Organic Medicinal Chemistry PDF

om i.l c m a @ g in a a n b b io a o d s o m INTRODUCTION...

om i.l c m a @ g in a a n b b io a o d s o m INTRODUCTION om.l c Medicinal Chemistry ________________________ and _________________________ of new agents for treating diseases. Principal domain: application of science (chemistry) towards drug design. ai Drug g m a @ An agent intended for use in the __________, __________, __________, __________, or ______________ of disease in humans or in in other animals. a n b Antibiotic b A substance produced by microorganisms, which has the capacity of inhibiting the growth and even of destroying other microorganisms. - Selman Waksman io a Root word: Antibiosis (literally “against life”) Antibiotic Characteristics o d s o m 1. Product of _______________ although it may be duplicated or even have been anticipated by chemical synthesis. 2. Synthetic product produced as a _________________________ of a naturally occurring antibiotic. 3. Antagonizes the growth or survival of one or more species of microorganisms. 4. Effective in low concentrations. INTRODUCTION om i.l c m a @ g in a a n b b io a o d m Cell Wall contains: s o Peptidoglycan layer Sugar (NAM and NAG) linked by peptides NAM: NAG: Antibiotics MOA om i.l c Cell Wall Inhibitors Protein Synthesis Inhibitors m a @ g Mnemonic: __________________ 1. Cephalosporins 2. Carbapenem 30s in a n 1. Tetracycline a 3. Penicillin b 2. Aminoglycoside b 4. Polypeptide/ Glycopeptide 5. Monobactam io a 50s o d 1. Lincosamide 2. Chloramphenicol s o m 3. Macrolide QUICK QUIZ! om 1. All of the following are cell wall inhibitors, except: i.l c A. Carbapenem m a g B. Cephalosporins @ C. Aminoglycosides D. Penicillins in a a n 2. Which of the following inhibits 30s? b b a A. Chloramphenicol io B. Tetracyclines C. Macrolides o d m D. Lincosamides s o PENICILLINS om.l c beta lactam ring (4 membered cyclic amide) thiazolidine ring (contains S) ai Nucleus: 6-aminopenicillanic acid (6-APA) PQ g m a @ in Microbial sources a n Penicillium _________________ (discovered by Fleming) b Penicillium _________________ (most common source) b io a Background o d m Accidentally discovered by Sir ____________________________ in 1929 s o Howard Florey and Ernst Chain introduced penicillin into therapy in 1928. They isolated penicillin using the process called “_________________________”. BEQ PENICILLINS om Issues with Penicillin i.l c 1. Water Insoluble -> added _________ m a g 2. Easily Excreted @ 1st solution: 2nd solution: in a n 3. Acid-labile -> substitution of ________________________ a 4. Easily degraded by penicillinase enzyme (B-lactamase) b 1st solution: a b io 2nd solution: o d Beta Lactamase/Penicillinase inhibitors s o m 1. Clavulanic acid 2. Sulbactam 3. Tazobactam QUICK QUIZ! om 1. The ring common among penicillins and cephalosphorins: i.l c a. Benzene ring m a g b. Beta-lactam ring @ c. Thiazole ring d. Phenothiazine in a a n b b 2. Increases serum levels and prolongs the activity of penicillin derivatives by io a blocking the latter’s tubular excretion: d A. Probenecid B. Indomethacin C. Propranolol m o D. Methyldopa s o QUICK QUIZ! om i.l c 3. Which of the following is a depot penicillin preparation? m a g A. Phenoxymethylpenicillin @ B. Benzathine penicillin C. Benzyl penicillin D. Cloxacillin in a a n b b io a 4. This is the process utilized by Florey and Chain in isolating penicillin: d A. Freeze drying B. Extraction m C. Chromatography o s D. X-ray o I. NATURAL PENICILLINS om A. Pen G aka: ___________________________ i.l c a Not effective when administered orally (inactivated by gastric juice) m _______________________ administered @ g DOC for: __________________ in a a n b b i o a B. Pen V aka: ___________________________ Acid stable o d m _______________ Administered s o II. AMINO PENICILLINS aka: ____________________________ om.l c Contains a-amino group (ionized/polar group) that can penetrate the outer cell membrane of Gram negative bacteria. ai A. Amoxicillin g m a Chemical name: D-a-Amino-p- hydroxybenzylpenicillin PQ @ in Better oral bioavailability than Ampicillin Orally administered a n b b B. Ampicillin io a d Poor GI absorption --> parenterally administered o Prodrugs of Ampicillin: PQ m o 1. Bacampicillin s 2. Cyclacillin 3. Hetacillin (reacting penicillin with acetone) III. Penicillinase Resistant Penicillin aka: ________________________ Contains bulky group ---> Steric hindrance om i.l c A. Methicillin m a g Drug of choice for: Penicillin-resistant Staphylococcus aureus @ Interstitial nephritis (renally excreted) in a Side effect: _______________________ (hypersensitivity reaction) n DOC for: _______________________ MRSA - _______________________ b a VRSA - _______________________ a b B. Nafcillin d io o Alternative for Methicillin (biliary excreted) m o Side effect: ___________________________ s Isoxazolyl Penicillins (Oxacillin, Cloxacillin, Dicloxacillin) IV. Antipseudomonal Penicillins om.l c A. Carboxypenicillins (acid-labile -> parenterally administered) 1. Carbenicillin ai m broader than any other known penicillin (attributed by carboxyl group) g @ 2. Ticarcillin Timentin: Ticarcillin + Clavulanate in a a n b B. Ureidopenicillins 1. Piperacillin a b io most potent of all ureidopenicillin d m o Acid-labile -> IV and IM Zosyn: Piperacillin+Tazobactam (8:1 ratio) s 2. Mezlocillin 3. Azlocillin o QUICK QUIZ! om 1. Benzyl penicillin is also known as: i.l c A. Penicillin G m a g B. Penicillin @ C. Oxacillin D. Ampicillin in a a n b b a 2. The chemical name is 2,6-dimethoxyphenylpenicillin: io A. Pen G B. Pen V o d m C. Methicillin o D. Nafcillin s QUICK QUIZ! om i.l c 3. Augmentin is a combination of: m a 4. Unasyn is a combination of: I. K salts of Clavulanic acid II. Amoxicillin I. Amoxicillin @ g II. Sulbactam Sodium III. Ampicillin in a III. Ampicillin Sodium n IV. Sulbactams IV. Clavulanic acid ba A. I and II a b A. I and II io B. II and III B. I and III d C. II and IV C. II and III D. III and IV m o D. II and IV s o CEPHALOSPORINS om beta lactam ring (4 membered cyclic amide) i.l c dihydrothiazine ring m a g Nucleus: 7-aminocephalosporanic acid Microbial sources a@ n in a Cephalosporium acremonium b b Background io a o d Interest in Cephalosporium fungi began in 1945 with Giuseppe Brotzu’s m discovery that cultures of C. acremonium inhibited the growth of a wide s o variety of Gram-positive and Gram-negative bacteria. CEPHALOSPORINS om Characteristics i.l c m a 1. Much more resistant to inactivation by beta-lactamases (Penicillinase) @ g 2. Cross sensitivity with penicillin. Alternative: _____________________ a 3. More effective in treating gram (-) infections than penicillin in n 4. Broad spectrum 5. Acid stable b a Cephamycin a b d io o Mnemonic: ______________________________________ s o m Cefoxitin, Cefotetan, Cefmetazole CEPHALOSPORINS om i.l c Additional Info: m a @ g 2. Third generations (Cefoperazone,in a 1. Ceftriaxone is the drug of choice for treatment of gonorrhea. a n Ceftazidime, Ceftriaxone) cross the b b blood brain barrier. It reaches cerebrospinal fluid. io a o d s o m QUICK QUIZ! om 1. A parenteral Cephamycin i.l c 3. Which is not true for cephalosporins? A. Cefoxitin a A. Broad spectrum m B. Cephalexin g B. Bactericidal @ a C. Ceftazidime C. Affected by penicillinases in D. Cefadroxil D. Acid-stable a n b b a 2. A fourth generation cephalosphorins 4. Cephalosporin C contains A. Cefoxitin d io A. Penicillanic acid B. Cefepime C. Cefamandole m o B. Thiazolidine ring C. Lactone ring D. Cefuroxime s o D. Dihydrothiazine ring CARBAPENEMS om.l c beta lactam ring (4 membered cyclic amide) pyrroline ring ai Characteristics g m a @ in 1. Resistant to beta-lactamase 2. Broad spectrum a n 3. Class II beta-lactamase inhibitor b b io a 1. Thienamycin o d s o m First carbapenem to be discovered First isolated from the fermentation of _____________________________________ CARBAPENEMS om 2. Imipenem i.l c m a g most successful of a series of chemically stable derivatives of thienamycin. @ a MOA: inhibition of cell wall synthesis associated with bonding to PBPs ___ and ___. in Problem: Easily degraded by _____________________________ n a ____________________: inhibits dihydropeptidase-1 enzyme b b ____________________: Imipenem + Cilastatin PQ io a Side effects: ___________________ (patients with renal failure) o d s o m CARBAPENEMS om 3. Meropenem i.l c m a g Second generation Carbapenem Does not cause seizure a @ in Exhibits greater potency against Gram-negative and anaerobic bacteria than imipenem. Less active against Gram-positive a n Not hydrolyzed by DHP-I. b b a Resistant to most beta-lactamases io o d s o m MONOBACTAMS om.l c Beta-lactam ring is not fused to another ring ai began with the isolation of sulfazecin from saprophytic soil bacteria in Japan and United States. m Since sulfazecin was found to be weak antibacterial agent, extensive studies led to the g @ development of Aztreonam. in a 1. Aztreonam a n b b io a AKA: ___________________________ for P. aeuroginosa o d Monobactam prepared by total synthesis MOA: It binds with high affinity to ________ in Gram negative bacteria only o m It is inactive against ________ bacteria and anaerobes. s Penicillin-binding proteins have the following properties: om.l c PBPs 1a and 1b: peptidoglycan synthesis associated with ___________________. i Inhibited: m a g Eg: PBP 2: maintaining the ___________________ of bacilli. a @ in Inhibited: Eg: a n b PBP 3: septum formation during cell division. b Inhibited: io a d Eg: o PBP 4: hydrolysis of _________________________ terminal peptide bonds of the cross-linking peptides. m o Inhibited: s POLYPEPTIDES om One of the most powerful bactericidal antibiotics i.l c S/E: _____________________________ m a 1. Vancomycin @ g in a a n Glycopeptide antibiotic containing 2 glycosidically linked sugar (_______________ and b b __________________) and a complex cyclic peptide Microbial source: io a d Effective only against Gram (+) bacteria o DOC for: ____________________________________ and ______________________ m o S/E: ______________________________ (due to rapid infusion), ototoxic and nephrotoxic s POLYPEPTIDES om 2. Bacitracin i.l c m a Microbial source: @ g a Isolated from debrided tissue from a compound fracture of 7-year-old Margaret Tracy. in MOA: Inhibition of mucopeptide cell wall synthesis (enhanced by _________) n a Effective only against Gram (+) bacteria b a b 3. Polymyxin B d io m o Microbial source: s o Effective against Gram (-) bacteria POLYPEPTIDES om 4. Gramicidin i.l c Obtained from tyrothricin, m a Microbial source: @ g a MOA: interferes with cell membrane functions by acting as an ionophore in bacterial cell in n membranes to cause the loss of potassium ion from the cell. b Effective against Gram positive bacteria a a b 5. Teicoplanin d io m o o Microbial source: s Effective only against Gram positive. Safe compared to Vancomycin. QUICK QUIZ! om i.l c 1. Imipenem is the most successful of a series of chemically stable derivatives of thienamycin in which the a primary amino group is converted to a non- nucleophilic basic function. Imipenem is also: m g A. 5-acetoimidothienamycin @ B. 5-methyl-3-phenyl-4-isoxazolyl penicillin C. N-formimidoylthienamycin in a n D. a-(1-methanesulfonyl-2-oxo-imidazolidino carbonyl-amino) benzylpenicillin b a 2. Primaxin is a combination of: a b io I. Tazocillin A. I and II II. Imipenem o d B. I and III m III. Piperacillin C. II and III IV. Cilastatin s o D. II and IV AMINOGLYCOSIDES om Composed of amino sugar linked glycosidically. i.l c Poorly absorbed following oral administration. m a g PQ SAR: Ring I - broad spectrum antibacterial; primary target for bacterial inactivating enzymes Orally administered: a @ n in 1. ___________________________ b a b 2. ___________________________ io 3. ___________________________ a o d Most are administered parenterally. s o m Do not cross the blood brain barrier Excreted by ___________________________ Not metabolized in vivo. AMINOGLYCOSIDES om Microbial Sources i.l c m a g A. Micromonospira: _____________ Eg: a@ in Microbial source: a n B. Streptomyces: _____________ b b Eg: io a d Microbial source: o Streptomycin A - m o Streptomycin B - s AMINOGLYCOSIDES om 1. Streptomycin i.l c m a g __________ aminoglycoside antibiotic to be used in chemotherapy. Discovered by __________________________ a @ in Acid hydrolysis yields ____________________ and _______________________ a n Only aminoglycoside used for tuberculosis. b b DOC: ____________________ aka _________________________ a Most effective of the group for the chemotherapy of TB, brucellosis, tularemia, and Yersinia io d infections m o s o AMINOGLYCOSIDES om 2. Neomycin i.l c m a Microbial source: Used for the treatment of GI infections @ g Most _________________ in a a n 3. Paromomycin b b Microbial source: io a 4. Spectinomycin o d o m Tx for: _____________________________ s AMINOGLYCOSIDES om 5. Kanamycin (Kantrex) PQ i.l c m a Microbial source: @ g a Kanamycin is almost pure Kanamycin A (least toxic of all forms) n in 6. Amikacin (Amikin) b a b Semisynthetic aminoglycoside first prepared in Japan. a io Structurally related to _____________________ o d Broadest spectrum of all aminoglycoside s o m AMINOGLYCOSIDES om i.l c 7. Gentamicin m a Microbial source: @ g in a 8. Netilmicin a n Semi-synthetic b b io a Microbial source: ______________________________ (prepared by reductive ethylation of Sisomicin) o d s o m AMINOGLYCOSIDES ADR om i.l c A: ________________________ m a @ g M: ________________________ (CI to patients with myasthenia gravis) I: ________________________ in a a n N: ________________________ (Most: _______________) b b O: ________________________ (Most: _______________) io a o d Vestibular damage: Gentamicin & Streptomycin s o m Auditory damage: Amikacin, Kanamycin, Neomycin Both: Tobramycin QUICK QUIZ! om i.l c a 1. The 1st aminoglycoside antibiotic to be used in chemotherapy: m A. Amikacin B. Gentamicin @ g a C. Streptomycin in D. Kanamycin a n 2. Acid hydrolysis of Streptomycin yields: b b a I. Streptidine io II. Streptobiosamine III. Deoxystreptamine o d A. I and II B. I and III s o m C. I and III D. I and II TETRACYCLINES om i.l c m a @ g in a n Compound of 4 fused ring b a Functional group: ______________________ b Advantage: _________________ of activity of any known bacterial agents. a io Effective against: Atypical bacteria (Mycoplasma, Rickettsia, Chlamydia) o d Disadvantage: _________________________ agent only s o m Note: Do not give bacteriostatic agent to __________________ patients TETRACYCLINES ADR om Chelate _______, _______, _______, and _______ salts i.l c They get deposited in newly forming _____________. m a Causes __________ discoloration of teeth. Causes __________ damage @ g in a Tetracyclines are distributed into the milk of lactating mothers and will cross the placental barrier into the fetus. a n Should not be given to: b b _____________ io a o d _________________ mothers Children below ____ years old s o m Highly phototoxic Causes ____________ syndrome - ingesting expired tetracycline TETRACYCLINES om 1. Chlortetracycline aka ___________________ i.l c Microbial source: m a g First tetracycline to be discovered (by ____________) 2. Demeclocycline a @ n in Causes photosensitivity reaction that produces erythema after exposure to sunlight. 3. Doxycycline b a a b io DOC: d Prophylaxis for __________________ o s o m 4. Minocycline Most _______________ tetracycline, and least _____________________ *Tigecycline is the first glycylcycline QUICK QUIZ! om i.l c a 1. The most effective agent in the treatment of Rickettsia, Mycoplasma and Chlamydia infection is: m A. Pen G Tetracycline @ g a Vancomycin in Gentamicin a n 2. Tetracycline is: b b a A. An intermediate spectrum, bactericidal io B. A broad spectrum, bacteriostatic o d C. A broad spectrum, bactericidal m D. An intermediate spectrum, bacteriostatic s o QUICK QUIZ! om 3. Ascorbic acid and tetracycline are: i.l c A. Enols m a g B. Esters C. Ethers a @ in D. Amines a n b b 4. Aluminum and calcium salts inhibit the intestinal absorption of which of the following agents? A. Isoniazid B. Chloramphenicol io a C. Erythromycin o d D. Tetracycline s o m MACROLIDES om Characteristics: i.l c m a g A. Large lactone ring B. Ketone group a @ in C. Glycosidically linked amino sugar (2-deoxy sugars) a n Advantage b b Can be given ________ io a o d ______________________ - first macrolide to be discovered s o m MACROLIDES om i.l c 1. Erythromycin m a Found in the soil of _________________ @ g a Microbial source: _____________________________ Discovered by: _____________________________ n in a Given to patient with allergy in ______________ antibiotics Enzyme inhibitor b b io a Estolate salt causes: _____________________________ d DOC: Diphtheria, Pertussis, Legionella – Respiratory tract infection o ADR: GI distress (abdominal cramps, diarrhea) m s o MACROLIDES 2. Clarithromycin aka: _____________________________.co m a i l m Increased acid stability and oral bioavailability Enzyme inhibitor @ g i n a Used in the tx of peptic ulcer disease 3. Azithromycin a n b b Given for 3 days io a d Food decreases its absorption by as much 50%. Administer at least 1 hour before or 2 o hours after meal. m o Not an enzyme inhibitor s LINCOSAMIDES om S-containing antibiotic i.l c 1st: Lincomycin m a g Microbial source: _________________________________ Disadvantage: easily excreted a @ in Solution: Added _________________ and __________________ group. a n b b 1. Clindamycin (Dalacin-C and Cleocin) o a Aka: 7-chloro-7-deoxy-lincomycin i d Broad spectrum antiobiotic that inhibit the growth of GI flora o m Clostridium difficile is resistant: It proliferate causing ___________________________________ s o Symptoms: GI distress, blood in stool Management: D/C, give vancomycin or metronidazole CHLORAMPHENICOL om Unclassified i.l c Isolated by ____________________________ m a Microbial source: ____________________________ @ g a Main metabolism: Glucoronidation Minor metabolism: Reduction and Hydrolysis n in a It can cross BBB DOC: ____________________________ b b a Alternative: ____________________________ io d ADR: Bone marrow depression --> ____________________________ o Toxic: _________________________ m s o QUICK QUIZ! om 1. 7 chloro-7-deoxy lincomycin: i.l c A. Clindamycin m a g B. Roxithromycin @ C. Spectinomycin D. Ilotycin in a a n b 2. This group is responsible for the bone marrow toxicity of chloramphenicol: b a A. NO2 group B. NH2 group d io o C. OH group m D. COOH group s o QUICK QUIZ! om 3. A macrolide antibiotic which was found in the soil of Iloilo: i.l c A. Achromycin m a g B. Albamycin @ C. Erythromycin D. Viomycin in a 4. Macrolide antibiotics have these common characteristics: a n I. Large lactone ring b b II. Ketone group io a III. A glycosidically linked amino sugar IV. An asymmetric carbon atoms in the acylamidopropanediol o d A. I only m B. II only s o C. I-III D. I-IV  om.l c Synthetic m ai g Antibacterial a n i n a @ d ioAgents a b b m o s o SULFONAMIDE om.l c Prototype: _____________________ (brilliant red dye) Active metabolite: _____________________ ai m Metabolism: Acetylation g MOA: Structural analogs of ____________. It competitively inhibit dihydropteroate synthase. @ a Active form of sulfonamide: ______________ form Folate Synthesis (DNA) n in b a a b d io m o s o SULFONAMIDE om i l c 1. Sulfamethoxazole + Trimethoprim (Bactrim,.Septra) m a Sulfamethoxazole: inhibits _____________________________________ g Trimethoprim: inhibits _____________________________________ @ Use: i n a n Tx and prophylaxis of _________ (common cause of mortality in HIV px) b a Tx for the first attack of _________ 2. Pyrimethamine +io a b Sulfadiazine o d m Use: Tx and prophylaxis of _____________________________________ s o SULFONAMIDE om i.l c 3. Silver sulfadiazine and Mafenide m a Mafenide S/E: @ g Use: Burn therapy: Prevention and treatment BEQ for bacterial infections in a 4. Sulfacetamide a n b b Use: Tx of _________________________ and other ocular infections 5. Sulfadoxine + d io a Pyrimethamine m o o Use: Tx of _________________________ P. falciparum malaria s SULFONAMIDE om ADR i.l c Crystalluria m a Rashes @ g Anemia (Hemolytic) Nausea in a Kernicterus a n Stevens Johnson Syndrome b b io a o d Other commonly used drugs that are sulfon- amides or sulfanilamide: m Tolbutamide (OHA) s o Furosemide (diuretic) Chlorathalidone (diuretic) SULFONES om Less effective than sulfonamides i.l c MOA: Analogue of PABA m a Dapsone (4,4’-diaminodiphenylsulfone or DDS) @ g i n a n DOC for ___________________ aka ________________ disease a b Tx of both lepromatous and tuberculoid types of leprosy b io a *Clofazimide: a reddish-brown dye, tx for leprosy)* o d s o m QUINOLONES om MOA: Inhibit ___________________ or ___________________ i.l c Prototype: ___________________(urinary antiseptic) m a g Most potent: ___________________ a @ ADR n in a Chelates: Zinc, Calcium, Magnesium, Bismuth, Ferrous and Ferric ions b b Phototoxic Most: ___________________ io a d Least: ___________________ o m Causes arthropathy (erosion of catilage) s o C/I: Below 18 yrs old QUINOLONES om i.l c m a @ g in a a n b b io a o d s o m NITROFURANS om.l c First _______________ compounds to be introduced into chemotherapy MOA: Inhibits DNA synthesis ai g m Drugs a @ in 1. _____________________ : Tx for burns (bacterial infection) n a 2. _____________________: Tx for bacterial or protozoal diarrhea b b 3. _____________________: Urinary antiseptic a io 4. _____________________: Used as antiprotozoal agent to treat trypanosomiasis and leishmaniasis. o d s o m NITROFURANS om 5. Metronidazole i.l c Tx for: TAGA m a Trichomoniasis: causes _____________________ @ g a Amoebiasis in Giardiasis: aka _____________________ Anaerobes a n b b ADR: _____________________, _____________________ io a d Reactive reduction product of Metronidazole: Nitroso m o o Nitroxide s Hydroxylamine Amine  Synthetic Antibacterial Agents QUICK QUIZ! om 1. Active form of the sulfonamide: i.l c 3. Sulfonamides are metabolized by humans principally by: A. Non-ionized B. Ionized A. Acetylation B. Oxidation m a C. Amphoteric C. Methylation @ g D. Oxo ring a D. Deamination in a n b 2. More potent optical isomer of ofloxacin b A. Levo B. Dextro io a C. Cis isomer o d D. Trans isomer s o m  om i.l c a Antifungal @ gm n a Agents a b b a n i d io m o s o ANTIFUNGAL AGENTS om i.l c m a ____________________: scientific study of fungi @ g Structural component of fungi: in a Cell membrane: ____________________ a n Cell wall: ____________________ b b io a o d s o m  om.l c 3 Types of Mycoses: 1. ______________________: outermost layer of the skin and hair. ai m Eg. Tine versicolor aka ______________________ Causative agents: ____________________ @ g a Under the microscope: Spaghetti with meatballs in appearance. in 2. ____________________: subcutaneous tissues. a n 3. ____________________: aka “____________________”, affecting internal organs b b a Common Types of Ringworms 1. Tinea manuum: d io o 2. Tinea pedies aka Athlete’s foot: 3. Tinea corporis: s 4. Tinea capitis: o m 5. Tinea cruris aka “____________________”: 6. Tinea unguium: POLYENES om Contains: i.l c Conjugated double bonds m a g Hydroxyl groups (OH) Mycosamine (glycosidically linked deoxyaminohexose) a @ n in 1. Amphotericin B b a a b Microbial source: ____________________________ io MOA: Creates a hole in a fungal cell membrane causing cytoplasmic contents to leak out. d o DOC: ____________________________ m s o POLYENES om i.l c 2. Nystatin (Mycostatin) m a Aglycone: ________________________ @ g Microbial source: ________________________ in a n DOC: ________________________ b a 3. Natamycin a b io Microbial source: ____________________________ d o DOC: ____________________________ m s o ECHINOCANADINS om MOA: Inhibition of ________________________ i.l c Effective against most species of Candida m a Eg: @ g a 1. 2. n in b a a b d io m o s o AZOLES om MOA: Inhibition of ________________________ i.l c m a @ g in a a n b b io a o d s o m AZOLES om i.l c m a @ g in a a n b b io a o d s o m ALLYLAMINES om Topical use only i.l c MOA: _________________________ inhibitor m a g Naftitine Tolnaftate a@ in Terbinafine (Lamisil) n Tx for _________________________ (Tinea unguium) a Shorter duration of therapy b b Applied once per day for a week io a ADR: Highly _____________________ o d s o m OTHERS om 1. Griseofulvin i.l c Antifungal antibiotic m a Microbial source: _________________________ @ g a Isolated originally as a “_________________________” in plants. in MOA: __________________________________________________ n Poor oral bioavailability b a b Solution: Micronized form io a Should be taken with _________________________ d DOC: _________________________ o s o m OTHERS om 2. Flucytosine i.l c Nucleoside antifungal agent m a g Prodrug @ Converted to ________________________ (active metabolite) MOA: inhibits ________________________ synthesis in a Synergistic with ________________________ a n 3. Propionic acid (0.01%) b b io a Natural antifungal agent found in the perspiration. 4. Undecylenic acido d s o m Tx for athlete’s foot. QUICK QUIZ! om 1. Which of the following is/are true regarding Griseofulvin? i.l c a I. It is recommended for the systemic treatment of refractory ringworm infections m g II. Its bioavailability is notoriously poor @ III. It is supplied in “microsize” and “ultramicrosize” forms in a n A. I, II and III B. I and II only b a 2. For the treatment of systemic mycosis, which of the following b C. I and III only antifungal agents can be administered by intravenous route? D. I and III only io a A. Miconazole d B. Amphotericin B m o C. Ketoconazole o D. Clioquinol s  om i.l c a Cancer @ g n m a Chemotherapy a b b a n i d io m o s o CANCER CHEMOTHERAPY om i.l c ___________: a group of diseases characterized by uncontrolled growth, and the spread of abnormal cells that left untreated may lead to death. m a g 1g tumor= __________ cancer cells (it becomes detectable) a @ in _______________: the uncontrolled growth of new tissue, the product of which is known as a tumor, a n and these tumors may be either malignant or benign. b ______________ tumors: capable of invading surrounding tissues and moving to distant locations in b a the body in a process known as metastasis io d ______________ tumors - mass of cells that does not invade neighboring tissue or metastasize. m o s o CANCER CHEMOTHERAPY om ____________: cancer of the blood characterized by increased WBC i.l c Polycythemia vera: cancer of the blood characterized by increased RBC m a g Sarcoma: Malignant tumor of connective tissues Carcinoma: Tumor in epithelial cells. a @ Cell Cycle n in b a G1: Growth a b G2: Growth and preparation for Mitosis d io a. Inhibited by ____________ (Elspar) and Prednisone a. Inhibited by _______________ and ___________________ o S: DNA Synthesis M: Mitosis (________________________) m a. Inhibited by _____________________ b. Inhibited by ________________________ s o I. ALKYLATING AGENTS om Common side effect: Alopecia i.l c m a 1. Nitogen Mustards @ g A. Chlorambucil in a n Tx for _________________________________ b a B. Cyclophosphamide a b io Converted to phosphoramide mustard and acrolein d o Acrolein causes ________________________________ m o Emergency drug - _______________ s I. ALKYLATING AGENTS om 2. Organoplatinum Compounds i.l c A. Cisplatin ADR: _______________ and _______________ m a Emergency drug: _______________ @ g in a B. Carboplatin a n ADR: _______________ b b io a 3. Alkylsulfonates o d m A. Busulfan s o ADR: ________________ and _________________ II. ANTITUMOR ANTIBIOTICS om.l c A. Anthracyclines Microbial Source: __________________________ ai m 1. Daunarubicin 2. Doxorubicin @ g a ADR: _________________ in Emergency drug: _________________ a n B. Bleomycin b b a Cytotoxic glycopeptide io Microbial source: __________________________ d o ADR: __________________________ C. Plicamycin s o m Microbial source: __________________________ Yellow source that melts at 180-183 degree Celsius III. ANTIMETABOLITES om.l c A. Folate Analogue 1. Methotrexate ai m MOA: Inhibits __________________________ ADR: __________________________ @ g a Emergency Drug: _______________________ or ______________________ in B. Purine Analogues a n b 6-Mercaptopurine, 6-Thioguanine, Fludarabine, Cladirabine, Azathioprin b C. Pyrimidine analogues io a o d 5-Fluorouracil, Cytarabine, Capecitabine, Gemcitabine D. Hydroxyurea s o m MOA: Inhibits ribonucleotide diphosphate reductase. Use: Tx of myelogenous leukemia and thrombocytosis IV. PLANT ALKALOIDS om A. Vinca Alkaloids i.l c a Plant Source: __________________________ Common Name:__________________________ g m @ MOA: Inhibit __________________________ Eg: __________________________ in a n Tx for Hodgkin’s Lymphoma B. Camptothecins b a a b Plant Source: __________________________ d io Common Name:__________________________ o MOA: Inhibit __________________________ m o Eg: Irinotecan, Topotecan, s Irinotecan: First-line treatment for metastatic colon cancer Topotecan: Treatment of small cell lung cancer IV. PLANT ALKALOIDS om.l c C. Podophyllotoxins Plant Source: __________________________ ai m Common Name:__________________________ (Mandrake) MOA: Inhibits __________________________ @ g Eg: Etoposide, Tenposide in a a n D. Taxanes b b io a Plant Source: __________________________ Common Name:__________________________ o d MOA: Promote __________________________ s o m Eg: Paclitaxel, Docetaxel V. SEX HORMONES om A. Selective Estrogen Receptor Modulators/ Antiestrogen i.l c 1. Tamoxifen m a DOC: __________________________ @ g a ADR: ______________________ cancer Tx: __________________________ (Depo-Povera) n in b a 2. Comiphene a b io Use: Fertility drug ADR: Multiple births o d s o m V. SEX HORMONES om B. Aromatase Inhibitor i.l c 1. Anastrozole m a @ g a C. Antiandrogens 1. Flutamide n in DOC: Prostate cancer ba a b io *Finasteride is the DOC for BPH. d MOA: 5-a-reductase inhibitor o m ADR: Hypertrichosis s o QUICK QUIZ! om 1. The plant containing the anticancer drug, vincristine and vinblastine: i.l c a A. Mayapple m B. Periwinkle C. European year @ g a D. Datura alba n in a 2. A very common adverse reaction of alkylating agents used in the treatment of cancer A. Alopecia b b a B. Miosis io C. Mydriasis D. Ataxia o d s o m QUICK QUIZ! om i.l c 3. A type of tumor which has the capability of invading surrounding tissues and moving to distant locations in the body in a process known as metastasis. m a g A. Malignant tumor @ B. Benign tumor C. A & B in a n D. None b a b 4. 1 gram mass of tumor is equivalent to: A. 100,000 cancer cells io a d B. 1 billion cancer cells C. 1 million cancer cells m o o D. None of the above s  om i.l c a Antitubercular @ gm n a Agents a b b a n i d io m o s o ANTITUBERCULAR AGENTS om i.l c m a @ g in a a n b b io a o d s o m TB SECOND LINE AGENTS om 1. Ethionamide i.l c Thioisonicotinamide series m a g Differs from INH series in 2-substitution which enhances its activity. @ 2. Cycloserine in a Microbial Sources: a n ________________________________ b b a ________________________________ io ________________________________ HERZ: Antitubercular agents o d o m DOTS: Directly Observed Treatment Short- course s  om i.l c a Antiviral @ g n m a Agents a b b a n i d io m o s o ANTIVIRAL AGENTS om i.l c m a @ g in a a n b b io a o d s o m ANTIRETROVIRAL AGENTS om i.l c m a @ g in a a n b b io a o d s o m QUICK QUIZ! om i.l c a 1. It has become the drug of choice in the treatment of genital herpes. m A. Amantadine B. Idoxuridine @ g a C. Acyclovir in D. Vidarabine a n b 2. Ethionamide is a second line treatment drug of choice for tuberculosis and is used in the treatment a b of INH-resistant tuberculosis or when patient is intolerant to INH and other drugs. What is the io structural difference with INH series? A. 5-substitution B. 2-substitution o d o m C. 4-substitution s D. 3-substitution QUICK QUIZ! om i.l c a 3. AZT or Azidothymidine is used in the treatment of: m A. Koch’s infection B. HIV or AIDS @ g a C. Carbuncle in D. Ringworm a n b b 4. What antibiotic caused a major advance in the treatment of tuberculosis? A. Isoniazid io a d B. Ethionamide C. Rifampicin D. Cycloserine m o s o  om i.l c a Antimalarial @ gm n a Drugs a b b a n i d io m o s o A. CINCHONA ALKALOIDS om 1. Quinine i.l c Use in the treatment of chloroquine-resistant P. falciparum m a Not indicated for prophylaxis @ g a Other indication: _________________________ in ADR: _______________________ a n 2. Quinidine b b Schizonticide io a o d Not indicated for malaria Primary indication: _________________________ s o m B. 4-Aminoquilonies om i.l c 1. Chloroquine and Hydroxychloroquine m a g Use in the prophylaxis and treatment of P. vivax, P. malariae and P. @ ovale and susceptible strains of P. falciparum a Other indication of Hydroxychloroquine: ________________________ in a n 2. Mefloquine b b a Use in the prophylaxis and treatment of chloroquine-resistant P. io falciparum and P. vivax o d PACOP: Newest and most potent agent for malaria s o m C. 8-Aminoquilonies om 1. Primaquine i.l c Not used as prophylaxis m a Radical cure for P. ovale and P. vivax @ g Indicated only to ________________________ form of malaria (outside RBC) in a a n b b io a o d s o m D. ARTERMISININ FAMILY om.l c Sesquiterpene lactone endoperoxide i Plant source: Dry leaves of sweet wormwood (qinghaosu): Artemisia annua Discovered by Tu Youyou m a 1. Artemisinin @ g a Natural, PO (water-insoluble) 2. Artemether n in Oral, rectal, IM (lipid-soluble, volatile) ba 3. Artesunate a b d io Oral, IV, IM, and rectal (water-soluble) 4. Dihydroartemisinin m o s o Oral (water-soluble); most potent but least stable Active form/principal bioactive metabolite of Artemisinin 5. Artemotil E. FIXED COMBINATIONS om 1. Sulfadoxine and Pyrimethamine (Fansidar) i.l c Prophylaxis and treatment of chloroquine- resistant P. falciparum m a 2. Atovaquone and Proguanil @ g in a Prophylaxis and treatment of P. falciparum resistant to other antimicrobial drugs n The combination is effective against both ____________________ and ____________________ Plasmodium a b b a 3. Artemether and Lumefantrine io These two antimalarials interfere with heme metabolism, thereby stopping development of the parasite in the d o erythrocyte states m 1st line in the treatment of confirmed uncomplicated and severe Plasmodium falciparum malaria, replacing s o CQ+SP combination Treatment of P. falciparum resistant to other antimalarial drugs ADDITIONAL INFORMATION om i.l c m a According to the WHO country profile for Philippines, the best treatment for severe malaria is: @ g in a Quinine+ Tetracycline/Doxycycline/ Clindamycin (Q + T/D/C) a n b Suppressive prophylaxis agents: Only effective at killing the malaria parasite once it b a has entered the erythrocytic stage. io o d s o m QUICK QUIZ! om 1. Drugs which act on erythrocytic cycle of malarial parasite: i.l c A. Will be effective for radical cure m a B. Will be effective for suppressive prophylaxis C. Will not be clinically effective @ g D. Will both be effective for prophylaxis and radical use in a a n b 2. Newest and most potent quinoline derivative for malaria: b a A. Amodiaquine B. Mefloquine d io o C. Atabrine m D. Daraprim s o QUICK QUIZ! om.l c 3. The drug most effective against malarial parasites in the liver but not effective against parasites within erythrocytes: ai m A. Primaquine B. Pyrimethamine @ g a C. Quinacrine in D. Chloroquine a n b b 4. In case of treatment failure following administration of primary drugs in P. falciparum malaria, the recommended treatment would be: A. Artesunate suppository io a o d B. Artemether-Lumefantrine C. Chloroquine + Primaquine m D. Quinine + Tetracycline/Doxycycline/ Clindamycin s o  om i.l c a Anthelmintic @ gm n a Drugs a b b a n i d io m o s o ANTHELMINTIC AGENTS om i.l c m a @ g in a a n b b io a o d s o m ANTHELMINTIC AGENTS om i.l c m a @ g in a a n b b io a o d s o m QUICK QUIZ! om i.l c 1. A depolarizing neuromuscular blocking agent that causes spastic paralysis to susceptible helminthes A. pyrantel pamoate m a g B. thiabendazole @ C. mebendazole D. niclosamide in a a n b 2. Mechanism of action of Thiabendazole a b A. Irreversibly blocks glucose uptake in susceptible helminths io B. Inhibits the helminths-specific enzyme fumarate reductase o d C. Prevention of the conversion of inosine monophosphate to xanthine monophosphat D. Irreversibly inactivates ornithine decarboxylase s o m  om i.l c a Antiprotozoal @ gm n a Agents a b b a n i d io m o s o ANTIPROTOZOAL AGENTS om i.l c m a @ g in a a n b b io a o d s o m  om i.l c a Local @ gm n a Anti-Infectives a b b a n i d io m o s o ANTISEPTIC om i.l c a Compounds that kill (-cidal) or prevent the growth of (-static) microorganisms when applied to __________ tissue. Ideal Antiseptic must have the following: g m _____________________ a @ _____________________ action n in b a _______ surface tension (so that it will spread into the wounds) a b Retain activity in the presence of body fluid io Non-irritating to the tissues d o Non-allergenic s o m Lack systemic toxicity Do not interfere with healing DISINFECTANT om.l c Is an agent that prevents transmission of infection by the destruction of pathogenic i microorganisms when applied to ________________ objects. m a 1. Alcohol and Alcohol Derivatives @ g in a ↑ number of C = ↑ activity (up to 8C’s). Branching decreases activity. a n b a. Alcohol, USP - Aka: Spiritus vini rectifcatus, Grain alcohol, Wine spirit b a Contains NLT ___% ethanol by volume io d i. Dehydrated alcohol aka __________ alcohol: Contains 99% ethanol by weight o ii. Denatured Alcohol: Ethanol that has been rendered unfit for use in intoxicating m s o beverages by the addition of other substances. iii. Completely denatured alcohol: Contains added _____________ and _________________ DISINFECTANT om i.l c a b. Isopropyl Alcohol aka ____________ Alcohol ___________ increases activity g m c. Ethylene Oxide a @ Epoxide (Cyclic Ether) n in b Flammable gas that liquefies at ___°C a a b Gas Sterilant - used to sterilize temperature sensitive medical equipment and certain io pharmaceuticals that cannot be heat sterilized in an autoclave. d o MOA: Alkyation s o m DISINFECTANT om 2. Aldehydes i.l c A. Formaldehyde solution, USP (HCHO) m a Aka: _____________ @ g Contains NLT ___% formaldehyde in a Embalming agent a n b b a B. Glutaraldehyde or Glutarol Brand name: Cidex d io Gas sterilant m o Use to sterilize temperature- sensitive medical equipment that cannot be heat s o sterilized in an autoclave. DISINFECTANT om.l c 3. Phenol and Derivatives ai Phenol coefficient: ratio of the dilutio