المنهج النهائي للفراما (Lecture 1) PDF

Lecture 1 Drugs:Compounds which show various biological function effects of therapeutic value when administered to living organisms. Are typically used for medical purposes to diagnose, treat, cure, or prevent...

Lecture 1 Drugs:Compounds which show various biological function effects of therapeutic value when administered to living organisms. Are typically used for medical purposes to diagnose, treat, cure, or prevent diseases. They can interact with specific targets in the body, such as proteins or enzymes, to produce a desired physiological effect. Can be synthetic or derived from natural sources. What are the IDEAL requirements of a drug? ❑ High efficacy in disease treatment ❑ Exerts very limited cytotoxicity & side effects ❑ Can be targeted to the desired site inside the body In practice, however, Drugs DO NOT behave in this way……. (a) Drugs, tend to distribute themselves anywhere in the tissues of the host. (b) Some cells, which were originally susceptible to a particular drug, may acquire a tolerance to that drug. (EVEN, In some cases it has been found that the drug actually reverses its action).  Pharmacology is the scientific discipline concerned Pharmacology: with the study of how drugs interact with biological systems and the effects they produce. It shows the understanding of drug mechanisms of action, their pharmacokinetics (absorption, distribution, metabolism, and excretion), pharmacodynamics (effects on the body), and toxicology (adverse effects). Pharmacology plays a crucial role in drug development, clinical practice, and the rational use of medications.  A pharmacopoeia is a comprehensive collection of Pharmacopoeia : guidelines for the preparation, quality control, and use of medicinal substances, and dosage forms. It serves as a reference book for pharmacists, physicians, and other healthcare professionals to ensure the quality, safety, and efficacy of drugs. Pharmacopoeias are usually published by official authorities or organizations and are periodically updated to reflect advances in pharmaceutical science and regulations.  A pharmacophore is the specific three-dimensional Pharmacophore: arrangement of atoms or functional groups within a molecule that is responsible for its biological activity and interaction with a target receptor. It represents the essential structural features of a molecule necessary for binding to a receptor and eliciting a biological response. Pharmacophore modeling is commonly used in drug design and discovery to identify and optimize lead compounds.  Chemotherapy refers to the use of synthestic or natural Chemotherapy:chemicals, drugs, (chemotherapeutic agents) to treat cancer by destroying or inhibiting the growth of cancerous cells. These drugs work by targeting rapidly dividing cells, which are characteristic of cancer cells. Chemotherapy may be used alone or in combination with other treatments such as surgery, radiation therapy, or immunotherapy, depending on the type and stage of cancer. While chemotherapy can be effective in killing cancer cells, it can also cause side effects due to its impact on normal, healthy cells in the body.  are chemical substances that are used to destroy or Disinfectants: inactivate microorganisms, including bacteria, viruses, and fungi, on surfaces or objects. Disinfectants work by disrupting the cell membranes, proteins, or nucleic acids of microorganisms, thereby killing them or rendering them incapable of reproducing. They are commonly used in healthcare settings, laboratories, households, and public spaces to prevent the spread of infectious diseases Examples of disinfectants include bleach (sodium hypochlorite), hydrogen peroxide, alcohol-based solutions, quaternary ammonium compounds, and phenolic compounds. It's important to follow manufacturer instructions and guidelines for proper dilution, contact time, and application methods when using disinfectants to ensure their effectiveness and safety.  are substances that are applied to living tissues (such as skin) Antiseptics: to reduce the risk of infection by inhibiting the growth and activity of microorganisms (bacteria, viruses, and fungi) Antiseptics work by either killing microorganisms (bactericidal) or inhibiting their growth (bacteriostatic) at the site of application. They are commonly used in healthcare settings, first aid situations, and personal hygiene routines to cleanse wounds, prepare the skin for medical procedures, and prevent the spread of infections. Examples of antiseptic agents include Alcohol-based solutions (e.g., ethanol, isopropyl alcohol) Hydrogen peroxide Chlorhexidine Iodine-based antiseptics (e.g., povidone-iodine) Benzalkonium chloride Silver nitrate Phenol derivatives Antiseptics are generally safe for use on intact skin but may cause irritation or allergic reactions in some individuals. It's essential to follow product instructions, guidelines, and precautions when using antiseptics to ensure their effectiveness and minimize the risk of adverse effects.  A vaccine is a biological preparation that stimulates the immune Vaccine: system to recognize and protect against specific infectious agents, such as viruses or bacteria. Vaccines typically contain inactivated forms of the pathogen, parts of the pathogen, or molecules that mimic the pathogen, known as antigens. When administered, vaccines trigger an immune response, leading to the production of antibodies and memory cells that provide immunity against future infections. Vaccines have been instrumental in controlling and eradicating numerous infectious diseases, saving millions of lives worldwide. ❑ Naming Drugs ▪ A proprietary name (trade name or brand name) identifies a commercial product and distinguishes it from other products. A proprietary name can be used only by the owner of the registered trademark. ▪ Each drug is also given a generic name that any pharmaceutical company can use to identify the product. The pharmaceutical company that develops a drug is allowed to choose the generic name from a list of 10 names provided by an independent group. ▪ Once a naturally occurring drug is isolated and its structure determined, it can serve as a prototype in a search for other biologically active compounds. ▪ The prototype is called a lead compound (i.e., a compound that plays a leading role in the search). ▪ Analogs of the lead compound are synthesized in order to find one that might have improved therapeutic properties or fewer side effects. ▪ The analog may have a different substituent than the lead compound, a branched chain instead of a straight chain, or a different ring system. Changing the structure of the lead compound is called molecular modification.  Lecture 2 ❑ Molecular Modification ▪ Cocaine comes from the leaves of Erythroxylon coca, a bush native to the highlands of the South American Andes. Cocaine is a highly effective local anesthetic, but it produces disturbing effects on the central nervous system (CNS), ranging from initial euphoria to severe depression. ▪ By dissecting the cocaine molecule: (a) removing the methoxycarbonyl group (b) cleaving the sevenmembered- ring lead to anesthetic activity without the damaging CNS effects. ‫االستراكشر‬ ‫للتوضيح‬  ❑ Random Screening ▪ Also known as a blind screen, is a search for a pharmacologically active compound without having any information about which chemical structures might show activity. ▪ Some tests can be done in vitro (in glass)—for example, searching for a compound that will inhibit a particular enzyme. ▪ Others are done in vivo—for instance, searching for a compound that will save a mouse from a lethal dose of a virus. ❑ The first compounds to be used by Ehrlich (1907) were organic dyes. ▪ Azo dyes effectively dyed wool fibers (animal protein) gave scientists the idea that such dyes might selectively bind to bacterial proteins, too. In vitro in antibacterial tests, but none showed any antibiotic activity. In vivo studies were done in mice that had been infected with a bacterial culture. Several dyes turned out to counteract gram-positive infections. The least toxic of these, Prontosil (a bright red dye), became the first drug to treat bacterial infections. The observation ‫امتحان‬ ▪ Prontosil was inactive in vitro but active in vivo. ▪ The dye was converted to an active compound by the mammalian organism. ▪ Scientists at the Pasteur Institute later investigated Prontosil, they noted that mice given the drug did not excrete a red compound. ▪ Urine analysis showed that the mice excreted para- acetamidobenzenesulfonamide, a colorless compound. Chemists knew that anilines are acetylated in vivo. ‫امتحان‬ ▪ So they prepared the nonacetylated compound (sulfanilamide). When sulfanilamide was tested in mice infected with streptococcus, all the mice were cured, whereas untreated control mice died. ▪ Sulfanilamide was the first of the sulfa drugs. ▪ Sulfanilamide is a bacteriostatic drug, not a bactericidal drug. A bacteriostatic drug : inhibits the further growth of bacteria. A bactericidal drug : kills the bacteria. ▪ Many successful drugs have been designed by using similar isosteric (like-size) replacements.  problems ▪ Drugs can be metabolized differently by different animals. Thus, an effective drug in a mouse may be less effective or even useless in a human. ▪ Regulating the dosages of both the virus and the drug. If the dosage of the virus is too high, it might kill the mouse in spite of the presence of a biologically active compound that could save the animal. If the dosage of the potential drug is too high, the drug might kill the mouse whereas a lower dosage would have saved it. (I) Sulphonamides “Sulpha Drugs” [Anti-bacterial] (6 examples) 1- Sulfanilamide (p-aminobenzene sulphonamides) ‫امتحان‬  Lead Modification (Lead Optimization) The most notable parameters that may need to be optimized include: potency; selectivity; absorption, distribution, metabolism, and excretion (ADME); and intel-lectual property position. 1. Potency The less will need to be administered to achieve the desired effect. 2. Selectivity There may be off-targets that are related to the intended target, with which it would be disadvantageous for the drug to interact. The cytochrome P450 (CYP) family of enzymes, which are responsible for the metabolism of many drugs. Inhibiting a CYP enzyme can inhibit the metabolism of other drugs that someone may be taking at the same time, leading to dramatic changes in the levels of the other drugs and lead to drug– drug interactions or accumulation of other drug LEAD MODIFICATION 1. Identification of the Active Part: The Pharmacophore Interactions of drugs with receptors, known as pharmacodynamics. Only a small part of the lead compound may be involved in the appropriate receptor interactions. The relevant groups on a molecule that interact with a receptor and are responsible for the activity are collectively known as the pharmacophore. The other atoms in the lead molecule, sometimes referred to as the auxophore. Some of the atoms, of course, are essential to maintain the integrity of the molecule and hold the pharmacophoric groups in their appropriate positions. Other atoms may be interfering with the binding of the pharmacophore, and those atoms need to be excised from the lead compound. her atoms in the auxophore may be dangling in space within the receptor and neither binding to the receptor nor preventing the pharmacophoric atoms from binding. Although these atoms appear to be innocuous, it is important to know which atoms these are, because these are the ones that can be modified without loss of potency and could be very important for solving pharmacokinetic problems.  The morphine Lecture 3 Family of analgesics bind to the μ opioid receptors. The pharmacophore is known and is shown as the darkened part. A decrease in potency on removal of a group will suggest that it may have been pharmacophoric, An increase in potency means it was auxophoric and interfering with proper binding, IF no change in potency will mean that it is auxophoric but not interfering with binding. ‫امتحان‬ Assume that the addictive analgesics morphine (R = Rʹ = H), codeine (R = CH3, Rʹ = H) heroin (R = Rʹ = COCH3) are the lead compounds  Removal of the dihydrofuran oxygen atom, which is not in the pharmacophore. ‫امتحان‬ Oxygen atom connects the cyclohexene ring to the benzene ring. its removal will result in a change in the conformation of the cyclohexene ring and an increase in the degrees of freedom of the molecule. Excision of the dihydrofuran oxygen gives morphinan (R = H) The hydroxyl analog, levorphanol (R = OH) is three to four times more potent than morphine as an analgesic, but it retains the addictive properties. Possibly, the additional conformational mobility allowed the molecule to better approximate its bioactive conformation.  Removal of half of the cyclohexene ring (also not in the pharmacophore), leaving ‫امتحان‬ only methyl substituents, gives benzomorphan (R = CH3). This compound shows some separation of analgesic and addictive effects; pentazocine (R = CH2CH = C(CH3)2; component of Talwin) is less potent than morphine (about as potent as codeine). But, has a much lower addiction liability. Although this analog is not more potent than morphine, it is less addicting.  Cutting away the methylene group of the cyclohexane fused ring also, surprisingly, has little effect on the analgesic activity in animal tests. Again, this excision removes the rigidity of the parent structure. ‫امتحان‬ Removal of all fused rings, for example, in the case of meperidine, gives an analgesic still possessing 10–12% of the overall potency of morphine. Although the potency is lower, it certainly will be much easier to synthesize analogs of meperidine than those of morphine. Even acyclic analogs are active. ‫امتحان‬ ▪ The tranquilizer Librium® is another drug that was discovered accidentally. Leo Sternbach synthesized a series of quinazoline 3-oxides, but none of them showed any pharmacological activity. One of the compounds was not submitted for testing because it was not the quinazoline 3-oxide he had set out to synthesize. Two years after the project was neglected a laboratory worker came across this compound while cleaning up the lab, and Sternbach decided that he might as well submit it for testing before it was thrown away. The compound was shown to have tranquilizing properties. When its structure was investigated, was found be a benzodiazepine 4-oxide. ▪ Librium® was structurally modified in an attempt to find other tranquilizers. Valium® is a tranquilizer almost 10 times more potent than Librium®. Rohypnol® is one of the so-called date-rape drugs. Xanax® is one of the most widely prescribed medications. ▪ Currently, there are eight benzodiazepines in clinical use as tranquilizers in the United States and some 15 others abroad.  Lecture 4 (III) Antibiotics ▪ Many micro-organism produce within themselves chemical substance, which, when excreated, interfere with the growth or metabolism of other micro – organism. ▪ Such compounds are known as antibiotics, and need to be present only in low concentration to bring about this antibiotic action. ▪ In 1929, Fleming discovered a mould of the penicillium species which inhibited the growth of certain bacteria. ▪ Antibiotics are classified on their chemical structures or according to the nature of their activity.  (1) The Penicillin ▪ It is a mixture of natural compounds having the molecular formula C9H11N2O4SR, and differing only in the nature of R. ▪ There are at least six natural penicillins. ‫امتحان‬ Pent-2-emylpenicillin (penicillin I or F) H H S CH3 R = CH 2CH=CHCH 2CH 3 RCOHN 5 21 6 CH3 Benzyl penicillin (penicillin II or G) 7 4 3 N H R = CH2C6H 5 O p- hydroxybenzyl penicillin (penicillin III or X) COOH R = p-hydroxybenzyl Penicillin n-Heptyl penicillin (penicillin IV or K) C9H11N2O4SR R = (CH2)6CH3 n-Amyl penicillin (Dihydro-F- penicillin) R = (CH2)4CH3 Phenoxy methyl penicillin (penicillin V) R = CH2OC6H5  ❑ Drugs as Enzyme Inhibitors ▪ Penicillin, for example, destroys bacteria by inhibiting the enzyme that synthesizes bacterial cell walls. ‫االستراكشر‬ ‫للتوضيح‬ ▪ Bacteria develop resistance to penicillin by secreting penicillinase, an enzyme that destroys penicillin by hydrolyzing its lactam ring before the drug can interfere with bacterial cell wall synthesis. ‫االستراكشر‬ ‫للتوضيح‬ ▪ Chemists have developed drugs that inhibit penicillinase. If such a drug is given to a patient along with penicillin, the antibiotic is not destroyed. This is an example of a drug that has no therapeutic effect itself, but acts by protecting a therapeutic drug. One penicillinase inhibitor is a sulfone, which is easily prepared from penicillin by oxidizing the sulfur atom with a peroxyacid. ▪ Because the sulfone looks like the original antibiotic, penicillinase accepts it as a substrate, forming an ester, as it does with penicillin. ▪ If the ester were then hydrolyzed, penicillinase would be liberated and, therefore, would be free to react with penicillin.  (IV) Drugs acting on the Central Nervous Lecture 5 System (CNS) Drugs which can affect the (C.N.S) are classified according to their mechanism of action into the following groups: (1) Analgesics: These drugs diminish pain without interference with consciousness. (2) Sedatives: These have a calming effect, and counteracts stimulation, irritation or excitement. (3) Tranquillisers: These drugs relieve anxiety and apprehension. (4) Hypnotics: These are drugs which produces sleep. (5) Anaesthetizes: These drugs inhibit the brain functions with loss of consciousness. (6) Narcotics: Drugs which produce deep hypons (sleep) and analgesia. (e.g. Morphine) (7) Psychototropic Drugs: These drugs affect the behavioral and mental conditions; e.g. Stimulates, antidepressants. (1) Analgesics (First & Second) FIRST: Compounds obtained from opium (e.g. morphine & codeine & thebaine) N.B. Synthetic compounds are used as morphine substitutes such as; Methadone & Phenomorphan ‫للمعرفه فقط‬ HO O Ph Me N CH3CH2 C C CH2 CH N Ph HCl H Ph Me Me phenomorphan methadon-HCl Methadone has a more powerful analysis action than morphine, and is used for case of severe pain. Second: Analgesic Antipyretics These drugs produce analgesia & reduce the high temperature of the body. These are THREE classes  (1) Salicylic Acid Derivatives: ‫امتحان‬ OH COOH COOH CONH2 COO OCOH3 OH Acetyl Salicylic Acid Salicylamide Salicylsal icylic Acid "Aspirin" "Salysal"  (2) Pyrazolone Derivatives: ‫امتحان‬ Me Me N CH2SO3Na N Me N O Ph Phenazone (Antipyrine) Dipyrone (Novalgin) Synthesis of NOVALGIN  (3) p-Aminophenol Derivatives:  e.g. Phenacetin ‫مش حفظ بس نفهمها‬ O EtO NH C Me Synthesis of Phenacetin (3) Oxazolidendiones and an Isoxazole (Anticonvulsant) (4) Pyrazole Derivatives (Antipyretic & Anti-inflammatory) (5) Imidazole Derivatives (Anti-trichomonal) Example: Synthesis of Azomycin (1) Pyridine-based Drugs Lecture 6 Example 2: Synthesis of Iproniazide (2) Piperidine-based Drugs Good Sedative Hypnotic agents  (3) Pyrimidine-based Drugs The finding that 2,4-diaminopyrimidines inhibit the growth of microorganisms by interfering with their utilization of folic acid led to an intensive search for anti-infective agents in this class of heterocyclic compounds. This work led to the development of at least two VERY successful anti- malarial agents. Example: Synthesis of Minoxidil (4) Barbituric Aid-based Drugs Example 1: Synthesis of Barbitol O R1 ‫مش حفظ بس نفهمها‬ R2 NH O N O H 68 (Sedative hypnotics) N.B. It has been in continuous use since 1903 and still one of the most widely used Sedative hypnotics.  Example 2: Synthesis of Cyclopal O R1 ‫مش حفظ بس نفهمها‬ R2 NH O N NH H 69 Cyclopal (Sleeping agent) N.B. ❑ The use of barbiturates as sleeping agents frequently leads to the so-called hangover on awakening. Unlike the more traditional hangover from alcohol, this syndrome often consists of a dulling of awareness for a considerable time. ❑ The long acting barbiturates act as sleeping pills. While the short acting drugs are used in surgery in conjunction with an inhalation anesthetic. (5) Pyrazine & Piperazine-based Drugs Example: Synthesis of Morephazine amide ‫مش حفظ بس نفهمها‬ O HCHO H2 N C C HN N N O H O N Morephazine amide (Anti-tubercular) ▪ Cancer is one of the most widespread and feared diseases in the world today - it is known to be difficult to cure. ▪ The main reason for this difficulty is that cancer results from the uncontrolled multiplication of modified normal cells. - About one in four people will get it in some form during their lifetime, and at the present time about one in five of all deaths are due to cancer. - Currently there are three major ways of treating cancer: radiation therapy, surgery and Chemotherapy. - All of these have significant limitations, but drugs offer the only approach to treat cases where the cancer has spread (metastasis) through the body. - Over the last fifty years about 500 000 natural and synthetic chemical compounds have been tested for anticancer activity, but only about 25 of these are in wide use today. - A major challenge is to design new drugs that will be more selective for cancer cells, and thus have lesser side effects. DESIGNING DRUGS TO COMBAT CANCER ▪ The drugs used to fight cancer belong to one of two broad categories. (1) Cytotoxic (cell killing) drugs. (2) Cytostatic (cell stabilising drugs). A bacteriostatic drug : inhibits the further growth of bacteria. A bactericidal drug : kills the bacteria. (1) Cytotoxic drugs: ▪ Cytotoxic drugs work by interfering with DNA replication. Because cancer cells are rapidly dividing they are rapidly synthesizing new DNA - and if this is damaged the cell will die. - There are three main groups of molecules that can be used to interfere with DNA replication: (a) Antimetabolites: molecules that appear to be nucleotides and so are incorporated into DNA, leading to non-functional DNA. (b) Alkylating agents: molecules that permanently attach to the DNA, distorting its shape. Unfortunately these also attach to many other molecules in cells. (c) DNA-binding agents: molecules that attach to the DNA chain, break it, disengage from the chain and then attach to another chain to repeat the process. These usually function in conjunction with an enzyme. Ex (1) In Cancer Cells ‫مش حفظ بس نفهمها‬ In Normal Cells ‫مش حفظ بس نفهمها‬ Ex (2) Enzymatic conversion of prodrug to active drug in cancer cells (2) Cytostatic drugs: - These drugs are designed to deactivate the altered enzymes that result from changes in the oncogene involved. - These drugs are not designed to kill the cell involved, but simply to prevent it from reproducing. - These drugs are theoretically 'cancer cell-specific' in that they target processes occurring only in cancer cells. ❑ Antiviral Drugs ▪ Viruses are smaller than bacteria. ▪ Virus consists of nucleic acid—either DNA or RNA— surrounded by a coat of protein. ▪ A virus penetrates a host cell or merely injects its nucleic acid into the cell. ▪ In either case, the nucleic acid is transcribed and is integrated into the host genome. ❖ Transcription (genetics), the copying of DNA into messenger RNA in gene expression. ❖ Genome is the entirety of an organism's hereditary information. ▪ Antiviral drugs: are analogs of nucleosides, interfering with DNA or RNA synthesis. In this way, they prevent the virus from replicating. Examples Acyclovir, the drug used against herpes viruses, has a three-dimensional shape similar to guanine. Acyclovir can, therefore, fool the virus into incorporating it instead of guanine into the virus’s DNA. Once this happens, the DNA strand can no longer grow. Cytarabine, used for acute myelocytic leukemia, competes with cytosine for incorporation into viral DNA. Cytarabine contains an arabinose rather than a ribose. The 2`OH group in the β-position prevents the bases in DNA from stacking properly. Lecture 7 Jaundice Causes: Liver problems, blocked bile ducts, hemolytic anemia (breakdown of red blood cells) in newborns. Symptoms: Yellowing of the skin and whites of the eyes, dark urine, pale stools, fatigue, nausea, and loss of appetite. Treatment: Treatment depends on the underlying cause. It may involve medications, surgery, or lifestyle changes. Cholera Causes: Caused by the bacterium Vibrio cholerae, transmitted through contaminated water or food. Symptoms: Severe diarrhea, vomiting, dehydration, muscle cramps, and weakness. Treatment: Rehydration therapy is essential to replace lost fluids and electrolytes. Antibiotics may also be used. Malaria Causes: Caused by Plasmodium parasites transmitted through the bite of infected mosquitoes. Symptoms: Fever, chills, sweating, headache, muscle aches, nausea, vomiting, and fatigue. Treatment: Antimalarial medications are effective in treating malaria. ANTI-CANCER Under supervision Prof: Ahmrd Fekri What is Cancer? Cancer cells :- are a normal cell in which a defect has occurred causing the cell to multiply abnormally and form a cancerous tumor but Not all types of cancer lead to the formation of tumors, as some types of cancer, such as leukemia, do not cause tumors to develop  Types of Anti-Cancer treatment Surgery Radiation Therapy Hyperthermia Pharmacotherapy Hyperthermia is a type of The use of substances When used to treat Radiation therapy is a type or drugs in the cancer, surgery is a treatment in which body of cancer treatment that treatment of cancer procedure in which a tissue is heated to as high uses high doses of surgeon removes as 113 °F to help damage radiation to kill cancer cancer from your body and kill cancer cells with cells and shrink tumors. it's the oldest and most little or no harm to normal effective treatment for tissue. some types of cancer. But can't use alone to treat cancer  Mechanism of action: The drugs used to fight cancer belong to one of two broad categories. (1) Cytotoxic (cell killing) drugs. (2) Cytostatic (cell stabilising drugs). Chemotherapy Cell cycle disruption DNA Damage Angiogenesis Apoptosis Induction Inhibition Drugs that interfere with the Drugs that directly damage Apoptosis, or programmed cell death, is a natural process that cell division process, the genetic material within Drugs that block the eliminates damaged or abnormal preventing cancer cells from cancer cells, causing cell formation of new blood cells. Some drugs can trigger replicating death vessels that feed tumor apoptosis in cancer cells by growth activating specific pathways or proteins involved in the apoptotic process.  *Loss of hair (alopecia) * Bone marrow General ADRs :- toxicity(myalosuepression) Anti-cancer drugs can * Impairad wound healing cause various side effects, depending on the specific * Sterility drug and the patient’s individual tolerance * Hepetotoxicity * Damage to GI epithelium Neutropenia * Carcinogenicity & teratogaenicity neutrovenia sadecrease in the number of whiteblood cells *mucosal ulceration * megaloblastic anaemia. *peripheral neuropathy.  Challenges in Anticancer Drug Development Tumor heterogeneity Drug Resistance TOXICITY Tumour heterogeneity describes the observation Resistance can occur that different tumour cells While newer can show distinct when cancer cells— chemotherapy drugs morphological and even a small group of have proven to be phenotypic profiles, cells within a tumor— more efficacious and including cellular contain molecular much less toxic than morphology, gene changes that make expression, metabolism, conventional drugs, motility, proliferation, and them insensitive to a toxicity can still not be metastatic potential. This particular drug before fully determined until phenomenon occurs both treatment even begins. clinical trial stages between tumours and within tumours.  Hormonal Therapy: Immunotherapy Targeted Therapy: Therapy: These derivatives work to This type of treatment targets change the balance of specific genes or proteins that This type of treatment is used to hormones in the body to contribute to the growth of enhance the immune system's prevent the growth of cancer cancer cells without affecting response to help it fight cancer.. cells that depend on hormones healthy cells. to grow.  Classes of chemotherapy :- Alkylating Antimetabolites Cytotoxic Microtubule agents antibiotics inhibitor Protien Monoclonal Miscellaneous Hormone kinase antibodies agents antagonists inhibirors Cyclophosphamide *Most commonly used alkylating Cisplatin: agent * It is a prodrug (requires the concentrations of platinum are biotransformation hepatic P450 highest in liver, prostate, and to be activated) kidney:somewhat lower in bladderFormula: cis-[Pt(NH3)2Cl₂] Uses: Treatment of advanced ovarian cancer, testicular bladder cancer 2- Cytotoxic antibiotics: anticancer drugs which drive the cell into apoptosis, causing arrest in tumour progression. Hence, they target the DNA or metabolic pathways which are important for cell replication Examples: Doxorubicin, bleomycin, mitomycin C 3- Antimetabolites : Anti-metabolitesare a group of molecules that impede DNA and RNA synthesis. Many of them have a similar structure to the building blocks of DNA and RNA.  Examples: - 5-fluorouracil(5-FU)Uses It is used on the skin to treat skin cancer and certain types of skin conditions that could become cancer. 4- Microtubule Inhibitors: Mechanism: Microtubule inhibitors disrupt the formation or function of microtubules, which are essential for cell division 5- Hormone Antagonists: Mechanism: Hormone antagonists interfere with hormone signaling pathways that are involved in promoting cancer growth. THANK YOU  A Brief Summary Anti Virals  Introduction Viruses i. Viruses are sub-microscopic intracellular parasites consist of either DNA or RNA and a protein coat. ii. They lack both cell wall and cell membrane and do not carry out metabolic processes. iii. Viruses possess only few or none of the enzymes involved in replication. Therefore, viruses need a host cell to utilize its enzymatic activity for their replication, existence and growth  Introduction Antiviral i. Drugs are a class of medication used for treating viral infections. Most antivirals target specific viruses, while a broad-spectrum antiviral is effective against a wide range of viruses. ii. Antivirals specifically target viruses and work by inhibiting the replication and spread of the virus within the host's cells. They are a vital tool in the management and control of viral diseases. Introduction Vaccines are preventive measures that prime the Vaccines immune system to recognize and fight specific viruses. Stimulate Immune Response: They contain harmless components (antigens) from the virus, triggering an immune response ypes f nti irus  Side Effects Common Side Effects - Headaches - Dizziness - Nausea or vomiting - Diarrhoea - Skin sensitivity to sunlight  Molecular modification One common molecular modification of acyclovir is the addition of a hydroxyl group to the molecule, resulting in the formation of its prodrug, valacyclovir. This modification increases the oral bioavailability of the drug, allowing for better absorption and conversion to acyclovir in the body. This modification enhances the effectiveness of the drug in treating viral infections such as herpes simplex virus and varicella-zoster virus. The chemical formula of acyclovir is C8H11N5O3 03  Evidence students CNS-DRUGS DR/ AHMED FEKRI Designed by BOODY  Definition The central nervous system CNS is made up of the brain and spinal cord. It’s part of the nervous system, the other part is the peripheral nervous system , which is made up of nerves that connect the brain and spinal cord to the rest of body.* The brain composed of the cerebrum, cerebellum and medulla Designed by BOODY  Modification Molecular modification #Morphin It works on μ-opioid receptor One of the molecular modifications is the levorphanol and we reached it by removing the dihydro phuran oxygen atom Turned out to be more potent 3 to 4 times and still addictive so not a solution Molecular Modification isn't only by removing , It can be by adding........ like Etrophine Which is 3200 more potent than Morphin it was used as a hypnotic for large animals #Amphetamine and methamphetamine after the first synthesis of amphetamine, Nagai synthesized methamphetamine from ephedrine is generally considered to be more potent than amphetamine. #Methamphetamine has a higher affinity for the receptors in the brain and has a longer duration of action compared to amphetamine. Both substances have similar effects on the central nervous system, including increased wakefulness, focus, and euphoria. Designed by BOODY  Topics 4 topics Designed by BOODY  CONCLUSIONS the diverse range of CNS drugs targeting neurological and psychiatric conditions through various mechanisms. It underscores the importance of understanding their risks and benefits for safe treatment. It also emphasizes their profound impact on mental, emotional, and physical states, necessitating careful regulation and ongoing advancements in development. It concludes by advising consultation with healthcare providers to manage potential side effects properly. Designed by BOODY Designed by BOODY  Caffeine CNS-DRUGS Cocaine Alcohol The most common drugs that affects on CNS:- Amphetamine Cannabis Heroin Etrophine Benzodiazepines Opioids Designed by BOODY  Side effects ------------- drowsiness Side effects anxiety Side effects irritation muscle memory loss relaxation hallucinations dizziness Designed by BOODY  1 Classification Classification of Drugs that act on the central nervous system (CNS) can be classified based on their primary effects: 1. An a l g e s i c s : These drugs relieve pain. They include opioids like morphine and non-opioids like acetaminophen (paracetamol). 2. S t i m u l a n t s : These drugs increase alertness, attention, and energy. Examples include amphetamines , cocaine, and caffeine. 3. An x i o l y t i c s : Also known as anti-anxiety drugs, these medications reduce anxiety. Examples include benzodiazepines like diazepam and non-benzodiazepines like buspirone. 4. Op i o i d s : These drugs act on opioid receptors to relieve pain and produce feelings of euphoria. Examples include morphine, heroin. 5. Ca n n a b i n o i d s : These drugs act on the cannabinoid receptors in the brain. Examples include marijuana (cannabis). 6. P s y c h e d e l i c s : These drugs alter perception, mood, and various cognitive processes. Examples include LSD. 7. In h a l a n t s : These are volatile substances that produce chemical vapors that can be inhaled to induce a psychoactive effect. Examples include nitrous oxide (laughing gas) and volatile solvents (e.g., glue, paint thinner). 8. Each of these categories includes a wide range of specific drugs, each with its own effects, risks, and potential for abuse or dependence.  2 Stimulants Stimulants are drugs that exert their action through excitation of the central nervous system. Psychic stimulants include caffeine, cocaine, and various amphetamines. These drugs are used to enhance mental alertness and reduce drowsiness and fatigue. However, increasing the dosage of caffeine above 200 mg (about 2 cups of coffee) does not increase mental performance but may increase nervousness, irritability, tremors, and headache. Heavy coffee drinkers become psychically dependent upon caffeine. If caffeine is withheld, a person may experience mild withdrawal symptoms characterized by irritability, nervousness, and headache. Produce electrical impulses that affect brain activity to treat certain medical conditions Amphetamine and methamphetamine after the first synthesis of amphetamine, Nagai synthesized methamphetamine from ephedrine is generally considered to be more potent than amphetamine. Methamphetamine has a higher affinity for the receptors in the brain and has a longer duration of action compared to amphetamine. Both substances have similar effects on the central nervous system, including increased wakefulness, focus, and euphoria.  3 Depressants Depressants Reduce arousal and calm neural activity Depressants and Their Effects on CNS Reduced Neural Activity Depressants slow down brain and spinal cord function. Induced Relaxation Promotes feelings of calm and sedation. Analgesic Properties Can also act as pain relievers. CNS depressant A. Sedative-hypnotic drugs The sedative-hypnotics are used primarily for two common disorders:- Anxiety. Insomnia. Sedative: Drugs that calm or quite the patient and reduce anxiety without induce normal sleep. Hypnotics: Drugs that initiate and maintain the normal sleep without loss of* consciousness. Classification of sedative- hypnotic drugs: 1. Benzodiazepines 2. Barbiturates  3 Depressants Structure of benzodiazepines and barbiturates  4 Analgesics ANALGESIC DRUGS Analgesia: refers to Analgesics and Their Effects on CNS Pain Perception Interference with pain signaling and interpretation. Neurotransmitter Modulation Impact on the transmission of pain signals in the CNS and absence of pain without the loss of consciousness. 1-Opioid: is any drug natural, semi synthetic or synthetic that has actions similar to those of morphine. Opioids are drugs of choice for moderate to severe pain that cannot be controlled with other classes of analgesics. 2-Opioid Analgesics: Powerful pain relievers. Originate from the opium poppy (plant). Opioid analgesics are the most effective analgesics and are used in the management of severe pain. 3-Opioid receptors: Three main classes of opioid receptors, designated as mu, kappa, and delta. From the pharmacologic perspective, mu receptors are the most important. This is because opioid analgesics act primarily through activation of mu receptors, although they also produce weak activation of kappa receptors 4- non-opioids like acetaminophen (paracetamol)  Antibiotics DEFINITION:- chemical substances produced microorganisms that are harmful to other microorganisms. HISTORY:- antibiotics began with the discovery of penicillin by Alexander Fleming in 1928. CLASSIFICATION OF ANTIBIOTICS:- 1- BASED ON CHEMICAL STRUCTURE Penicillins Contain a ß-lactam ring in theirStructure WIDELY USED TO TREAT INFECTIONS INCLUDING SKIN INFECTIONS, CHEST INFECTIONS AND URINARY TRACT INFECTIONS (UTIS) Tetracyclines Have a four-ring structure with variousfunctional groups attached COMMONLY USED TO TREAT ACNE AND ROSACEAE Macrolides Have a macrocyclic lactone ring with one or more deoxy sugars attached USED TO TREAT LUNG AND CHEST INFECTIONS, AND AS ALTERNATIVE TO PENICILLIN Aminoglycosides Have amino sugars connected by glycosidicbonds. USUALLY ONLY USED IN HOSPITAL TO TREAT VERY SERIOUS ILLNESSES INCLUDING SEPTICAEMIA Sulfonamides Have a sulfonamide group attached to anaromatic ring. Used to treat bacterial infections respiratorytract infections and some skin infections tions Quinolones Have a glycosylated cyclic or polycyclicpeptide core. USED TO TREAT A WIDE RANGE OF INFECTIONS 2-Types of Antibiotics according to ways of work:- kills the bacteria. These drugs usually interfere with either bactericidal the formation of the antibiotic bacterial cell wall or its cell contents. Example penicillin. stops bacteria from bacteriostatic multiplying 3-TYPES OF ANTIBIOTICs according to their spread and effect These antibiotics are effective against a wide Broad-spectrum range of bacteria, both Gram-positive and Gramnegative. These antibiotics target specific types of bacteria, Narrow-spectrum often Grampositive or Gram-negative, and are more selective in their action. These antibiotics kill bacteria by disrupting Bactericidal essential cellular processes, leading to their death  Mechanism of Action 1-CELL WALL SYNTHESIS some antibiotics interfere with the formation or structural integrity of thebacterial cell wall, causing the cell to rupture and die. 2-PROTEIN SYNTHESIS other antibiotics disrupt the process of protein synthesis in bacterial cells, preventing them from producing the necessary protein for survival growth. 3-DNA REPLICATION certain antibiotics target the bacterial dna, interfering with its replication and preventing the bacteria from reproducing. Methods of molecular modification 1-Adding Functional Groups:- This method involves introducing additional chemical groups to the antibiotic molecule to modify its properties and enhance its effectiveness.  2-Altering Side Chains:- Changing the side chains of the antibiotic molecule can lead to improved pharmacokinetic properties and interaction with bacterial targets. 3-Synthesizing Analogues:- The synthesis of analogs with different substituents allows for the exploration of diverse chemical structures to find more potent antibiotics. Examples on molecular modifications ERYTHROMYCIN: THE FIRST MACROLIDE DISCOVERED. AZITHROMYCIN: KNOWN FOR ITS IMPROVED ABSORPTION AND FEWER SIDE EFFECTS CLARITHROMYCIN: A DERIVATIVE OF ERYTHROMYCIN WITH SIMILAR BENEFITS ANTIBIOTIC RESISTANCE:- A major public health concern, as it can make bacterial infections more difficult to treat and increase the risk of complications and mortality. Sometimes, bacteria causing infections are already resistant to prescribed antibiotics. Bacteria may also become resistant during treatment of an infection.  A common misconception is that a person's body becomes resistant to specific medicines. Medicine resistance happens when bacteria develop ways to survive the use of medicines meant to kill or weaken them. If a germ becomes resistant to many medicines, treating the infections can become difficult or even impossible. In some cases, the antibiotic-resistant illness can lead to serious disability or even death. Resistance can happen if the bacterial infection is only partially treated. To prevent this, it is important to finish taking the entire prescription of antibiotics as instructed, even if your child is feeling better. CONTRAINDICATIONS FOR ANTIBIOTICS Allergy: If a person has a known allergy to a specific antibiotic or antibiotic class, they should not receive that antibiotic. Drug Interactions: