PHARM MED ORG
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| 🇬🇧 | 🇬🇧 |
| Structure determines function The structure of a compound determines the biological effects it has. | Structure-Activity Relationships |
| Medicinal chemistry also involves the discovery of __ for the treatment of diseases and the systematic study of the structure-activity relationships of the active compounds. | New chemical entities |
| Is the relationship between chemical structure and pharmacological activity for a series of compounds. | Structure-activity relationship (SAR) |
| Drug Discovery Cycle | 1 Compound Collections 2 Primary Assays 3 Secondary Assays 4 Lead Compounds and SAR 5 Structural Characterization of Protein-Ligand Complex 6 Design 7 Chemical Synthesis 8 Clinical Candidate |
| Drug Emphasis | 1. Chemically structural feature, physico-chemical property, stability. 2. Biological effect, adverse effects, biotransformation etc. 3. Structure-activity relationship, drug targets in living bodies as well as mode of action. |
| The important role of Drugs in human society | Improving both the individual quality of life and life expectancy. 1. Bacterial and virus infections: polio, smallpox, tuberculosis and related diseases have, to a very major extent, become minor public health concerns. 2. An increase in life expectancy resulting from drug therapy has also led to a shift in population demographics toward a more healthy, elderly population. 3. Drug regimens for birth control have improved individual life choices and the quality of life. 4. HIV protease and reverse transcriptase inhibitors for the treatment of HIV infections have changed a disease with a fatal prognosis to a potentially chronic one. 5. Cancer is also being viewed as a potentially chronic, rather than fatal disease with newer, non-cytotoxic approaches. |
| Early investigations of natural products | In the so-called pre-scientific era, Drugs of Antiquity folk remedies were in use |
| New drugs will be discovered or invented by investigating __ and __ | Human genomics, human disease genomics |
| Drugs of Antiquity Examples | 1 Ma huang (ephedrine) 2 Ipecacuanha (emetine) 3 Coca leaves (cocaine) 4 opium 5 squill 6 hyoscyamus |
| New drugs will be discovered or invented by investigating __ and __ | Human genomics, human disease genomics |
| The Middle Ages, glorified antimony and its salts in elixirs as cure-alls in the belief that chemicals could cure disease. | Paracelsus (1493–1541) |
| New drugs will be discovered or invented by investigating __ and __ | Human genomics, human disease genomics |
| The 19th century | Age of Innovation and Chemistry. |
| New drugs will be discovered or invented by investigating __ and __ | Human genomics, human disease genomics |
| The isolation of morphine | Friedrich Sertürner,1803 |
| New drugs will be discovered or invented by investigating __ and __ | Human genomics, human disease genomics |
| The isolation of emetine from ipecacuanha | Pierre-Joseph Pelletier,1816 |
| New drugs will be discovered or invented by investigating __ and __ | Human genomics, human disease genomics |
| Synthesis of acetic acid | Adolph Kolbe, 1845 |
| New drugs will be discovered or invented by investigating __ and __ | Human genomics, human disease genomics |
| Synthesis of Methane | Pierre Berthelot, 1856 |
| New drugs will be discovered or invented by investigating __ and __ | Human genomics, human disease genomics |
| 1840s, the first use of synthetic organic chemicals were introduced for anesthesia during a tooth removal, such as ___, ___, and ___. | 1 nitrous oxide 2 ether 3 chloroform |
| New drugs will be discovered or invented by investigating __ and __ | Human genomics, human disease genomics |
| In 1853, Henry How heated morphine with __, hoping to convert the alkaloid to __. He obtained, however, a new substance of the __. | 1 methyl iodide 2 codeine 3 quaternary salt of morphine |
| New drugs will be discovered or invented by investigating __ and __ | Human genomics, human disease genomics |
| Isolated cocaine | Albert Niemann,1860 |
| New drugs will be discovered or invented by investigating __ and __ | Human genomics, human disease genomics |
| __ isolated the active ingredient, ___, from the Calabar bean | 1 Albert Niemann,1864 2 physostigmine |
| New drugs will be discovered or invented by investigating __ and __ | Human genomics, human disease genomics |
| Salicylic acid was introduced as a possible cure for __, in what year? | Typhoid fever, 1875 |
| New drugs will be discovered or invented by investigating __ and __ | Human genomics, human disease genomics |
| After 1930’s: The development of new drugs was speeded greatly by the close combination of __ and __. | Medicinal Chemistry, Experimental Pharmacology |
| Was formed by using metabolic products as lead compounds. | Theory of antimetabolite |
| In the year __, the first drug used for treating cancer as a biological alkylating agent was __, which began tumor chemical therapy | 1940s, nitrogen mustard |
| In the year __, first β-Adrenergic blocking agent, __, was marketed. | 1964, Propranolol |
| New drugs will be discovered or invented by investigating __ and __ | Human genomics, human disease genomics |
| Receptor Used as Drug Target | 1 M acetylcholine receptor 2 adrenergic receptor 3 angiotensin receptor 4 dopamine receptor 5 serotonin receptor 6 opioid receptor |
| Drugs effecting on receptors | 1 Agonist 2 Antagonist 3 Partial agonist |
| It has less activation or less cellular activity | Partial Agonist |
| ACE Inhibitors block what? | Block Angiotensin I from converting into Angiotensin II |
| AT1 receptor effects | 1 Vasoconstriction 2 Sympathetic activation 3 Cell proliferation 4 Aldosterone release 5 Renal sodium resorption |
| AT2 receptor effects | 1 Vasodilation 2 Inhibition of cell growth 3 Apoptosis |
| Adrenergic Receptors | 1 Alpha-1 2 Alpha-2 3 Beta-1 (Heart and Kidneys) 4 Beta-2 (Lungs) |
| Alpha 2 Inhibits what? | 1 Norepinephrine release 2 Acetylcholine release 3 Insulin release |
| Types of Enzymes as Drug Target | 1 Angiotensin Converting Enzyme (ACE) 2 Cycloxygenase (COX2) 3 β-Lactamase 4 Acetylcholine Esterase |
| Drugs effecting on enzyme | Enzyme Inhibitor |
| Enzyme present in bacteria | Lactamase - can degrade penicillin |
| ACE Inhibitor effects | 1 Dry cough 2 Increase Bradykinin |
| HMG CoA Reductase Inhibitors | 1 Pravastatin 2 Lovastatin |
| Blocks calcium access to cells | Calcium Channel Blockers, less contractility less conductivity to the heart |
| Drugs Affecting on Ion Channel | 1 Calcium Channel Blocker 2 Potassium Channel Blocker 3 Sodium Channel Blocker |
| They bind to two nuclear enzymes, inhibiting DNA replication | Fluoroquinolones |
| Ion Channels | 1 Calcium Ion Channel 2 Potassium Ion Channel 3 Sodium Ion Channel 4 Chloride Ion Channel |
| Common names by national or international nomenclature commissions | INN International Non-proprietary Names for Pharmaceutical Substance |
| Chemical Name | International Union for Pure and Applied Chemistry (IUPAC) and International Union of Biochemistry (IUB) |
| The biochemical changes that occur on drugs or other foreign compounds, the purpose of which is to facilitate elimination from the body | Drug Metabolism |
| Without Drug Metabolism, __ can remain indefinitely in the body | Xenobiotics (substances that are foreign to the body) |
| Most metabolic products are less pharmacologically active a. True b. False | A. True exceptions; Where the metabolite is more active Where the metabolite is toxic Where the metabolite is carcinogenic |
| Metabolite is more active Inactive drug is converted to active metabolite | Prodrugs ex. Erythromycin-succinate |
| The metabolite is toxic | Acetaminophen |
| It causes conversion of an active drug to inactive or less active metabolites called as what? | Pharmacological inactivation |
| It causes conversion of an active to more active metabolite called as what? | Bioactivation or toxicological activation |
| It causes conversion of an inactive drug to active metabolites called as what? | Pharmacological activation |
| What are the advantages of Prodrugs? | 1 Increased absorption 2 Elimination of an unpleasant taste 3 Decreased toxicity 4Decreased metabolic inactivation 5 Increased chemical stability 6 Prolonged or shortened action |
| Sites of Drug Biotransformation | 1 Gastrointestinal Tract 2 Liver 3 Blood Circulation |
| It means drug metabolism occurring before the drug enters the systemic circulation | First Pass Metabolism |
| First Pass Metabolism results in what? | Decreased bioavailability Decreased therapeutic response |
| Presence of these in the intestine may be important in carrying out hydrolysis of many ester prodrugs | Esterases and Lipases |
| Can hydrolyze glucuronide conjugates excreted in the bile, thereby liberating the free drug or its metabolite for possible reabsorption | Intestinal beta-glucuronidase |
| Metabolic Enzymes | 1 Microsomal enzymes 2 Non-microsomal enzymes |
| 1 Microsomal enzymes are found in __ 2 Non-microsomal enzymes are found in __ | 1 Smooth ER of liver cells 2 Cytoplasm and mitochondria of liver cells |
| It is a pigment that, with CO bound to the reduced form, absorbs maximally at 450nm | Cytochrome P450 (Hemoprotein) |
| Converts the parent drug to a more polar metabolite by introducing or unmasking a functional group (-OH, -NH2, -SH, -COOH). | Phase I 'Functionalization reactions' |
| Arenes to Arenols | Oxidation of Aromatic Moieties (4th or para position attachment of OH) |
| . | Oxidation of Aromatic Moieties (4th or para position attachment of OH) |
| Epoxide Hydrolase | Oxidation of olefinic bonds (Double bond broken down to two OH attachments) |
| . | Oxidation of Olefinic Bonds (Double bond broken to two OH) (Epoxide Hydrolase) |
| . | Oxidation of Olefinic Bonds (Double bond broken to two OH) (Epoxide Hydrolase) |
| . | Benzylic Carbon Hydroxylation (Stearic Hindrance) (Attach OH to carbon attached to an aromatic ring or phenol group) |
| . | Benzylic Carbon Hydroxylation (Stearic Hindrance) (Attach OH to carbon attached to an aromatic ring or phenol group) |
| . | Oxidation of Allylic Carbon Atoms (Attachment of OH to --> C-C=C (allylic)) |