Pharmacology Final 2
Terms
undefined, object
copy deck
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Chloramphenicol:
MOA: Binds reversibly to the ____ subunit of the bacterial ribosome
__________ broad spectrum antibiotic
Active against both gram (+) & gram (-):
Neisseria meningitides
Haemophilus influenzae
Some -
50S
Bacteriostatic
hepatic failure -
Chloramphenicol-Clinical Uses
mostly obsolete due to toxicity & resistance
Maybe considered for use in treatment of serious infections:
Typhus or Rocky mountain fever in children < 8yrs where _________ is contra-indicated
-
Tetracycline
meningococcal meningitis
50-100 mg/kg/day in 4 divided doses -
Chloramphenicol - Adverse Effects
GI disturbances – N/V, diarrhea
__________ - alteration of normal microbial flora
Bone Marrow disturbances -
Decreased _______ production-doses >50mg/kg/day x 1-2wks
_________ †-
Oral or vaginal candidiasis
red cell
Aplastic anemia
Grey baby syndrome -
Chloramphenicol - drug Interactions
prolonged t½ & increased serum concentrations of:
________
________
__________ - tolbutamide, chlorpropamide
antagonize bactericidal drugs such as _____ & _______ -
Phenytoin
Warfarin
Anti-diabetics
PCNs, Aminoglycosides -
TETRACYCLINE: OVERVIEW
TCNs are _________ broad spectrum antibiotics
Mechanism of Action:
Inhibit protein synthesis- bind to the ___ subunit of the bacterial ribosome -
bacteriostatic
30S -
TETRACYCLINE : ACTIVITY
Active against g(+)& g (-) bacteria (_______):
Chlamydia
Mycoplasmas
Protozoa
Anaerobes
Antibacterial activity of most TCNs similar except:
TCN resistant strains may remain sus -
atypicals
doxycycline & minocycline -
TETRACYCLINE: RESISTANCE
Decreased _________ accumulation due to either impaired influx or efflux
_________ protection due to production of proteins that interfere with TCN binding ribosome
Enzymatic _________ of TCN -
intracellular
Ribosome
inactivation -
TETRACYCLINE: PHARMACOKINETICS
Absorption impaired by _____
Absorption impaired by divalent ______ - Ca, Mg, Fe, Al, dairy products, antacids
Widely distributed to tissue & blood, fluid except for _____
Minocycline – -
food
cations
CSF
saliva
meningococcal
bones & teeth -
TETRACYCLINE: PHARMACOKINETICS
_________ - unlike other TCNs, eliminated by non renal mechanisms
Doxy- does not accumulate significantly in renal failure - TCN of choice in __________
Dose: ________ (tetracycline, Oxytetracycline)
Dos -
Doxycycline
renal insufficiency
250-500mg PO qid
100mg PO qd or bid -
TETRACYCLINE:CLASSIFICATION
Short Acting TCNs (t½ 6-8hrs)
Chlortetracyline
Tetracycline (______®)
Oxytetracycline (_______®)
Intermediate Acting TCNs (t½ 12hrs)
Demeclocyline (________®)
Methacycline (_ -
Achromycin
Terramycin
Declomycin
Rondomycin
Vibramycin
Minocin -
TETRACYCLINE - CLINICAL USES.
1.TCNs are drugs of choice for infections with:
_________
_________
_________
2. Used in combination regimens (w/ PPI) to treat gastric & duodenal ulcers caused by __________
3. -
Mycoplasma pneumoniae
Ricketsiae
Spirochetes
Helicobacter pylori
vibrio
chlamydia -
TETRACYCLINE - CLINICAL USES
Also used for treatment of:
Exacerbation of bronchitis - ______
Pneumonia - TCN + _____
Acne - _______
Lyme disease
Relapsing fever
SIADH - ______
Elimination of menigococal carrier sta -
doxy
3rd gen cephalosporin
minocycline
demeclocyline
rifampin -
TETRACYCLINE - CLINICAL USES.
Used with ________ to treat Plague, Tularemia, Brucellosis
Used in protozoa infections caused by __________ or ___________ -
Aminoglycosides
entamoeba histolytica or Plasmodium falciparum -
TETRACYCLINE - DOSING
Tetracycline -
Adults: _________
Children (8yrs & older): _________
Methacycline - _________
Demeclocyline - ________
Doxycycline - _________
Minocycline - _______ -
250-500mg PO QID
20-40mg/kg/day in 4 divided doses
100mg po 1-2x/day
300 mg PO bid
100mg IV/PO qd or bid
100mg po bid
Doxycycline -
Precautions:
All TCNs chelate ______
Do not give with _____, antacids or ferrous sulfate
Contraindications:
Avoid in ________ & children < ___ of age to avoid deposition in bones & teeth -
metals
milk
pregnant women
8yrs -
TETRACYCLINE: ADVERSE EFFECTS
GI- _________ → direct irritation of GI tract (give with food to decrease effects)
_________
Oral or Vaginal __________
___________ - C. difficile
Bone & teeth structure - teeth _________ -
N/V, diarrhea
Pruritis
candidiasis
Pseudomembranous enterocolitis
discoloration -
TETRACYCLINE: ADVERSE EFFECTS
Liver toxicity –hepatic necrosis with daily doses of ______
_______ toxicity- renal tubular injury (All TCNs accumulate – except _________)
Local _______ injury - IV venous thrombosis, IM painful irritatio -
4gm IV
Kidney
doxycycline
tissue
Demecocycline
Minocycline -
MACROLIDES- OVERVIEW
MOA: Inhibition of protein synthesis by binding to ____ ribosomal RNA
_________ maybe inhibitory or bactericidal esp. at high concentrations for susceptible organisms
Prototype drug: Erythromycin - 1952
-
50S
Erythromycin
Clarithromycin & Azithromycin -
ERYTHROMYCIN PHARMACOKINETICS
Erythromycin ____ - destroyed by stomach acid
Must be given as ________
_____ & ______ are acid resistant & better absorbed
_____ impairs absorption
Excreted in bile & feces
Adjustme -
base
enteric coated
Stearates & esters
Food
renal failure
dialysis
placenta -
ERYTHROMYCIN ANTIMICROBIAL ACTIVITY
Effective against ____ organism especially:
Pneumococci
Streptococci
Staphylococci
Corynebacteria
Also effective against
Mycoplasma
Legionella
Chlamydia
C.Pneumon -
g (+)
ampicillin
cephalosporin -
ERYTHROMYCIN ANTIMICROBIAL ACTIVITY
Active against ___ organisms such as:
Neisseria species
Bordetella pertusis
Treponema Pallidum
Campylobacter specie
Haemophilus influenzae
Rikettsiae (some species - G (-)
-
ERYTHROMYCIN CLINICAL USES:
Drug of choice for __________ infections (diphtheria ,corynebacterium sepsis)
Prophylaxis against ________ during dental procedures in persons with valvular disease - _______ is a better alternative
As a PCN su -
corynebacterium
endocarditis
Clindamycin
staph & strept
CAP
chlamydia -
MACROLIDES-ERYTHROMYCIN DOSING
Erythromycin base, stearate or estolate
Adults _________
Children _________
Estolate is best absorbed, greatest risk of ADR
_______ preferred b/c of less GI SE
E. Ethylsuccinate __ -
250-500mg PO q6hr
40mg/kg/day PO
Stearate
400-600mg PO Q6hrs
1gm PO + Neomycin
0.5-1gm q6hrs -
MACROLIDES-ERYTHROMYCIN ADR
GI - ________, N/V & diarrhea-gut stimulation
Liver toxicity (esp estolate) - _________: fever, jaundice, impaired liver function
_______ rxns - fever, eosinophilia, rash -
Anorexia
cholestatic hepatitis
allergic -
MACROLIDES: ERYTHROMYCIN DRUG INTERACTIONS
Inhibits cytochrome P450 enzymes causing increased serum concentrations for drugs like:
Theophylline
_________ (Oral)
Cyclosporine
_________
________ -
Anticoagulants
Methylprednisone
Digoxin -
MACROLIDES: ERYTHROMYCIN-RESISTANCE
3 Mechanisms exist
Reduced ________ of cell membrane or active efflux
Production of _______ that hydrolyze macrolides
Modification of _________ -
permeability
esterases
ribosomal binding site -
MACROLIDES - CLARITHROMYCIN(______®)
Derived from erythromycin - addition of methyl group
MOA- same as erythromycin
Antibacterial activity:
Same as erythromycin, except active against _____
Erythromycin resistant ____ &am -
BIAXIN
MAC (mycobacterium avium complex)
staph & strept -
CLARITHROMYCIN - KINETICS
Has improved acid stability & _____ absorption, compared to erythromycin
Metabolized in the _____; major metabolite eliminated in urine
Dose
__________
XL ________
Pts w/ CrCl < 50ml/mi -
oral
liver
500 mg PO bid
1 gm qd
250mg q24hrs -
CLARITHROMYCIN
Drug Interactions –similar to erythromycin
Advantages over Erythromycin
Lower frequency of _________
Less frequent ______
Otherwise, therapeutically equivalent
Disadvantages over erythromcyin
-
GI intolerance
dosing
costly -
MACROLIDES-AZITHROMYCIN (_________)
Derived from erythromycin by addition of a methyl group
Microbial activity & clinical uses similar to clarithromycin- active against M.avium, T. gondii, H. influenzae
Highly active against _______
-
ZITHROMAX
chlamydia
staph & strept -
AZITHROMYCIN KINETICS
Half Life : 2-4 days; allows for __ dosing, shorter duration
Penetrates most tissues except the ____
Give __________ meals
Does not inactivate the Cytochrome P450enzymes therefore free of drug interactions -
QD
CSF
1hr before or 2hrs after -
AZITHROMYCIN DOSING
Available IV & PO
CAP: __________
Chlamydia cervicitis, urethritis: ________
Above as effective as 7 days of doxycycline -
LD 500mg, then 250mg IV/PO q24hrs x 4days
1gm PO x1 dose -
________
Are semi-synthetic 14 member ring macrolides
Differ from erythromycin by the substitution of a 3 keto group - KETOLIDES
-
KETOLIDES - TELITHROMYCIN (_______)
Active against:
S.pyogenes
S. pneumoniae
H.Influenzae
Moraxella catarrhalis
N. gonorrhea
*Mycoplasma*
*Legionella*
*Chlamydia*
Bacteriodes fragilis - *Anaerobe*
T. - Ketek
-
KETOLIDES - TELITHROMYCIN
Oral bioavailabilty – 57%
Tissue penetration good
Metabolized by ______, eliminated by biliary & urinary route
Treatment of respiratory tract infections including ____: Acute exacerbation of bronc -
liver
CAP
Streptococcal
800mg PO qd -
VARIOUS ANTIMICROBIALS: ________ - Derivative of Lincomycin
MOA- Inhibition of protein synthesis, by binding to the ____ subunit of the bacterial ribosome -
CLINDAMYCIN
50S -
CLINDAMYCIN: Antimicrobial Activity
_____ & ______ coverage -
Streptococci
Staphylococci
Pneumococci
Bacteriodes & other anaerobes
Enterococci & g (-) organisms resistant to Clindamycin in contrast to - G+ & anaerobic
-
CLINDAMYCIN: Kinetics
Excreted in liver bile & urine
Penetrates into _______
Half life 2.5hrs
Typical Dose:
PO ________
IV ________
PID Dose: ______
Abscess dose: ______ -
abscesses
150-300mg PO q6hrs
600-900mg IV q8hrs
900 mg IV q8hrs
600 mg IV q8hrs then PO -
CLINDAMYCIN: Clinical Uses
Severe _______ infections
Combined with _______ or _______ for penetrating wounds & abscesses
Clindamycin + _______, effective alternative to Bactrim for ___________ -
anaerobic
aminoglycosides or cephalosporins
Primaquine
pneumocystis carinii -
CLINDAMYCIN: Adverse Effects
GI- N/V, severe diarrhea & ________ (use Flagyl or Vanc qid to treat)
Dermatological - _______
Impaired _____ function -
enterocolitis
skin rashes
liver -
Various Antimicrobials: Streptogramins
Quinupristin-Dalfopritin (________)
________ for most organisms except enterococcus faecium
Active against multi-drug resistant strains of S. Pneumoniae, MSSA, MRSA
T1/2 - 1hr
Prolonge -
Synercid
Bactericidal
7.5mg/kg IV Q8-12hrs
Pain
central line -
Sulfonamides Overview
MOA: structural analogues of _____
Inhibit growth of organisms by reversibly blocking ____________
Divided into 3 groups
__________
__________
__________
Plus IV Sulfamethoxazole/trimethoprim -
PABA
folic acid synthesis
Oral Absorbable
Oral Non-absorbable
Topical -
Sulfonamides Antimicrobial Coverage
Inhibit growth of _______ bacteria including:
Nocardia
Chlamydia trachomatis
Protozoa (some)
Enteric bacteria such as:
E. Coli
Klebsiella
Salmonella
Shigella
Ente -
both gram (+) and gram (-)
rikettsiae -
Sulfonamides – Oral Absorbable Kinetics
Classified into 3 categories based on _____:
Short Acting
Medium Acting
Long Acting
Well absorbed into body fluids, CNS & CSF
Excreted in urine
Dose adjustment n -
half life
renal impairment -
Sulfonamides –Oral Absorbable (Clinical Uses)
Infrequently used as a ____ agent
Formerly drugs of choice for infections such as:
Pneumocystis carini pneumonia
Toxoplasmosis
Nocardiosis
Used in fixed combination -
single
trimethoprim/sulfamethoxazole -
Sulfonamides – Oral Absorbable (Clinical Uses)
Many strains formerly susceptible to organism listed below, but now ______:
Meningococci
Pneumococci
Streptococci
Staphylococci
Gonococci - resistant
-
Sulfonamides – Oral Absorbable
SULFISOXAZOLE & SULFAMETHOXAZOLE - short to medium acting
Used to treat ____
Dose ________
SULFADIAZINE - Achieves therapeutic conc. In CSF
First treatment for acute _________ whe -
UTI
1gm PO QID
toxoplasmosis
pyrimethamine -
Sulfonamides – Oral Absorbable
SULFADIAZINE + pyrimethamine = synergistic
Pyrimethamine (Daraprim)-_________, potent inhibitor of dihydrofolate reductase
Dose: Sulfadizine _______ plus Pyrimethamine ____________
Combination g -
antiprotozoa
1gm po qid
75mg po x 1 dose, then 25mg po qd
folic acid 10mg po qd -
Sulfonamides – Oral Non Absorbable
SULFASALAZINE (________)
widely used to treat _________ & other inflammatory bowel disease
Dose
LD: __________
MD: __________ -
Azulfidine
ulcerative colitis
1 gm tid or qid
1 gm bid -
Sulfonamides – Oral Non Absorbable
SULFADOXINE – only long acting sulfonamide in US
Results in prolonged levels
Sulfadoxine + Pyrimethamine = _______
1 tab = __________
Dose acute malaria: ________
Prophylaxi -
Fansidar
Sulfadoxine 500mg + Pyrimethamine 25mg
2-3 tabs x 1 dose -
Sulfonamides – Topical Agents
SODIUM SULFACETAMIDE
______ soluntion & oint
Used to treat _________ & adjunctive treatment for trachoma
MAFENAMIDE ACETATE
Used topically to prevent bacterial colonization in -
Ophthalmic
conjunctivitis
burn wounds
metabolic acidosis -
Sulfonamides – Topical Agents
SILVER SULFADIAZINE (_________)
Less _____ topical sulfonamide
Preferred over Mafenamide for prevention of ________ of burn wounds -
Silvadene
toxic
infection -
Sulfonamides - Adverse Effects
For sulfonamides & their derivatives (thiazide, loop diuretics, diazoxide & sulfonylureas, cross allergenic)
Most common adverse effects:
_____
Skin ______
Exfoliative dermatitis
-
Fever
Rashes
Photosensitivity
Diarrhea -
Sulfonamides - Adverse Effects
________ – rare (<1%) but potentially fatal type of skin & mucous membrane eruption
________ disturbances - May precipitate in urine producing crystalluria, hematuria & obstruction
e -
Stevens Johnson’s syndrome
Urinary
NaHCO3
fluids -
Sulfonamides - Adverse Effects
___________ Disturbances -
Hemolytic & Aplastic anemia, granulocytopenia, thrombocytopenia
Risk of _________ in newborns if taken at end of pregnancy -
Hematopoietic
kernicterus -
Sulfonamides - combination drugs
_________ - inhibits bacterial dihydro folic acid reductase
_________ - inhibits activity of dihydro folic acid reductase of protozoa
Trimethoprim + sulfonamide or
Pyrimethamine + sulfonam -
TRIMETHOPRIM
PYRIMETHAMINE
bactericidal -
Sulfonamides - Trimethoprim Clinical Uses
Trimethoprim:
Can be given alone in ____
Dose - ________
Trimethoprim/Sulfamethoxazole:
Pneumocystis Carini
Shigellosis
Salmonella
Respiratory Organisms
Ha -
UTI
100mg po bid -
Sulfonamides - Trimethoprim
UTI:
Bactrim DS (Trimethoprim ____/sulfamethoxazole ____) given q12hrs
Prophylaxis of recurrent UTI:
___ tab Bactrim DS 3x/wk x months
Salmonella/shigella:
Bactrim DS _______
-
Trimethoprim 160mg / sulfamethoxazole 800mg
0.5 tab
1 tab q12hrs
80mg trimethoprim / 400mg sulfamethoxazole -
Sulfonamides - Trimethoprim
Pneumocystis Carini:
80mg trimethoprim/400mg sulamethoxazole per 5ml in 125ml D5W over 60-90mins
Dose: 5mg/kg 3-4x/day based on ________ portion of agent
Typical dose: __________ -
Trimethoprim
15-20ml IV q6-8hrs -
Sulfonamides - Trimethoprim Adverse Effects
________
N/V
Vasculitis
____ damage
____ pts –fever, rashes, leukopenia, diarrhea -
Leuokopenia
Renal
AIDS -
Acetaminophen Antidote:
N-Acetylcysteine (_________) -
also for carbon tetrachloride OD
LD: __________
MD: __________
Admit pt for 3 days
_______ - IV form
dose: ________
admit for only 1 day -
Mucomyst
140 mg/kg PO
70 mg/kg q4hr for 17 doses
Acetadote
150 mg/kg over 1 hr then 50 mg/kg over 4 hrs then 100 mg/kg over 16 hrs -
Acetaminophen Overdose:
Peds - follow adult dosing
dilute to 5%
ineffective if _________ is used prior to administration
If pt vomits w/in 1 hr - _________ -
activated charcoal
repeat dose -
Potential hepatotoxic serum acetaminophen leves at intervals after ingestion:
4 hr -
6 hr -
10 hr -
20 hr -
24 hr -
dont check levels earlier than ___ b/c hasnt reached peak yet -
150 mcg/mL
100 mcg/mL
50 mcg/mL
8 mcg/mL
3.5 mcg/mL
4 hrs -
Acetaminophen Overdose:
administer Mucomyst for levels > ____ at ___ hrs
toxic concentrations w/ probably hepatoxicity - _________ -
150 mcg/mL at 4 hrs
> 200 mcg/mL at 4 hrs or 50 mcg/mL at 12 hrs -
Mucomyst: other indications
adjunctive mucolytic therapy in pts w/ abnormal or viscid mucous secretions such as _________ or _________
Usual Dose: nebulize _______ -
COPD or Cystic fibrosis
6-10 mL of 10% solution OR 3-5 of 20% solution -
Mucomyst: other indications
prevention of radio contrast induced renal dysfunction
Dose: ________ beginning the day before the procedure
dilute with juice or soda - 600 mg PO bid x2 days
-
Ethylene Glycol/Methanol Antidote: _______
LD - ________
MD - non drinkers ________
MD - dialysis pts ________
MD - alcoholics ________
MD - alcoholics on dialysis ________ -
Ethanol
600-700 mg/kg IV/NG/PO
non drinker: 66-154 mg/kg/hr
alcoholics: start at 154 mg/kg/hr
dialysis pts: 169 mg/kg/hr
alcoholics on dialysis: 257 mg/kg/hr -
Ethanol:
has great affinity for enzymes responsible for methanol metabolism (ADH)
give IV or PO to maintain Ethanol level at > _______ thereby saturating ADH w/ Ethanol in the liver
Give Ethanol when:
methanol level is > _ -
100 mg/dl
20 mg/ml
30 ml -
continue tx unitl ethylene glycol or methanol level is < _____
Fomepizole (_______) inhibits elimination of ethanol
administration w/ concomitant ethanol ingestion, not recommended since toxic ethanol levels may result
Ethanol ADR -
10 mg/dl
Antizol
Hematologic
Cardiovascular -
Fomepizole (Antizol)
also an antidote for ethylene glycol or methanol OD
IV dose:
LD - ________
MD - ________
continue MD until level is < ______ & pt is asx w/ normal pH
PO Dose:
LD - _________
-
LD - 15 mg/kg IV
MD - 10 mg/kg q12hr x 4 doses then 15 mg/kg q12hr
20 mcg/dl
LD - 15 mg/kg PO q12hr
MD - 5 mg/kg q12hr x 1 dose then 10 mg/kg q12hr
LD - 10 mg/kg PO
MD - 5 mg/kg bid up to 36 hrs then 10 mg/kg bid up to 96 hrs -
Fomepizole (Antizol):
in cases of renal failure, _____ should be considered in addition to Antizol
Monitor during Tx b/c of:
severe metabolic acidosis
elevated anion gap
significant creatinine increase
Check:
-
dialysis
EEG
20 mg/dl -
Fomepizole (Antizol):
Administer dilute doses in at least ____ NS or D5W, infuse over ____
Do not give w/ _____ b/c toxicity can occur
a pre-existing ethanol level does not preclude the use -
100 ml
30 min
ethanol -
Fomepizole (Antizol) ADR:
____ - bradycardia, tachycardia, hypotension
____ - dizziness, HA, seizure, abnormal sense of smell, roaring in ears, agitation, anxiety
_____ - lipid abnormalities, hypertriglyceridemia
____ - mild nausea, b -
CV
CNS
Endocrine
GI
Ocular -
Rattlesnake/Copperhead Antidote: Polyvalent crotalid antivenim immune fab (________)
LD: _________
can repeat dose in 1 hr is sx are not controlled
MD: _________ -
Crofab
4-6 vials over 1 hr
2 vials q6hrs for 18 hrs (3 more doses) -
Rattlesnake/Copperhead Antidote: Crofab
use w/in ___ of snake bites
local sx (______) & neuro manifestations (_____) improve during a 1 hr infusion
local sx can recur in 6-18 hrs
coagulopathy (________, _______) has been evident -
6 hrs
swelling
myokimia
thrombocytopeniz, hypofibrinogenemia -
Crofab MOA:
bind & neutralize venom toxins
facilitate the re-distribution & ulimate elimination from affected body tissue
ADR: ________
Cost: 2 vials = $8920 - hypersensitivity rxns
-
Digoxin Antidote: Digoxin immue fab (_______)
_____ will bind approximately 0.5 mg digoxin or digitoxin
DOSE (in vials): (serum digoxin conc [ng/ml] x wt [kg])/100
levels higher than ____ requires the antidote
Normal dig l -
Digibind
38 mg
4-6 ng/ml -
Digoxin Antidote: Digoxin immue fab ovine (_______)
available in 40 mg vials
shorter half life
dosing is same as Digibind
costs less - Digifab
-
Digoxin Antidote
Infuse IV over _____ using 0.22 micron filter
Life threatening - __ vials (760 mg) IV
Adult or peds acute ingestion - if unknown amt give ___ vials (380-400 mg) IV, observe response then repeat prn
Pediatric ch -
30 mins
20 vials
10 vials
1 vial -
Methylphenidate (________) can cause ___________
also called MAOI crisis
caused by inhibited uptake of serotonin -
Ritalin
Serotonin syndrome -
Dehydroeipandrosterone (DHEA)
Indications (3) -
weight loss
aging
Alzheimer's dz -
Melatonin
Sleep
Dose: __________
Jet Lag
Dose: __________ -
.3-10 mg (max 20 mg)
5-8 mg -
Feverfew
Garlic
Gingseng
Gingko Biloba - All are CI w/ anticoagulants
-
Echinacea - usually taken at the first sign of a cold
reduces ________ - duration
-
Gingko Biloba
Effects:
increase blood flow
decreased viscosity
antioxidant effects
Tx for cerebral insufficiency
Dose: ___________
ADR: GI (______), ______
affects _______ fxn - causes bleeding -
120-240 mg given 2-3 divided doses
Nausea, vomiting
platelets -
Tetanus Prophylaxis:
if a bite in minor & the wound is clean, a shot is not indicated unless it has been _____ since last dose
If wound is major and/or not clean, a prophylaxis Td shot is recommended if it has been more than ___ since last -
10 yrs
5 yrs -
Rabies Immunization:
pts w/ a bite from a ______ dog are at higher risk for infxn
Pre-exposure prophylaxis (3)
Post-exposure prophylaxis (5) -
non-provoked
0, 7, 21 days
0, 3, 7, 14, 28 days -
_______ is when you administer an antigen to the host to induce the formation of antibodies
can be inactivated (killed) or attuenuated (live)
_______ is when you transfer immunity to a host
animal or human immunoglobins are used
-
active immunity
passive immunity
200-400 mg - all vaccinations doses are __________
- 0.5 mL IM per dose
-
Antidote for bradyarrhythmia-producing drugs (B-blockers, CCB, digitalis glycosides): _______
dose:_______ -
atropine sulfate
1-2 mg IV, repeat q15-30min prn -
GI decontamination: ________
Iron overload: _______
Dose: _______ -
activated charcoal
deferoxamine mesylate (Desferal)
15 mg/kg/hr IV -
Benzodiazepine antidote: ________
Dose: ________
Opoid antidote: _______
Dose: ______
Oral sulfonyurea antidote: _________
also used for diarrhea -
flumazenil (Romazicon)
0.2 mg IV over 30 secs
naloxone (Narcan)
0.4-2mg IV, may repeat at 2-3min intervals up to 10 mins
octreotide (Sandostatin) -
Warfarin antidote: _______
dose: ________
Enoxaparin or Heparin Antidote: _________ -
phytonadione (vitamin K)
2.5-10mg SC/PO/IM
rarely up to 50mg
may repeat in 6-8hrs
protamine sulfate -
Polyenes (5)
1. Amphotericin B
o Conventional Formulation (___________)
o Lipid Formulations (_______,_______,_______)
2. __________ -
Fungizone
Abelcet, Ambisome, Amphotec
Nystatin -
Polyenes (5)
MOA: binds to ________ causing loss of cell membrane integrity and leakage of cellular contents (cell dies). - ergosterol
-
_________
o Ampho B -- Conventional formulation
o More ________than lipid formulations (use lower doses)
o Requires test dose – _ mg in __ ml D5 over 20-30min -
Fungizone
nephrotoxic
1mg in 20ml -
Fungizone
o Adverse Effects:
o ________/electrolyte imbalance – supplement with K/Mg
o ___-like sx – give benedryl or Tylenol
o Extravasation
o ______tension
o GI effects – N/V/D -
Nephrotoxic
Flu
Hypotension -
Fungizone
Dose
Available __only
General dosing:
o _______ mg/kg/day IV
o Empirical tx (neutropenic pt) Low dose
o Proven fungal inf. high dose
__________
o total dose up to 3.6g over 11 months
___funga -
IV
0.25 – 1 mg/kg/day IV
Aspergillosis
CNS : INTRATHECALLY
Lung : INTRACAVITARY
Urinary Tract Mycosis -
Fungizone
Indications
Potenially life-threatening fungal infections
**___________**
Candidiasis (if life threatening)
_____________
Cryptococcosis
Amer Mucocutaneous ___________
____________
Basidiobolus -
Aspergillosis
Coccidioidomycosis
leishmaniasis
Histoplasmosis -
Lipid Formulations (Abelcet, Amphotec, Ambisome)
o Less ________– can use higher doses
o Expensive
o Adverse Effects:
o Hypotension
o GI: N/V/D - nephrotoxic
-
Lipid Formulations (Abelcet, Amphotec, Ambisome)
General Dosing:
o_______ mg/kg/day IV - 3 – 5 mg/kg/day IV
-
Lipid Formulations (Abelcet, Amphotec, Ambisome) Indications:
Patients with severe fungal infections who are unable to tolerate __________ - conventional formulation (Fungizone)
-
Abelcet
o Ampho B -- Lipid Complex
General dosing:
o __ mg/kg/day IV
TX:
___________
Blastomycosis
Candidiasis
_____________
Leishmaniasis
Systemic _________ -
5 mg/kg/day IV
Aspergillosis
Cryptococcal meningitis
mycosis -
___________
o Ampo B – Cholesterol Sulfate Complex
o Not used much due to infusion reactions
Aspergillosis
o ____ mg/kg/day
o MAX: 7.5 mg/kg/day
Candidiasis (non-FDA)
o _______ mg/kg/day -
Amphotec
3-4 mg/kg/day
3.9 – 6 mg/kg/day -
________
o Ampo B – Liposome
Cryptococcal meningitis (HIV)
o ___ mg/kg/day IV once daily
_________(Aspergillus, candida, or Cryptococcus)
o 3-5 mg/kg/day
Visceral ____________
Mycosis, empiric tx for ____ -
Ambisome
6 mg/kg/day IV once daily
Systemic mycosis
leishmaniasis
febrile neutropenia -
Nystatin (Mycostatin)
o Not used to tx _______ inf.
o Topical & Oral suspension
o Low cost
o Adverse Effects
o Oral: N/V/D
o Topical: ____, skin irritaion -
systemic
rash -
Nystatin (Mycostatin)
Oral ______ (Candidiasis)
Candida __________
Candidiasis of skin
GI _________
___________ Candidiasis
***Not Used for Systemic Infections -
Thrush
Vaginitis
Mycoses
Mucocutaneous -
Nystatin (Mycostatin)
Candida Vaginitis
o vaginal cream (100,000 U/g)
o _________ daily - 100,000 units VAGINALLY qd
-
Nystatin (Mycostatin)
Mucocutaneous Candidiasis
o Apply powder ______daily to affected area
Candidiasis of skin
o *same dose as above* - 2-3 x
-
Nystatin (Mycostatin)
GI Candidiasis (non-esophageal)
o Oral suspension (100,000 U/ml)
o ___________ tid SWISH & Swallow
Oral Candidiasis
o ___________ units suspension qid OR
o 200,000-400,000 U troche units -
500,000 U (5ml) – 1,000,000 U (10ml) tid SWISH & Swallow
300,000 – 400,000 -
Antifungals: Echinocandins (3)
MOA: Blocks the synthesis of β (1.3)-D-glucan, an important part of the________
o Excellent coverage of ________species
o Advantages: improved safety profile and limited drug interactions
o Disadvantage -
cell wall
Candida
PO bioavailability -
Caspofungin (________)
o Safety Concerns
o Adjust for ________ insufficiency (35mg MD)
o ________ rxns
o No need to adjust in renal insuff.
o Better SE profile -
Cancidas
hepatic
Infusion site -
Caspofungin (Cancidas)
Indications
Refractory invasive _________
Candidal septicemia
Candidal intra-abdomina ____________
__________(empirical tx) -
Aspergillosis
abcess or peritonitis
Febrile Neutropenia -
Caspofungin (Cancidas)Dose
Available IV only
Typical dose
o LD: __ mg IV (day 1)
o MD: __ mg daily
Esophageal Candidiasis
o 50mg daily
o ________ better (PO) -
LD: 70mg IV (day 1)
MD: 50 mg daily
diflucan -
Micafungin (_________)
o _________dosing
o Safety concerns:
o ___________rxns
o ___________rxns
o Exacerbation of ________ impairment -
Mycamine
Prophylaxis
Infusion site
Hypersensitivity
renal -
Micafungin (Mycamine) IV ONLY
Prophylaxis for Candidiasis
o Stem Cell Transplant
o __ mg daily
Esophageal Candidiasis
o ___ mg daily -
50 mg daily
150 mg daily -
Anidulafungin (_________)
o Has shown superiority over diflucan in tx of ________
o Safety concerns
o Worsening of _______ fxn -
Eraxis
candidemia
hepatic -
Anidulafungin (Eraxis)
Available IV only
Candidemia & ________ disseminated candidiasis
o LD: ____mg (day 1)
o MD: ____mg daily
Esophageal Candidiasis
o LD: ____mg (day 1)
o MD: ___ mg daily -
Intra-abdominal and peritoneal
LD: 200 mg (day 1)
MD: 100 mg daily
LD: 100mg (day 1)
MD: 50 mg daily -
Antifungals: Antimetabolites (1)
MOA: Converted to 5-fluorouracil inside the fungal cell and inhibits thymidylate synthetase and interferes with ________
Flucytosine (______) -
DNA synthesis
Ancobon -
Flucytosine (Ancobon)
Rarely used due to SE and limited indications
Used in combo with _____ for severe infections
Drawbacks:
______ quickly develops
Extreme caution with _______
Adverse Effects:
Skin Dz
-
Ampho B
Resistance
renal impairment
N/V/D
liver enzymes -
Flucytosine (Ancobon): Dosing
Candidiasis (meningitis or pulmonary)
Cryptococcosis (septicemia, endocarditis, UTI, pulmonary) - _________ - 50 – 150 mg/kg/day PO in 4 equal doses
-
Antifungals: Triazoles (5)
MOA: Block the activity of 14-α-demethylase which inhibits ________ synthesis (an essential part of the cell membrane)
all triazoles impact __ system -
ergosterol
CYP -
Antifungals: Triazoles
Fluconazole (______)
DOC for ________
Effective against most Candida species EXCEPT:
C. krusei
C. glabrata
Good coverage of Cryptococcus
PO is less expensive
Drawbacks:
Inhibitor -
Diflucan
Candida albicans
molds
renal insufficiency
SJS -
Antifungals: Triazoles
Fluconazole (Diflucan) - dosing
Available IV & PO
Candida Vaginitis - ________
Esophageal or Oral Candidiasis -
LD: ________
MD: ________
Candiduria - _______
Pr -
150 mg PO 1 x dose
LD: 200 mg IV/PO
MD: 100 mg QD
50-200 mg IV/PO QD
400 mg IV/PO qd
LD: 400 mg IV/PO
MD: 200 mg qd
400 mg IV/PO qd -
Antifungals: Triazoles
Fluconazole (Diflucan) - Indications
Candidiasis - Generally 1st line in tx of ______
________ infections -
C. albicans
Cryptococcal -
Antifungals: Triazoles
Itraconazole (_______)
Broader spectrum than Diflucan
Covers ________
Covers C. glabrata
Drawbacks:
Does not cross ____ – not effective against cryptococcal meningitis
Strong inhibitor of -
Sporanox
aspergillus
BBB
increase
Hepatic toxicity -
Antifungals: Triazoles
Itraconazole (Sporanox) - dosing
Available PO & IV
Aspergillosis, Blastomycosis, Histoplasmosis
PO: ________
IV: ________
Febrile Neutopenia (empiric tx)
IV: ________
O -
PO: 200 mg qd or bid
IV: 200 mg bid for 4 doses; then 200 mg qd
200 mg bid for 4 doses; then 200 mg qd
200 mg BID x 1 wk, 3 wks off, then 200 mg BID x 1 wk
200 mg qd x 12wks
200 mg qd
200 mg solution swish/swallow qd
100-200 mg swish/swallow qd -
Antifungals: Triazoles
Voriconazole (______)
Spectrum similar to itraconazole (broader than diflucan) but better coverage of:
Aspergillosis
Fusarium
Can switch from ______ as sx improve
Reserved for very sick – can send h -
Vfend
IV to PO
Visual
elevated LFTs -
Antifungals: Triazoles
Voriconazole (Vfend)
Available IV & PO
Invasive Aspergillosis, Disseminated Candidiasis, Fusarium infection, Monosporium apiospermum infection - ________
Candidal Septicemia - _________
-
6 mg/kg IV q 12hrs for 2 doses; then 4 mg/kg IV Q 12hrs
6 mg/kg IV q 12hrs for 2 doses; then 3 mg/kg IV Q 12hrs
200 mg PO q 12hrs (pt >40kg)
100 mg PO q 12hrs (pt <40kg)
200-300 mg PO q 12hrs (>40kg)
100-150 mg PO q 12hrs (<40kg) -
Antifungals: Triazoles
Voriconazole (Vfend) - indications
______(DOC along with Ampho B)
Fusarium
Monosporium apiospermum
Candida species resistant to _________ -
Aspergillosis
Fluconazole -
Antifungals: Triazoles
Ketoconazole (______)
Seldom used PO due to adverse events - Fatal ________
Effective as a topical tx
Effective against dimorphic fungi:
Histoplasmosis
Blastomycosis
Coccidioidomycosis
Not f -
Nizoral
hepatic necrosis
systemic infections
testosterone
libido
Menstrual -
Antifungals: Triazoles
Ketoconazole (Nizoral)
Available PO & Topical
PO Dose: ________
Candidiasis of the skin - ______ daily
Dandruff - _____ daily to wet hair
Pityriasis Vesicolor - _____ dail -
200-400 mg qd
2% cream topically
2% shampoo
2% shampoo
2% cream or gel
2% cream daily OR 200-400 mg PO daily -
Antifungals: Triazoles
Posaconazole (_______)
New in market
Used prophylaxis during ________
Good coverage of yeasts and molds
Safety concerns:
Severe _______ reactions
Drug interactions (CYP3A4)
________, _ -
Noxafil
neutropenia
hepatic
Arrythmias, QT -
Antifungals: Triazoles
Posaconazole (Noxafil)
Available in Oral suspension only
Dose - _________
Indications:
Disseminated _______(prophylaxis in severely immunocompromised)
________(prophylaxis) -
200 mg (5ml) orally tid
Candidiasis
Aspergillus -
o Candida
o C. albicans __________ is DOC - Fluconazole (Diflucan)
-
o Aspergillosis (typicall __wks of therapy)
o DOC:
 Conventional Ampho B (________)
• 1 mg/kg/day IV (increase to 1.5 if low dose not working)
 _________(Vfend)
• 6 mg/kg IV q 12hrs x 2; then 4 mg/kg IV q12hrs
†-
10 WKS
Fungizone
Voriconazole -
Aspergillosis
Alternatives
 ________ (Sporanox)
• ____ mg IV q __ hrs x 2; then 200 mg IV qd OR 200mg PO tid
_________(Cancidas)
• __ mg IV x 1; then __ mg IV qd -
Itraconazole
200 mg IV q 12hrs x 2
Caspofungin
70mg IV x 1; then 50 mg IV qd -
o Cryptococcosis
o Alternatives
 _________ – can use in place of fluconazole
• ___ mg PO bid -
Itraconazole (Sporanox)
200 mg PO bid -
o Blastomyces
o DOC:
 Itraconazole (Sporanox)
• ___mg PO bid for ____months
 Ampho B (Fungizone)
• ______mg/kg/day IV for ________wks
o
Alternatives
 Fluconazole
• ______ mg PO qd -
200 mg PO bid for 6-12 months
0.5 -1 mg/kg/day IV for 6-12 wks
400-800 mg PO qd -
o Histoplasmosis
o DOC
 __________(Sporanox)
• 200 mg PO bid for ___ months
 Ampho B (________)
• 0.5 – 1 mg/kg/day IV for ____ wks
o Alternatives
 __________
• 400-800 mg PO qd -
Itraconazole
6-18
Fungizone
10-12
Fluconazole