1. Nature and Nomenclature of Drugs

2. Nature of drugs Physical Structure Chemical structure Solid (aspirin)
Liquid (nicotine, ethanol)
Gas (nitrous oxide)
Chemical structure
Protein, lipid, carbohydrate
Weak acid or weak base
Amine (primary, secondary, tertiary)

3. Characteristics of an Ideal Drug?
Selective (e.g. if you give a drug for heart, it should only work on the heart)
It should have minimum adverse effects
Temporary (it does not change the function permanently)
It should be highly effective (efficacious) at low doses (potent)
Dose-related (controllable)
It should be safe in a wide range of doses (therapeutic index)
It should have convenient dosing regimens

4. How are Drug Responses Produced?
Drug actions are mediated by 3 ways:
Acting on somatic or psychic processes or functions
Correction of deficiencies
Toxic action on pathogenic microorganism

5. How are Drug Responses Produced?
By interaction with active binding sites called Drug Targets (e.g. receptors, enzymes, ion channels etc.)
Drug may be agonist or antagonist for the receptors

6. DRUG REACTIVITY AND DRUG-RECEPTOR BONDS
Drugs interact with receptors by means of chemical forces or bonds. These are of three major types:
Covalent: Covalent bonds are very strong and in many cases not reversible under biologic conditions.
Electrostatic: Electrostatic bonds are weaker than covalent bonds. Electrostatic bonding is much more common than covalent bonding. Electrostatic bonds vary from relatively strong linkages between permanently charged ionic molecules to weaker hydrogen bonds
Hydrophobic: Hydrophobic bonds are usually quite weak and are probably important in the interactions of highly lipid-soluble drugs. Drugs that bind through weak bonds to their receptors are generally more selective than drugs that bind by means of very strong bonds.
DRUG REACTIVITY AND DRUG-RECEPTOR BONDS
Drugs interact with receptors by means of chemical forces or bonds. These are of three major types: covalent, electrostatic, and hydrophobic. Covalent bonds are very strong and in many cases not reversible under biologic conditions. Thus, the covalent bond formed between the acetyl group of aspirin and cyclooxygenase, its enzyme target in platelets, is not readily broken. The platelet aggregation–blocking effect of aspirin lasts long after free acetylsalicylic acid has disappeared from the bloodstream (about 15 minutes) and is reversed only by the synthesis of new enzyme in new platelets, a process that takes several days. Other examples of highly reactive, covalent bond-forming drugs are the DNA-alkylating agents used in cancer chemotherapy to disrupt cell division in the tumor.
Electrostatic bonding is much more common than covalent bonding in drug-receptor interactions. Electrostatic bonds vary from relatively strong linkages between permanently charged ionic molecules to weaker hydrogen bonds and very weak induced dipole interactions such as van der Waals forces and similar phenomena. Electrostatic bonds are weaker than covalent bonds.
Hydrophobic bonds are usually quite weak and are probably important in the interactions of highly lipid-soluble drugs with the lipids of cell membranes and perhaps in the interaction of drugs with the internal walls of receptor "pockets."
The specific nature of a particular drug-receptor bond is of less practical importance than the fact that drugs that bind through weak bonds to their receptors are generally more selective than drugs that bind by means of very strong bonds. This is because weak bonds require a very precise fit of the drug to its receptor if an interaction is to occur. Only a few receptor types are likely to provide such a precise fit for a particular drug structure. Thus, if we wished to design a highly selective short-acting drug for a particular receptor, we would avoid highly reactive molecules that form covalent bonds and instead choose molecules that form weaker bonds.
A few substances that are almost completely inert in the chemical sense nevertheless have significant pharmacologic effects. For example, xenon, an "inert" gas, has anesthetic effects at elevated pressures.

7. Drug Properties Influencing Drug Actions
Drug Size
The molecular size of drugs varies from very small (lithium ion, MW 7) to very large (eg, alteplase [tPA], a protein of MW 59,050).
However, most drugs have molecular weights between 100 and
The specificity of drug action requires a drug molecule must be sufficiently unique in shape, charge, and other properties
To achieve such selectivity, a molecule should be at least 100 MW units in size.
Drugs much larger than MW 1000 do not diffuse readily between compartments of the body
The molecular size of drugs varies from very small (lithium ion, MW 7) to very large (eg, alteplase [tPA], a protein of MW 59,050). However, most drugs have molecular weights between 100 and The lower limit of this narrow range is probably set by the requirements for specificity of action. To have a good "fit" to only one type of receptor, a drug molecule must be sufficiently unique in shape, charge, and other properties, to prevent its binding to other receptors. To achieve such selective binding, it appears that a molecule should in most cases be at least 100 MW units in size. The upper limit in molecular weight is determined primarily by the requirement that drugs must be able to move within the body (eg, from the site of administration to the site of action). Drugs much larger than MW 1000 do not diffuse readily between compartments of the body (see Permeation, in following text). Therefore, very large drugs (usually proteins) must often be administered directly into the compartment where they have their effect. In the case of alteplase, a clot-dissolving enzyme, the drug is administered directly into the vascular compartment by intravenous or intra-arterial infusion.

8. Drug Shape
The shape of a drug molecule must be such as to permit binding to its receptor site via the bonds just described.
Optimally, the drug's shape is complementary to that of the receptor site in the same way that a key is complementary to a lock.
DRUG SHAPE
The shape of a drug molecule must be such as to permit binding to its receptor site via the bonds just described. Optimally, the drug's shape is complementary to that of the receptor site in the same way that a key is complementary to a lock. Furthermore, the phenomenon of chirality (stereoisomerism) is so common in biology that more than half of all useful drugs are chiral molecules; that is, they can exist as enantiomeric pairs. Drugs with two asymmetric centers have four diastereomers, eg, ephedrine, a sympathomimetic drug. In most cases, one of these enantiomers is much more potent than its mirror image enantiomer, reflecting a better fit to the receptor molecule. If one imagines the receptor site to be like a glove into which the drug molecule must fit to bring about its effect, it is clear why a "left-oriented" drug is more effective in binding to a left-hand receptor than its "right-oriented" enantiomer.
The more active enantiomer at one type of receptor site may not be more active at another receptor type, eg, a type that may be responsible for some other effect. For example, carvedilol, a drug that interacts with adrenoceptors, has a single chiral center and thus two enantiomers (Figure 1–2, Table 1–1). One of these enantiomers, the (S)(–) isomer, is a potent -receptor blocker. The (R)(+) isomer is 100-fold weaker at the receptor. However, the isomers are approximately equipotent as -receptor blockers. Ketamine is an intravenous anesthetic. The (+) enantiomer is a more potent anesthetic and is less toxic than the (–) enantiomer. Unfortunately, the drug is still used as the racemic mixture.

9. Criteria for drug classification
Drugs can be classified in many ways based on
Chemical structure
Cholinesters
Organophosphates
Catecholamines
Location of action
Cardiac glycosides
Autonomic drugs

10. Criteria for drug classification
Purpose of medication
Antihypertensive
Diuretic
Antiemetic
Analgesic
Name of plant
Opium alkaloids
Cardiac glycosides
Belladonna alkaloids

11. Prescription vs Over the Counter Drugs
Prescription Drugs
These drugs that cannot be obtained from a pharmacy without a registered physician’s prescription.
Over-the-Counter (OTC) Drugs
These drugs are available without a physician’s prescription for self-treatment of a variety of complaints. Some drugs are approved as prescription drugs but later are found to be very safe and useful for patients without the need for prescription.
Potential problems with OTC drugs
Taking these drugs could mask the signs and symptoms of underlying disease making diagnosis difficult
Taking these drugs with other drugs can result in drug interactions
Can result in drug overdoses
Orphan Drugs. Drugs that have been discovered but are not financially viable and therefore have not been “adopted” by any drug company. Orphan drugs ay be useful in treating a reare disease, or they may hav potentially dangerous adverse effects. Orphan drugs are often abandoned after preclinical trials or phase 1 studies. The orphan drug act of 1983 p4ovided tremendous financial incentive to drug companies to adopt these drug and develop them. These incentives help the drug company put the drug through the rest of the the testing process, even throught he market for the drug in thelong run may be very small (as in the case of a drug to treat a reare neurological disease that affects only a small number of people).

12. Sources of drugs
Natural Sources: Substances obtained directly from nature
Plants
Animals / Humans
Micro-organisms
Minerals
Inorganic metals
Semi-synthetic
Synthetic
Bio-synthetic
Dronabinol used for nausea and vomiting (delta-9-tetrahydrocannabinol)

13. Sources of drugs Natural from Plants
Active principles are found in roots, leaves and seeds in 3 forms:
Glycosides
Cardiac glycoside Digoxin ( from the Foxglove plant)
Alkaloids
Morphine (from Poppy capsules),
Atropine (from Belladonna leaves)
Quinine (from bark of Cinchona tree)
Castor oil (from castor seed)

14. Sources of drugs Natural from animals / humans Hormones
Heparin from Pig or Ox liver,
Insulin from Pig or Ox pancreas
Gonadotrophins from urine of pregnant women
Plasma or serum from blood
Thyroxin from Pig or Ox thyroid gland
Cod Liver Oil from Cod fish Liver

15. Sources of drugs Natural from micro-organisms Antibiotics
Penicillin from Penicillium notatum,
Streptomycin from Streptomyces griseus,
Bacitracin from Bacillus

16. Sources of drugs Minerals
Calcium, Magnesium, Aluminium, Sodium, Potassium & Iron salts,
Liquid paraffin from petroleum.
Inorganic metals
Iodine
Lithium
Radioactive elements: Iodine (I131)

17. Sources of drugs Semi synthetic drugs
Prepared by chemical modification of natural drugs in labs.
Ampicillin from Penicillin-G,
Semisynthetic cephalosporin's from 7-amino cephalosporinic acid

18. Sources of drugs Synthetic Drugs
Prepared by chemical synthesis in pharmaceutical laboratories
Sulphonamides
Salicylates
Barbiturates
Benzodiazepines

19. Sources of drugs Synthetic / semisynthetic Drugs
Technical advances allow scientists to alter a chemical with proven therapeutic effectiveness to make it better.
Sometimes, a small change in chemical’s structure can make that chemical more useful as a drug – more potent, more stable, less toxic.
These technological advance have led to the development of groups of similar drugs, all of which are derived from an original prototype, but each of which have slightly different properties, making a drug more desirable in a specific situation.

20. Sources of drugs Bio-Synthetic Drugs
Scientists use genetic engineering to alter bacteria to produce chemicals that are therapeutic and effective.
Prepared by cloning of human DNA into bacteria such as E. Coli.

21. Sources of drugs Bio-Synthetic Drugs
Technique is called Recombinant DNA technology (or Genetic Engineering)
Cells are obtained from animals or human that produce required substance (e.g. a hormone)
Isolation of DNA or DNA fragment encoding the substance
Transfer of encoding DNA fragment to bacteria (E- coli) via plasmids (Gene cloning)
The transformed E-coli synthesizes the new substance

22. Sources of drugs Examples of Bio-Synthetic Drugs Human Insulin
Human Growth Hormones
Human Hepatitis B Vaccine

23. Sources of Drug Information
Saudi MOH Drug List (see notes below)
Pharmacopoeias
“Up to date” website
Elsevier “Gold standard” Clinical Pharmacology website
Micromedex (
Drug labels (see next slide)
Package inserts
Drug references (e.g. Physician’s drug reference)
Journals
Internet (e.g. wikipedia)
Saudi Drug Formulary is available at:

24. Drug Nomenclature Chemical name Generic name (Official, Approved)
Based on the chemical composition and structure
Generic name (Official, Approved)
This is usually the abbreviated form of the chemical name
This name is used and chosen by official bodies
Proprietary name (Brand name, Company name)
the name given by the company which markets the drug
It is the commercial property of a pharmaceutical company
It indicates a particularly formulation of a particular substance by a particularly manufacturer

25. Generic Drugs vs Brand Name Drugs
Generic name:
When a company brings a new drug onto the market, the firm has already spent substantial money on research, development, marketing and promotion of the drug. A patent is granted that gives the company that developed the drug an exclusive right to sell the drug as long as the patent is in effect under it’s brand name e.g. generic name for metformin is “METFORMIN” (used for treating diabetes)
Brand name:
Are copies of generic-name. In other words, their pharmacological effects are exactly the same as those of their generic-name counterparts e.g. for diabetes “METFORAL” or “GLUCOPHAGE”
Brand drugs are only cheaper because the manufacturers have not had the expenses of developing and marketing a new drug….but be careful about brand drugs from underdeveloped countries
Generic drugs are copies of brand-name drugs that have exactly the same dosage, intended use, effects, side effects, route of administration, risks, safety, and strength as the original drug. In other words, their pharmacological effects are exactly the same as those of their brand-name counterparts.
An example of a generic drug, one used for diabetes, is metformin. A brand name for metformin is Glucophage. (Brand names are usually capitalized while generic names are not.) A generic drug, one used for hypertension, is metoprolol, whereas a brand name for the same drug is Lopressor.
Many people become concerned because generic drugs are often substantially cheaper than the brand-name versions. They wonder if the quality and effectiveness have been compromised to make the less expensive products. The FDA (U.S. Food and Drug Administration) requires that generic drugs be as safe and effective as brand-name drugs.
Actually, generic drugs are only cheaper because the manufacturers have not had the expenses of developing and marketing a new drug. When a company brings a new drug onto the market, the firm has already spent substantial money on research, development, marketing and promotion of the drug. A patent is granted that gives the company that developed the drug an exclusive right to sell the drug as long as the patent is in effect.
As the patent nears expiration, manufacturers can apply to the FDA for permission to make and sell generic versions of the drug; and without the startup costs for development of the drug, other companies can afford to make and sell it more cheaply. When multiple companies begin producing and selling a drug, the competition among them can also drive the price down even further.
So there's no truth in the myths that generic drugs are manufactured in poorer-quality facilities or are inferior in quality to brand-name drugs. The FDA applies the same standards for all drug manufacturing facilities, and many companies manufacture both brand-name and generic drugs. In fact, the FDA estimates that 50% of generic drug production is by brand-name companies.
Another common misbelief is that generic drugs take longer to work. The FDA requires that generic drugs work as fast and as effectively as the original brand-name products.
Sometimes, generic versions of a drug have different colors, flavors, or combinations of inactive ingredients than the original medications. Trademark laws in the United States do not allow the generic drugs to look exactly like the brand-name preparation, but the active ingredients must be the same in both preparations, ensuring that both have the same medicinal effects.

26. Drug Nomenclature
Since several companies market the same drug under different proprietary names, which creates unnecessary confusion
Whenever possible drugs should be prescribed by their GENERIC names
Chemical name: Acetyl-p-aminophenol
GENERIC name: Paracetamol or
(acetaminophen in the USA)
Proprietary name: Panadol, Calpol, Adol, Fevadol

27. QUESTIONS?

28. THANK YOU