Nursing 3703
Pharmacology
By Linda Self

• Intracellular parasites
• Enter host, bind to receptors on cell membranes
• Use cellular metabolic activities for replication
• May be DNA or RNA viruses

• DNA viruses incorporate into chromosomal
DNA, produce new viruses
• RNA viruses must be converted to DNA by
reverse transcriptase in order to replicate

• Induce antibodies and immunity
• Protein coat allows host recognition as foreign vs. self
• Exception is influenza

• Herpes Simplex 1 and 2
• Cytomegalovirus
• Influenza
• RSV
• Rotavirus
• HIV and AIDS

• Catalyst was AIDS
• Both for Tx of AIDS and for opportunistic infections

• Poliomyelitis
• Measles
• Rubella
• Varicella
• RSV
• HPV
• Herpes Zoster
• Yellow Fever
• others

• Attenuated vaccines generally safe
• Do not use in patients who are: pregnant, on steroids, receiving immunosuppressants or antineoplastiacs, undergoing radiation Tx or who are immunodeficient

• Zovirax (acyclovir) for herpes labialis, varicella, herpes zoster, genital herpes
• Famvir (famciclovir) for zoster and genital herpes
• Valtrex (valacyclovir) for herpes labialis, zoster, recurrent genital herpes
• Famvir and Valtrex need titration in renally impaired

• H=hemagglutinin
• N=neuramidase
• April 2009
• Quadruple reassortment
• Tx—Tamiflu (oseltamivir) or Relenza
(zanamivir) or Flumadine (rimantadine)
• Tx for 5 days
• Relenza can cause bronchospasm

• To short course of infection, must be started within 48h
• Thereafter, ? may decrease severity

• Virazole (ribavirin)
• Administered by inhalation
• Can cause bronchospasm

• Hepatitis B—Hepsera (adefovir), Epivir
(lamivudine)
• Hepatitis C—peginterferon alfa 2a and
Virazole (ribavirin)

• Unique features
• 2 proteins on surface of virus bind with 2 sites on CD4+ cell
• Virus infiltrates into genetic material
• Reverse transcriptase enzyme enables virus to become double stranded DNA

• Once double-stranded DNA, like the host cell,
HIV can infiltrate cell nucleus of target cell
• Gains entry into target cell nucleus with aid of
Integrase
• Following integration and replication, long protein chain is cleaved. Pieces then form into new viral particle

• Cleavage is accomplished with aid of protease
• See page 568

• Nucleoside reverse transcriptase inhibitors
• Nucleotide reverse transcriptase inhibitors
• Non-nucleoside reverse transcriptase inhibitors
• Protease inhibitors
• Entry inhibitors

• Always used in combination
• Target enzymes or receptor sites
• Specific guidelines for pregnancy

• Prototype is AZT
• Similar structurally to DNA components
(adenosine, guanosine, cytosine or thymidine)
• Affect thymidine, thus inhibit reverse transcriptase
• Slow progression but do not cure
• Didanosine, Ziagen (abacavir), AZT
(zidovudine), Epivir (lamivudine)

• Also inhibit reverse transcriptase
• Differ structurally from nucleoside RTI so circumvent resistance
• Viread (tenofovir)
• Used to Tx hep B as well

• Directly bind with reverse transcriptase
• Used in combination with NRTIs
• Viramune (nevirapine) and Sustiva (efavirenz)

• Inhibit action of protease
• Most protease inhibitors metabolized by cytochrome p450 system
• Many drug interactions
• Liver toxicities
• Lipid abnormalities
• Hyperglycemia
• lipodystrophies

• Prezista (darunavir), Crixivan (indinavir),
Viracept (nelfinavir), Norvir (ritonavir),
Invirase (saquinavir)

• Combovir (stavudine and zidovudine)
• Trizivir (abacavir, lamivudine and zidovudine)
• Decrease pill burden

• Fuzeon (enfuvirtide)
• Selzentry (maraviroc)
• Do not act on enzymes but rather affect glycoproteins that allow binding and fusion of the virus to the CD4+ cell

• Still in clinical trials

• Mild or life threatening
• Widely present in environment
• Dermatophytes—tinea capitis, tinea pedis, tinea cruris, tinea corporis
• Examples: Candida, Aspergillosis,
Cryptococcus, Histoplasmosis, B

• Development of antifungals difficult because fungal cells closely resemble human cells
• Polyenes—Amphotericin B, Nystatin
• Azoles—Sporonox (itraconazole), Nizoral
(ketoconazole), Diflucan (fluconazole)
• Echinocandins—Eraxis (anidulafungin),
Cancidas (caspofungin)

• Give in D5W
• Use separate line
• In line filter depending on formulation
• Adverse effects:
Infusion reaction with chills, fever, tachypnea
Treat with Benadryl, Tylenol or steroids
• Nephrotoxicity most serious SE

• Indicated for life-threatening fungal infections such as aspergillosis, blastomycosis, candidiasis, coccinioidomycosis, crytococcis and histoplasmosis
• Drug concentrations are highest in inflamed tissues

• Lamisil (terbinafine)
• griseofulvin

• Same mechanism of action as Amphotericin B
• Too toxic for systemic use

• Largest group of commonly used antifungals
• Can be used topically or systemically
• Prototype is Nizoral (ketoconazole0
• All azoles are contraindicated in pregnancy

• Less toxic than ampho
• Many drug interactions
• Poor absorption if achlorhydric
• Some hepatotoxicity
• Can be given orally

• Synthetic, broad spectrum against candidiasis, cryptococcis, coccidioidomycosis
• Not effective against aspergillosis
• PO or IV
• Fewer side effects than ketoconazole
• Does not require gastric acidity, does not cross blood-brain barrier
• Reduce dosage in renal failure

• Similar to Diflucan
• Drug of choice for blastomycosis, histoplasmosis and sporotrichosis
• Good for suppressive Tx in AIDS patients w/histo
• Contraindicated for dermatophytic infections and onychomycoses in heart failure patients
• IV or PO
• Many drug interactions

• First chicocandin antifungal
• Affects glucan in fungal cell wall leading to leakage of cellular contents
• Indicated for Tx of invasive aspergillosis who cannot take or do not respond to Fungizone or
Sporanox

• Can cause thrombophlebitis
• Abnormalities in blood count
• Liver impairment
• Drug interactions
• Mix only with normal saline, infuse over at least one hour

• For dermatophyte infections of the scalp and nails and for extensive skin eruptions
• Drug binds to keratin, over time the infected tissues are shed and replaced by uninfected tissues
• Need 3-8 weeks to Tx ringworm
• Up to one year for onychomycoses

• Side effects: GI upset, skin rash, insomnia, fatigue, hepatotoxicity, blood dyscrasias and peripheral neuritis
• Take with fatty meal
• May affect efficacy of OCP
• Coumadin may warrant adjustment

• Synthetic with broad spectrum of activity
• Inhibits an enzyme needed for synthesis of ergosterol, a structural component of fungal cell membranes
• Good for Tx of ringworm, nails
• hepatotoxic

• Aspergillosis—Sporonox, Amphotericin B
• Blastomycosis—Sporonox, Amphotericin B
• Candidiasis—varies r/t area of infection
Oral
Cutaneous
Vaginal
Systemic

• Histoplasmosis—Sporanox
• PCP—Bactrim, pentamidine, dapsone, others
• Cryptococcis-Amphotericin B
• Coccidioidomycosis- azole to Amphotericin B

• Found in soil, decaying plant matter, cellars
• May be found in cereals, powdered milk, peanuts, cashews, coffee beans
• Characterized by granulomatous lesions of lungs,skin, eyes, nose, urethra and may infiltrate to vital organs
• Occurs in debilitated and immunocompromised
• Tx w/ Amphotericin or Sporonox

• Found in soil, organic debris around chicken houses, bird roosts and caves inhabited by bats
• Develops when spores are inhaled
• Tx with Sporanox, possibly Ampho

• Yeast infection commonly affects those on abx therapy, inhaled steroids, diabetics, those on antineoplastic Tx or on steroids or who have
AIDS
• Presents as: vaginal candidiasis, skin candidiasis, oral candidiasis or systemic disease

• Systemically—Amphotericin B
• Vaginally-Lotrimin (clotrimazole), Diflucan
• Oropharyngeal, esophageal, vaginal and systemic—Diflucan PO or IV

• Organisms that live within, upon or at expense of another organism to survive
• Include protozoa, helminths, scabies and pediculi

• Include amebiasis, giardiasis, malaria, toxoplasmosis and trichomoniasis
• Single celled, may be saprophytes. Usually contracted by oral-fecal route, by contaminated water or by bite of an insect.

• Common in Africa, Asia and Latin America
• In US, more likely in homosexuals and bisexual men and in those who travel to areas with poor sanitation

• Drugs used are classified according to site of action
• Extraintestinal e.g. liver—use Aralen
(chloroquine)
• For Intestinal use Yodoxin (lodoquinol)
• Flagyl is effective for intestinal and extraintestinal amebiasis
• May also use tetracycline or doxycycline as they alter bacterial flora

• Caused by Giardia lamblia
• Spread by food or water contaminated with feces with encysted forms of organism
• Also can contract by person to person transmission in day cares, institutions and in homosexual or bisexual men

• Seen in campers who drink water
• Causes diarrhea
• Can progress to chronic condition with malabsorption, wt. loss, anorexia
• Can result in B12 deficiency
• Tx is Flagyl

• Seen in tropics
• Rare in US
• Caused by four species of protozoa of genus
Plasmodium-vivax, malariae, ovale and falciparum
• Transmitted by the Anopholes mosquito
• Antimalarials act at different stages in life cycle

• Chloroquine with primaquine is used for prophylaxis
• Lariam (mefloquine) for prevention and Tx, better in more resistant forms
• Plaquenil (hydroxychloroquine) used to Tx erythrocytic malaria
• Daraprim (pyrimethamine) folic acid antagonist also used in prevention

• Quinamm (quinine) prototype
• Derived from bark of cinchona tree
• Sometimes still used for leg cramps
• Replaced by agents with fewer SE

• Vaginal infection caused by Trichomonas vaginalis
• Contracted sexually
• Treat both partners
• Flagyl is Tx

• Infestation with parasitic worms
• Some types of worms penetrate body tissues or produce larvae that migrate to blood, lymph, lungs, liver or other sites
• Some anthelminthics act locally, some systemically

• Effective for hookworms, pinworms, roundworms, whipworms
• May be useful with tapeworms
• Prevents uptake of glucose necessary for parasitic metabolism
• Only 10% is absorbed systemically

• Used for various parasitic infections, most useful in stronguloidiasis
• Also used for resistant lice

• Parasitic infestations of the skin
• Scabies by the itch mite called the Sarcoptes scabeii
• Scabies caused by one of three types of lice: pediculosis capitis, pediculosis corporis and pediculosis pubis

• Permethrins drug of choice for both
• Two applications recommended
• Pediculosis is a 1% preparation (Nix)
• Scabies used a 5% cream (Elimite)
• Permethrins safest
• Second line use Lindane (gamma benzene hexachloride)

• Ovide (malathion) is a pediculicide for head lice
• Rid (pyrethrin) for pediculosis