and are involved in the mobility of cells.

Tubulin is crucial to cell division. When a cell is about to divide, its microtubules depolymerise to give tubulin which then repolymerise to form a structure called a spindle which then serves to push apart the two new cells and to act as a framework on which the chromosomes of the original cell are transferred to the nuclei of the daughter cells. Drugs that target tubulin and inhibit this process are useful anticancer agents.

Transport Proteins Transport proteins are present in the cell membrane and act as the cells smugglers smuggling the important chemical building blocks of amino acids, sugars, folic acid and nucleic acid bases across the cell membrane such that the cell can synthesise its proteins, carbohydrates and nucleic acids.

The molecules to be smuggled are polar structures that cannot pass through the hydrophobic cell membrane by themselves. The transport proteins have hydrophobic residues on their outer surface which interact favourably with the hydrophobic centre of the cell membrane. They also have binding sites that can bind a polar molecule such as an amino acid, stow it away in a hydrophilic pocket and ferry it across the membrane to release it on the other side. 3 Enzymes and Receptors The most important drug targets are enzymes and receptors which are dealt with in the lecture proper.

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APPENDIX 3 STRUCTURES OF NUCLEIC ACIDS 1 DNA (Deoxyribonucleic acid) Like proteins, DNA has a primary, secondary and tertiary structure. A Primary Structure of DNA DNA has only four building blocks the nucleosides deoxyadenosine, deoxyguanosine, deoxycytidine and deoxythymidine.

Each nucleoside is constructed from two components a deoxyribose sugar and a base. The sugar is the same in all four nucleosides and only the base is different. The four possible bases are two bicyclic purines (adenine and guanine) and two smaller pyrimidine structures (cytosine and thymine).

The nucleoside building blocks are joined together through phosphate groups which link the 5-hydroxyl group of one nucleoside unit to the 3hydroxyl group of the next.

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Secondary Structure of DNA Watson and Crick solved the secondary structure of DNA by suggesting that two DNA chains arrange together in a double helix of constant diameter. In the structure, the nucleic acid bases are paired between the two chains, adenine pairs with thymine via two hydrogen bonds and guanine pairs with cytosine with three hydrogen bonds. The fact that adenine always bind to thymine, and cytosine always bind to guanine means that the chains are complementary to each other. It is now possible to see how replication (the copying of genetic information) is feasible. If the double helix unravels, a new chain can be constructed on each of the original chains. In other words, each of the original chains acts as a template for the construction of a new and identical double helix. The DNA code for proteins is in the form of a triplet code where each amino acid is coded by a set of three nucleotides, e.g. GGC is glycine.

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The secondary structure of DNA the double helix

Tertiary Structure of DNA DNA is an extremely long molecule, so long in fact that it would not fit into the nucleus of the cell if it existed as a linear molecule. It has to be coiled into a more compact three-dimensional shape which can fit into the nucleus a process known as supercoiling. This process requires the action of a family of enzymes called topoisomerases, which can catalyse the seemingly impossible act of passing one stretch of DNA helix across another stretch. They do this by temporarily cleaving one or both strands of the DNA helix to create a temporary gap, then resealing the strands once the crossover has taken place.

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Supercoiling allows the efficient storage of DNA, but the DNA has to be uncoiled again if replication and transcription are to take place. If uncoiling did not take place, the unwinding process that takes place during replication and transcription would lead to increased tension due to increased supercoiling of the remaining DNA double helix. The same topoisomerase enzymes are responsible for catalyzing the uncoiling process, so inhibition of these enzymes would effectively block transcription and replication.

RNA (Ribonucleic acid) The primary structure of RNA is similar to DNA except that the sugar present is ribose not deoxyribose and uracil replaces thymine as one of the bases.

Base pairing between nucleic acid bases can occur in RNA, with adenine pairing to uracil and cytosine pairing to guanine but this occurs within the same chain and RNA does not exist as a double helix. There are three types of RNA molecules with different cellular functions. They are messenger RNA (mRNA), transfer RNA (tRNA) and ribosomal RNA (rRNA). These three molecules are crucial to the process by which protein synthesis takes place. Although DNA contains the genetic code for proteins, it cannot produce these proteins directly. Instead RNA takes on that role, acting as the crucial middleman between DNA and proteins.

Functions of RNA in Protein Synthesis A molecule of mRNA represents a copy of the genetic information required to synthesise a single protein. Its role is to carry the required code out of the nucleus to the rough endoplasmic reticulum (RER) which is studded with ribosomes to synthesise the protein. The segment of DNA which is copied is called a gene, and the process involved is called transcription.

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