ANTIBACTERIAL AND ANTI-INFECTIVES (PART 2) Flashcards
etiologic agent of pulmonary TB
mycobacterium tuberculosis
most common site for the development of TB is the ___ (85% of patients)
lungs
most infectious TB patients
those with:
- cavitary pulmonary disease
- laryngeal TB
typical TB lesion
epithelioid granuloma with central caseastion necrosis
a cough of ___ weeks or more is already suspicious for PTB
2 weeks
symptoms of TB (along with cough)
- night sweats
- weight loss
- anorexia
- unexplained fever and chills
- chest pain
- fatigue
- body malaise
true or false: absence of fever excludes TB
false
true or false: physical findings are of little utility of PTB
true
what are the drugs used for TB?
RIPES
Rifampicin (R)
Isoniazid (H/INH)
Pyrazinamide (Z)
Ethambutol (E)
Streptomycin (S)
usual dose of isoniazid (H/INH)
5 mg/kg max 300 mg
usual dose of rifampicin (R)
10 mg/kg max 600 mg
usual dose of of pyrazinamide (Z)
25 mg/kg max 2 g (2000 mg)
usual dose of ethambutol (E)
15 mg/kg
usual dose of streptomycin (S)
15 mg/kg max 1 g (1000 mg)
- inhibits FATTY acid synthase and MYCOLIC acid synthesis
- excellent BACTERICIDAL activity against both intracellular and extracellular actively dividing MTB
- BACTERIOSTATIC against slowly dividing organisms
isoniazid (H/INH)
- binds to and inhibits mycobacterial DNA-dependent RNA polymerase = blocking RNA synthesis
- both intracellular and extracellular BACTERICIDAL activity, both in dividing and non-dividing MTB
rifampicin (R)
- has sterilizing activity
- most active antimycobacterial agents available and therefore cornerstone of FIRST-LINE TB treatment
rifampicin (R)
- exact mechanism is unclear but FATTY acid synthetase-I may be the primary target
- more active against SLOWLY replicating organisms than against actively replicating organisms
pyrazinamide (Z)
- active only in ACIDIC environment (pH < 6)
- found within phagocytes or granulomas
pyrazinamide (Z)
- inhibits ARABINOSYLTRANSFERASES involved in cell wall synthesis
- inhibits the formation of ARABINOGALACTAN and LIPOARABINOMANNAN
ethambutol (E)
- BACTERIOSTATIC antimycobacterial agents which provides synergy with other drugs
- LEAST potent against MTB
ethambutol (E)
- inhibits protein synthesis by binding at 30s mycobacterial ribosome
- BACTERICIDAL against dividing MTB but has only low-level early bactericidal activity
streptomycin (S)
what category?
- new PTB (bacteriologically or clinically diagnosed)
- new extra-PTB (bacteriologically or clinically diagnosed), except CNS/bones or joints
category I
what category?
- new extra-PTB (CNS/bones or joints)
category Ia
what category?
- pulmonary or E-PTB, previously treated drug-susceptible TB (bacteriologically or clinically diagnosed), except CNS/bones or joints
category II
what category?
- relapse
- treatment after failure
- treatment after lost to follow-up (TALF)
- previous treatment outcome unknown (PTOU)
category II
what category?
- E-PTB (CNS/bones or joints), previously treated, drug susceptible TB (bacteriologically or clinically diagnosed)
category IIa
what category?
- standard regimen drug-resistant (SRDR): rifampicin resistant TB or multi-drug resistant TB
- XDR TB regimen: extensively drug-resistant TB
drug resistant TB
alternative TB treatment regimen (initial and continuation) for:
category I
initial: 2 HRZE
cont: 4 HR / 4 HZE
alternative TB treatment regimen (initial and continuation) for:
category Ia
initial: 2 HRZE
cont: 10 HR
alternative TB treatment regimen (initial and continuation) for:
category II
initial: 2 HRZES and 1 HRZE
cont: 5 HRE
alternative TB treatment regimen (initial and continuation) for:
category IIa
initial: 2 HRZES and 1 HRZE
cont: 9 HRE
alternative TB treatment regimen (initial and continuation) for:
drug resistant TB
individualized based on prev. treatment and drug sensitivity
management for RIFAMPICIN caused GI intolerance
give medication at bed time
management for RIFAMPICIN caused orange-red urine
reassure patient
management for RIFAMPICIN caused flu-like symptoms
give anti-pyretics
management for PYRAZINAMIDE caused arthralgia due to hyperuricemia
give aspirin or NSAID
management for IZONIAZID caused burning sensation in feet (peripheral neuropathy)
give pyridoxine (vit b6) 100-200 mg daily; 10 mg daily for prevention
management for STREPTOMYCIN caused pain at injection site
warm compress
management for ANY DRUG caused mild skin reactions
give anti-histamines
which drug causes this MAJOR side effect?
- severe skin rash (hypersensitivity)
- jaundice due to hepatitis
any drug
which drug causes this MAJOR side effect?
- impairment for visual acuity and color vision due to optic neuritis
ethambutol (E)
which drug causes this MAJOR side effect?
- hearing impairment, tinnitus, and dizziness due to damage of CN VIII
streptomycin (S)
which drug causes this MAJOR side effect?
- oliguria or albuminuria due to renal disorder
streptomycin (S) and rifampicin (R)
which drug causes this MAJOR side effect?
- psychosis and convulsion
isoniazid (H/INH)
which drug causes this MAJOR side effect?
- thrombocytopenia, anemia, and shock
rifampicin (R)
what are the drugs that affect fungal membranes?
- amphotericin B
- azoles
what drugs are under azoles?
- itraconazole
- ketoconazole
- miconazole
- fluconazole
- clotrimazole
- voriconazole
- binds to ERGOSTEROL, a major components of fungal cell membranes
- forms amphotericin pores that alter membrane stability and allow LEAKAGE of cellular contents
amphotericin B
- indications: topical infections, initial treatment for severe fungal infections (ex: candida albicans, histoplasma capsulatum, cryptococcus neoformans)
- AE: chills, fever, impaired renal functions
amphotericin B
- inhibit the cytochrome p450 mediated sterol demethylation of lanosterols to ergosterol in fungal membranes
- broad spectrum antifungals
azoles
- replaced ketoconazole for the treatment of all mycoses
- used topically for DERMATOPHYTE INFECTIONS and mucotaneous candidiasis or as shampoo for SEBORRHEIC dermatitis
itraconazole
- drug of choice for DISSEMINATED BLASTOMYCOSIS
- inhibition of cytochrome p450 metabolism (CYP3A4), increases or decreases metabolism of many drugs leading to toxicity
- SE: gastric upset, itching, rashes, headache
itraconazole
- used of topical application
- used in DERMATOPHYTE infections (tinea pedis, ringworm, and cutaneous and vulvovaginal cadidiasis)
miconazole and clotrimazole
used topically for CANDIDA infections of the skin, mucous membranes and intestinal tract
nystatin
- useful for OROPHARYNGEAL and SYSTEMIC CANDIDIASIS
- penetrates CSF
fluconazole
- DOC for crytptococcal meningitis and disseminated histoplamosis
- inhibits CYP3A4 and CYP2C9
- AE: nausea, vomiting, diarrhea, and reversible alopecia
fluconazole
- actively transported into fungal cells and is converted to 5-fluorouracil and subsequently to 5-fluorodeoxyuridylic acid
- inhibits THYMIDYLATE synthetase and thus pyrimidine and nucleic acid synthesis
flucytosine
- resistance develops rapidly, rarely used as a single drug but often used in COMBINATION with other antifungals
- relatively non toxic
- AE: depression of bone marrow function
flucytosine
- infecting organism of amebiasis
- ingested in cyst form
- divides in the colon
- can invade the intestinal wall to cause severe dysentery
entamoeba histolytica
- used for INTESTINAL AMEBIASIS as for AMEBIC LIVER ABSCESSES
- active agents for giardia intestinalis and t. vaginalis
metronidazole and tindazole
- show activity against many anaerobic bacteria
- AE: disulfram-like reactions, teratogenic effects
metronidazole and tindazole
most important parasitic disease in humans
malaria
in humans the ___ cycle is responsible for malaria
erythrocytic cycle
malaria is a protozoan disease caused by 4 species of ___
plasmodium
malaria is transmitted by the bite of infected ___
anopheles flavirostris
what malaria drug regimen?
- first line treatment in probable and confirmed falciparum malaria that is not severe
CQ + SP
chloroquine + sulfadoxine/pyrimethamine
what malaria drug regimen?
- second line drug for cases which did not respond to adequate CP + SP
- not reco for pregnant and children < 8
A-L
artemether-lumefantine
what malaria drug regimen?
- third line drug for those who did not respond to second line
- DOC for severe malaria
Q+TD
quinine + tetracycline/doxycycline
(Q + clindamycin for pregnant and children)
what malaria drug regimen?
- given as single dose to confirmed p. falciparum to prevent transmission
- given for 14 days to confirmed p. vivax to prevent relapse
- only drug that can eradicate extrahepatic stages of parasite
primaquine
DOC for p. vivax cases
chloroquine
malarial drug side effects:
- megaloblastic anemia
- pancytopenia
- pulmonary infiltration
pyrimethamine
malarial drug side effects:
- anaphylaxis
- urticaria
- fever
artemether
malarial drug side effects:
- cinchonism
- tinnitus
- high-tone hearing loss
- hypoglycemia
- bitter taste
quinine
malarial drug side effects:
- massive hemolysis in G6PD deficiency
primaquine
malarial drug side effects:
- nausea
- dysphoria
- pruritus
- retinopathy (>100 g)
chloroquine
drugs used for severe falciparum malaria
AAQQ
- artesunate
- artemether
- quinine dihydrochloride
- quinidine
drugs for malaria prophylaxis
- doxycycline
- primaquine
- atovaquine/proguanil
- chloroquine
- mefloquine (pregnant)
when using malaria prophylaxis, it should be started ___ before potential exposure and for ___ after leaving the area
2 weeks,
8 weeks
- active against NEMATODE (ROUNDWORM) infections
- bind with high affinity to parasite free B-TUBULIN to inhibit polymerization and microtubule assembly
albendazole and mebendazole
- irreversibly inhibit glucose uptake by nematodes = glycogen depletion and decreased ATP production
- immobilizes the intestinal parasite, then cleared from GI tract
albendazole and mebendazole
- DOC for cysticercosis and cystic hydatid disease
- AE: GI distress during short term therapy
- potentially teratogenic
albendazole
- active against cestode (tapeworm) and trematode (fluke) infections
- causes PARALYSIS of the worm due to increased cell membrane permeability of calcium
praziquantel
- most effective drug against all types of fluke infections (schisto, parago)
- AE: fever and rashes, contraindicated in ocular cystercosis
praziquantel
- active againts cestode (tapeworm) and trematode (fluke) infections
- inhibits parasite RESPIRATION
- alternative for fasciola hepatica and as an alternative to praziquantel for acute pulmonary paragonimiasis
bithionol
what are the antiherpes virus drugs
- acyclovir
- penciclovir and docosanol
- ganciclovir
- foscarnet
- PURINE analog, required viral THYMIDINE KINASE to inhibit the activity of viral DNA polymerase
- does not eradicate latent virus
acyclovir
- used as TOPICAL cream to treat herpes
- D___ prevents fusion with the HSV envelope with cell membranes, thereby inhibiting viral penetration
penciclovir and docosanol
DEOXYGUANOSINE analog that inhibits replication of CMV
ganciclovir
inhibits viral DNA and RNA polymerase and HIV reverse transcriptase
foscarnet
what are the anti-influenza agents?
- amantadine and rimantadine
- zanamivir and oseltamivir
interact with the M2 protein of the proton channel of the virus to inhibit the uncoating and replication of the viral RNA in infected cells
amantadine and rimantadine
- used to treat ORTEHOMYXOVIRUS (influenza A), administered within the first 48 hours of symptoms and as prophylaxis
- AE: mild CNA effects, GI dysfunctions, teratogenic effects
amantadine and rimantadine
- NEURAMINIDASE inhibitors
- treatment and prophylaxis of acute uncomplicated influenza infection (influenza A and B)
- AE: abd pain, GI dysfunctions (O), bronchospasm (Z)
zanamivir and oseltamivir
- acts by inhibiting HIV encoded RNA dependent DNA polymerase (reverse transcriptase)
- combination therapy with NRTI with drugs from the other classes of antiretroviral agents is most effective (reduced likelihood of resistance)
AE: metabolic acidosis, hepatic toxicity
antiretroviral drugs
examples of antiretroviral drugs
- zidovudine
- didanosine
- stavudine
- lamivudine
a medicine that reduces your chances of getting HIV from sex or injection drug use
PrEP (pre-exposure prophylaxis)
2 pills approved for use as PrEP
truvada and descovy
PrEP for people at risk through sex or injection drug use
truvada
PrEP for people at risk through sex, not for people assigned female at birth who are at risk through receptive vaginal sex
descovy
the only shot approved for use as PrEP, for people at risk through sex who weight at least 77 pounds (35 kg)
apretude
use of antiretroviral drugs after a single high risk event to stop HIV seroconversion
PEP (post exposure prophylaxis)
PEP must be started as soon as ___ hours within a possible exposure
72 hours
covid 19 medication:
- adults, children > 12
- start ASAP, must begin wihtin 5 days of when symptoms start
- taken at home, PO
nirmatrelvir and ritonavir (paxlovid)
covid 19 medication:
- adults and children
- start ASP, must begin within 7 days of when symptoms start
- IV infusions at a facility for 3 days
remdesivir (veklury)
covid 19 medication:
- adults
- start ASAP, must begin within 5 days of when symptoms start
- taken at home, PO
molnupiravir (lagevrio)