Drugs Targeting the CNS

Drugs Targeting the CNS • Parkinson • Epilepsy • Hypnotics • General Anesthetics • Anxiolytics • Antidepressants

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

Antimicrobials Unit X

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

classification • Susceptible organism • Narrow spectrum, broad spectrum • Antibacterial • Antiviral • antifungal

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

Mechanism of action • Antimetabolites • Inhibitors of viral enzymes

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

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

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

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

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

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

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

Appropriate prophylactic use • Surgery • Bacterial endocarditis • Neutropenia • others

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

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

classification • Narrow spectrum – penicillinase sensitive • Narrow spectrum – penicillinase resistant • Broad spectrum penicillins • Extended-spectrum penicillins

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

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

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

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

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

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

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

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

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

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

Most given parenterally • Some can cause bleeding tendencies • allergy

First generation • Prophylaxis against infection in surgical patients • Gram positive infection

Second generation • Some pneumonias • Otitis, sinusitis, respiratory tract infections

Third generation • Menigitis • Gram negative bacilli • Gonorrhea, proteus, salmonella, klebsiella

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

Aztreonam – monobactams • Gram-negative aerobic bacteria • IM, IV

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

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

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

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

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

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

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

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

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

Zithromax – respiratory tract infections, others • Not as much nausea

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

Adverse effects – pseudomembranous colitis, diarrhea, rashes, hepatotoxicity

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

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

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

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

Drugs Targeting the CNS