Pharm/Bioterrorism Flashcards
(133 cards)
1
Q
physiological cause of gout
A
increased uric acid in the blood (hyperuricemia)
above 6-7 mg/dl serum
2
Q
risk factors of gout
A
higher in men
women increased risk after menopause
3
Q
idiopathic causes of gout
A
renal retention of urate
hypertension, obesity, hyperlipidemia
increased urate production
4
Q
causes of renal retention
A
drug-diuretics, aspirin (could also cause increase in cell turnover)
renal damage
metabolic
5
Q
enzyme defects related to gout
A
increased phosphoribosylpyrophosphate synthetase
decreased hypoxanthine guanine phsophoribosyl transferase
6
Q
local causes of gout
A
low temperature
low pH
7
Q
role of immune system in gout
A
granulocytes phagocytize urate crystals
release kinins and lysosomal enzymes from granulocytes
increased lactic acid production and local decrease in pH
leads to increased deposition of urate crystals
8
Q
excretion of urate in kidneys
A
filtered at glomerulus
actively reabsorbed in PT (S1 100%)
active secretion in PT (S2 50%)
active reabsorption in late PT and DT (S3 80%)
overall 10% initially filtered at glomerulus is excreted
9
Q
non-drug therapy of gout
A
avoid obesity-foods high in purine content
avoid dehydration-keep concentration in serum lower through proper hydration
avoid alcohol-decrease in ADH leads to increased concentration
10
Q
MOA colchicine
A
antimitotic, anti-inflammatory
decrease leukocyte mobilization
decrease lactic acid and histamine
decrease release of inflammatory glycoprotein
inhibition of leukotriene synthesis by inhibiting lipoxygenase pathway
11
Q
toxicity colchicine
A
GI disturbance (N/V/D) chronic-risk of aplastic anemia, agranulocytosis, myopathy, alopecia
12
Q
uses colchicine
A
acute attacks (DOC with NSAIDs) prophylactic use to prevent acute attacks
13
Q
MOA allopurinol
A
antimetabolite of hypoxanthine which inhibits xanthine oxidase
competitive at low concentrations, noncompetitive at high concentrations (metabolite alloxanthine is noncompetitive at all concentrations)
14
Q
uses allopurinol
A
preferred in patients with impaired renal function (does not increase urate levels)
chronic gout
secondary hyperuricemia
15
Q
allopurinol and 6MP
A
inhibits biotransformation of 6MP
should reduce dose of 6MP when both drugs are being used
16
Q
toxicity allopurinol
A
rash, fever, vasculitis, hepatotoxicity, bone marrow toxicity
17
Q
acute attacks with allopurinol
A
fluctuations in serum urate levels
colchicine or NSAID to prevent acute attacks
18
Q
MOA febuxostat
A
inhibition of xanthine oxidase, non-purine drug that forms a stable complex with xanthine oxidase
19
Q
pharmacokinetics febuxostat
A
absorption reduced by magnesium hydroxide and aluminum hydroxide antacids
slightly reduced absorption by food
20
Q
uses febuxostat
A
hyperuric patients
not for patients with asymptomatic hyperuricemia
21
Q
toxicity febuxostat
A
liver function abnormalities, nausea, joint pain and rash
22
Q
acute attacks with febuxostat
A
fluctuations in serum urate levels
colchicine or NSAID to prevent acute attacks
23
Q
MOA rasburicase
A
recombinant urate oxidase enzyme that catalyzes the oxidation of uric acid into soluble allantoin; lowers levels better than allopurinol
24
Q
uses rasburicase
A
pediatric patients with leukemia, lymphoma, and solid tumors who are receiving cancer chemo that result in cell lysis and hpyeruricemia
25
decreased efficacy rasburicase
antibody against enzyme
26
toxicity rasburicase
hemolysis in G6PD, methemoglobinemia, acute renal failure and anaphylaxis
27
MOA uricosuric agents (probenecid and sulfinpyrazone)
competitively inhibits active reabsorption of urate by primarily URAT-1 in proximal tubule of nephron to increase urate excretion
28
low doses probenecid
inhibit active secretion (more sensitive system) of urate to cause UA retention
29
toxicity probenecid
GI irritation with aggravation of peptic ulcer
30
intrarenal urate stone formation probenecid
increase fluid intake or alkalinize urine
31
uses probenecid
chronic gout
hyperuricemic states
sufinpyrazone may decrease platelet aggregation (MI prophylaxis)
32
benzbromarone
increases urate excretion without urate retention
not in US
good for patients with decreased renal function or patients allergic to probenecid
33
acute attacks with probenecid
may precipitate an acute attack
| colchicine or NSAID can be used prophylactically
34
NSAID MOA
```
selective cox2 inhibitors
decrease inflammation (except acetaminophen)
```
35
FDA approved NSAIDs for gout
indomethacin, naproxen, sulindac
36
aspirin for gout
DO NOT USE
| decrease urate secretion but increase risk of renal calculi
37
elderly gout treatment
NSAIDs or glucocorticoids over colchicine if patient has cardiac, renal, or GI diseases
38
glucocorticoids for gout
acute gout when other treatments fail
| ex. prednisone
39
percutaneous absorption
exclusively diffusion process
40
rate limiting step in percutaneous absorption
permeation through stratum corneum
41
ways to increase amount of drug in receptor phase
increase diffusion coefficient
increase concentration of donor drug
increase solubility (Km)
(direct relationship)
42
ways to decrease amount of drug in receptor phase
increase thickness of skin
| inverse relationship
43
tachyphylaxis
diminished biological effect after repeated usage-occurs after repeated steroid application
44
most common allergic reaction
dermatologic reactions
45
drug idiosyncrasy and drug intolerance MOA and side effects
nonimmune mediated
thrombocytopenia (ranitidine, linezolid, vanco)
GI side effects (N/D) with ABX
46
pseudoallergic MOA
nonimmune mediated
| release of mediators from mast cells and basophils (opioids)
47
risk factors for allergic reactions
chemical structure-similar structures may cause cross sensitivity
molecular weight-high molecular weight increases change or low with hapten/carrier
route of administration-paraenteral vs. topical
reaction may present on repeat exposures
48
carrier and hapten as immunogenic compound
carrier and hapten are immunogenic compound
requires covalent binding
hapten-reacts with a specific antibody (low molecular weight prevents it from being immunogenic by itself)
can undergo biotransformation or photoactivation to become activated and immunogenic
insulin does not require binding for immune response
49
type I hypersensitivity
anaphylactic (IgE mediated)
50
type II hypersensitivity
cytotoxic antibodies
51
type III hypersensitivity
immune complexes
52
type IV hypersensitivity
cell mediated (delayed)
53
anaphylaxis
acute, life threatening allergic reaction
skin-pruritis, urticaria, erythema, angioedema
GI-N/V/D, abdominal pain
resp-chest tightness, stridor, bronchospasm
CV-hypotension, tachy, dysrhythmias
onset 30-120 mins after exposure
54
fatal anaphylaxis
asphyxia due to laryngeal edema or CV collapse
55
serum sickness
resulting from soluble circulating immune complexes that form under conditions of antigen excess
onset-7 to 14 days
presentation-fever, malaise, lymphadenopathy
56
common causes of serum sickness
cephalosporins, antivenim (equine serum leads to allergic reaction)
57
drug fever
CNS-alters temperature or stimulate release of endogenous pyrogens from WBC (TNF and IL1)
direct-tumor cell destruction
onset-7 to 10 days
temperature pattern is highly variable
58
common agents for drug fever
amphotericin B, antimicrobials
59
Jarisch-Herxheimer Reaction
follows antibiotic treatment for spirochetal and bacterial infections
sudden release of bacterial components from injured and/or killed bacteria
symptoms-rigors, fever, hypotension
60
classic causes of JHR
louse borne relapsing fever or tick borne refractory fever
61
common agents causing JHR
TCN, doxy, Pen G
62
drug induced autoimmunity
SLE
hemolytic anemia
renal interstitial nephritis
hepatic hypersensitivity reaction/toxic hepatitis
63
SLE
drugs with hydrazine or amino group linked to aromatic ring (procainamide, hydralazine, isoniazide, phenytoin)
common-fever, rash, malaise, arhralgias, myalgias
several months after beginning drug
64
common agents of SLE
procainamide, hydralazine, isoniazid, phenytoin, quinidine, penicillamine
65
Interstitial nephritis
fever, rash and eosinophilia
| proteinuria, hematuria, eosinophiluria
66
mechanism interstitial nephritis
antibodies to drug-basement membrane complex
67
common agents of interstitial nephritis
antistaphylococal penicillins (methicillin, ox, clox, diclox, nafcillin), cimetidine, sulfonamides
68
hepatic hypersensitivity reaction
drug or metabolite acts as hapten to induce an autoimmune reaction
eosinophilia, fever, rash, granulomas
69
common agents of hepatic hypersensitivity
erythromycin, penicillins
70
vasculitis
inflammation and necrosis of blood vessels
limited to skin but can involve multiple organs
most common-palpable purpuric lesions
usually over lower extremities
71
dermatologic reactions
```
erythematous maculopapular rash (most common)
urticaria/angioedema
fixed drug eruptions
phototoxicity/photoallergy
eczematous contact dermatitis
erythema multiforme
SJS
TEN
```
72
maculopapular rash
symmetrical, flat red rash
begins on extremities in ambulatory or back of bedridden patients
spares palms and soles
73
common causes of maculopapular rash
penicillins, antibiotics, anticonvulsants
74
urticaria/angioedema
blood plasma leaking out of small blood vessels due to histamine release
wheals with surrounding eryhtema
angioedema-facial and periorbital
75
common agents of urticaria/angioedema
antibiotics, NSAIDS, anticonvulsants
| lisinopril/ACEi can also cause angioedema
76
fixed drug eruptions
single or multiple edematous, pigmented lesion
frequently dark red, violet or brownish pink
reappear in same location when drug reinitiated
77
common agents fixed drug eruptions
PCN, TCN, cipro, bactrim
| NSAIDs, quinidine, sulfonamides
78
phototoxicity
immediately after drug treatment after a short exposure to sunlight
UV light results in drug emitting energy that can damage tissue
79
photoallergy
activated by long wavelength sunlight
erythema/edema progress to urticarial, eczematous papulovesicular or exudative eruptions
UV light+drug or metabolite as hapten+ tissue antigen=complete antigen
80
common causes of phototoxicity/photoallergy
TCN, carbamazepine, griseofulvin, coal tar derivatives, oral contraceptives
81
eczematous contact dermatitis
new rash develops
normally during topical treatment of pre-existing dermatosis
new rash becomes eryhtematous, indurated, and vesicular
82
erythema multiforme
begins as round, small, erythematous macule
target lesions on hands, feet, limbs, mucous membranes, and face
often preceded by mild upper respiratory symptoms
83
common causes of erythema multiforme
antibiotics, anticonvulsants, NSAIDs
84
Stevens Johnson syndrome
mucosal and conjunctival edema
high fever, myalgias, arthralgias
more severe erythema multiforme
85
complications of Stevens Johnson syndrome
keratitis
conjunctival scarring
blindness
86
common causes of SJS
sulfas, anticonvulsants, NSAIDs
87
Toxic epidermal necrolysis
begins with malaise and fever
erythematous rash progresses to large flaccid bullae-become confluent, epidermis sloughs in large sheets, leaving exposed raw dermis
88
common causes of TEN
antibiotics, anticonvulsants, NSAIDs
89
Rhinitis/asthma
possibly IgE mediated allergy from agents that can cause anaphylaxis
90
causes of rhinitis/asthma
NSAIDs, sulfites
91
acute infiltrative and chronic fibrotic pulmonary reaction
cough and dyspnea
92
causes of fibrotic pulmonary reaction
nitrofurantion, bleomycin
93
hematological reactions
```
eosinophilia
bone marrow aplasia (aplastic anemia)
hemolytic anemia (drug induced antibody)
thrombocytopenia
granulocytopenia (agranulocytosis)
```
94
common causes of eosinophilia
antibiotics
| digitalis
95
aplastic anemia
pancytopenia
signs/symptoms-fatigue, weakness, stomatitis, easy bruising, petechiae
may appear after the drug has been discontinued
96
common causes of aplastic anemia
dose dependent-chemotherapy
idiosyncratic-chloramphenicol
drug binding (IgG antibodies attack)
antibiotics, anticonvulsants, NSAIDs
97
hemolytic anemia-drug/drug metabolite
IgG antibodies attack and destroy through complement
| penicillins, cephalosporins
98
hemolytic anemia-immune complexes
adsorb to erythrocyte surface
innocent bystander
quinidine
99
hemolytic anemia-IgG antidrug metabolite
antibody binds eryhtrocyte
antibody coated cells phagocytized
coombs positive
methyldopa, penicillin
100
thrombocytopenia-drug/drug metabolite
heparin
101
thrombocytopenia-innocent bystander
quinidine, antibiotics
102
thrombocytopenia-drug+HLA antigens
drug-platelet combination is recognized as non-self resulting in destruction by autoantibodies
gold salts
103
symptoms of thrombocytopenia
petechiae, blisters in mouth
risk of bleed higher
intervention must occur
104
symptoms of agranulocytosis
chills, fever, sore throat
105
management of drug allergies
discontinuation of the agent when possible
treatment of adverse clinical signs and symptoms
substitution of another drug or agent
desensitization
skin testing for penicillin allergy
enter allergic reaction into patient chart-avoid mistakes in future
report ADR to FDA-medwatch program to collect phase IV info
106
Naranjo scale
probability of allergic rxn related to medication in question
definite, probable, possible, doubtful
107
cause of smallpox
variola major
108
importnat subfamily of poxviridae
chordopoxvirinae
109
orthopoxvirus genus members
vaccina, variola, cowpox
110
molluscipoxvirus genus members
molluscum contagiosum
| not seen until AIDS comes along
111
structural characteristics of vaccinia
largest and most complex
oval or brick shape
double stranded DNA with covalently linked termini
envelope, biconcave core, lateral bodies
112
importance of vaccinia in viruses
can accommodate a genome with additional DNA sequences artificially or naturally added (25 kb)
113
Guarnieri bodies
cytoplasmic inclusion bodies that correspond to viral replication sites
114
location of replication
entirely in cytoplasm
115
Attachment
receptor-GAG (glycan amino glycan)
| internalize through viropexis
116
Uncoating
host cell enzyme remove outer envelope and lateral bodies
activation of core enzymes including viral DNA-RNAP to make immediate early mRNA
immediate early proteins for second step of uncoating
117
early proteins
enzymatic activities for viral DNA replication
| includes DNA dependent DNAP, thymidine kinase, exonucleases
118
late proteins
from progeny DNA
| form structural proteins
119
maturation and assembly
MT allow virus particles to move to surface to egress
| one layer synthesized, one from cell
120
clinical manifestations of variola
enters through UR tract
transient viremia to internal organs and bone marrow
second viremia-first on face and then spreading centrifugally
121
lesions of variola
macule to papule to umbilicated vesicle to pustule to crust and scarring
involves dermis and epidermis
umbilicated
lesions are on palms of hand and soles of feet
122
benefit of incubation period
can vaccinate
| severe fever 1-4 days prior to rash (important prodromal symptom)
123
detection of variola
eosinophilic cytoplasmic inclusions in SPV infected skin cells
IF specifically directed to SPV antigens (hemagglutinin) for early detection
later-antibodies directed against viral antigens detected in patient serum
124
transmission of variola
only in man
person to person contact-not infectious during incubation period and first day of prodrome
infectious when rash appears and progresses to crust
125
vaccination
live attenuated vaccine
| each generation becomes more avirulent
126
vaccinia gangrenosa
low T cell
| spreading lesion with necrosis of skin and muscles
127
generalized vaccinia
occurs in patients with agammaglobulinemia or normal children
often fatal
resembles generalized herpes virus infections
128
eczema vaccinatum
localize vesicles in areas of acne, eczema
129
fetal vaccinia
vaccination of mother
| still births or recovers
130
postvaccinal encephalitis
hypersensitivity or viral invasion of CNS sudden onset at 12 day
often fatal
complications may be greater than risk of smallpox
131
vaccinia immune globulin
administered to immunocompromised individuals with vaccinia infections
132
Rifamyacin
inhibits morphogenesis by preventing proteolytic processing of precursor protein to smaller protein product (P4A to 4A)
133
molluscum contagiosum
wart like, umbilicated
usually found in genital region
must remove central core of lesion to eliminate infection
