exam 3 Flashcards
echinocandins
candida
aspergillus
polyenes
candida
aspergillus
histoplasma
blastomyces
coccidioides
broadest!
Broadest spectrum of all antiFUNGAL drugs; rough side effects
polyenes
azoles
candida (most)
aspergillus (most)
some:
cryptococcus
histoplasma
blastomyces
flucytosine
candida
cryptococcus
antifungal target:
cell wall synthesis
echinocandins
“itching to cross the wall”
antifungal target:
cell membrane pores alteration
polyenes
“Pores=Polyenes”
antifungal target:
Ergosterol (Cell Membrane) Synthesis
azoles
“azOLes = ergosterOL”
antifungal target:
Nucleic Acid Synthesis
5-flucytosine
“cytosine”
MOA
INHIBIT (1, 3) β-D-glucan synthase, which synthesizes B (1, 3) glucan fibrils, which are essential to the _____ _____
echinocandins
cell wall
__________fungin
echinocandins
what is the biggest disadvantage of echinocandins
IV administration only
MOA
Amphipathic compounds, bind to ergosterol in the cell membrane create pores, pores change the membrane permeability and allow increased leakage of intracellular components death of fungi occurs
polyenes
amphotericin B
nystatin
polyenes
Drug of choice for the treatment of life-threatening invasive/systemic fungal infections
NOT affected by renal or hepatic function!
amphotericin B
3 main adverse effects of amph B
infusion reaction
(cytokine =IgG); premedicate!
nephrotoxicity (permanent!)
anemia (reversible!)
antifungal
- Monitor kidney function, electrolytes, CBC
decreases K and mag
amph B
what 3 drugs are used to premedicate with amph B
tylonel
benadryl
hydrocortisone
lipid formulations
amph B
benefits and drawbacks
Slowly releases AmphB; reduced risk of nephrotoxicity
Reduced incidence of infusion reactions
20-50x more expensive*
2 examples of lipid form of amph B
abelcet (complex)
ambisome (vehicle/pod)
cmax is higher!
polyenes
antagonistic with _________*
azoles
“A=A”
Azoles eliminate ergosterol, but this is the target of polyenes (amph B)
polyenes
synergistic with _________ + _____________*
echinocandins
flucytosine
Inhibit fungal 14 a-demethylase (CYP450-CYP51) reduction in ergosterol levels cell membrane permeability issues
Levels of squalene and lanosterol go up increased toxicity
azoles
All systemic AZOLE antifungals are ____azoles; except for ketoconazole, which is an imidazole*
TRIazoles (3 nitrogens)
except for ketoconazole (2 nitrogens)
Fungistatic=low dose
fungicidal=high dose
azoles
which azole is oral only
itraconazole
which azole IS the only one that is RENALLY eliminated*
which 2 azoles have the vehicle (renal toxic)
fluconazole
posaconazole, voriconazole
which azole does NOT cause QT prolongation***
isavuconazole, “isabella”
which azole has significant safety concerns regarding ORAL tablets
Ketoconazole “Killer”
severe liver injuries
adrenal insufficiency
QT prolong
lots of drug-drug interactions
which drug means you should NOT give AZOLES
warfarin
which 2 azoles require acidity “take with a coke”
ITRAconazole
VORIconazole
“itra + vori are acidic hoes”
which azole is contraindicated in CHF
ITRAconazole
can cause photosensitivity and visual disturbances*
azole
VORIconazole
what part of the azole causes nephrotoxicity*
the VEHICLE it is in
cresemba is a prodrug that does NOT have this vehicle
- MOA
Fluorinated analog of the nucleobase cytosine
related to 5 FU (an anticancer drug); can impact both DNA and RNA synthesis; fungal cells have cytosine permease (an enzyme) that brings flucytosine (5-FC) into the cell gets converted to 5-FU (by cytosine deaminase) gets converted into nucleotides get incorporated into RNA and DNA
flucytosine
inhibits RNA/protein + DNA synthesis
which 2 enzymes are involved with flucytosine
permease: brings it into the cell
deaminase: converts to 5-FU
true or false
2 enzymes permease and deaminase make flucytosine SELECTIVE since they do not exist in humans
true
which antifungal is NEVER used alone
flucytosine
which antifungal class is the ONLY one that causes QT prolongation
azoles (triazoles)
true or false
all viruses depend on host to replicate
true
what is the ONLY antiVIRAL that is CIDAL*
hep C drugs
what type of ssRNA is similar to our RNA
positive ssRNA
where are most antiviral targets
nucleic acid replication
what does mimicking mean for antivirals*
Mimicking means you bypass the 1st step of phosphorylation (which is often rate limiting) you already start with a monophosphate
true or false
once a person is infected with HERPES, they are infected for life
true
patients with renal dysfunction (2)
decrease dose
extend dosing interval
MOA
o NucleoSIDE analog, inhibits viral DNA synthesis - blocks viral DNA polymerase
Activated by a viral kinase (the virus has their own kinase*)
o Only the infected cells will activate/phosphorylate the drug into triphosphate
acyclovir + ganciclovir
herpes
which antiVIRAL is good for solid organ transplant
HIV patients*
ganciclovir
o Inhibits spermatogenesis → USE CONTRACEPTION
o Bone marrow suppression
o Carcinogenic
o Teratogenic
ganciclovir
what are the 2 drugs that are good for CMV, HSV (herpes) RESISTANT antivirals
cidofovir (mimics monophosphate = bypasses 1st step of phosphorylation*)
foscarnet (keeps triphosphate from binding, NO phosphorylation)
what is the most common form of herpes resistance
mutations in viral kinases
what are the 2 newest herpes antivirals
letermovir (bone marrow transplant)
maribavir
Current treatments are NOT curative
Disease IS preventable with a vaccine
hep B
all HBV (hep B) antiviral agents inhibit HBV ________________
polymerase
Lactic acidosis, severe hepatomegaly
Can cause HIV resistance in patients with unrecognized or untreated HIV
hep B (HBV) antivirals
which HBV antiviral is
active against HIV, but is NOT approved to use with HIV*
adefovir
what 3 drugs can be used for HBV or HIV
tenofovir disoproxil
tenofovir alafenamide
epivir
what drug is the BEST for HIV or HBV
tenofovir ALAFENAMIDE
(less in the plasma, less nephrotoxicity/bone toxicity)
no vaccine
treatment can eliminate it
hep C
what is the most common genotype of hep C
1B
what is the direct acting antiviral targets (DAA) for
hep C HCV
antiviral
________buvir*
NS5B polymerase (blue) inhibitors
HCV hep C
“B= Buvir”
antiviral
__________asvir*
NS5A cofactor (orange) inhibitors
HCV hep C
“A= Asvir”
antiviral
__________previr*
NS3/4A protease (green) inhibitors
HCV hep C
“Previr=Protease”
true or false
NON-nucleoside (nucleotide) does NOT need to be phosphorylated
true
true or false
hep C drugs are often combined (hitting at 2 targets)
true
which drugs are
contraindicated with strong INDUCERS of Pgp/CYP3A4
means it will DECREASE levels
DAA (hep C)
antacids, H2, PPIs (absorption reduced)
amiodarone (bradycardia)
CYP3A4 inducers
DAA drugs (hep C)
what are the 4 main HIV drugs involved in blocking* 1) attachment
2) interaction
or
3) fusion
“entry inhibitors”
fostemsavir
maraviroc
ibalizumab
fuzeon
MOA
inhibit the reverse transcriptase inhibitor, preventing formation of DNA from HIV RNA
reverse transcriptase inhibitors
nucleoside/tide require _______________ (competitively inhibit RT)
NON-nucleoside/tide do NOT require _________________
(non-competitive binding to RT)
phosphorylation
Class Boxed Warning:
lactice acidosis with hepatomegaly with steatosis
NRTIs (nucleoside/tide RT inhibitors)
for HIV
hypersensitivity reactions, test for HLA-B1507
Abacavir (does NOT require renal dosing)
which HIV drug is good for labor/childbirth
Zidovudine
which 2 HIV classes have CYP450 interactions
NNRTIs (NON nucleoside/tide RT inhibitors)
protease inhibitors
MOA
Prevent the covalent insertion/integration of HIV + prevent formation of HIV provirus
integraase inhibitors
“____________tegravir”
Due to extensive first pass metabolism (and Pgp transport), administer with a PK Booster!
what are the 2 boosters* they INHIBIT CYP3A4, protect from metabolism
Protease inhibitors (PIs)
ritonavir
cobicstat
MOA
Competitively inhibit the cleavage of non-functional viral precursor proteins into functional proteins
protease inhibitors
antiviral
adverse effects include
insulin resistance
hyperlipidemia
protease inhibitors
what combos of drugs are used for pre-exposure prophylaxis for HIV
- Tenofovir alafenamide + emtricitabine (Descovy)
- Tenofovir disoproxil + emtricitabine (Truvada)
what are most common flu types
A, B
MOA
Blockage of the neuraminidase enzyme that normally cleaves the virus that is tethered to the host cell now the virus is PERMANENTLY tethered to the infected host cell
tamiflu, relenza,
rapivab (IV ONLY)
(flu)
inhibits endonuclease activity of RNA polymerase, prevents cap-snatching (normally, the flu virus “steals” the cap from our mRNA to replicate)
xofluza
which antifungal causes bone marrow suppression*
flucytosine
which antifungal binds to ergosterol
amph B (polyenes)
which antifungal reduces cell membrane integrity by blocking synthesis of ergosterol
azoles
which antifungals cause histamine reactions
echinocandins
which adjunctive measure is used to LESSEN nephrotoxicity for amph B
normal saline infusion (not benadryl!)
A patient in the ICU on IV fentanyl (CYP3A4) started on IV VORICONAZOLE***(inhibitor CYP3A4) should be monitored for:
resp depression and sedation
Which of the following are true regarding the azole antifungals? 3
hepatotoxic
teratogenic
affect metabolism of other drugs
Which PK booster has protease inhibitory activity
rotonivir
someone is infected with a HSV-2 strain that LACKS thymidine kinase activity and should be treated with
cidofovir
foscarnet
(herpes resistant drugs)
Which one of the following is an anti-HSV agent that is dependent on viral thymidine kinase phosphorylation
acyclovir
which herpes antiviral does NOT require phosphorylation in order to inhibit viral DNA sysnthesis
foscarnet
ganciclovir resistant CMV strain responds to cidofovir suggesting that ganciclovir resistance is LIKELY due to
mutation in KINASE
absorption of this antiviral is REDUCED with polvalent cations (chelation)
integrase inhibitors
Which anti-HIV drug class is associated with rashes
Non-nucleoside/tide reverse transcriptase inhibitors
___________irine
does NOT require phosphorylation
antiviral
NON-nucleotide/side RT inhibitors (NNRTIs)
ESTER-linked is
C=O with ?
O
“Queen Ester with Boobs”
AMIDE-linked is
C=O with ?
N
LA’s
metabolism: plasma esterases, shorter acting, less stable
ESTER-linked
LA’s
metabolism: P450 enzymes, longer acting, more stable
AMIDE-linked
LA’s
allergy more likely (PABA)
ESTER-linked
what type of subunit is involved in LA’s sodium channel
alpha subunit
(4 domains)
Voltage sensor component of the sodium channel
S4+ segment
When the S4+ Segment senses a voltage change, the formation of the ______ changes
pore
what part does the LA bind to
inactivation region (H/P)
protonation =
ionization (when it works on the sodium channel)
what is the only LA that does not have to be protonated to work
(does NOT have an amine group)
benzacaine
4 parts of the LA
aromatic ring
ester/amide “link”
hydrocarbon chain
amiNe group (ionizable region)
what is the most common aromatic ring
benzine (6 figure)
increasing the size of the ___ group will increase lipophilicity
R group
longer R group/longer chain means _______ potent
more potent!
true or false
the MORE acidic the pH, the LESS likely the LA will work (due to the HIGHER concentration of protons)
true
more likely to be ionized/protonated and be unable to cross the membrane
what are the 2 things that affect binding to sodium channel
pKa
pH
a ________ pKa results in FASTER onset of action
LOWER pKa
what does frequency dependence depend on
rate of dissociation
LAs prefer to target RAPIDLY depolarizing tissues
__________, ____________ drugs dissociate more rapidly
smaller, lipophilic
Overall Effectiveness of LAs
* Depends on:
(4)
o Hydrophobic/lipophilic character
o Ability to ionize
o Overall affinity (kd) for binding site
o Frequency of channel opening
how do lipid emulsion infusions work
lipophilic version of the LA will be trapped inside the lipid molecule the free plasma concentration begins to drop the plasma concentration goes down the drug leaves the neuron goes into the droplet metabolizes eliminated
EUTECTIC mixture of local anesthetic
___________ the melting point
lidocaine + prilocaine
LOWERS the melting point
what are the main receptors for
vestibular
M1!!
H1?
what are the main receptors for
CTZ
D2
5HT3
chemoreceptors
NK receptors?
what are the main receptors for
vomiting center
H1
M1
5HT3
what are the 2 types of drug that works centrally and peripherally for NAUSEA
5HT3 (zofran)
cannabinoids (agonists)
true or false
antihistamines work on the H1 + M1 receptors
true
antimuscarinic effects (dry mouth, urinary retention)
example of antimuscarinic motion sickness drugs
scopolamine
antihistamine as well:
antivert
dramamine
benadryl
which 5HT3 has the highest risk for QT prolongation
(dont give prophylactically)
dolasetron
what are the 3 drugs that are great for DELAYED emesis*
palonosetron
netupitant
akynzeo (combo of both!)
examples of NK1 antagonists (N/V)
fosaprepitant
aprepitant
netupitant*
cinvanti
akynzeo
P450 enzyme interactions
block D2 + M1 + H1
compazine
phenergen
reglan
olanzapine (antipsychotic)
amisulpride
EPS symptoms
which D2 antagonist is associated with QT prolongation
amisulpride (D2 + D3)
N/V
low level ____
moderate level ____
high level ____
2
3
4
what are considered N/V supplements
D2 receptor (phenergen, olanzapine)
benzos
what is a contraindication for laxatives
bowel obstruction
surfactant laxatives are stool ____________
softeners
docusate
what is the most abused class of laxatives
stimulants
what are the 3 antimotility/antisecretory agents for diarrhea
lomotil (diphenoxylate has abuse potential, so combined with atropine)
pepto bismol
imodium
what are good antimicrobial agents for diarrhea
fluoroquinolones (____floxacin)
azithromycin
parasites = flagyl
what drugs have very low systemic absorption
IBS drugs
which IBS drug is a sodium/hydrogen transport exchange inhibitor
IBS-Rella (ibsrella)
NHE3 inhibitor
- Used to “reset” microflora
o Activity against anaerobic and gram-negative bacteria, including c-diff
rifaximin
what 2 drugs for IBS have RESTRICTED use*
lotrenex (black box ischemic colitis)
zelnorm
disease
ANY portion of the GI tract
intermittent-transmural lesions
Crohn’s
disease
COLON/distal intestine
continuous-superficial lesions
ulcerative colitis
modified aspirin, cleaved into 2 parts
(sulfa + 5ASA)
___________zine
DEPENDENT ON ACTIVATION OFTEN
salicylates
_____ cells stimulate parietal (proton pump) cells
ECL cells
what are 4 ways to limit acid production
vagus nerve (Ach)
histamine
gastrin/CCK
blocking proton pump/parietal
pH of parietal cell =
pH of lumen =
pH of parietal cell = 7
pH of lumen = 2
why do PPIs have long lasting effects
irreversibly bind
MUST be systemically absorbed to work (enteric coating)
PPIs interact with CYP2C19, resulting in Plavix dose being __________***
reduced! risk of clotting/restenosis
which H2 is off the market for neuro issues
Zantac
Tagamat has sex issues
these drugs are good for aspiration prophylaxis
H2 antagonists
what is a drug-drug interaction with sucralfate (coating agent)
quinolone abx (ciprofloxacin)
pepto bismol can cause _____________ of the stool
darkening (benign)
what is a PGE-1 analog that is category x for pregnancy and helps prevent NSAID gastric ulcers*
misoprostol
what is the standard therapy for peptic ulcer disease*
clarithromycin
amoxicillin
if allergy: flagyl
PGP INHIBITOR! for pamora (movantik) opioid drugs would cause what
decrease in analgesia
or
a central effect
which drug exerts its pharmacological effects by directly inhibiting leukocyte extravascular migration
natalizumab
which drug exerts its pharmacological effect by directly promoting ion movement from the gastrointestinal epithelial cell into the lumen of the GI tract
lubiprostone
what drug is good for the proximal small intestine
mesalamine (5ASA)
what are the 2 M phase drugs**
vinca
taxanes
both involved in microtubules
neurotoxicity, NMB issues
true or false
doxorubicin is cell cycle NON specific
true
cell cycle NON specific are ______ dependent
dose
cell cycle specific are ______ dependent
schedule/time
chemo drugs
Vesicants
emetogenic
given on intermittent schedule (monitor for neutropenia)
alkylating agents
what chemo drugs have a highly toxic compound (acrolein) what drug should be given + what should be done**
mesna
+
hydration
nitrogen mustards (cyclophosphamide)
what are 3 effects of cisplatin **
electrolyte disturbances (HYPOmagnesemia)
NMB issues
emetogenesis
anthracycline CHEMO drugs
___________rubicin
what is the broadest activity + HIGHEST CARDIOTOXICITY risks?
DOXOrubicin (treatment=iron chelating agent= dexrazoxane)
very high doses
CHF NOT responsive to digoxin
MOAs of CHEMO drug class
1) DNA intercalator
* Sit in the middle of DNA/penetrating DNA, cause disruption
2) Inhibit Topoisomerase II
* Helps unwind DNA strands; inhibiting DNA synthesis
3) Generate Reactive Oxygen Species (ROS)
* Can cause significant tissue damage; cardiac toxicity
Anthracyclines
what are 2 adverse effects of anthracyclines
cardiotoxicity
radiation recall reaction
MOA chemo drugs*
Interferes with the synthesis of normal DNA/RNA bases and/or the incorporation of these bases into DNA/RNA
anti-metabolites
MOA chemo drugs*
Inhibits the enzyme DHFR (which is normally used for one-carbon-transfer reactions)
Inhibits dTMP synthesis cannot make thiamine inhibition of DNA synthesis
methotrexate (MTX)
what is the rescuer for MTX chemo drug
leucovorin
what are the adverse effects of anti-metabolites (MTX)
GI tract issues
thrombocytopenia
“central” regimen chemo drugs
taxanes
______taxel
hypersensitivity reactions with taxanes can be reduced with what*
____________ P450 metabolism
liposomal formulation
“saturable” = strict dosing regimen
which chemo drug has a risk of pulm toxicity with HIGH O2 flows and cutaneous toxicity*
bleomycin
the enyzme bleomycin hydrolase is NOT found in these locations
MOA chemo drug
Molecule has a DNA-binding region + iron-binding domain at opposite ends
By forming a complex with iron, the drug “shunts” the passage of electrons to molecular oxygen
Results in the formation of ROS aka FREE RADICALS
bleomycin
Which of the following CHEMO drugs is associated with alterations in serum electrolytes, which may require dosage changes of neuromuscular blocking agents?
cisplatin (hypomagnesium)
Renal toxicity due to which of the following drugs can usually be circumvented or diminished by MESNA administration?
cyclophosphamide
MOA
o Inhibit COX-1 and COX-2, which inhibits prostaglandins
o Different Types of Prostaglandins:
PGI2: normally causes vasodilation + inhibits clotting
* This is the good guy!
TXA: normally causes vasoconstriction + promotes clotting
* This is the target!
NSAIDs
steroids inhibit __________________
phospholipase
which COX is
constitutively expressed/stays constant
organ issues
1
which COX is
inducible (10-18x)
more involved in PAIN
2
what are the 2 black box warnings of NSAIDs
(NON-aspirin!)
CV risks
GI risks
what are the 3 different combos for patients with GI risks for NSAIDs
Celebrex!!
NSAID + PG analog (misoprostol)
NSAID + PPI
NSAIDs ___________ sodium water retention
increase
what can lead to incrased risk of BLEEDING with NSAIDs
SSRIs
SNRIs
glucocorticoids
anticoags, platelet inhibitors
what 2 drugs can lead to increased risk of renal toxicity with NSAIDs*
ACE inhibitors (_______pril)
ARBs (_______sartans)
baby aspirin inhibits COX __
full dose aspirin inhibits COX __ + __
COX 1 only =baby dose
COX 1+ 2= full dose, other NSAIDs
who is at high risk of pseudo-allergy with NSAIDs (NOT celebrex)
asthma
nasal polyps
what is a treatment for salicylism
sodium bicarb
activated charcoal
glucose, K
should you take aspirin or other NSAID first
take aspirin first
space out the drugs
which NSAID shouldnt be used for chronic therapy or intraop due to bleeding risk
ketorolac
which NSAID has sulfa risk
celebrex (lasix is worse)
can tylonel cause renal damage
yes
MOA
o 1) DECREASE calcium (channel INHIBITION) influx = excitatory NT release
o 2) INCREASE potassium (channel ACTIVATION) efflux = hyperpolarizing neuron
opioids
what are the 4 serotonergic drugs for opioids**
can cause serotonin syndrome!!!
meperidine
methadone
fentanyl
tramadol
which opioid blocks NMDA and monoamines
methadone
Highest risk of unintentional OD death from resp depression
methadone
Which opioid blocks 5HT + NE
tramadol
What 2 opioids are activated by 2D6**
tramadol
codeine
INHIBITOR of 2D6= no helpful analgesia, but you would still have serotonin effects!
what 2 drugs are good for opioid use disorder
buprenex
methadone
tylonel
Normally, the toxic metabolite is immediately taken care of by GLUTHATHIONE; with large doses, this enzyme is depleted
N-acetylcysteine
___ cells recognize particular epitopes
B cells
“________ ________” occurs to check for self-recognition B-cell is eliminated
this is where autoimmune diseases start
Check Process
“_________ ______________”: critical step in activation*
When the B cell encounters the antigen, it requires coactivation by a helper T-cell
Linked Recognition
PRIMARY immune response 1st Ig___**
2nd Ig___
1st: IgM
2nd: IgG
SECONDARY immune response
IgG!!!
Each antibody can bind to ___ identical antigens
2
what are the 5 main antibody classes based on
structure of the CONSTANT/Fc domain
antibody:
bound to surface of B cells, main first type
IgD
antibody:
gland secretions
IgA
antibody:
basophils/mast cells
IgE
antibody:
first to be secrete in response to antigen
IgM
(immune complexes)
antibody:
largest/most diverse class
IgG
___ cells bind to MHC I or II
T cells
cytotoxic or memory T cell
CD8
helpter T cell
CD4
CD8/cytotoxic/memory T cells binds to what
infected, NON immune cells
MHC I
CD4/helper T cells binds to what
antigen-presenting cells
immune cells
MHC II
What stimulates the shift from IgD IgG, IgM, IgE, etc
T helper cells (CD4) secreting cytokines
hypersensitivity reactions*
IgE mediated
mast cells
omalizumab
drug-induced
Type I
hypersensitivity reactions*
IgG
CD8/cytotoxic
complement activation
ADCC (antibody dependent cell-mediated cytotoxicity)
Type II
hypersensitivity reactions*
IgM
immune complex
complement activation
neutrophils
Type III
hypersensitivity reactions*
cell mediated (no antibody)
T helper cells, activated macrophages
Type IV
hypersensitivity reactions*
blood transfusion reactions
II
hypersensitivity reactions*
rheumatoid arthritis
lupus
III
hypersensitivity reactions*
poison ivy
sulfa drugs (bactrim)
contact derm
IV
what are the 3 common drugs that cause drug-hypersensitivity
penicillin
cephalosporins
local anesthetics
specificity of antibodies is due to the presence of
hypervariable regions
what type of T cell is involved in linked recognition
CD4 helper
what is released from mast cells
cytokines, leukotrienes, histamine, heparin
pH of 7.5 = what form?
pH of 8.5 = what form?
the LOWER the pH, the MORE ionized
