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BIMM118 Drugs Targeting the CNS Parkinson Epilepsy Hypnotics General Anesthetics Anxiolytics Antidepressants.

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Presentation on theme: "BIMM118 Drugs Targeting the CNS Parkinson Epilepsy Hypnotics General Anesthetics Anxiolytics Antidepressants."— Presentation transcript:

1 BIMM118 Drugs Targeting the CNS Parkinson Epilepsy Hypnotics General Anesthetics Anxiolytics Antidepressants

2 BIMM118 Diabetes mellitus Pancreas: Islets of Langerhans: site of hormone production –A (alpha) cells – produce Glucagon –B (beta) cells – produce Insulin –D (delta) cells – produce Somatostatin Insulin and Glucagon are the major regulators of blood glucose

3 Antimicrobials Unit X

4 BIMM118 Selective toxicity Injure target organism without affecting the host Can accomplish this by attacking processes that critical to microbial well-being, but that don’t affect mammals Bacterial cell wall Inhibition of an enzyme unique to bacteria Disruption of bacterial protein synthesis

5 BIMM118 classification Susceptible organism Narrow spectrum, broad spectrum Antibacterial Antiviral antifungal

6 BIMM118 Mechanism of action Cell wall Cell membrane permeability Lethal inhibition of bacterial protein synthesis Nonlethal inhibition of bacterial protein synthesis Drugs that inhibit bacterial synthesis of nucleic acids

7 BIMM118 Mechanism of action Antimetabolites Inhibitors of viral enzymes

8 BIMM118 Microbial drug resistance Organisms – staphylococcus aureus, enterococcus faecalis, enterococcus faecium, pseudomonas aeruginosa and mycobacterium tuberculosisi

9 BIMM118 Microbes may increase manufacture of drug-metabolizing enzymes (penicillins) Microbes may cease active uptake of certain drugs (tetracyclines) Changes in receptors which decrease antibiotic binding and action May synthesize compounds that antagonize drug actions

10 BIMM118 Antibiotic use promotes the emergence of drug-resistant microbes – especially the use of broad-spectrum antibiotics The more the use – the greater the chance

11 BIMM118 Delaying the emergence of resistance Prescribed only when needed Narrow-spectrum Limit use of newer drugs Minimize giving antibiotics to livestock

12 BIMM118 selection Identify the infecting organism Drug sensitivity of the infecting organism Host factors – site of infection, host defenses, allergies, inability of drug of choice to penetrate the site of infection, unusual susceptibility of the patient to toxicity

13 BIMM118 Cultures must be obtained prior to initiation of therapy Drug sensitivity may or may not be done

14 BIMM118 Antibiotic combinations Severe infection Mixed infections Prevention of resistance – tuberculosis Decreased toxicity Enhanced antibacterial action

15 BIMM118 Appropriate prophylactic use Surgery Bacterial endocarditis Neutropenia others

16 BIMM118 Inappropriate uses Viruses Treat FUO Improper dosage Inadequate information Omission of surgical drainage

17 BIMM118 Weaken bacterial cell wall Penicillins – cause the bacterial wall to weaken and take up water and burst Mechanisms of resistance – inability to reach targets and inactivation of penicillins by bacterial enzymes

18 BIMM118 classification Narrow spectrum – penicillinase sensitive Narrow spectrum – penicillinase resistant Broad spectrum penicillins Extended-spectrum penicillins

19 BIMM118 Penicillin G Against most gram positive, gram negative cocci and nonpenicillinase-producing strains of Neisseria gonorrhoeae, anaerobic bacterial and spirochetes

20 BIMM118 Sodium penicillin Potassium penicillin Procaine penicillin Benzathine penicillin – highly sensitive Not given orally IM usually Only sodium and potassium given IV

21 BIMM118 allergy Most common cause of drug allergy Prior exposure required but may not be known May have cross-sensitivity to cephalosporins

22 BIMM118 Penicillinase-resistant penicillins Resistant to inactivation by beta-lactamases Naficillin Oxacillini Cloxavillin Dicloxacillin Methycillin – resistant strains – respond to vancomycin and/or rifampin

23 BIMM118 Broad spectrum penicillins Ampicillin – strep, pertussis, proteus, e.coli, salmonella, shigella and h influenzae Diarrhea and rash – most common side effects

24 BIMM118 Amoxicillin – more acid resistant Less diarrhea Amoxicillin with clavulanate – augmentin (inhibits bacterial beta- lactamases)

25 BIMM118 Extended spectrum penicillins Ticarcillin Carbenicillin indanyl Mezlocillin Pipercillin Pseudomonas, enterbacter, proteus, klebsiella Given with aminoglycoside for pseudomonas

26 BIMM118 Drugs that weaken bacterial cell wall II Cephalosporins, imipenem, astreonam, vancomycin, teicoplanin, fosfomycin

27 BIMM118 cephalosporins Most commonly used antibiotic Similar to penicillins Bactericidal First generation highly susceptible – to beta-lactamases

28 BIMM118 generations 1-4 Increasing in activity against gram-negative bacterial and anaerobes Increasing resistance to destruction by beta-lactamases Increasing ability to reach cerebrospinal fluid

29 BIMM118 Most given parenterally Some can cause bleeding tendencies allergy

30 BIMM118 First generation Prophylaxis against infection in surgical patients Gram positive infection

31 BIMM118 Second generation Some pneumonias Otitis, sinusitis, respiratory tract infections

32 BIMM118 Third generation Menigitis Gram negative bacilli Gonorrhea, proteus, salmonella, klebsiella

33 BIMM118 imipenem Broadest antimicrobial spectrum of any drug – good for mixed infections – always given in conjunction with cilastatin to inhibit destruction of imipenem by renal cells Carbapenems – new class of beta-lactam antibiotics Only given – IV, IM Nausea, vomiting, diarrhea, rash

34 BIMM118 Aztreonam – monobactams Gram-negative aerobic bacteria IM, IV

35 BIMM118 Vancomycin Pseudomembranous colitis MRSA Other serious infections Oral for GI infection Mostly given slow IV Ototoxicity, hypotension (with rapid IV infusion), thrombophlebitis

36 BIMM118 Bacteriostatic inhibitors of protein synthesis Tetracyclines, macrolides, clindamycin, chloramphenicol, spectinomycin and dalflopristin/quinupristin Suppress bacterial growth and replication but do not kill Second-line agents

37 BIMM118 tetracyclines Broad-spectrum Inhibit protein synthesis – suppress bacterial growth Gram-positive and gram-negative bacterial – rickettsia, spirochetes, brucella, chlamydia, myocoplasma, helicobacter pylori and vibrio cholerae

38 BIMM118 Due to use – has increasing bacterial resistance Infectious diseases, acne, PUD, periodontal disease, rheumatoid arthritis

39 BIMM118 Adverse effects GI Bones and teeth Suprainfection Hepatotoxicity Renal toxicity Photosensitivity Orally, IV, and IM

40 BIMM118 macrolides Inhibit bacterial protein synthesis Azithromycin, erythromicin, clarithromycin, dirithromycin Effective against most gram-positive bacterial as well as some gram-negative bacterial May be good alternative to those allergic to PCN

41 BIMM118 Therapeutic uses May be used as an alternative patients allergic to penicillins – respiratory tract infections Legionella Pertussis Diphtheriae Mycoplasmic pneumoniae strep

42 BIMM118 Oral, IV Adverse effects - GI, Liver, suprainfection of the bowel, thrombophlebitis Clarithromycin – not as much nausea (h. pylori), respiratory tract

43 BIMM118 Adverse effects – GI, dizziness, h/a restlessness Candida infections Tendon rupture – not for children under 18 yrs. Should not be taken with milk or food Watch for bleeding – elevates warfarin levels

44 BIMM118 Zithromax – respiratory tract infections, others Not as much nausea

45 BIMM118 clindamycin Cleocin – given for specific conditions Causes pseudomembranous colitis Inhibits protein synthesis Anaerobic bacteria – streptococci, some pelvic and abdominal infections Given orally, IV, IM

46 BIMM118 Adverse effects – pseudomembranous colitis, diarrhea, rashes, hepatotoxicity

47 BIMM118 aminoglycosides Bactericidal inhibitors of protein synthesis Narrow-spectrum – aerobic gram-negative bacilli Gentamycin, tobramycin, amikacin

48 BIMM118 Amikacin – least susceptible to resistance E.coli, Klebsiella pneum., serratia, proteurs mirabilis, pseudomonas Reserved for serious infections due to aerobic gram-negative bacilli Most given IM or IV

49 BIMM118 Binds tightly to renal tissue – easily causes nephrotoxicity Ototoxicity Reduce dosage in patients with renal disease Narrow therapeutic range – peak and trough levels (avoid high trough levels) – not greater than 2mcg/ml

50 BIMM118 Neomycin – often given topically, eye, ear, skin Also given – orally prior to surgeries of the bowel, suppress bowel flora

51 BIMM118 Sulfonamides and trimethoprim Broad-spectrum – disrupt synthesis of tetrahydrofolic acid – inhibits synthesis of folic acid Doesn’t hurt our cells because our cells take up folic acid from our diet Bacterial cells make their own and sulfonamides disrupt this process

52 BIMM118 Resistance – prevalent – Works on gram positive cocci, gram negative bacilli, actinomycetes, chlamydiae, some protozoa Primary usage – urinary tract infections, mostly due to E. Coli Hypersensitivity, Stevens-Johnson syndrome, hemolytic anemia, kernicterus, renal damage

53 BIMM118 Sulfisoxazole – (Gantrisin)good for urinary tract Trimethoprim – given for urinary tract infections Azo-Sulfisoxazole (sulfonamide-phenzaopyridine) antibacterial agent with an analgesia combo

54 BIMM118 Trimethoprim-sulfamethoxazole Trade names – Bactrim, Cotrim and Septra Potentiation Urinary tract infections, pneumocystis carinii, otitis media, GI infections, bronchitis Oral, IV

55 BIMM118 Urinary tract infections Community acquired – usually E. coli Hospital acquired – Klebsiella, proteus, pseudomonas, staph, enterobacter Acute cystitis – single dose, short course, conventional therapy Acute urethral syndrome – dysuria, frequency, urgency, pyuria – chlamydia, gonorrhea, gardnerella

56 BIMM118 Recurrent UTIs Reinfection – often with females – 1-2 per year will be treated as separate infection More frequently – long term prophylaxis with lower doses of certain drugs Relapse – recolonization – may also require long term therapy, may need surgical procedure – depending on cause

57 BIMM118 Acute pyelonephritis Infection of the kidney – patient will be “sicker” Mild – moderate infection will be treated on outpatient with oral agents Severe infection – hospital and IV antibiotics

58 BIMM118 Acute bacterial prostatitis Bacterial infection of the prostate Usually E.coli from indwelling catheter, surgical manipulation, instruments

59 BIMM118 nitrofurantoin Macrodantin – urinary tract antiseptic – broad-spectrum antimicrobial Staph, strep, e.coli Lower urinary tract only Orally – GI, pulmonary reactions, hematologic, peripheral neuropathy

60 BIMM118 Antimycobacterial agents Slow growing microbes, therapy needs to be prolonged Tuberculosis – epidemic proportions due to resistant strains, AIDS People may harbor the organism but may have no symptoms (inactive) May be in lungs only – may be disseminated throughout body

61 BIMM118 Transmitted by inhalation of sputum particles (coughing, sneezing) Rapid response by immune system (phagocytes) keeps most individuals from developing obvious signs and symptoms Necrosis of lung tissue can be result – if patient develops clinical disease

62 BIMM118 Screening very important especially in high-risk populations PPD, CXR, sputum evaluations – cultures best but take longer Drug resistance is becoming more concerning – highest multi- drug resistance in New York City

63 BIMM118 treatment Must always consist of two or more drugs to which the organism is sensitive Decrease the incidence of resistance Decrease the incidence of relapse Usually starts with daily therapy – four drugs – isoniazid, rifampin, pyrazinamide, ethambutol (2 months)

64 BIMM118 treatment Then after, four months of isoniazid and rifampin Multidrug-resistant tubercle bacilli – treatment may start with as many as seven drugs – treatment will last longer Special considerations in those with HIV infection

65 BIMM118 Directly observed therapy – to promote compliance Continuing evaluation of treatment – cultures, CXR, symptoms Prophylaxis therapy – patients who have had recent known exposure, HIV, patients with known exposure and immunosuppression

66 BIMM118 isoniazid First – line primary agent Suppresses bacterial growth by inhibiting synthesis of mycolic acid (component of cell wall) Oral and IM Peripheral neuropathy, hepatoxicity, anemia, GI distress

67 BIMM118 rifampin Broad-spectrum antibiotic Inhibits protein synthesis Always given in conjunction with other antituberculosis drug Can cause hepatoxicity Discoloration of body fluids, GI, rash, flu-like syndrome

68 BIMM118 pyrazinamide May be used with rifampin, isoniazid, and ethambutol initially Hepatotoxic – GI, arthralgia,rash

69 BIMM118 ethambutol Bacteriostatic – most strains are sensitive Optic neuritis – blurred vision and lack of color discrimination Allergic reactions, GI disturbances, elevated uric acid levels

70 BIMM118 Fluoroquinolones Ciprofloxacin – bactericidal – inhibits bacterial DNA replication Administered orally or IV Respiratory tract infections, GI, bones, joints, etc. Not useful against infections caused by anaerobes

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