Pharm II Lecture 6

 -HIV-1: subtype most commonly found in ________

-AIDS:  CD4 count less than ____cell/mm3  OR
History of an opportunistic infection:
i.e., unexplained fever for greater than __ weeks, thrush, pneumocystis carinii pneumonia, toxoplasmosis, cryptococcal meningitis, histoplasmosis, mycobacterium avium, others

-US

 

-200

 

-2

-What does teh Western blot look for? 

 

-When does seroconversion usually occur?

 

-A minimally significant change in viral load is considered to be a ____-fold increase or decrease

-Lower limits of detection include ____ copies /mL

-anti-HIV Abs..(gold standard..99% spec/sens)

 

-3 weeks PI (range 2wks-6mo)

 

-3-fold

 

-400 copies/mL (ultrasensitive gets down to 20-50 copies/mL)

-Those on antivirals should have viral titer loads lower than ___ copies/mL by 6 mo.

-when are they monitored?

-Normal CD4+ cell counts are ____-____ cell/mm3
-CD4+ cell counts should be measured every __-__ months in patients on or off antiretroviral therapy

-Fewer than 50

 

-every 3-4 months

 

– 800-1,200

 

-3-6 months

-The most common HIV symptom is what?

 

-2nd most?

 

-To achieve therapeutic goals what must the compliance rate of HIV pts be to their meds?

-Fever

 

-Muscle/joint aches

 

-95%

What HIV stage is this: HIV DNA enters the host cell’s nucleus, where an HIV enzyme integrase “hides” the HIV DNA within the host cell’s own DNA.

 

-Now teh HIV DNA is called a _______.

-Integration

 

-provirus

-What do NUCs (NRTI’s) do?

;

-What are the class toxicities?

;

-What are S/S for lactic acidosis?

-PREVENTS VIRAL RNA FROM BECOMING DNA; Inhibits viral replication.

;

-Lactic Acidosis; severe Hepatomegaly with steatosis (fatty stools)

;

-N/V, Abd pain, Wt loss, Malaise

-Which Entry/Fusion Inhibitor is this?:

Fusion Inhibitor
MOA : Binds to gp41 on HIV surface inhibiting HIV binding to CD4 cell

;

-What is the other Entry/Fusion Inhibitor?

;

-Enfuvirtide (T20;chemical name) – Fuzeon;

;

– Maraviroc (MCV) – Selzentry;

Which Nuc am I:

– Dose: every 12 hours
o;;; Only therapy available in IV form
o;;; Adverse Effect: Macrocytic Anemia (so we can use this to monitor drug adherence)
o;;; Do not use with Zerit (Stavudine-d4T) due to antagonism (they work in the same area)

;

;

;

-AZT or Zidovudine-Retrovir

Which Nuc am I?;

Dose: every 12 or 24 hours, depending on mg.
o;;; No dose adjustment needed in renal impairment.
o;;; M184V resistance issue, but it could be used as an advantage
o;;; Also can be used for hepatitis B treatment

;

;

-Lamivudine-Epivir (3TC)

Which Nuc am I:

;

Dose: every 24 hours with or without food
o;;; Well tolerated, SKIN DISCOLORATION no significant drug interactions
o;;; M184V resistance issue, but it could be used as an advantage

;

;

-;;; Emtricitabine-Emtriva-FTC

Which Nuc am I?

Dose: every 12 or 24 hours, depending on mg.
o;;; EtOH increases levels up to 41%
o;;; Adverse effects: HYPERSENSITIVITY
;;;; PRESCREEN: We see a greater hypersensitivity rxn if pt tests positive for HLA- B* 5701
;;;; Rash and Fever most common;;;; Severity increases with each dose
;;;; NEVER rechallenge pts
;;;; Counsel all pts ab warning S/S: BIG FAT HAIRY DEAL!!!! Have them contact prescriber IMMEDIATELY.

;

;

;;;; Abacavir-Ziagen-ABC;;;

;

What are these teh risk factors for?

Female gender
Obesity
Prolonged use of NRTI;s
Controlled virus;a weird SE since this is the goal

;

;

;

;Lactic Acidosis by using NRTI’s (Nucs)

T/F…All NRTI’s are prodrugs?

;

-What is the good drug resistance strain that can develop in response to certain Nucs?

-True

;

-Strain M184V

NucleoTIDE reverse transcriptase inhibitor

Dose:; 300mg po every 24 hours
Adjust dose in renal impairment
Adverse effects:
Asthenia, D/N/V, headache, flatulence, renal insufficency

;

;

Viread (tenofovir) or TDF

Which Nuc am I?:

;; Dose: every 12 hours
o;;; Dose reduction in renal impairment
o;;; Avoid use w/Retrovir (AZT) due to antagonism
o;;; Use w/caution w/Videx (ddI) due to increased risk of L. acidosis, peripheral neuropathy, and pancreatitis
o;;; AE:; lipdystrophy, dose related peripheral neuropathy, hyperlipidemia


;

;

; Stavudine-Zerit-d4T

-Binds to reverse transcriptase at a different site to inhibit HIV replication
-Resistance is an issue
Must be dose adjusted in liver impairment
Class toxicities: rash and hepatic toxicity
Lots of drug interactions;.helps distinguish the individual drugs.

;

;

;

NNRTI’s (non-nucleside reverse transcriptase inhibitors)

Which NNTRI am I?:

-Dose:  600mg po every 24 hours (HS)
Contraindication:
Pregnancy, 1st trimester

May cause false positive cannabinoid test

Adverse effects: CNS side effects are unique to EFV (~50%)(ABNORMAL DREAMS)

 

 

 

Sustiva® (efavirenz or EFV)

T/F…if one NNRTI develops a resistence…try another?

 

-T/F…you can use a Nuc and NNRTI together?

-False…resistent to one=resistence to all.

 

-True…they work in different places.

NNRTI:

 

 

Dose: every 12 hours; take WITH food!
o    AE: rash, nausea
o    Has a different resistance pathway

 

 

   Etravirine-Intelence-ETV

NNRTI:

 Dose: every 24 hours x 14 days; then increase to every 12 hours
o    Dose differences due to AUTOINDUCTION—affects itself by increased metabolism
o    AE: rash, hepatotoxicity
o    TONS of drug rxns

 

 

 

    Nevirapine-Viramune-NVP

NNRTI:

  Dose: every 8 hours → prob won’t see this med due to compliance
o    AE: rash, increased LFTs
o    May inhibit its own metabolism
o    Separate 2 hours from antacids b/c it needs acidic environment to be absorbed.

 

 

 

⇒    Delavirdine-Rescriptor-DLV

INTEGRASE INHIBITOR:

   Dose: every 12 hours
o    Inhibits the catalytic activity of HIV-1 integrase, an HIV-1 encoded enzyme that is required for viral replication.
o    No food restrictions
o    AE: mild

 

 

– Raltegravir-Isentress-RAL (inhibits formation of Provirus)

-What is the class SE/toxicities of Protease Inhibitors?

 

-What is teh MOA of Protease Inhibitors?

-Whole Class: Must be dose adjusted for liver impairment; lots of drug interactions; lots of toxicities (Hypergly, hyperlipid, inc Tris, Increased bleeding in hemophiliacs, Lipodystropy, OSTEONECROSIS)

 

-Prevent cleavage of HIV, resulting in immature noninfectious viral particles.

Which PI am I?

    Dose: every 12 hours
o    NOT USED BY ITSELF; USED TO BOOST OTHER PROTEASE INHIBITORS!!!
o    AE: Taste perversion

 

 

Ritonavir-Norvir-RTV   

Which PI am I?

 

Dose: every 8 hours (TID) → won’t see it much
o    Take w/low fat meal or on empty stomach
o    Drink >48 oz water daily
•    Causes kidney stones
•    Increased incidence with boosted regimens

 

 

 

   Indinavir-Crixivan-IDV

Which PI am I:?

 

Dose: every 12 hours WITH food
o    Oral solution contains 42% alcohol

 

 

 

Lopinavir/ritonavirKaletra-LPV/r

Which PI am I?

 

Dose: every 24 hours
o    TDF  decreases it’s levels…so increase dosage if taken with TDF

-Interactions with H2 blockers, PPI’s, and CCB’s

-Decreased hyperlipidemia (use in CAD pts)

;

;

;

; Atazanavir-Reyataz-ATV

Which PI am I:

;

Doses: depends on na;ve or experienced pt.
o;;; Caution w/sulfa allergy

-Naive pt will get higher doses initially (1400mg po BID) vs. Experienced (700 mb po BID with RTV 100 mcg po bid)

;

;

;

; Fosamprenavir-Lexiva-f-APV

Which PI am I?

;

Dose: BID w/RTV BID
o;;; Caution w/sulfa allergy

Take with food

;

;

; Darunavir-Prezista-DRV

Which PI am I?:

Dose: BID w/RTV BID
o;;; Capsules contain EtOH-be careful!
o;;; Caution w/sulfa allergy
o;;; Decreased Abavavir-Ziagen-ABC ;;;;; Zidovudine-Retrovir-AZT Levels
o;;; Separate from Didanosine-ddl by at least 2 hours

;

;

;

; Tipranavir-Aptivus-TPV

Preferred Initial Regiments for new HIV pt: PICK ONE OF THESE

;

;;;; _______ + Ritonavir – QD
;;;; ________ + Ritonavir – QD
;;;; _______ + Ritonavir ; QD or BID
;;;; ________ + Ritonavir – BID
;;;; _______ ; QD

-Atazanavir (ATV)

;

-Darunavir (DRV)

;

-Lopinavir (LPV)

;

-Fosamprenavir (f-APV)

;

Efavirenz

Preferred Initial Regiments: ADD ONE OF THESE

;

;;;; Tenofovir + ________
;;;; Tenofovir + _______
;;;; _______ + Lamivudine; ; In pregnant women only

;

-Emtricitabine(FTC NRTI)

;

-Lamivudine (3TC NRTI)

;

-Zidovudine (AZT NRTI)

HIV regiments to avoid:

;;;; ______therapy
;;;; ___-drug combinations
;;;; ____ drug combinations all from same class
;;;; _____ NRTI regimens:; ABC/AZT/3TC/TDF
;;;; _______ in first trimester

-monotherapy

;

-Two

;

-Three

;

-Quadruple

;

-Efavirenze

HIV REGIMENS TO AVOID

;;;; Generally not recommended: ___/AZT/3TC
;;;; Cannot be recommended: ____/AZT/3TC

-_____urea

; Stavudine + ________ – antagonism

;;;; Stavudine + ________ – toxicities

;;;; Lamivudine + ______ ; similar products

;

-ABC

-TDF

hydroxyurea

-Zidovudine

-Didanoside

-Emtricitabine

Which HIV Drug class SE profile am I?
Hepatotoxicity
Hyperglycemia
Hyperlipidemia
Triglycerides
Increased bleeding in hemophiliacs
Lidodystrophy
Osteonecrosis

;

;

;

PI’s

When is the only time we should really use the NNRTI Viramune (nevirapine..NVP)?
-Reserved for use when
 CD4 count <250 (women)
CD4 count <400 (men)

Which PI am I?:

Drug interactions:

H2 blockers
PPI’s
Calcium channel blockers

 

 

-Reyataz (Atazanavir or ATV)

-Who has a higher risk for abacavir hypersensitivity reaction (ABC HSR)…whites or blacks?

 

-THose who usually have a ABC HSR are also positive for what allele?

-Whites

 

-HLA-B*5701

 

T/F Nevirapine is a NNRTI that is okay to use on those who have severe hepatic impairment?

 

-Recommended guidelines for naive retroviral pts: 

__-NNRTI + __NRTI

or

__PI (boosted with __) + __NRTI

-False….DO NOT

 

1-NNRTI + 2-NRTI

or

1 PI (boosted with Ritonavir) + 2 NRTI

 

Who can’t have Lopinavir/ritonavir BID?

;

-Atazanavir + Indinavir are not recommended together b/c they cause?

;

-Saquinavir / Darunavir / Tipranavir are all only virologic when used with?

-Pregnant women.

;

-Jaundince and Hyperbillirubinemia

;

-Ritonavir (booster PI)

What happens when we combine the NRTI’s Didanosine (ddl)and Stavudine (d4T)?

 

-NRTI’s:; Why shouldn’t Lamivudine (3TC) + Emtricitabine (FTC) be used together?

-High risk of toxicities (esp peripheral neuropathy)

 

-They have similiar resistence profiles and therefore have little additive benefit when used together.

What Opportunistic HIV infection am I:?

Fever
Exertional dyspnea
Dry cough
O2 saturation
LDH> 500 mg/dL
X-ray showing symmetrical infiltrates
CD4 count <200 mm3

-Pneumocystis jiroveci pneumonia (PCP)

 

Treatment for PCP?

 

-Adjunct if PO2 levels are below 70mmHg?

-Can Clindamycin also be used as alternative?

-If Atovaquone is used as alternative…how often is it dosed?

-TMP 15mg/kg/day +SMZ 75mg/kg/day po or IV 3-4 divided doses

-Prednisone

Yes if used with primaquin...Clindamycin 600 mg IV q8h or 300-450mg po q6h + primaquine 30 mg base po qd
– 750mg PO with meal bid

When do you prophylact for PCP?

 

-What should you use?

 

-When do you stop?

-When CD4 is less than 200

 

-Bactrim DS…DAILY (3x weekly show to be ineffective)

 

-When CD4 back over 200 for THREE MONTHS

Which HIV Opp Dz am I?:
Fever
Night sweats
Weight loss
Diarrhea
Abdominal pain
Positive AFB from blood, liver, bone marrow or lymph nodes (can take 7-21 days)
CD4 cell count less than 50/mm3

 

 

 

Mycobacterium avium complex (MAC)

Tx for MAC?

 

-Stop Tx when?

Clarithromycin 500 mg po bid + ethambutol 15 mg/kg/d po ± rifabutin 300 mg po qd

 

-Stop when CD4 count >100/mm3 for 6 months and received 12 months of treatment and asymptomatic

Primary Prophylaxis for MAC is what?

 

-Stop when?

Azithromycin 1,200 mg po once per week

 

-Can stop when CD4 cells are greater than 100/mm3 for 3 months

Which HIV Opp Inf am I:
Focal neurologic defect
Headache
Fever
+ anti-T. gondii IgG (blood and/or CSF)
2 or more ring enhancing lesions on MRI
CD4 cell count less than 100/mm3

 

 

-Toxoplasma gondii encephalitis

Toxo gondi encephalitis Tx: Preferred regimen: treat for at least __ weeks
_______ 200 mg loading dose, then 50-75 mg po qd + ______ 10-20 mg po qd + ________ 1-1.5 g po QID

-6 weeks

-Pyrimethamine, leucovorin, sulfadiazine

Which HIV Opp Inf am I:?

Symptoms and Diagnosis
Fever
Headache
+ cryptococcal antigen in CSF +/- blood
CSF usually shows ↑ protein and mononuclear pleocytosis
Can have cryptococcal infections at other sites (skin, lung)
CD4 cell count less than 100/mm3

 

 

 

Cryptococcal meningitis

Tx for Crypto meng?

 

-Prophylactic Tx for Crypto meng is?

 

-Stop when?

Ampho B 0.7-1.0 mg/kg/d IV ± flucytosine 100 mg/kg/d po 14 days then fluconazole 200 mg po bid x 8 weeks

 

Fluconazole 200 mg daily

-Discontinue secondary prophylaxis when CD4 cells are greater than 100-200/mm3 for 6 months, initial therapy is completed, and
patient is asymptomatic

WHich HIV Opp Inf am I?:

Fever
Weight loss
Fatigue
Often with lung, marrow, GI tract, +/-CNS involvement
H. capsulatum can be detected in urine, blood, respiratory tract secretions, marrow, CSF or focal lesions
CD4 cell count <100/mm3

 

 

 

Histoplasmosis (Histo)

Histo Tx?

 

-Prophylaxis?

 

-Stop when?

 

 

-Preferred regimens:
Ampho B 0.7-1.0 mg/kg/d IV 3-14 days THEN
Itraconazole 200 mg po bid x 12 weeks

 

itraconazole 200 mg po daily

 

-Discontinue after
12 months if CD4 >150 mm/3,
on ART for greater than 6 months and
urine and serum antigen is less than 4.1 units.

-Histo: What is a key consideration when deciding whether or not to prophylax for someone with a CD4 count below 100

 

-Where are CMV infections CD4 counts usually below?

-Are you in an Endemic area (Southeast/Miss River basin)

 

-50

Decreased visual acuity (floaters, field defects, flashes of light)
Funduscopic exam:
 perivascual yellow-white retinal infiltrates +/-
intraretinal hemorrhage (cottage cheese and ketchup)
Extraocular CMV:
esophagitis
colitis
pneumonia

 

 

 

CMV

 

 

-What is main thing to consider when treating CMV?

 

-Which group gets what?

-Vision-threatening or not.

Vision threating lesion:
Intraocular ganciclovir implant every 6-8 months + valganciclovir 900 mg bid x 14-21 days, then 900 mg daily
Peripheral lesions:
Valganciclovir 900 mg bid x 14-21 days, then 900 mg daily

T/F…Live-Attenuated Vaccines are usually effective with one dose

 

-T/F…Inactivated vacciens cause fewer site reactions and require only 1 dose?

-True *except those administered orally (to name some live attenuateds…Yellow Fever, Nasal Flu mist, Zoster, and MMR)

 

-False, generally 3-5 doses are required

Polysacchararides are teh preferred Vaccine for those under 2 yo?
-Less effective for this age group (ex. pneumonococcal, meningicoccal, Salmonella Typhi, and HIb) (IT IS IMPORTANT TO NOTE THAT SOME ARE STILL GIVEN THIS WAY though usually conjugated (examples HiB, mening, pneumococcal)
What is this describing?: Additional chemical in vaccine that increased the immunogenicity of the antigen
Increased antibody production
Increases response in poor responders
Allows for lower doses
Aluminum salts were introduced in 1926

 

 

-Vaccine Adjuvants (Hib, HPV, PCV7, DTap, and DT all use them)

-How long should a SubQ needle be?

-Where should an IM injection be given on an infant?

 

-IM needle lengths depend on?

-5/8 of an inch (inj at 45 degree angle)

-Thigh Muscle (Quad area)…Adults get Deltoid of course

Age group (Newborn:5/8 inch
Infant: 1 inch
Older Children: 5/8* to 1¼inch
Adolescent/adult: 1 to 1½ inch

 

When are DTaP boosters to be given?

-What does DTaP vaccine cover?

-Which is adult strength ‘D’ or ‘d’

-every 10 years

Diptheria toxin generally given in combination with tetanus toxoid AND acellular pertussis vaccine [DTaP]

-‘d’

For those with recent traumatic wounds how do we help them with passive immuninity to Tetanus?

 

-For which age group is the HIb Vaccine reccommended?

 

-What type of vaccine is it and what is the most common adverse rxn?

-T Ig or Tetanus Immunoglobulin

 

-Those under 5 yo (natural immunity develops from thence on)

 

– IM conjugate vaccine… Erythema (25%),

Which Flu virus (A or B) is more prone to mutation?

 

-Optimal time for Flu vaccine is?

 

-What age group can have Live Attenuated Flu vaccine?

-A

 

-October – mid November

 

5-49 (those 5-8 need split doses)

What does this group of pts represent:

Patients >50
Nursing home residents
Adults/children with CV or pulmonary dz
Adults/children with chronic dz/immunsupp
Children/teens receiving aspirin therapy
Pregnant women

Flu vaccine (Very high risk populations…they definately need the vaccine)
Heptavelent vaccine, contains conjugated capsular polysaccharide of 7 serotypes
Administration:  IM
Indicated for children <2
Adverse effects:  generally mild, injection site reactions and fever

 

 

 

Pneumonococcal Conjugated Polysaccharide Vaccine

-Which Pneumonococcal vaccine covers 23 serotypes of S. pneumo and is recommended for those over 2yo.

 

-Where should Rabies Ig be administered post exposure?

 

-What allergy might Rabies vaccine trigger?

-Unconjugated Pneumonococcal Polysacc Vaccine.

 

-Around potential infiltrated wound (DONE IM…never IV)

 

-Thimerosal

-Which rotavirus vaccine provides teh most protection (against the most Rota strains)

 

-What allergy shouldn’t be given Rubella vaccine

-Rotateq; (live, oral, pentavalent vaccine)…

;

-Neomycin allergic people

WHo better seroconverts to Varicella vaccine (adults or children)?

;

-How must this vaccine be stored?

;

-Post-exposure prophylaxis indicated?

;

-What allergy is contraindicated?

-Single dose results in 94% seroconversion in children, but only 80% in adults

;

-Frozen

;

-Yes 3-5 days Post-Exp

;

-Neomycin

When must Varicella Ig be administered Post-Exp?

;

-HPV vaccine: ACIP recommends routine vaccination of females __-__ years of age with __ doses of quadrivalent HPV vaccine

;

-Cancerous strains?

-within 48 hours (may only attenuate infection)

;

-11-12 yo with 3 doses (Vaccination is recommended for females 13-26 years of age who have not been previously vaccinated)

-16 and 18

What preservative is possibly linked to Autism and contains 50% mercury?

;

-What is the reporting site should a pt of yours experience a new adverse event due to vaccination?

;

-What is imp to document in these events?

;

-Thimersol (DD, TT, Td, and Influ all can have this)

;

-VAERS ; Vaccine Adverse Event Reporting System

;

-Lot number of the injection

x

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