Term
inhibits penetration of RNA viral particles into the host cell
inhibits early stages of viral replication by blocking the uncoating of the viral genome and the transfer of nucleic acid into the host cell.
resistance develops within days of treatment |
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Definition
| MOA of amantadine and rimantadine |
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Term
rapidly and completely absorbed from GI tract
crosses the BBB and it is distributed in saliva, nasal secretions, and breast milk
no evidence of metabolism
excretion: unaltered drug via glomerular filtration and tubular secretion |
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Definition
| ADME of amantadine and rimantadine |
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Term
CNS (at therapeutic levels): minor and resolve despite continuation of therapy (dizziness, nervousness, difficulty in concentrating, and insomnia)
more serious CNS effects in patients with decreased renal function and high doses (seizures, delirium)
tremors/parkinsonian patients
depression
orthostatic hypotension
psychosis
urinary retention
congestive heart failure
GI: nausea, diarrhea, constipation, and anorexia |
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Definition
| ADRs of amantadine and rimantadine |
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Term
antihistamines or anticholinergic drugs: CNS adverse effects
drugs that undergo active tubular secretion may alter amantadine excretion
sulfonamide/trimethoprim: increase amantadine toxicity |
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Definition
| drug interactions of amantadine and rimantadine |
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Term
| mutations cause antigenic changes on HG and NA |
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Definition
| what is the main determinant of antigenicity and host immunity? |
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Term
removes sialic acid from surface glycoproteins during viral maturation
required to produce infectious particles
lowers viscosity of mucin layer of the respiratory tract |
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Definition
| what is the function of neuraminidase? |
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Term
zanamivir and oseltamivir
NA-catalyzed removal of sialic acid residues from a glycoprotein
the cleavage of sialic bonds facilitates the spread of viruses by enhancing adsorption to cell surface receptors -> increases the infective level of the virus
in the absence of sialic acid cleavage, viral aggregation or inappropriate binding to hemagglutinin occurs -> no spread of the virus
[image] |
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Definition
| MOA of neuraminidase inhibitors |
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Term
similar structure to sialic acid
zanamivir:
[image]
guanidine group is believed to increase binding affinity to NA
effective via the nasal, INTRAPERITONEAL AND IV ROUTES (BUT NOT CLINICALLY USED); inactive via oral administration
oseltamivir:
[image]
more binding sites to NA
[image]
top is normal function, bottom is action of NAI
NAI will get in the active site of NA, stabilize the enzyme by forming a complex and NA will not be able to break the HG/sialic acid bond, virus cannot escape from the host cell
TRANSITION STATE BASED INHIBITION - zanamivir and oseltamivir resemble the transition state of sialic acid, but have higher binding affinities to NA than sialic acid
resistance is due to mutation/changes in the enzyme binding site |
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Definition
| MOA of zanamivir and oseltamivir |
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Term
PRODRUG
metabolism:
[image]
active metabolite is the free acid, other metabolites are a hydroxylation of the side chain
absorption: oral and rapidly absorbed and cleaved by esterases in GI tract and liver - bioavailability 80%
distribution: well distributed (volume of distribution = extracellular water)
excretion: prodrug and metabolite eliminated in urine |
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Definition
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Term
low (<5%) oral bioavailability (oral inhalation or dry powder)
after inhalation: 15% lower RT, 80% oropharnyx, overall bioavailability = 20%
90% eliminated in the urine, no recognized metabolites |
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Definition
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Term
nausea, abdominal discomfort, vomiting
GI complaints resolve within 1-2 days with continuing therapy
headache
no clinically significant drug interactions |
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Definition
|
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Term
well tolerated in ambulatory patients
breezing and bronchospasm observed in influenza infected patients
not recommended for treatment of patients with underlying airway disease
no drug interactions reported |
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Definition
|
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Term
5 membered ring instead of 6 membered ring
addition of both features of oselamivir and zanamivir: guanidine group and lipophilic side chain)
peramivir has more binding sites than oseltamivir and zanamivir = increased binding affinity |
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Definition
structural features, similarities/differences between peramivir and other NAIs?
[image]
[image] |
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Term
emergency use authorized by FDA
Only IV - beneficial b/c IV will work faster
not metabolized
renally eliminated
no pediatric information available |
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Definition
|
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Term
| Mycobacterium avium-intracellulary Complex (MAC) |
|
Definition
| what is the most common opportunistic bacteria in AIDS patients? |
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Term
found in habitats such as water and soil
few are INTRACELLULAR PATHOGENS of humans and animals
facultative INTRACILLULAR PATHOGENS usually infecting MONONUCLEAR PHAGOCYTES (macrophages)
SLOW GROWING with a generation time of 12-18 hours (20-30 minutes for E. coli)
ACID-FAST BACILLI (AFB): staining used instead of gram staining
[image]
HYDROPHOBIC with a high lipid content in the cell wall
unique cell envelope: mycolic acids and arabinogalactan bridges/linkages = virulence factors
peptidoglycan layer - much like gram + (doesn't have an outer cell wall like gram -)
cytoplasmic membrane - mannophosphoinositide = virulence factor
cell wall is unique in structure and complexity
suggested to be responsible for mycobacterium: pathogenicity or virulence, multiple drug resistance, cell permeability, immunoreactivity, inhibition of antigen responsiveness, disease persistence and recrudescence (a new outbreak after a period of abatement or inactivity) |
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Definition
| characteristics of mycobacteria |
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Term
Mycobacterium tuberculosis - pulmonary and extrapulmonary TB
Mycobacterium kansaii - non-tuberculosis Mycobacterium - pulmonary infections
Mycobacterium avium - pneumonia, skin, endophthalmitis
Mycobacterium fortuitum - pulmonary infections
Mycobacterium marinum - skin and soft tissue infections |
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Definition
| mycobacterial pathogens and the diseases they cause |
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Term
isoniazid
rifampin
rifapentin
streptomycin
ethambutol
pyrazinamide |
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Definition
| 1st line antimycobacterial drugs |
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|
Term
specific for mycobacteria
BACTERICIDAL against replicating bacilli
BACTERIOSTATIC (at best) against dormant or semidormant populations
effective against intracellular and extracellular abcteria
after treatment mycobacteria loses its acid fastness -> meaning isoniazid interferes with cell wall development
ISONIAZIDE IS A PRODRUG that must be activated by a bacterial enzyme that in M. tuberculosis is called KatG (catalase peroxidase enzyme)
KatG couples the isonicotinic acid with NADH, this complex binds tightly to InhA blocking the action of fatty acid synthase
this process inhibits the synthesis of mycolic acid (required for the mycobacterial cell wall) |
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Definition
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Term
administration: oral and IM
absorption: rapid from the GI tract (better with empty stomach)
plasma concentrations (same for oral and IM)
does not bind to plasma protein - distribution throughout body water
CSF - substantial levels are achieved
passes through placenta and breast milk
metabolized by acetylation in the liver
[image]
isoniazid and metabolites are excreted in the urine
the metabolites are less toxic and more rapidly excreted
no effect on patients with liver disease |
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Definition
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|
Term
neurotoxicity:
peripheral neuritis (numbness and tingling in lower extremities, sometimes parestesias, muscle ache)
CNS side effects (excitability, from irritability to seizures)
hepatotoxicity: subclinical hepatic injury, hepatitis
allergic reactions: fever, rash
drug interactions: alcohol and aluminum-containing antacids |
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Definition
| ADRs and drug interactions of isoniazid |
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Term
very active against mycobacteria, gram +, and Neisseria species
low penetration into gram -
active against SLOW GROWING AND SLOW METABOLIZING, NON GROWING bacilli
inhibition of RNA synthesis: interacts directly with DNA-dependent RNA polymerase (DDRP)
non-covalent but tight binding - has no effect on transcription initiation, it inhibits elongation of full length transcripts: inhibits ELONGATION, protein synthesis must have started in order for rifampin to bind to the active site
more active than ethambutol and as effective as isoniazid
used in combination to prevent resistance |
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Definition
| MOA of rifampin and rifapentine |
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Term
absorption: decrease when taken right after a meal or with p-aminosalicylate (PAS), well absorbed from GI tract
Distribution: distributes widely in tissues and fluids, it can penetrate into leukocytes and kill intracellular bacteria, penetrates into nerves, about 85% bound to plasma proteins
metabolized by the liver (deacetylation)
excreted in the bile - drug and metabolites |
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Definition
| ADME of rifampin and rifapentine |
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Term
direct toxicity:
anorexia, nausea, mild abdominal discomfort, diarrhea
headache, drowsiness, ataxia, dizziness, fatigue
MAY GIVE A RED-ORANGE COLOR TO URINE, FECES, SALIVA, SWEAT, AND TEARS
hepatitis (especially in alcoholics) - transamidase levels must be monitored
immune mediated toxicities:
a flu-like syndrome (fever, chills, muscle-ache, headache, dizziness)
commonly during the third to sixth month of therapy
dose related
common in the intermittent or interrupted administration (bi-weekly or once weekly) |
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Definition
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Term
absorption inhibited by p-aminosalicylate
hyperglycemia has been reported (increase glucose intestinal absorption)
reduces serum half life of: coumarin anticoagulants, quinidine, narcotics, glucocorticoids, thyroxin, dapsone, oral contraceptives
with drugs used for the treatment of HIV: antivirals, antiinfectives, immunosuppresants, psychotropic drugs, nifedipine Ca channel blocker, sedatives |
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Definition
| drug interactions of rifampin |
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Term
good absorption after oral administration
considered more active than rifampin
induces hepatic CYP 3A4 and CYP 2C8/9
oral administration during intense phase of chemotherapy
lower relapses observed |
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Definition
|
|
Term
(+) enantiomer 200-500 times more active
BACTERIOSTATIC
active only against mycobacteria
Mycobacterium avium complex (MAC) is resistant
active against DIVIDING BACTERIA
enters bacteria through passive diffusion
inhibits the incorporation of mycolic acids into the cell wall: ethambutol mimics the building blocks of mycobacterial cell walls (mycolic acid), ethambutol is incorporated into the cell wall making it weak
given in combination so other drugs can get through the weak cell wall and exert their effects |
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Definition
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Term
absorbed rapidly and extensively from the GI
distribution: 20-30% plasma protein binding, enters the CSF, pulmonary parenchyma and caseous tuberculosis lesions, passes across placenta
metabolized by the liver (by alcohol dehydrogenase to an aldehyde)
excreted by the kidneys (drug and metabolites) |
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Definition
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|
Term
absorbed rapidly and extensively from the GI
distribution: 20-30% plasma protein binding, enters the CSF, pulmonary parenchyma and caseous tuberculosis lesions, passes across placenta
metabolized by the liver (by alcohol dehydrogenase to an aldehyde)
excreted by the kidneys (drug and metabolites) |
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Definition
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Term
generally well tolerated
occasionally mild GI upset, abdominal pain, allergic reactions (dermatitis, pruritis, anaphylaxis)
retrobulbar neuritis (dose related)
peripheral neuropathy |
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Definition
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Term
VERY ACTIVE WHEN THE MEDIUM HAS AN ACIDIC PH - ionized form is active form
thought to be a prodrug - pyrazinamide is converted to pyrazinoic acid (active form) through pyrazinamidase (endogenous mycobacterial enzyme)
[image]
changes in the pH may be the killing effect of pyrazinamide: changes the pH inside the mycobacterium, killing it |
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Definition
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|
Term
absorption: GI tract
Distribution: wide and penetrates into cells
Metabolism: hydrolysis to pyrazinoic acid which is oxidized by xanthine
excreted in the urine |
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Definition
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Term
flushing (but no hypersensitivity)
mild nausea and anorexia
renal failure: hyperuricemia (inhibition of uric acid excretion)
liver injury: dose related hepatotoxicity (transaminase levels should be monitored)
arthralgia |
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Definition
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Term
aminoglycoside
most of the mycobacterium are sensitive
BACTERICIDAL
poor penetration into cells: diffusion through the outer membrane and electron dependent process to penetrate the cell membrane
protein synthesis inhibitor that binds to the 30s ribosomal subunit |
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Definition
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Term
aminoglycoside
most of the mycobacterium are sensitive
BACTERICIDAL
poor penetration into cells: diffusion through the outer membrane and electron dependent process to penetrate the cell membrane
protein synthesis inhibitor that binds to the 30s ribosomal subunit |
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Definition
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|
Term
kanamycin
ethionamide
p-aminosalicylic acid
capreomycin |
|
Definition
| second line agents for TB |
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Term
effective against inta and extra cellular bacilli
similar MOA as isoniazid but no cross resistance with isoniazid has been reported
inhibits the synthesis of mycolic acid (cell wall building block) |
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Definition
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Term
oral administration
widely distributed
extensively metabolized by sulfoxidation, N-methylation, and deamination
[image]
metabolites excreted in the urine |
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Definition
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|
Term
inhibitor of cell wall synthesis
acts in the 1ST STEP OF CELL WALL SYNTHESIS, will replace the D-Ala-D-Ala terminal of building block |
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Definition
|
|
Term
oral administration
widely distributed in tissues and fluids
excreted in urine
neurotoxic |
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Definition
| ADME and ADR of cycloserine |
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Term
folic acid synthesis inhibitor
BACTERIOSTATIC |
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Definition
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|
Term
well absorbed (GI tract)
widely distributed, penetrates caseous tissue (damaged or necrotic tissue; cheeselike), low CSF levels
nausea, vomiting, diarrhea, epigastric distress |
|
Definition
| ADME and ADRs of p-aminosalicylate |
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Term
cyclic peptides
strongly basic antibiotic
inhibits protein chain elongation = protein synthesis inhibitor
IM administration
nephrotoxic and ototoxic
[image] |
|
Definition
| MOA and ADRs of capreomycin |
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