• Shuffle
    Toggle On
    Toggle Off
  • Alphabetize
    Toggle On
    Toggle Off
  • Front First
    Toggle On
    Toggle Off
  • Both Sides
    Toggle On
    Toggle Off
  • Read
    Toggle On
    Toggle Off
Reading...
Front

Card Range To Study

through

image

Play button

image

Play button

image

Progress

1/109

Click to flip

Use LEFT and RIGHT arrow keys to navigate between flashcards;

Use UP and DOWN arrow keys to flip the card;

H to show hint;

A reads text to speech;

109 Cards in this Set

  • Front
  • Back
Asthma Overview
-excessive irritability of the respiratory tree caused by extrinsic (pollen) and intrinsic (infection/stress) factors
-asthmatics can be NSAID and aspirin sensitive
-don't think of it as just trouble breathing, the factors listed lead to a chronic inflammatory process which causes
-bronchiole constriction, hypertrophy of bronchial smooth muscle, submucosal edema, hypersecretion of viscous mucous and mucous plugs
Asthma Early and Late Phase
-inflammatory mediators cause a early and late phase response
early - Inflammation factor stimulates mast cell to release histamine, proteases (heparin), PAF, and leukotrienes leading to bronchoconstriction. Some drugs block the formation of leukotrienes by blocking lipooxygenase or the leukotriene receptor
-late phase: The early phase mast cells also release chemotactic factors which attract eosinophils, neutrophils, and lymphocytes). These inflammatory cells take 3-4 hours to migrate to the site and then release cytokines (TNFa) and major basic protein which starts the inflammatory process over again with bronchoconstriction and bronchial hyperactivity
-MBP damages the epithelium and makes it more sensitive to future attacks
Changes in Treatment
-In the past it was thought that asthma was pathology of the bronchail smooth muscle so B2 agonist were used for everything
-Now that we realize the inflammatory component, antiinflammatory drugs are used as a prophylaxis and B2 is used for acute attacks or to prevent exercise-induced asthma
Corticosteroids (Glucocorticoids) 1
-potent anti-inflammatory agent used in a inhaler, oral, and topical
-Two major effects
1) Blocks PLA2 so no AA made so no prostaglandin and leukotrienes. Without these, inflammatory cell migration is hindered
2) Permissive effect on the NS by increasing the number of B2 receptors in human lung tissue and WBC (mast cells). B2 stimulation causes adenylate cyclase to convert ATP to CAMP. Additional CAMP in the lungs leads to bronchodilation, in WBC it leads to blocked mast cell degradulation
-Corticosteroids take a while to work because their receptor is intracellular and they work at the transcription level. Therefore, they are not good for the early phase/acute asthmatic attack
Topical Steroids
1) Topical Aerosols - Drug of choice because it deposits the drug at the lungs directly so a lower dose is used and less systemic absorption
-Names: Beclovent, Flovent, Azmacort, Aerobid
-AE: Due to lower immune system in mouth, candidal infections occur frequently. Serious side effects like osteoporosis, cushings, or hyperglycemia are less frequent
Oral Steroids
-These are used for acute attacks when the patient has become tolerant to B2 therapy
-The orals are the best at restoring B2 sensitivty by increasing receptor density and sensitivity at the receptor
-The time course is always 10 days because 2 weeks can leads to cushing's, osteoporosis, infection, and hyperglycemia
-Drugs include prednisolone and methylprednisolone
Non-Steroidal Prophylactic Drugs
-These prevent mast cell degranulation by decreasing Ca++ influx (mast cell degranulation is like NT release at the terminal)
-Due to this they can inhibit early and late phase hypereactivity
-Used in exercise induced and chronic asthma
-Can be mixed with more toxic drugs (b2 agonist, corticosteroids, and theophylline) to reduce the toxic dose
-Least toxic of the antiasthmatics because a permanently charged molecule and not systemically absorbed
-infrequently leads to coughing, dry mouth, allergic reaction
-Intal and Tilade
Leukotriene Modifiers
Leukotrienes stimulate bronchoconstriction, capillary permeability (edema) of bronchi smooth muscle, stimulate mucous secretion and impair mucociliary clearence
-These drugs with reduce LUKE synthesis by inhibiting lipooxygenase or they block the leukotriene receptor
-Don't work in acute attacks because a pill, or all well as steroid in clearing the airways, but can be taken PO orally and very effective against NSAID induced asthma
-Lipoxygenase Inhibitor - Zyflo is taken PO every 6 hours for chronic asthma. Can lead to elevation in life enzymes and also inhibits C29 and 1A2 so problematic when taken with warfarin or theophylline
Leukotriene Receptor Antagonist - Singulair is the most common LUKE drug because it is only taken once a day and no liver toxicity or warfarin interaction. Accolate does the same thing but it's BID, a 2C9 inhibitor, and raises liver enzyme levels
Beta-2 Drugs
-stimulates B2 on bronchioles and mast cells which creates more cAMP

1) Isoproterenol - Inhalant stimulates B1 and B2 so increased heart rate is a side effect. Not used often
2) Epinephrine - Only used for emergency situation like status asthmaticus when nothing else is working. Stimulates alpha 1 and the betas so you get tachycardia and alpha 1 constricts airway BV so mucosal edema is reduced. Can be a inhaler or SubQ/IM injection
3) Ephedrine - Slow acting pill that stimulates alpha 1 and the beta's directly (causes release of catecholamine) and indirectly. Can cause tachyphlaxis (lowering of receptor), tachycardia, crosses BBB so cause nervousness and insomia, and helps with noctural wheezing
Beta-2 Selective Agonist
1) Alupent - inhalant and pill. LIke isoproterenol but OH group moved so it has B2 selectivity until you push the dose
2) Brethaire - inhalant and injection. Greater selectivity than alupent
3) Albuterol - Inhalant and pill, great B2 selectivity and long acting
4) Serevent - Inhalant which is the slowest onset but longest acting. Not used for acute attacks. Less tolerance because of infrequent dosing
Theophylline
-Blocks phosphodiesterase 3/4 so CAMP is not broken down and it can prevent mast cell degranulation and help with bronchial dilation
-Also blocks adenosine receptor so inhibitory adenosine doesn't get to the CNS, instead catecholamine release is stimulated
-Used in severe attacks if someone is not responding to EPI
-Has a low therapeutic index and is a 1A2 substrate so erthrymycin/ciproflaxin increase its blood levels, and phenobarbital and carbamazepine decrease blood levels
Atrovent
-permanently charged atropine-like molecule which blocks acetylcholine (increase in asthmatics) action at the lung ACH receptor (M3) - This leads to decrease release of mediator release
-Slow onset, saliva production is blocked leading to xerostomia (major AE)
-Albuterol + ipatropium = combivent
Antifungal Overview
-Fungal infections becoming more prevalent due to immunocompromised state in AIDS patients, more aggressive chemo diminishes WBC, and broader antibiotics reduce normal bacteria in the GI, urinary tract, and oral cavity
-Fungi have reduced selective toxicity because they are eukaryotic and similar to mammalian cells
-Fungal infections can be local or systemic so we want to avoid blood circulation for the locals. FOr the systemic infections they are life threatending so the medication is heavy duty
Amphotericin B
-Amphotec and Fungizone
-Isolated from soil fungus it binds the primary sterol of the fungi cell membrane (ergosterol) causing holes in it. It also binds to human cholesterol leading to toxicity upon IV admin. Two ways to give the drug
1) Topical/Oral (Fungizone) - Used for localized infection in the oral cavity and GI. Given as a lozenge (troche) or liquid. Not absorbed in the blood stream because it's a large polar molecule
2) IV (Amphotec) - Used for serious systemic infections. Upon infusion it can cause infusion rnx, nephrotoxicity (dose-limiting), leukopenia, anaphylactics (given HI receptor blocker ahead of time). Major advance is the liposomal formulation so the amphotec has 1) affinity to the ergosterol, 2) affinity to the liposome, and 3) affinity to the cholesterol. Hopefully when it encounters cholesterol it just stays in the liposome
Nystatin
Mycostatin
-Similar to amphotec but too toxic for injection so given locally as a ointment, rinse, or lozenge.
-Not absorb in systemic circulation cause too large and polar
-Good for oral fungal infection
-Given every 6 hours for 10 days
-Have a foul/bitter taste
Flucytosine
Ancabon
-Prodrug that is converted to 5-flurouracil when fungi take it up, and it disrupts fungal RNA and protein synthesis
-5-FU is a cancer chemo agent so it causes toxicity including bone marrow suppression
Griseofulvin
Fulvicin
-Taken P.O with fatty meals it helps with dermatophytic infection of the skin, scalp, and under nails.
-Interferes with fungal cell division of the mitotic spindle
-Can lead to granulocytopenia (decrease neutrophil count), photosensitivity (4 rings)
-As a cytochrome P-450 inducer it lowers warfarin/oral contraceptive levels
-As a P-450 inducer it increasing the liver production of porphyrin rings so it's contraindicated in patients with acute intermittent porphyria
Azole Antifungal Drugs 1
General - Nice T.I. and block a range of systemic fungal infections. Work by blocking P-450 in the fungus so lanosterol is not converted to ergosterol. Also inhibits human P-450 so a number of 3A4 drugs increase

1) Ketoconazole (nizoral) - Great affinity for human 3A4 so levels increase of cyclosporine, terfenadine, warfarin, and astemizole. Best absorb at a low pH so taken with OJ or a meal, whereas antacids and H-2 blockers slow it down. Can decrease synthesis of human adrenal and gonadol steroid hormones leading to gynecomastia, infertility, and menstrual irregularities
Azole Antifungal Drugs 2
2) Itraconzole (Sporanox) - Similar absorption, drug interactions, and spectrum as nizoral

3) Fluconazole (Diflucan) - Most common systemic azole, used for oropharyngeal/esophargyngeal candidas, and because of the good CNS penetration it's used for meningitis. It also has the lowest affinity for P-450 so fewest drug interactions

4) Clotrimazole (lotrimim and mycelex and monistat) - Common topical cream for vaginal candidiasis, athletes foot, and oral/pharyngeal candidiasis. Good compliance
Antivirals Against Herpes
Acyclovir (Zovirax) - Major drug against herpes and varicella. Phosphorylated once by virus and then twice by host (only if host is infected). This triphosphate inhibits viral DNA synthesis. Pretty well tolerated

2) Valacyclovir (Valtrex) - Prodrug that is converted to acyclovir in GI first pass.

3) Ganciclovir (Cytovene) - LIke acyclovir but directed against cytomegalovirus. Can cause bone marrow suppression leading to neutropenia and thrombocytopenia
Antiretroviral Therapy
-HIV patients are placed on a combo of 2 RT inhibitors and a protease inhibitor due to HIV resistance to just one or the other

Protease Inhibitors - INdinavir, Ritonavir, Saquinavir
-At the end of HIV cycle large polyproteins are cleaved by a HIV protease. These drugs interfere with this process.
-Can cause elevated blood glucose and lipid levels plus lipodystophy
-Also can cause P-450 inhibition
Antiretroviral Therapy - RT Inhibitors
1) Zidovudine (AZT/Retrovir) - FIrst to be approved. Prevents viral RNA from making viral DNA. Cause bone marrow suppression

2) Didanosine (DDI, Videx) - Combined with AZT to prevent HIV resistance. Can cause pancreatitis (lethal) and hyperuricemia

3) Lamivudine (Epivir) - Similar to didanosine but less pancreatitis so people switch from DDI to epivir recently

4) Efavirenz (Sustiva) - For people who get pancreatitis or bone marrow suppression with the above 3 nucleotide RT inhibitor, this one is well tolerated and non-nucleotide. Used in triple therapy w/o protease inhibitor (3 RT i guess...)
Entry and Fusion HIV Inhibitors
-Prevent HIV from entering healthy CD4+ T-cells
1) Maraviroc (Selzentry) - Attach themselves to CCR5 receptor on the surface of CD4 so HIV can't bind to it
2) Enfuvirtide (Fuzeon) - Binds to HIV gp120/41 proteins
-Can lead to fever, cough, flu-like symptoms, and hepato/cardio toxicity
-Can lead to serious cancer/infection due to blockage of other immune CCR5+ cells
Integrase Inhibitors
Raltegravir (Isentress) - Once bound to CD4 T-cell surface, this drug prevent HIV from injection its DNA into the host cell.
-Profile is good but can cause muscle toxicity so avoid mixing with drugs like statins that cause myopathies and rhabdomyolysis
Flu Drugs
Amantadine (Symmetrl) and Rimantadine (Flumadine) - Given during early flu and these lower symptoms by inhibiting the viral uncoating process. FLumadine doesn't have the following problem but symmatrel is also used for Parkinson's so it increases DOPA release leading to these side effects (nervous, psychosis)

2) Zanamivir (Relenza) and Oseltamivir (Tamiflu) - Taken before the flu to prevent or during the first days to ease the symptoms. THese neuraminidase inhibitors prevent flu neuraminidase from breaking the flu free from the cell membrane of a infected cell
Relenza is a spray that can cause bronchospasm is patient has asthma
Tamiflu is available in the oral form
Antibiotic General
-bacteriacidal are better than bacteriostatic because they are more efficient and less dependent on the host
-Cidal gold standard is penicillin V
-Static gold standard is tetracyclin
-want to target parts of the bacteria (cell wall) that aren't in eukaryotes
Antibiotic Drug Overview
-static + static = additive (2)
-cidal + cidal = synergisitc (>2)
-static + cidal = antagonist (<2)

Cidal:
1) Penicillin V and cephalosporin have 10% cross reactivity, don't give someone penicillin allergic cephalosporin. Penicillin works well with odontogenic bacteria
2) Metronidazole blocks alcohol metabolism (dilsulfram effect) and also inhibits 2C9 (increase warfarin). Works by shredding bacteria DNA in anaerobes
3) Quinolones like ciprofloxacin block DNA gyrase
4) Aminoglycosides work against gram negative by inhibiting protein synthesis. So potent that even though this mechanism is bacteriostatic, it kills the cell

When combining cidals choose 2 with different mechanisms. For example penicillin pokes holes in the membrane allowing metro to come in and fragment DNA easier
-Static and cidal don't work because cell needs to be growing for a static to take effect
Antibiotic Drug Overview 2
Bactericidal:
-mostly inhibit protein synthesis
-erythromycin and clarithromycin are p450 inhibitors. Even though azithromycin looks like these two, it's a bit bigger so it doesn't fit into the p450 active site
-clindamycin is great before a procedure and for perio infections due to its affect on aerobes
-sulfonamides inhibit folic acid synthesis so they are good for UTI and opportunistic infections like AA or PG, not for dontogenic infections (caries)
Drugs Overview Part 3
-more in common drug target has with our bodies, the more side effects there are

1) Cell Membrane Synthesis Inhibitors - Nystatin, Vancomycin, Ampho. B
2) Protein Synthesis Inhibitors - Tetracyclin, Aminoglycosidase (30s), Erythromycin and Clindamycin (50s). Some side effects since we have ribosomes
3) DNA Synthesis Inhibitors - Quinolones and metronidazole, rifampin. Bacteria and human DNA close enough to have toxicity
4) Folic Acid - Sulfonamides, since we ingest folic acid this isn't too bad
5) Cell Wall Synthesis - Very well tolerated since we don't have a cell wall. Penicillin, cephalosporin, vancomycin
Rifampin Study
-Good against TV
-Rifampin lowers the blood levels of oral contraceptives (can tell because ethinyl estradiol levels are reduced and this inhibits ovulation)
Rifampin induces 3A4 in the liver and gut
-Saw this with other bacteria and postulated the enterohepatic recirculation theorgy where EE cannot move to the blood stream when SO4 or glucuronic acid is added. Colonic bacteria which are wiped out by antibiotics usually remove these groups allowing EE to reutnr to the blood stream.
-Result is that since tests are inconclusive you should at least tell your patients on antibiotics to use a condom
Spectrum
-The range of pathogens to which a antibiotic is active
-Would rather use a narrow than broad spectrum
-Problem with broad spectrum is that you knock out the normal flora and introduce new bacteria that cause problems. For example, once GI bacteria knocked out, new bacteria come in and cause diarrhea. Another example is candida overgrowth and finally you can have a small Pseudomembranous colitis population in the GI (10%) turn into a larger one and you will shit your intestine membrane
Penicillins Intro
Penicillin 1 - Inhibits cell wall synthesis in growing bacteria (cidal). Has a 4 member beta-lactam ring that does the trick and is destroyed by high acid or beta-lactamase (penicillinase)
-Low toxicity and is filtered in the kidney unchanged
-Staph is resistant to penicillin
-Amoxicillin is the second generation penicillin
Penicillin Subclasses
1) Narrow Spectrum - Penicillin G and V (most used in dentistry)
-G given IM/IV cause stomach acid breaks it down.
-V is the DOC for odontogenic infections
-G and V target G+ strep and non-penicillinase staph, G- Neiserria, and anaerobes fusobacterium and porphyromonas


2) Broad Spectrum - Amoxicillin and ampicillin
-Good for UTI, URI, and Gonoccal infection, so better than penicillin for G-
-Ampicillin has erratic oral absoprtion
-Amoxicillin is the best absorbed (TID) and the DOC for prophylaxis antibiotics in someone susceptible to endocarditis. Has a long half life
-Can give amoxicillin with clavulanic acid (augmentin) to increase spectrum of amoxicillint o increase penicillamase buds. Clauvanic acid tricks the bacteria into attacking its B-lactam ring and then inhibits it. Reserved for sinus infection

3) Broadest - Carbenicillin and ticarcillin. Fight gram negative
4) Penicillinase Resistant - Staphicillin (becoming resistant) and oxacillin
Dosing of Penicillin V
Adult - 500mg q6h for 7-10 days and 1000mg for more severe

Child - 3 to 6mg/pound q6h for 7-102 days.

-Avoid taking it around meal time
Broadest Spectrum Penicillins
-Good for serious G- including proteus (GI), bacteroides (jaw fracture), and pseudomonas (burn victims), urinary and GI tract infections
-Inactivated by B-lactamase
Penicillinase Resistant Drugs
-These drugs are ONLY for bacteria that produce penicillinase like staph and G- bacilli because they are less effective on bacteria that penicillin work normally on
1) Methicillin - nephrotoxic and poor oral absorption
2) Bactocil/Prostaphlin - Better oral absorption

Overdose or antibiotics has produced staph's that are super bacteria...
1) Produce penicillinase that destroy penicillin
2) Have a efflux pump that shoots out tetracyclin
3) Alters its ribosome so erythromycin can't target it anymore
Penicillin Toxicity
1:10 have mild toxicity - GI problem, candida overgrowth
-Give them a H-1 receptor blocker (antihistamine) like benadryl
1:10,000 are allergic - if you're allergic to one penicillin then you're allergic to them all
-Give them epinephrine IM, SubQ, SubL because IV takes too long and can be cardiotoxic
-In this case epinephrine acts as a physiologic antagonist and alpha-1 gets rid of vasodilation, beta-1 makes the heart pump blood, and beta-2 helps you breathe and shunts blood to the important survival organs
Cephalosporins
-Punches hole in bacteria cell wall and is bactericidal
-Protect beta-lactam ring better but has cross allergenicity due to structure similarity with penicillin
-Addition generations lead to broader use, with the most popular as 1st Gen Keflex, and later Gens given IV
-In denistry they are taken before procedure in people with joint replacements because staph like to hide here. Popular cephalosporins in these cases is keflex and velosef. Only use in specific cases
-Has more toxicity than penicillin because broader spectrum and attacks G+ and G-
Macrolide Antibiotics
-attack bacteria 50s ribosome, bacteriostatic
-The 14 ringers like erythromycin and clarithromycin inhibit 3A4 whereas the 15 ring Z-Pak don't

1) Erhythromycin - Good for diptheria, legionairre's, mycoplasma, and bordatella but less effective than Pen V for odontogenic infections especially anaerobes. Poor absoprtion in the GI and cause SI side effects and inhibits P-450 3A4 and 1A2 (problem when taken with statins and cyclosporin)

2) Clarithromycin - Similar to E-mycin but quicker absorption and longer t-1/2 with less side effects. Given as a prophylaxis for patients at risk for endocarditis in penicillin allergic individuals
Toxicity Studies
1) As a 3A4 inhibitor the E-mycin and C-mycin can elevate blood levels of seldane causing torsades de pointes
2) Mixing C-mycin and heartburn drug cisapride leads to blood level accumulation and elongated QT interval
3) Mixing C-mycin and anti-psychotic pimozide leads to elevated blood levels
Drugs that interact with E and C-mycin
1) Seldane, astemizole, cisapride, pimozide - ventricular arrhythmia
2) Bromocriptine (parkinson agent) - dyskinesias, hypotension
3) Tegretol (anti-convulescent) - vertigo, drowsiness, confusion
4) Cyclosporine - immunosuppression
5) Theophylline - tachycardia and seizures
6) Statins - rhabdomyolysis and kidney failure
7) Pines and Ca-Blockers - Hypotension
8) Warfarin - Bleeding
9) Midazolam - Loss of protective reflexes
Z-Pack
-Good for URI, LRI, skin, soft tissue, and perio. abscesses
-Long t1/2 and better tolerated than erythromycin so dosing is only 5 days
-Taken up by phagocytes and delivered to the infected site
-Given to endocarditis patients as a prophylaxis if penicillin allergic
Tetracycline
-Shorter acting lower potency is tetracycline, longer acting and higher potency is doxycycline and minocycline (acne)
-4 rings so causes photosensitivity
-PO absorption can be reduced by divalent and trivalent cations which it chelates. Solution, don't take this within 2 hours of eating or drinking
-Bacteriostatic since inhibit 30S ribosome and act very broad with G+, G-, and anaerobes
-Help in periodontal disease by inhibintg collagenase and metalloproteineases allowing periodontal reattachment. Is able to do this because tetracycline accumulates in the gingival crevicular fluid after systemic administration
-Cause more GI problems and superinfections (broad) than penicillin. Penicillin really better except perio infection
Tetracycline Products
-Directly place in periodontal pockets - Acticite tetracycline fiber
-Helps reduce pocket depth because perio pathogen sensitive to this and it inhibits collagenase and metalloproteinase
-A better option for quicker delivery and no removal is doxycycline hyclate called atridox. Flows into the pockets, stays and is released from a polymer
3) PerioChip which is chlorhexidine. Lower levels than the other two methods.
Clindamycin
-A 50s ribosome inhibitor which is static at low doses and cidal at high
-Absorbed PO and transported via macrophage and WBC
-Great prophylactic endocarditis and late joints for penicillin allergy
-Good in chronic bone infections and odontogenic infections
-Good for endo because its attacks anaerobes when these people don't respond to penicillin
-Can cause a rash, diarrhea, and pseudomembraneous colitis (associated with parenteral formula)
Pseudomembraneous Colitis
-Caused by clindamycin, cephalosporin, broad spectrum penicillin
-Also associated with older age, diabetes, H-2 blockers, diuretics
-Treat symptoms of diarrhea via hydration and electrolytes
-Treat bacteria with vancomycin (PO cause that's where bug is) and metronidazole
-DONT use narcotics because constipatory effect leads to lots of gas
Metronidazole
-Bactericidal only for anaerobes (not faculative) by disrupting DNA
-Good against periodontal disease, endo infection, and oral surgery. Usually combine with penicillin or cephalosporin to get synergisitc effect. Comes in a gel for perio infection
-Used for trichomonas, amebas, giardia, and anaerobes
-Causes disulfiram effect (acid-aldehyde build up), stomatitis, perhaps teratogen, 2C9 inhibit with warfarin for bleeding, and less lthium clearence so kidney damage
Fluroquinolones
-Ciprofloxacin is used for URI, LTI, and Perio (faculative anaerobes)
-Bactericidal DNA gyrase inhibitor
-Worked with facultative G- so usually mixed with metronidazole to be G- broad spectrum
-Inhibited by divalent and trivalent cations, 4 rings like tetracycline
-Can get into tendons and stiffen them up
-Inhibits 1A2 so methylxanthines like theophylline build up and lead to arrhythmia
Prevention of Infective Endocarditis
-Although these patients are most at risk from chewing/brushing at home and gingival bleeding allowing alpha-hemolytic streptococci to the heart, they are advised to take antibiotics before visiting the dentist
-Cardiac conditions most associated with endocarditis include rheumatic heart disease with murmur, prosthetic heart valves, previous endocarditis, and congenital cardiac malformations, cardiac transplantation recipients with valvulopathy. Mitral valve prolapse was taken off the list, as was pacemakers and innocent murmurs
-Congenital heart diseases include unrepaired cyanotic CHD, a CHD repaired with prosthetic material within 6 months, a repaired CHD with residual defects
-Amoxicillin is the drug of choice. Went from 3g before and 1.5 6h after to 2g before
-For patients allergic to penicillin you can use 600mg clindamycin 1hr before, 500mg azithromycin/clarithryomycin 1h before, or 2g cephalosporin (cephalexin or cephradine) 1h before if their allergy to penicillin isn't immediate type hypersensitivity
Prosthetic Joint Patients
-Only people with previous joint infection, people withint 2y post-op of surgery, or those immunocompromised (insulin-dependent diabetes, RA, lupus, hemophilia) should get prophylaxis antibiotics
-Take cephalosporin or amoxicillin 2g 1h before or 600mg clindamycin 1h before if allergic to penicillin
-Major bud in joint infection is staph which is not numerous in the mouth unless immunocompromised
Prevention of Postoperative Infections
-Not recommended by Hersch in healthy patients because indiscriminate use leads to resistant strains and developing antibiotic allergies
Endocarditis
-dental procedures cause a MINORITY of the cases, incubation is less than 2 weeks (if after 2 weeks in your office they get it then they didn't get it from you), no controlled clinical trials have been done, physicians know less than dentist about antibiotic regimens for this
Dental Procedures for Endocarditis at risk patients and prophy is ok
-Extractions
-Apicoectomies
-Root canal therapy
-Rubber dam placement
-Periodontal surgery
-Scaling and root planning
-Biopsies
-Placement of local delivery systems
-Intraligamental injections
-Placement or removal of orthodontic bands
Penile Implants
...don't give prophy for this...gross!
Herbal Overview
-no longer fringe medicine, these are studied more and can be included in insurance
-Under the Dietary Supplement Health and Education Act companies can claim a structure/function (boost the immune system) but not a diagnostic claim (cures high cholesterol or lupus)
-These are classified as food by the FDA so they are except from normal FDA review. However, FDA uses 3rd party researchers and if they are proved unsafe they can be pulled. Example is mood promoter ma huang getting pulled because it contained ephedra and caused arrhythmias and stroke in patients with heart condition
Gingko Biloba
-scientifically shown that extract increase vasodilation and cerebral blood flow to help in short term memory loss, headaches, tinnitus, dementia, and alzheimer's.
-As a blood thinner this can lead to bleeding and a mild GI upset
-With used with antiplatelet and anticoagulants you get more bleeding
Saw Palmetto
-it lower inflammatory and inhibits DHT it's useful for benign prostatic hypertrophy and irritable bladder
-People with prostate cancer may be fooled into thinking they're treating hypertrophy symptoms
Kava Kava
-no problem scientifically to relieve anxiety
-Has lactones which relax muscles, anxiety, and convulscents. Works at GABA or Cl- level to treat nervousness and insomnia. Has topical anesthetic effect in oral cavity
-high doses cause psychomotor impairment and ataxia. Long term associated with skin rash
-Supraadditive effect with other CNS depressents leading to depression
Aloe Vera
-When applied topically it acts as a anesthetic and antibacterial. When internally it's a laxative
-Can lead to GI cramps
-All the GI problems can interfere with absorption of medicine taken PO
Astragalus
-Boost immune system, strengthen the heart, enhance memory
-Reduce blood glucose and inhibit platelet aggregation
-If the patient is diabetic and on insulin then this may drop their blood glucose too low. If they are on another anti-coagulant then it can cause too much of a blled
Bilberry Fruit
-An astringent used to treat inflammation of the mouth and throat
-As a tea it can treat diarrhea
-Antiplatelet effects and hypoglycemia
-Be careful when mixing this with diabetic drugs or other blood thinners
Dong Quai
-A female health tonic reported to help with fibrocystic breast disease, premenstrual syndrome, and painful periods of menopause
-Associated with photosensitivity
-Can mix with other hypotension drugs and antiplatelet drugs
Echinacea
Immune system stimulator
-May aggravate autoimmune disorders
-Can counteract drugs that act as immunosuppresents like corticosteroids and anticancer drugs
Garlic
-Used as a digestive aid and to treat hypertension and hyperlipidemia. Can lower LDL and raise HDL
-People can get allergic reaction to this and excess bleeding
-Can mix with drugs that act as antiplatelets

St. John's Wort
-Very well studied cousin of prozac it helps with depression and anxiety and menstral cramps
-High doses associated with photosensitivity so don't mix with tetracycline
-A 3A4 and 1A2 inducer so it decrease blood levels of statin, cyclosporins, oral contraceptives, and warfarin
Histamine Receptor's
H-1: Found in smooth muscle, the endothelium, and the brain. The agonist is 2-methyl histamine (inositol/DAG). Causes classic allergy symptoms like vasodilation (due to NO2 spill), edema leading to itchiness, hypotension, reflex tachycardia, bronchoconstriction, triple response
-Triple response is where histamine put under skin you get a red raised bullseye due to capillary vasodilation, a swelled area due to edema, and then another ireegular red area known as the flare response due to histamine spreading out and activating free nerve endings
-histamine released from WBC, neurons in the brain for peripheral pain reception, and in stomach cells called enterochromaptin which binds parietal cells forcing them to release acid
Histamine Receptor's 2
H-2: Found in gastric mucosa, cardiac muscle, and mast cells. Agonist is 4-methyl histamine (cAMP, adenylate cyclase).
-Causes HCL/pepsin release from parietal cells and when bound to mast cell it prevents further histamine degranulation so it acts as a negative autoreceptor

H-3: Found in presynaptic terminal in brain neurons. Stimulated by R-alpha methyl histamine (G protein) - Causes decreases NT release and may help in psychiatric disorder
Uses of antihistamines
-allergies, sleeping aids/sedatives, motion sickness, parkinson's, local anesthetic when allergic to ester/amides
Antihistamines
1) Ethanolamines (Benadryl/Dramamine) - Blocks H-1 receptor and anti-muscarinic (needed for helping with motion sickness).
-Very sedating since ACH is a stimulator in the brain and blocking this causes drowsiness
-Excellent motion-sickness
-Local anesthetic activity
-Good Parkinson's because ACH is usually weighing down DOPA in this disease
-Leads to anticholinergic ADR like dry mouth
Ethylenediamines and Piperazines and Alkylamines
Ethylenediamines - Triplenamine and pyrilamine.
-Moderate sedation (used as a OTC sleeping aid), anticholinergic ADR
-Similar to benadryl but X=N and Y is removed

Piperazines - Cyclizine and Meclizine
-Slight sedation and excellent anti-motion sickness

Alkylamines - Chlor-Trimeton. Common component of OTC cold medications
Phenothiazines
-Promethazine - anti-adrenergic, anti-dopaminergic, anti-cholinergic
-Very sedating and awesome anti-emetic so used by pediatric dentist. Used in combo with other sedatives so not only is less used, but due to anti-emetic effect the kids won't vomit from chloral hydrate. However, as just a anti-emetic it's an overkill
-Local anesthetic activity
-Anti-cholinergic ADR
-Extrapyramidal effects because it blocks dopamine and people have parkinson like symptoms
-2D6 inhibitor so it blocks hydrocodone transformation
-alpha-1 blocker can lead to postural hypotension
2nd Generation Anti-Histamines
-Terfenadine, Astemizole, Allegra, Claritin, Zyrec - Bulky and polar so don't pass BBB and non-sedating
-Good for hay fever
-Terfenadine and astemizole reacted with the macrolides and ketoconazole leading to arrhythmia so it was taken off the market. Allegra, the active metabolite of terfenadine replaced it
Types of Cancer Genes
-Proto-Oncogene - growth-promoting or death inhibiting cellular gene that undergoes a gain of function mutation and becomes a oncogene: Ex: Her-2/BCL-2
-Tumor Suppressor Genes - Regulate and inhibit inappropriate growth - p53, BRCA-1/2
-DNA Mismatch Repair - Correct spontaneous error in DNA. Ex. MLH, MSH, and one associated with heredital colorectal cancer. Kind of like a TSG
-Epigenetics - Non DNA mechanism that activates a oncogene in inhibits a TSG
Pathways Changed by a Tumor
1) Signal Transduction
2) Cell Cycle Transition - In BC the excess of CDK trick the cell into immediately moving to the next phase of the cell cycle
3) Apoptosis - Recognized by p53 which turns on arrest or apoptosis genes
4) Immortality - Non-cancer genes lose some of the telomerase repeat seqeunce each time they divide until they stop dividing. Cancer genes have telomerase which add on this sequence
5) Angiogenesis - Hypoxia inside a tumor drives the pro-angiogenic factors which make a new vascular bed from pre-existing one. VEGF is involved.
6) Invasion and Metastasis - Tumors release proteases to leave their environment and adherence facotrs to bind to a new one
Tumor Growth Kinetics
-Early on the tumor has the most growth. This is the best time to target it by a chemo drug
-When a tumor gets large it's growth is restricted by space, blood supply, and nutritional needs
-The threshold between detection (10^9) and death is small, only 10 doublings
Cancer Diagnosis
-Markers can be used to detect, and more effectively, diagnose how well treatment is going
TNM Staging - T (tumor size), N (spread to the lymph nodes?), M (metastasis)?
-Tumor requires 50% reduction to be considered in remissal
Treatment Approaches with Chemotherapy
Induction Therapy - First step to shrink the tumor or see how it responds
Adjuvant Therapy - GIven in association with something else like surgical resection or radiation to keep the cancer from coming back
Neoadjuvant - Given to shrink the tumor first before something like surgery or chemo is done. In this case, shrinkage first gives the best prognosis
Cancer Chemo Targets
Cell Cycle: G1 (RNA/protein for DNA synthesis), S, G2 (RNA/Protein for Mitosis), Mitosis, Go
1) Cell Cycle Phase Agents - Things like methotrexate act at a certain phase of the cell. Prolonged exposure but not high doses can help
2) Non-Cell Cycle (Alyklating agents) - Can kill in any phase of the cell cycle so give whenever and higher dose usually ends up killing more
Death curve of chemotherapy
-Drugs usually kill the same fraction of chemo when administered
-Need to wait a specific period of time to give another dose so body can heal
-Once the # of cancer cells is low enough, the bodies immune system can take care of the rest
-This is known as first-order kinetics in regard to tumor death
-Never exactly first order because some cells are resistant while other's grow so slowly that they are not effected by the chemo agent
Key Points
-MTD - maximum tolerated dose given where non-life threatening side effects are produced
-DLT - dose-limiting toxicity where serious life-threatening toxicity is produced
-Dose Intensity - amount of drug over a period of time. Drug density is when a drug is given more often. Can produce a nice reduction in cancer but also more side effects
Dosing Strategies
1) Dosing - Determined by body surface, body weight, or flat dosing
2) Administration - Want the drug localized to the tumor site
-Gliadel wafers for brain tumors
-IP chemo for ovarian cancer
Toxicity
-occur in cells that divide more rapidly (bone marrow, ovary, testes, GI, hair follicles)
-Toxicity requires drug to be held, dosage reduced, or a change in drugs
1) BM Suppression - Most common toxicity. Lowest level of platelets in blood is the Nadr
2) GI - oral stomatitis/mucostitis leading xerostomia, nasua/vomit, lower GI problem like diarrhea
3) Dermatologic - alopecia, skin/nail changes,
4) Immune System - Immunosuppression/allergies
5) Hyperuricemia, Kidney Stones, Gout (Tumor Lysis Syndrome) - Prevented by giving allopurinol beforehand
Specific Organ Toxicity
1) Renal - Cisplatin causing tubular defects and electrolyte disturbances. Hydrate and give diuresis to prevent
2) Cariomyopathy - Doxorubicin and trastuzumab. These lead to angina, MI, CHF. Can limit the dose or give a iron chelator dexrazoxane to get rid of free radicals
3) Neurotoxicity - Cisplatin, vincristine, paclitaxel. Causes neuropathy
4) Pulmonary Toxicity - bleomycin, busulfan
5) Bladder Toxicity - Cyclophosphamide, ifosfamide. Prevent with hydration, diuresis, and mesna (binds and detoxifies acrolein, the metabolite of the two drugs up above)
Alkylating Agents
Action: form alkyl bond with nucleotides inhibiting DNA replication/transcription

Agent: Cyclophosphamide

Use: Leukemia, lymphoma, breast cancer, testicular cancer

DLT: myelosuppression
Platinum Analogs
MOA: Similar to alkylating agents but platinum added to DNA

Agent: Cisplatin

Unique Feature: Renal insufficiency

Cancers: Testicular, lung, ovarian, head and neck

DLT: neuropathy and myelosuppression
Nitrosoureas
MOA: similar to alkylating agents

Agent: Carmustine

Unique: Cause pulmonary fibrosis

Cancer: Crosses the BBB so good for brain tumors

DLT: myelosuppression, alopecia
Miscellaneous Alkylating Agents
Agent: Bleomycin

Unique: Pulmonary fibrosis (DLT) and not a lot of myelosuppression

Cancers: Testicular, lymphomas, head and neck
Topoisomerase I Inhibitors
MOA: Binds to the topo I-DNA complex which prevents resealing of DNA and causes single strand DNA breaks

Agent: Irinotecan

Unique: Prodrug cleaved to lots of metabolites including SN-38 which causes diarrhea (DLT) that is treated with atrophine

Cancer: Colorectal cancer

DLT: Diarrhea and myelosuppression
Topoisomerase II Inhibitors
MOA: Act as intercalculators which trap the DNA-enzyme complex leading to double strand breaks. Get in the DNA planar rings leading to conformational distortion. Generate free-radicals which are toxic

Agent: Doxorubicin - Has 4 cyclic rings so its a anthrocyclic drug

Cancer: Many including breast and lymphoma

DLT: myelosuppresion, cardiotoxicity, stomatitis
Antimetabolites
-structural analog of metabolite and interfere with normal synthesis of nucleic acid by acting as a precursor or intermediate. Either compete for key enzymes or are incorporated into the DNA

1) Pyrimidine Antagonist
MOA: Fluorinated pyrimidines metabolized to fdUMP which interferes with thyidylate synthase so no thymidine is made and DNA synthesis is arrested.

Agent: Fluorouracil (5-FU) - Used for breast and GI cancer. Cause myelosuppression and diarrhea
Antimetabolites 2
2) Folate Analog Metabolic Antagonist - Bind to dihydrofolate reducatase so active folate is not made. Without this there is no thymidine and DNA/RNA synthesis is stopped

Agent: Methotexate - Protein bound and nephrotoxic at high doses. Cause bone marrow suppression and stomatitis

3) Cytidine Analogs - Once phosphorylated intracellularly to the active triphosphate it competes with deoxycitidine foir DNA polymerase and inhibits DNA synthesis

Agent: Cytarabine - Good for leukemia and leads to myelosuppression and stomatitis
Microtubule Interactive Agents
1) Vinca Alkaloids - Inhibit tubulin polymerization so no mitosis.
Agent: Vincristine - peripheral neuropathy

2) Taxanes - Bind tubulin and inhibit disassembly of the microtubule apparates. Block pre-mitosis (G2-M)
Agent: Paclitaxel - Not water soluble so requires a cremaphor dilent for IV injection. Can cause myelosuppression and neuropathy
Miscellaneous
1) Asparaginase - Breaks down asparagine which kills cancers that require exogenous asparagine for their protein synthesis. Used for leukemias and lymphomas
Hormonal Agents
-Effect in tumors that come from tissue sensitive to hormones and that retain the hormone receptor

1) Estrogen Receptor Modulators
Tamoxifen - Estrogen antagonist and agonist used for breast cancer

2) Corticoidsteroids - Retard DNA synthesis via inhibition of glucose transport or phosphorylation so no energy for the cell.
Biologic Response Modifiers
-stimulate elements of the body's immune mechanism

1) Hematopoietic Growth Factors - Stimulate production and function of white blood cells and helps counteract myelosuppression by giving it 24 hours after the chemo agent

a) Filgrastim - Turns on progenitor cells and increase production rate of WBC. Lets us increase chemo dose whereas before there would be too much immunosuppression
Biologic Response Modifiers
2. Monoclonal Antibodies
a) Trastuzumab - Blocks HER-2 receptor so no dimerization and cell signaling. Instead there is cellular cytotoxicity and no proflieration. Used for breast/gastric cancer
Signal Transduction Inhibitors
-Interupt cell signaling. Popular pathways are the mTOR, EGF, and kinase inhibitors

1) Gleevec - In Chronic myelogenous leukemia (CML) there is a 9:22 chromosomal aberattion leading to a Bcr-Abl tyrosine kinase that is a oncogene. Gleevec binds the ATP binding site of this kinase and prevents signal cascade.
-Not cytotoxic. Induced by p450-3A4. Cause fluid retention

2) Erlotinib - Inhibits EGFR tyrosine kinase so no signaling at the internal site whereas...
3) Cetuximab - Targets external domain of ERBB1 receptor

4-5) Torisel and Afinitor interfere with mTOR signaling pathway. Sensitive to p450 inducers (all of the STI).
Anti-Angiogenic
-Block VEGF-R or a VEGF-R ligand
1) Avastin - A antibody against VEGF-R used for colorectal cancer.
-All anti-angiogenesis increase hypertension, thrombolysis, and inhbit wound repair
Specifics
-Target certain genotypes of a tumor

1) Crisompandi - For lung cancer positive for lymphoma kinase

2) Mirafinib - Inhibits raf-kinase, a mutated form of b-raf that 70-80% of melanoma cells have
Emergency Drugs 1
1) Laryngospasm - Give some succinylcholine which is kept in the fridge

2) Asthmatic Attack - Give some a B2-agonist in a inhaler. Alupent, Proventil, or Brethaire. Occur frequently with custom tray dust

3) Angina - Give 1 nitroglycerin tablet every 5 minutes up to 3 doses. Can cause hypotension and methhemoglobnemia
Emergency Drugs 2
4) Allergic Reaction - If mild then use benadryl IM. If serious switch to epinephrine SubQ/SubL. Top 3 allergens are NSAID/Aspirin, Penicillin, and things with sulfonamide linkage

5) Convulsions - Use diazepam and have antagonist flumanizil ready. Be prepared for loss of protective reflexes

6) Prevent addition platelet aggregation during MI - aspirin

6b) - Respiratory Depression from Narc Overdose - Give .4mg naloxone IM/iV followed by 50mg naltrexone PO when patient wakes up
Emergency Drugs 3
7) Pain from a MI - Nitrous oxide, merperidine, or morphine

8) Hypoglycemia
Conscious - Begin to act weird and may begin to pass out. Give 3-4o every 5 min carbohydrates like orange juice or cake frosting under the tongue
Unconscious - Give 1mg glucagon IM and call 911

9) Poisioning - Syrup of Ipecac 15-30mg PO. Triggers cholinergic and CMZ at vomiting center
Vomiting Centers 1
Motion Sickness - ACH bind muscarinic receptor in the ear. Give anti-cholinergic like scopalamine or a H-1 blocker

ACH bind receptor in the stomach

-Giving something that releases NE will stop the vomiting center
Vomiting Center 2
-Opioids, chemo drugs, and hormones activate chemoreceptor trigger zone leading to dopamine and serotonin release at the vomiting center
1) Stop the dopamine side with compazine or trimethobenazamide
2) Stop the serotonin side by giving something like odanserotonin right before chemo.
Ulcer Overview
-naming depends on where it's located. If the erosion is in the mucosa then it's erosion, if it's in the submucosa then it's a ulcer
-a ulcer in the stomach is a peptic ulcer, when in the SI it's a duodenal ulcer (majority of ulcers)
-GERD predisposes you to esophageal cancer
Treating GERD and Ulcers
-Can use medical and non-medical interventions
-For the non-medical, daily life style changes can make a difference. Losing weight, smoking cessation, and avoliding certain foods like alcohol, fried, once with acid, and chocolate can help
-For the medical treatments these are aimed at the parietal cells in the stomach which release acid.
-The drugs target the H-2 receptor, muscarinic receptor, the Hcl-K proton pump, and PG
-The proton pump inhibitors (most powerful) and the H-2 blockers are the most popular
Prostaglandin and Proton Pump Drugs for GERD
PG: Cause the parietal cells to release more acid. A popular PG analog is called misoprostol. This drug is given to people who suffer from NSAID related ulcers. Therefore, they have combined NSAIDs and misoprostol in one bill called anthrotec

Proton Pump Inhibitors: Highest level of symptom relief
-Prilosec, Prevacid, and Nexium (S-isomer) of prilosec
-Metabolized by P450-C19 so don't mix with valium or propranolol
Muscarinic Blockers and Histamine-2 Receptor Blockers
Muscarinics - Although muscarinic blockers like pirenzepine and atropine work, the GI muscarinic receptors are the weakest so the side effects outweigh the benefits

H-2 Receptor Blockers: In order of 1/2 life is tagamet, zantac, and pepcid.
-Well tolerated but people form tolerance to them and absorption is decreased by food
Promotility Agents
-In GERD motility is a problem. These drugs can increase esopheageal spinchter pressure, decrease pyloric spinchter pressure, or stimulate peristalsis
-Most popular is Reglan. Can lead to tardive dyskinesia since it's a DOPA receptor antagonist. Also a cholinergic receptor agonist which is good for motility
-Cisapride - For those who have no other choice this drug releases ACH to help with peristalsis, closes the eso. spinchter and opens the pyloric spinctor
Other Ulcer Drugs
1) Antibiotics - Given to people who have ulcers from H. Pylori. Include clarithromycin and amoxicillin.

2) Antacids - Neutralize HCL for breakthrough pain
-Tums has calcium which is also good for osteoporosis
-Better drugs are mylox and mylantin which are 50% magnesium hydroxide and 50% aluminum hydroxide. Avoid diarrhea/constipation side effects

3) Crater Blockers - For people who can't tolerate PPI or H-2 blockers this drug (Carafate) blocks the hole in ulcers by binding to the acid stomach lining.