Rapid Review Flashcards
1
Q
Abdominal pain, diarrhea, leukocytosis, recent abx (clindamycin)
A
Clostridium difficile infection
2
Q
Achilles’ tendon xanthoma; accelerated atherosclerosis (MI before age 20)
A
Familial hypercholesterolemia IIa - absent/defective LDL receptors; increased cholesterol levels
3
Q
Increased chylomicrons and triglycerides in blood; pancreatitis; NO increased risk for atherosclerosis; “creamy” layer in supernatant
A
Hyperchylomicronemia (I) - lipoprotein lipase deficiency or ApoC2 deficiency (cofactor for LPL)
4
Q
hypertriglyceridemia >1000 mg/dL; acute pancreatitis
A
Hypertriglyceridemia (IV) - hepatic overproduction of VLDL
5
Q
adrenal hemorrhage, hypotension, DIC
A
Waterhouse-Friderichsen syndrome (meningococcemia)
6
Q
Anaphylaxis following blood transfusion
A
IgA deficiency
7
Q
arachnodactyly, lens dislocation, aortic dissection, hyperflexible joints
A
Marfan syndrome (fibrillin defect)
8
Q
Athlete w/ polycythemia (inc EPO and inc RBC mass)
A
secondary to erythropoietin injection
9
Q
bilateral acoustic schwannomas; juvenile cataracts; meningiomas; ependymomas
A
neurofibromatosis type 2 - NF2 gene on chromosome 22
10
Q
cafe-au-lait spots, cutaneous neurofibromas, optic gliomas, pheochromocytomas, Lisch nodules (pigmented iris hamartomas)
A
Neurofibromatosis type 1 - Von Recklinghausen disease (NF1 gene on chromosome 17)
11
Q
bilateral hilar adenopathy, uveitis
A
Sarcoidosis
12
Q
black eschar on face of pt w/ DKA
A
Mucor or Rhizopus fungal infection
13
Q
Blue line on gingiva
A
Burton line - lead poisoning
14
Q
bone pain, bone enlargement, arthritis
A
Paget disease of bone (increased osteoblastic & osteoclastic activity)
15
Q
bounding pulses, diastolic heart murmur, head bobbing
A
aortic regurg
16
Q
cafe-au-lait spots (unilateral), polyostic fibrous dysplasia, precocious puberty, multiple endocrine abnormalities
A
McCune-Albright syndrome (mosaic G-protein signaling mutation)
17
Q
cervical LAD, desquamating rash, coronary aneurysms, red conjunctiva, strawberry tongue
A
Kawasaki disease - treat w/ IVIG and aspirin
18
Q
Cherry-red spot on macula
A
Tay-Sachs (ganglioside accumulation)
Niemann - Pick (sphingomyelin accumulation)
Central retinal artery occulusion
19
Q
chest pain, pericardial effusion/friction rub, persistent fever post-MI
A
Dressler syndrome - autoimmune mediated post-MI fibrinous pericarditis
2-12 wks after acute MI
20
Q
child with fever later develops red rash (slapped cheeks) on face that then spreads to body
A
parvovirus B19
21
Q
chorea, dementia, caudate degeneration
A
Huntington disease (AD “CAG” repeat expansion)
22
Q
chorioretinitis, hydrocephalus, intracranial calcifications
A
Congenital toxoplasmosis (ToRCHES)
23
Q
Chronic exercise intolerance with myalgia, fatigue, painful cramps, myoglobinuria
A
McArdle disease - skeletal muscle glycogen phosphorylase deficiency
24
Q
conjugate horizontal gaze palsy, horizontal diplopia
A
Internuclear ophthalmoplegia (damage to MLF)
25
continuous machine-like murmur
PDA - close w/ indomethacin; keep open w/PGE analog
26
cutaneous/dermal edema due to connective tissue deposition
Myxedema due to hypothyroidism, Graves disease (pre-tibial)
27
cutaneous flushing, diarrhea, brochspasm
carcinoid syndrome (right sided cardiac valve lesions, inc 5-HIAA)
28
dermatitis, dementia, diarrhea
Pellagra (niacin/B3 deficiency)
29
dilated cardiomyopathy, edema, alcoholism/malnutrition
Wet BeriBeri (thiamine/B1 deficiency)
30
dry eyes, dry mouth, arthritis
Sjogren - autoimmune destruction of exocrine glands
31
dysphagia (esophogeal web), glossitis, iron deficiency anemia
Plummer Vinson syndrome - may progress to esophageal squamous cell carcinoma
32
elastic skin, hypermobile joints, increased bleeding tendency
Ehlers-Danlos syndrome - type IV collagen defect
Type III collagen defect in vascular subtype
33
episodic vertigo, tinnitus, sensorineural hearing loss
Meniere disease (increased endolymph leading to distention of endolymphatic system and damage to vestibular and cochlear components)
34
erythroderma, LAD, HSM, atypical CD4+ T-cells (skin and/or blood)
mycosis fungoides or Sezary syndrome
35
facial muscle spasm upon tapping
Chvostek sign - hypocalcemia
36
fat, female, fertile, forty
Cholelithiasis (gallstones)
37
fever, cough, conjunctivitis, coryza, Koplik spots followed by maculopapular rash that starts at head and spreads downward
Measles
38
golden-brown rings around peripheral cornea
Kayser-Fleischer rings - accumulation of Copper - Wilson Disease
39
Gout, intellectual disability, self mutilating behavior in a boy
Lesch-Nyhan syndrome - HGPRT deficiency (XR)
40
hamaratomatous GI polyps, hyper-pigmentation of mouth/feet/hands/genitals
Peutz-Jeghars syndrome - inherited, benign polyposis that can cause bowel obstruction; inc. GI cancer risk
41
HSM, pancytopenia, osteoporosis, aseptic necrosis of femur, bone crises
Gaucher disease (glucocerebrosidase deficiency)
42
hereditary nephritis, sensorineural hearing loss, cataracts
Alport syndrome (mutation in collagen IV)
43
hyperphagia, hypersexuality, hyperorality, hyperdocility
Kluver-Bucy syndrome (bilateral amygala lesion)
44
posthepatic venous thrombosis
| Abdominal pain, ascites, hepatomegaly
Budd - Chiari Syndrome
45
hypoxemia, polycythemia, hypercapnia, "blue bloater"
chronic bronchitis: hyperplasia of mucous cells
46
indurated, ulcerated genital lesion
Painless -> chancre due to primary syphilis
Painful w/ exudate -> chancroid due to H ducreyi
47
infant w/ cherry-red spot on macula, HSM, neurodegeneration
Neimann-Pick (sphingomyelinase deficiency)
48
infant with cleft-lip/palate, microcephaly or holoprosencephaly, polydactyly, cutis aplasia
Trisomy 13 (Patau)
49
Infant with hypoglycemia and hepatomegaly
Cori disease - debranching enzyme deficiency
Von Gierke disease - glucose -6-phosphatase deficiency
50
infant with microcephaly, rocker-bottom feet, clenched hands, structural heart defect
Edwards syndrome (Trisomy 18)
51
jaundice, palpable distended non-tender gallbladder
Courvoisier sign - distal obstruction of biliary tree
52
male child, recurrent infections (bacterial, enteroviral, giardia), no mature B-cells
Bruton disease - X-linked agammaglobinemia (defective BTK tyrosine kinase)
53
mucosal bleeding and prolonged bleeding time
defective platelet aggregation due to lack of GpIIb/IIIa - Glanzmann thrombasthenia
54
multiple colon polyps, osteomas/soft-tissue tumors, impacted/supernumerary teeth
Gardner syndrome (FAP)
55
muffled heart sounds, distended neck veins, hypotension
cardiac tamponade
56
myopathy (infantile hypertrophic cardiomyopathy) and exercise intolerance
Pompe disease due to lysosomal alpha-1,4-glucosidase deficiency
57
neonate w/ arm paralysis following difficult birth
Erb-palsy (waiter's tip) - traction/tear of upper roots (C5-C6)
58
no lactation postpartum, absent menstruation, cold intolerance
Sheehan syndrome - pituitary infaction
59
nystagmus, intention tremor, scanning speech, bilateral INO
multiple sclerosis
60
painful raised red lesions on pads of fingers/toes
Osler nodes - infectious endocarditis or immune complex deposition
61
painless erythematous lesions on palms and soles
Janeway lesions - infectious endocarditis, septic emboli/microabcesses
62
Palpable purpura on butt/legs, joint pain, abdominal pain (child) hematuria
Henoch-Schonlein purpura - IgA vasculitis affecting skin and kidneys
63
Pancreatic, pituitary, parathyroid tumors
MEN1 (AD)
64
Dyspnea, hyperventilation, "pink puffer"
Emphysema: centriacinar - smoking; panacinar - alpha1-antitrypsin deficiency
65
Polyuria, renal tubular acidosis, growth failure, electrolyte imbalance, hypophosphatemic rickets
Fanconi syndrome - multiple combined dysfunctions of the proximal convoluted tubule
66
Pruritic, purple, polygnal, planar papules and plaques
Lichen Planus
67
Ptosis, miosis, anhidrosis
Horner (sympathetic chain lesion)
68
Pupil accommodates but does not react
Neurosyphilis - Argyll Robertson pupil
69
rapidly progressing limb weakness that ascends following GI/UR infection
Guillain-Barre - acute inflammatory demyelinating polyradiculopathy
70
rash on palms and soles
Coxsackie A, secondary syphilis, Rocky Mountain spotted fever
71
Recurrent cold (non-inflamed) abscesses, unusual eczema, high serum IgE
Hyper IgE syndrome
72
red "current jelly" stools
Acute mesenteric ischemia (adults)
| Intussusception (children)
73
red, itchy, swollen rash of nipple/areola
Paget disease of the breast - underlying malignancy
74
red urine in the morning and fragile RBCs
paroxysmal nocturnal hemoglobinuria (absent DAF/GPI) - RBC destruction by complement
75
renal cell carcinoma (bilateral), hemangioblastomas, angiomatosis, pheochromocytoma
von Hippel-Lindau (tumor suppressor gene mutation)
76
retinal hemorrhages with pale centers
Roth spots - bacterial endocarditis
77
short stature, cafe-au-lait spots, thumb/radial defects, increased tumors/leukemias, aplastic anemia
Fanconi anemia - genetic loss of DNA crosslink repair; often progresses to AML
78
Situs inversus, chronic sinusitis, bronchiectasis, infertility (male)
Kartagener syndrome (dynein arm defect affecting cilia)
79
skin hyperpigmentation, hypotension, fatigue
Primary adrenocortical insufficiency (Addison disease) - increase ACTH and increase alpha-MSH production
80
streak ovaries, congenital heart disease, horseshoe kidney, cyctic hygroma at birth, short stature, webbed neck, lymphedema
Turner syndrome - 45XO
81
Swollen gums, mucosal bleeding, poor wound healing, petechia
Scurvy - Vitamin C deficiency - can't hydroxylate proline/lysine for collagen synthesis
82
telangiectasias, recurrent epistaxis, skin discoloration, arteriovenous malformations, GI bleeding, hematuria
Osler-Weber-Rendu syndrome
83
thyroid tumors, parathyroid tumors, pheochromocytoma
MEN2A (AD Ret mutation)
84
thyroid tumors, pheochromocytoma, ganglioneuromatosis
MEN2B - AD Ret mutation
85
Unilateral facial drooping involving the forehead
LMN CNVII palsy (UMN spares forehead)
86
urethritis, conjunctivitis, arthritis in male
reactive arthritis (HLA-B27)
87
Vascular birthmark - "port wine stain" on face
nevus flammeus (benign but assoc w/ Sturge-Weber syndrome)
88
Sporatic port-wine stain, tram-track calcifications, ipsilateral leptomenigeal angioma, intellectual disability, early onset glaucoma, epilepsy
Sturge-Weber Syndrome - GNAQ activating mutation affecting small blood vessels
89
anticentromere antibodies
Scleroderma (CREST)
90
Anti-GBM antibodies
Goodpasture syndrome (glomerulonephritis and hemoptysis)
91
Antihistone antibodies
Drug induced SLE (hydralazine, isoniazid, phenytoin, procainamide)
92
Anti IgG antibodies
Rheumatoid arthritis
93
Antimitochondrial antibodies
Primary biliary cirrhosis
94
P-ANCA
microscopic polyangiitis and Churg-Strauss
95
C-ANCA
Wegener
96
Antinuclear antibodies (Anti-smith and anti-dsDNA)
SLE (type III hypersensitivity)
97
anti-platelet antibodies
Idiopathic thrombocytopenic purpura
98
anti-topoisomerase antibodies
diffuse systemic scleroderma
99
Basophilic stippling on RBCs
sideroblastic anemia or Lead poisoning
100
hypertension, hypokalemia, metabolic alkalosis
Conn syndrome - primary hyperaldosteronism
101
Arnold-Chiari malformation
herniation of cerebellar tonsils and vermis through foramen magnum w/ aqueductal stenosis and hydrocephalus
posterior fossa malformation
102
Dandy-Walker malformation
agenesis of cerebellar vermis with cystic enlargement of the 4th ventricle (fills the enlarged posterior fossa)
associated w/ spina bifida and hydrocephalus
103
syringomyelia
cystic cavity w/in spinal cord
anterior commissure white fibers damaged first - "cape-like" bilateral loss of pain and temperature sensation in upper extremities (ususally C8-T1)
104
Taste sensation - tongue
```
CN VII (facial) - anterior 2/3
CN IX (glossopharyngeal) - posterior 1/3
CN X (vagus) - epiglottis
```
105
Pain Sensation - tongue
```
CN V3 (trigeminal) - anterior 2/3
CN IX (glossopharyngeal) - posterior 1/3
```
106
Motor innervation - tongue
CN X (vagus) - palatoglossus - elevates posterior tongue during swallowing
CN XII (hypoglossal) - hyoglossus (retracts/depresses), genioglossus (protrudes), styloglossus (trough for swallowing)
107
norepinephrine - change in disease
increased in anxiety, decreased in depression
108
norepinephrine - location of synthesis
locus ceruleus (pons)
109
dopamine - tuberoinfundibular pathway
connects hypothalamus and pituitary; dopamine dependent tonic inhibition of prolactin
110
Dopamine - change in disease
increased in Huntington
| Decreased in Parkinson and depression
111
5-HT - change in disease
serotonin
decreased in anxiety, decreased in depression
112
5-HT - location of synthesis
Raphe nuclei - pons, medulla, midbrain
113
Acetylcholine - change in disease
increased in Parkinson
| decreased in Alzheimer, Huntington
114
Acetylcholine - location of synthesis
basal nucleus of Meynert
115
GABA - change in disease
decreased in anxiety
| decreased in Huntington
116
GABA - location of synthesis
nucleus accumbens
117
Mesolimbic-Mesocortical dopaminergic pathway
regulates behavior; hyperactive in schizophrenia
118
nigrostriatal domaminergic pathway
coordination of voluntary movement; decreased in Parkinson
119
Hypothalamus - roles
"TAN HATS"
Thirst and water balance, adenohypophysis control, neurohypophysis releases hypothalamic hormones, hunger, autonomic regulation, temperature regulation, sexual urges
120
hypothalamic inputs
OVLT - senses change in osmolarity
| Area postrema -responds to emetics
121
Site of ADH production
supraoptic nucleus (hypothalamus)
122
site of oxytocin production
paraventricular nucleus (hypothalamus)
123
Lateral area of hypothalamus
hunger
destruction leads to anorexia, failure to thrive
inhibited by leptin
124
ventromedial area of hypothalamus
satiety - stimulated by leptin
destruction (via craniopharyngioma) leads to hyperphagia
125
anterior hypothalamus
cooling (parasympathetic)
126
posterior hypothalamus
heating (sympathetic)
127
suprachiasmatic nucleus of hypothalamus
circadian rhythm - releases norepinephrine which acts on pineal gland - releases melatonin
128
Awake/eyes open - EEG waveform
Beta (highest frequency, lowest amplitude)
129
Awake/eyes closed - EEG waveform
Alpha
130
Non-REM - stage N1 EEG wave form
Theta
| Light sleep
131
Non-REM N2 sleep stage - EEG waveform
```
deeper sleep (bruxism)
Sleep spindles and K complexes
```
132
Non-REM N3 sleep stage - EEG waveform
deepest non-REM sleep - sleepwalking, night terrors, bedwetting
Delta (lowest frequency, highest amplitude)
133
REM sleep - EEG waveform
loss of motor tone, increased brain O2 use, increased/variable pulse/BP; dreaming and penile/clitoral tumescence; memory processing function
Beta
134
VPL nucleus of thalamus
pain, temp, pressure, touch, vibration, proprioception
input - spinothalamic tract and DC/ML
output - primary somatosensory cortex
135
VPM nucleus of thalamus
face sensation, taste
input: trigeminal and gustatory pathway
output: primary somatosensory cortex
136
LGN nucleus of thalamus
Vision
input: CN II
output: calcarine sulcus
137
MGN nucleus of thalamus
Hearing
input: superior olive and inferior colliculus of tectum
output: auditory cortex (temporal lobe)
138
VL nucleus of thalamus
motor
input: basal ganglia, cerebellum
output: Motor cortex
139
Limbic system
hippocampus, amygdala, fornix, mammillary bodies, cingulate gyrus
"Feeding, fleeing, fighting, feeling, sex"
140
MCA stroke
motor cortex - contralateral paralysis of upper limb and face
sensory cortex - contralateral loss of sensation in upper limb and face
temporal lobe (Wernicke) - aphasia if dominant; hemineglect if non-dominant
frontal lobe (Broca) - aphasia if dominant; hemineglect if non-dominant
141
ACA stroke
Motor cortex - contralateral lower limb paralysis
Sensory cortex - contralateral lower limb loss of sensation
142
Lenticulostriate artery stroke
striatum/internal capsule - contralateral hemiparesis/hemiplegia
*Lacunar infarct secondary to HTN
143
ASA stroke
lateral corticospinal tract - contralateral hemiparesis in upper & lower limbs
medial lemniscus - decreased contralateral proprioception
caudal medulla - ipsilateral hypoglossal dysfunction (deviates ipsilaterally)
144
PICA stroke
Lateral medulla
vomiting, nystagmus (vestibular nuclei)
decreased pain and temp sensation from ipsilateral face (spinal trigem nucl) and contralateral body (lateral spinothalamic tracts)
dysphagia and hoarseness and decreased gag reflex (nucl ambiguus)
ipsilateral Horner (sympathetics)
ataxia and dysmetria (inferior cerebellar peduncle)
145
AICA stroke
Lateral pons (vestibular nuclei, facial nucleus, spinal trigeminal nucleus, cochlear nuclei, sympathetics); Middle and inferior cerebellar peduncles
Vomiting, vertigo, nystagmus, paralysis of face, decreased lacrimation/salivation, decreased taste from anterior 2/3 of tongue, decreased pain and temperature of ipsilateral face and contralateral body, ataxia, dysmetria
146
PCA stroke
occipital cortex and visual cortex - contralateral hemianopia with macular sparing
147
Basilar artery
Locked in syndrome
preserved consciousness and blinking w/ quadraplegia, loss of voluntary facial, mouth, and tongue movements
148
AComm stroke
more commonly aneurysm - visual field defects due to impingement of cranial nerves
149
PComm aneurysm
CN III palsy - eye is "down and out" with ptosis and mydriasis
150
urinary incontinence, ataxia, cognitive dysfunction in elderly person
"wet, wobbly, wacky" = normal pressure hydrocephalus
151
Amyotrophic lateral sclerosis - lesion sites
anterior motor horn (LMN)
| lateral corticospinal tract (UMN)
152
Amyotrophic lateral sclerosis - symptoms
combined UMN and LMN with no sensory or oculomotor deficit; onset in middle age
153
Amyotrophic lateral sclerosis - familial mutation
Superoxide dismutase 1 mutation - free radical injury in neurons
154
Tabes dorsalis
tertiary syphilis - degeneration of dorsal columns and roots
impaired sensation and proprioception, progressive sensory ataxia
absence of DTRs and +Romberg sign
155
Vitamin B12 deficiency (cobalamin)
subacute combined degeneration - demyelination of DC, lateral corticospinal tracts and spinocerebellar tracts
ataxic gait, paresthesia, impaired position and vibration sense
156
Poliomyelitis - causes
poliovirus (fecal-oral) - replicates in oropharynx and small intestine. spreads to CNS via bloodstream. infection destroys anterior motor horn (LMN death)
157
Poliomyelitis - symptoms
LMN lesions + infection (fever, malaise, headache, etc)
158
poliomyelitis - clinical findings
CFS with increased WBCs and slight increase in protein (no increase in glucose)
virus can be recovered from stool or throat
159
spinal muscular atrophy (Werdnig-Hoffman disease)
congenital degeneration of anterior horns of spinal cord - LMN lesions
"floppy baby" w/ hypotonia and tongue fasciculations (median death ~7 mo)
Autosomal recessive
160
frataxin
regulates mitochondrial iron - mutation leads to loss of regulation and increased iron with free radical damage
GAA repeat - Friedreich Ataxia
161
staggering gait, frequent falling, nystagmus, dysarthria, pes cavus, hammer toes, diabetes mellitus, hypertrophic cardiomyopathy, kyphoscoliosis
Friedriech Ataxia - GAA repeat in frataxin gene on chromosome 9
degeneration of spinocerebellar tracts (ataxia)
degeneration of DC and DRG (loss of position sense and vibration)
162
Biceps reflex
C5,C6
"pick up sticks"
163
Achilles reflex
S1, S2
| "buckle my shoe"
164
Patellar reflex
L3, L4
"kick the door"
165
triceps reflex
C7, C8
"lay them straight"
166
cremaster reflex
L1, L2
"testicles move"
167
anal wink reflex
S3, S4
"winks galore"
168
structures through the optic canal
CN II (optic), ophthalmic artery, central retinal vein
169
structures through superior orbital fissure
```
CN III (oculomotor)
CN IV (trochlear)
CN V1 (trigeminal - ophthalmic nerve)
CN VI (abducens)
ophthalmic vein
sympathetic fibers
```
170
Structures through foramen rotundum
CN V2 - maxillary nerve
171
structures through foramen ovale
CN V3 - mandibular nerve
172
structures through the foramen spinosum
middle meningeal artery (branch of maxillary artery)
173
Structures through the jugular foramen
```
CN IX (glossopharyngeal)
CN X (vagus)
CN XI (accessory)
jugular vein
```
174
structures through foramen magnum
spinal roots of CN XI (accessory)
brain stem
vertebral arteries
175
low frequency hearing
at the apex of the basilar membrane near helicotrema (wide and flexible)
176
high frequency hearing
at the base of cochlea (thin and rigid)
177
noise-induced hearing loss
damage to stereociliated cells in organ of Corti - loss of high frequency hearing first
178
Hyperacusis
due to CNVII injury leading to paralysis of stapedius
179
Hyperopia
eye too short for refractive power of cornea and lens - light focused behind the retina
(farsightedness)
180
Myopia
eye too long for refractive power of lens and cornea - light focused in front of retina
(nearsightedness)
181
presbyopia
age-related impaired accommodation (focusing on near objects)
necessitates reading glasses
182
deposition of yellowish extracellular material (drusen) with gradual decrease in vision and scotomas
Dry macular degeneration due to chronic oxidative damage
| prevent progression with multivitamin and antioxidant supplements
183
rapid loss of vision (scotomas), grey-green subretinal discoloration with adjacent fluid/hemorrage
Wet macular degeneration - secondary to choroidal neovascularization
treat with anti-VEGF
184
decreased bilateral pupillary constriction when flashlight is shone in affected eye relative to unaffected eye (swinging flashlight test)
afferent pupillary defect - Marcus Gunn pupil due to optic nerve damage or severe retinal injury
185
one sided anopia
optic nerve lesion
186
homonymous hemianopia
optic tract lesion
187
upper quadrant anopia
Meyer loop lesion (temporal lobe)
| MCA (temporal lobe)
188
lower quadrant anopia
```
dorsal optic radiation lesion (parietal lobe)
MCA stroke (parietal lobe)
```
189
hemianopia with macular sparing
PCA infarct
190
conjugate gaze palsy with nystagmus
INO (MLF lesion)
| nystagmus in "good eye"
191
opioid analgesics - MoA
agonists at opioid receptors
decrease synaptic transmission - open potassium channels, close calcium channels
inhibit release of ACh, NE, 5-HT, glutamate, substance P
192
Butorphanol - MoA
kappa-opioid receptor agonist and mu-opioid receptor partial agonist - produces analgesia
193
Butorphanol - clinical use
pain (migraine, labor)
| less respiratory depression than full opioid agonists
194
Butorphanol - toxicity
opioid withdrawal symptoms if pt is taking full opioid agonist b/c competition for opioid receptors
not easily reversed w/ naloxone
195
tramadol - MoA
very weak opioid agonist, inhibits 5-HT and NE reuptake
196
Tramadol - clinical use
chronic pain
197
tramadol - toxicity
similar to opioids
decreases seizure threshold
serotonin syndrome
198
ethosuximide - MoA
blocks thalamic T-type calcium channels
199
ethosuximide - clinical use
absence seizures
200
ethosuximide - toxicity
GI, fatigue, headache, urticaria, Stevens-Johnson syndrome
201
Benzodiazepines (seizure) - MoA
diazepam/lorazepam
increase GABAa action (potentiate)
202
Benzodiazepines (seizure) - clinical use
first line for acute status epilepticus
| also use for eclampsia seizures
203
Benzodiazepines (seizure) - toxicity
sedation, tolerance, dependance, respiratory depression
204
Phenytoin - MoA
increases sodium channel inactivation (zero order kinetics)
205
Phenytoin - clinical use
Simple, Complex, Tonic-clonic
prophylaxis for status epilepticus
206
Phenytoin - toxicity
**CYP450 inducer; SLE-like syndrome; Stevens-Johnson syndrome; teratogenic
nystagmus, diplopia, ataxia, sedation, gingival hyperplasia, hirsutism, peripheral neuropathy, megaloblastic anemia, LAD, osteopenia
207
carbamazepine - MoA
increases sodium channel inactivation
208
carbamazepine - clinical use
simple, complex, tonic-clonic seizures
trigeminal neuralgia
209
carbamazepine - toxicity
```
Blood dyscrasia (agranulocytosis, aplastic anemia)
liver toxicity
Stevens-Johnson
Inducer of CYP450
teratogenic
SIADH
diplopia
```
210
Valproic acid - MoA
increases sodium channel inactivation
| increases GABA concentration by inhibiting GABA transaminase
211
sonic hedgehog gene
patterning along anterior-posterior axis; CNS development (mutation - holoprosencephaly)
212
wnt-7 gene
organization along dorsal-ventral axis
213
FGF gene
stimulates mitosis of mesoderm - lengthening of limbs
214
Hox (homeobox) genes
segmental organization in craniocaudal direction
codes for transcription factors
Hox mutations - appendages in wrong locations
215
1st aortic arch
maxillary artery
216
2nd aortic arch
stapedial artery and hyoid artery
217
3rd aortic arch
common carotid and proximal internal carotid artery
218
4th aortic arch
on the left - aortic arch
on the right - proximal part of right subclavian
(4th arch = 4 limbs = systemic circulation)
219
6th aortic arch
proximal part of pulmonary arteries and ductus arteriosus
220
IL-1
osteoclast activating factor
secreted by macrophages
Fever, acute inflammation
Activates endothelium expression of adhesion molecules
Induces chemokine secretion to recruit WBCs
221
IL-6
secreted by macrophages
| caused fever and stimulated production of acute phase protein
222
IL-8
secreted by macrophages
| major chemotactic factor for neutrophils
223
IL-12
secreted by macrophages
induces differentiation of T cells into Th1 cells
activates NK cells
224
TNF-alpha
secreted by macrophages
mediates septic shock
activates endothelium - causing WBC recruitment and vascular leak
225
IL-2
secreted by all T cells
| stimulates growth of helper, cytotoxic, and regulatory T cells and NK cells
226
IL-3
secreted by all T Cells
| supports growth and differentiation of bone marrow stem cells (like GM-CSF)
227
Interferon-gamma
secreted from Th1 cells
secreted by NK cells in response to IL-12 from macrophages - stimulates macrophages to kill phagocytosed pathogens
activates NK cells to kill virus infected cells
increases MHC expression and antigen presentation by all cells
228
IL-4
secreted by Th2 cells
induces differentiation into Th2 cells
promotes growth of B cells
enhances class switching to IgE and IgG
229
IL-5
secreted by Th2 cells
promotes differentiation of B cells
enhances class switching to IgA
stimulates growth and differentiation of eosinophils
230
IL-10
secreted by Th2 cells
modulates inflammatory response
decreases expression of MHC-II and Th1 cytokines
inhibits activated macrophages and dendritic cells
231
anti-inflammatory cytokines
TGF-beta and IL-10 - attenuate immune response
232
widespread thrombosis of graft vessels leading to ischemia/necrosis within minutes of transplant
hyperacute transplant rejection - pre-existing recipient antibodies react to donor antigen
T2HSR
activates complement
233
vasculitis of graft vessels with dense interstitial lymphocytic infiltrate
acute transplant rejection (w/in weeks to months)
cellular rejection - CD8+ T cells activated against donor MHCs
humoral rejection - recipient antibodies against donor antigen develop after transplant
Prevent/reverse with immunosuppressants
234
proliferation of vascular smooth muscle and parenchymal fibrosis in transplanted organ - arterioscelerosis
chronic transplant rejection - months to years after transplant
CD4+ T cells respond to recipient APCs presenting donor peptides, including allogenic MHC, and secrete cytokines
cellular and humoral components
235
maculopapular rash, jaundice, diarrhea, HSM following bone marrow or liver transplant
Graft vs host disease
grafted immunocompetent T cells proliferate in immunocompromised host and reject host cells with "foreign" proteins - leads to severe organ dysfuntion
236
endocrine hormones that use cAMP signaling pathway
FSH, LH, ACTH, TSH, CRH, hCG, ADH (V2), MSH, PTH, calcitonin, GHRH, glucagon
"FLAT ChAMP" + calcitonin, GHRH, glucagon
237
endocrine hormones that use cGMP signaling pathway
ANP, BNP, NO (EDRF)
- vasodilators
238
endocrine hormones that use IP3 signaling pathway
GnRH, Oxytocin, ADH (V1), TRH, Histamine (H1), Angiotensin II, Gastrin
"GOAT HAG"
239
endocrine hormones that use intracellular receptor for signaling
Vitamin D, Estrogen, Testosterone, T3/T4, Cortisol, Aldosterone, Progesterone
"VETTT CAP"
240
Intrinsic tyrosine kinase signalling
MAP kinase pathway - growth factors
Insulin, IGF-1, FGF, PDGF, EGF
241
receptor associate tyrosine kinase singaling
JAK-STAT pathway - PIGGLET
Prolactin, Immunomodulators (cytokines), GH, G-CSF, Erythropoietin, Thrombopoietin
242
Penicillin and cephalosporin - resistance mechanism
Production of beta-lactamases, which cleave the beta-lactam ring structure; change in penicillin-binding proteins; change in porins
243
aminoglycoside - mechanism of resistance
Formation of enzymes that inactivate drugs via conjugation reactions that transfer acetyl, phosphoryl, or adenylyl groups
(Gentamicin, Neomycin, Amikacin, Tobramycin, Streptomycin)
244
macrolides and clindamycin - mechanism of resistance
Formation of methyltransferases that alter drug binding sites on the SOS ribosomal subunit
Active transport out of cells
Macrolides - erythromycin, azithromycin, clarithromycin
245
tetracyclines - mechanism of resistance
Increased activity of transport systems that "pump" drugs out of the cell (plasmid encoded transport pumps)
tetracycline, doxycycline, minocycline
246
sulfonamides - mechanism of resistance
Change in sensitivity to inhibition of target enzyme; increased formation of PABA; use of exogenous folic acid
sulfamethaxazole, sulfisoxazole, sulfadiazine
247
fluoroquinolones - mechanism of resistance
Change in sensitivity to inhibition oftarget enzymes; increased activity of transport systems that promote drug efflux
ciprofloxacine, norfloxacin, levofloxacin, ofloxacin, moxifloxacin, gemifloxacin, enoxacin
248
chloramphenicol - mechanism of resistance
Formation of inactivating acetyltransferases
249
Inhibition of bacterial cell-wall synthesis
Penicillins, cephalosporins, imipenem/meropenem, aztreonam, vancomycin
250
Inhibition of bacterial protein synthesis
Aminoglycosides, chloramphenicol, macrolides, tetracyclines, streptogramins, linezolid
251
Inhibition of folic acid synthesis
sulfonamides, trimethoprim, pyrimethamine
252
Penicillin - MoA
Bacterial cell wall is cross-linked polymer of polysaccharides and pentapeptides - Penicillins interact with cytoplasmic membrane-binding proteins (PBPs) to inhibit transpeptidation reactions involved in cross-linking, the final steps in cell-wall synthesis
253
Penicillin (narrow spectrum, beta-lactamase sensitive: penicillin G and V) - clinical use
streptococci, pneumococci, meningococci, Treponema
pallidum
254
penicillin - toxicity
hypersensitivity reactions, hemolytic anemia
255
Very narrow spectrum, beta-lactamase resistant: nafcillin, methicillin, oxacillin - clinical use
known or suspected staphylococci (not MRSA)
256
Broad spectrum, aminopenicillins, beta-lactamase sensitive: ampicillin and amoxicillin - clinical use
gram-positive cocci (not staph), E. coli, H. influenzae, Listeria monocytogenes (ampicillin), Borrelia burgdorferi (amoxicillin), H. pylori (amoxicillin)
257
Extended spectrum, antipseudomonal, beta-lactamase sensitive: ticarcillin, piperacillin - clinical use
increased activity against gram-negative rods, including Pseudomonas aeruginosa
258
cephlosporins - MoA
beta-lactam drugs that inhibit cell wall synthesis - same as penicillins
less susceptible to penicillinases
bactericidal
259
First generation cephalosporins: cefazolin, cephalexin - clinical use
Spectrum: gram-positive cocci (not MRSA), E. coli, Klebsiella pneumoniae, and some Proteus species (PEcK)
Common use in surgical prophylaxis
Pharmacokinetics: none enter CNS
260
Second generation cephalosporins: cefotetan, cefaclor, cefuroxime - clinical use
Spectrum: gram positive cocci and increased gram-negative coverage, including some anaerobes
Pharmacokinetics: no drugs enter the CNS, except cefuroxime
HEN PEcKS : H.flu, Enterobacter, Neisseria, Proteus mirabilis, E.coli, Klebsiella, Serratia
261
Third generation cephalosporins: ceftriaxone (IM) and cefotaxime (parenteral), ceftazidime - clinical use
Spectrum: gram-positive and gram-negative cocci (Neisseria gonorrhea), plus many gram-negative rods
Ceftriaxone - meningitis, gonorrhea, Lyme disease
Ceftazidime - pseudomonas
Pharmacokinetics: most enter CNS; important in empiric management of meningitis and sepsis
262
Fourth generation cephalosporins: cefepime (IV) - clinical use
Even wider spectrum - increased activity against pseudomonas
Resistant to most beta-lactamases
Enters CNS
263
fifth generation cephalosporins - ceftaroline - clinical use
broad gram positive and gram negative - including MRSA
does NOT cover pseudomonas
264
cephalosporins - toxicity
hypersensitivity (cross-react w/ penicillin)
autoimmune hemolytic anemia
disulfiram-like reaction
vitamin K deficiency
increase nephrotoxicity of aminoglycosides
265
carbapenems - MoA
same as penicillin - beta-lactamase resistant
Imipenen, meropenem, ertapenem, doripenem
266
carbapenems - clinical use
Imipenen, meropenem, ertapenem, doripenem
- Gram-positive cocci, gram-negative rods (e.g., Enterobacter,
Pseudomonas spp.), and anaerobes
Important in-hospital agents for empiric use in severe life-threatening infections
267
Imipenem - pharmokinetics
Imipenem is given with cilastatin, a renal dehydropeptidase inhibitor,
which inhibits imipenem's metabolism to a nephrotoxic metabolite
Both drugs undergo renal elimination- decrease dose in renal dysfunction
268
carbapenems - toxicity
imipenem, meropenem, ertapenem, doripenem
GI distress
Drug fever (partial cross-allergenicity with penicillins)
CNS effects, including seizures with imipenem in overdose or renal dysfunction
269
monobactam (aztreonam) - MoA
- Same as for penicillins and cephalosporins
- Resistant to beta-lactamases
270
monobactam (aztreonam) - clinical use
• Uses:
IV drug mainly active versus gram-negative rods
No cross-allergenicity with penicillins or cephalosporins
synergistic with aminoglycosides
271
vancomycin - MoA
Binding at the D-ala-D-ala muramyl pentapeptide to sterically hinder the transglycosylation reactions (and indirectly preventing transpeptidation) involved in elongation of peptidoglycan chains
Does not interfere with PBPs
272
vancomycin - clinical use
Gram positive only -
| MRSA
Enterococci
Clostridium difficile (backup drug)
273
vancomycin - resistance
Vancomycin-resistant staphylococcal (VRSA) and enterococcal (VRE) strains emerging
Enterococcal resistance involves change in the muramyl pentapeptide "target" such that the terminal D-ala is replaced by D-lactate
274
vancomycin - toxicity
- "Red man syndrome" (histamine release)
- Ototoxicity (usually permanent, additive with other drugs)
- Nephrotoxicity (mild, but additive with other drugs)
- Thrombophlebitis
275
aminoglycosides - MoA
Gentamycin, Neomycin, Amikacin, Tobramycin, Streptomycin
Bind 30S ribosomal subunit - inhibit initiation complex, cause misreading of mRNA, block translocation
Bactericidal, accumulated intracellularly in microorganisms via an
02-dependent uptake (anaerobes are innately resistant)
276
Aminoglycosides - clinical use
Gentamycin, Neomycin, Amikacin, Tobramycin, Streptomycin
Useful spectrum includes gram-negative rods; gentamicin, tobramycin,
and amikacin often used in combinations
Synergistic actions occur for infections caused by enterococci (with penicillin G or ampicillin) and P. aeruginosa (with an extended-spectrum penicillin or third-generation cephalosporin)
Neomycin for bowel surgery
Streptomycin used in tuberculosis; is the DOC for bubonic plague and tularemia
277
aminoglycosides - toxicity
Gentamycin, Neomycin, Amikacin, Tobramycin, Streptomycin
Nephrotoxicity (6 to 7% incidence) includes proteinuria, hypokalemia, acidosis, and acute tubular necrosis-usually reversible, but enhanced by vancomycin, amphotericin B, cisplatin, and cyclosporine
Ototoxicity (2% incidence) from hair cell damage; includes deafness (irreversible) and vestibular dysfunction (reversible); toxicity may be enhanced by loop diuretics
Neuromuscular blockade with decreased release of ACh-may enhance effects of skeletal muscle relaxants
278
tetracyclines - MoA
tetracycline, doxycycline, minocycline
Bacteriostatic - bind to 30S subunit of ribosomes and prevent attachment of aminoacyl-tRNA
limited CNS penetration
279
tetracycline - clinical use
tetracycline, doxycycline, minocycline
Broad-spectrum antibiotics, with good activity versus chlamydia and mycoplasmal species, H. pylori (GI ulcers), Rickettsia, Borrelia burgdorferi
also used to treat acne
280
tetracycline - toxicity
tetracycline, doxycycline, minocycline
GI distress, discoloration of teeth and inhibition of bone growth in children, photosensitivity
contraindicated in pregnancy
do not take with calcium, magnesium, iron - divalent cations decrease intestinal absorption
281
chloramphenicol - MoA
blocks peptidyltransferase at 50S ribosomal subunit
| bacteriostatic
282
chloramphenicol - clinical use
meningitis (H.flu, neisseria, s. pneumo)
| Rocky Mountain spotted fever
283
chloramphenicol - toxicity
```
anemia (dose dependent)
aplastic anemia (dose independent)
grey baby syndrome (lack liver UDP-glucuronyl transferase)
```
284
clindamycin - MoA
blocks peptide transfer at 50S ribosomal subunit
| bacteriostatic
285
clindamycin - clinical use
anerobic infections - baceriodes, c. perfringens - in aspiration pneumonia, lung abscesses, oral infections (above the diaphragm)
invasive group A strep
286
clindamycin - toxicity
C. difficile overgrowth
fever
diarrhea
287
Linezolid - MoA
inhibits protein synthesis by binding 50S subunit and preventing formation of initiation complex
288
Linezolid - clinical use
gram positive including MRSA and VRE
289
Linezolid - toxicity
bone marrow suppression, peripheral neuropathy, serotonin syndrome
290
Macrolides - MoA
azithromycin, clarithromycin, erythromycin
inhibit protein synthesis by blocking translocation
binds to the 23S rRNA of the 50S subunit
bacteriostatic
291
macrolides - clinical use
azithromycin, clarithromycin, erythromycin
atypical pneumonia, STIs (chlamydia), gram positive cocci (strep), B. pertussis
292
macrolides - toxicity
azithromycin, clarithromycin, erythromycin
MACRO:
GI Motility, Arrhythmia (prolonged QT), acute Cholestatic hepatitis, Rash, eOsinophilia
increase serum concentration of theophyllines and oral anti-coags
Clarithromycin and erythromycin - inhibit CYP450
293
trimethoprim - MoA
inhibits bacterial dihydrofolate reductase
| bacteriostatic
294
trimethoprim - clinical use
in combo w/ sulfonamides
TMP-SMX - sequential block of folate synthesis
UTIs, shigella, salmonella, pneumocystis jirovecii, toxoplasmosis prophylaxis
295
trimethoprim - toxicity
megaloblastic anemia, leukpenia, granulocytopenia
"Treats Marrow Poorly"
296
Sulfonamides - MoA
inhibit folate synthesis
PABA antimetabolites inhibit dyhydropteroate synthase
bacteriostatic (-cidal w/ TMP)
297
sulfonamides - clinical use
gram positives, gram negatives, Nocardia, Chlamydia
triple sulfas or sulfamethoxazole (SMX) for UTI
298
sulfonamides - toxicity
hypersensitivity reactions
hemolysis if G6PD deficient
nephrotoxicity (tublointerstitial nephritis)
photosensitivity
kernicterus (infants)
displaces other drugs from albumin (warfarin)
299
fluoroquinolones - MoA
ciprofloxacin, norfloxacin, levofloxacin, ofloxacin, moxifloxacin, gemifloxacin, enoxacin
inhibit prokaryotic enzymes - topoisomerase II (DNA gyrase) and topoisomerase IV
bactericidal
CANNOT TAKE W/ ANTACIDS
300
fluoroquinolones - clinical use
ciprofloxacin, norfloxacin, levofloxacin, ofloxacin, moxifloxacin, gemifloxacin, enoxacin
gram-neg rods - urinary and GI tracts
pseudomonas, neisseria
some gram-positives
301
fluoroquinolones - toxicity
ciprofloxacin, norfloxacin, levofloxacin, ofloxacin, moxifloxacin, gemifloxacin, enoxacin
Tendonitis, tendon rupture
Phototoxicity, rashes
CNS effects (insomnia, dizziness, headache)
Contraindicated in pregnancy and in children (inhibition of chondrogenesis)
302
daptomycin - MoA
lipopeptide that disrupts cell membrane of gram+ cocci
303
daptomycin - clinical use
S.aureus skin infections (MRSA)
bacteremia, endocarditis, VRE
**NOT for pneumonia - inactivated by surfactant
304
daptomycin - toxicity
myopathy, rhabdomyolysis
305
Metronidazole - MoA
forms toxic free radical metabolites in the bacterial cell that damage DNA
bactericidal, antiprotozoal
306
metronidazole - clinical use
GET GAP on the Metro
Giardia, Entamoeba, Trichomonas, Gardnerella vaginalis, Anaerobes. H.Pylori (part of triple therapy)
anaerobic below the diaphragm
307
metronidazole - toxicity
disulfram-like rxn w/ alcohol
| headache, metallic taste
308
M. tuberculosis - treatment/prophylaxis
Rifampin, Isoniazid, Pyrazinamide, Ethambutol
Isoniazid - prophylaxis
309
M. avium-intracellulare - treatment/prophylaxis
more drug resistant than TB - azithromycin or clarithromycin + ethambutol (can add rifabutin or ciprofloxacin)
azithromycin, rifabutin - prophylaxis
310
M. leprae - treatment
long-term - dapsone and rifampin for tuberculoid form
| add clofazimine for lepromatous form
311
rifamycins (rifampin/rifabutin) - MoA
inhibit DNA dependent RNA polymerase
312
rifamycins (rifampin/rifabutin) - clinical use
TB
delay resistance to dapsone in leprosy
meningococcal prophylaxis in contacts of children w/ H. influenzae B
313
rifamycins (rifampin/rifabutin) - toxicity
minor hepatotoxicity and drug interactions (rifampin increases CYP450)
orange body fluids
rifabutin preferred in pts w/ HIV - less CYP450 stimulation
314
rifamycins (rifampin/rifabutin) - resistance
mutations reduce drug binding to RNA polymerase
monotherapy = rapid resistance
315
isoniazid - MoA
decreases synthesis of mycolic acids
bacterial catalase-peroxidase needed to convert into active metabolite (mutations leading to underexp. of KatG -> resistance)
316
isoniazid - clinical use
solo prophylaxis against TB
317
isoniazid - toxicity
neurotoxicity, hepatotoxicity (10-20%)
prevent neurotoxicity w/ pyridoxine (B6)
318
pyrazinamide - MoA
uncertain - prodrug that is converted to active drug
| intracellular activity
319
pyrazinamide - clinical use
TB
320
pyrazinamide - toxicity
hyperuricemia, hepatotoxicity
321
ethambutol - MoA
decreases carbohydrate polymerization of mycobacterium cell wall by blocking arabinosyltransferase
322
ethambutol - clinical use
TB
323
ethambutol - toxicity
red-green colorblindness
324
amphotericin B - MoA
binds ergosterol (unique to fungi) - forms membrane pores that allow leakage of electrolytes
325
amphotericin B - clinical use
serious, systemic mycoses
intrathecally for fungal meningitis
supplement K and Mg b/c altered renal tube permeability
326
amphotericin B - toxicity
fever/chills, hypotension, nephrotoxicity, arrhythmias, anemia, IV phlebitis
hydration will decrease nephrotoxicity
327
Nystatin - MoA
binds ergosterol (unique to fungi); forms membrane pores that allow leakage of electrolytes
topical use only
328
Nystatin - clinical use
oral candidiasis
diaper rash
vaginal candidiasis
329
Flucytosine - MoA
inhibits DNA and RNA biosynthesis by conversion to 5-fluorouracil by cytosine deaminase
330
Flucytosine - clinical use
systemic fungal infections in combo w/ amphotericin B
| meningitis - cryptococcus
331
Flucytosine - toxicity
bone marrow suppression
332
Azoles - MoA
inhibit fungal sterol (ergosterol) synthesis by inhibiting the CYP450 complex that converts lanosterol to ergosterol
333
azoles - clinical use
local and less serious systemic fungal infections
fluconazole - chronic suppression of cryptococcal meningitis in AIDS pts and candidal infections of all types
Itraconazole - blastomyces, coccidioides,
clotrimazole and miconazole - topical
334
azole - toxicity
testosterone synthesis inhibition (ketoconazole - gynecomastia)
liver dysfunction - inhibits CYP450
335
terbinafine - MoA
inhibits fungal enzyme squalene epoxidase
336
terbinafine - clinical use
dermatophytoses
337
terbinafine - toxicity
GI upset, headaches, hepatotoxicity, taste disturbance
338
echinocandins - MoA
caspofungin, micafungin
inhibit cell wall synthesis by inhibiting synthesis of Beta-glucan
339
echinocandins - clinical use
caspofungin, micafungin
invasive aspergillosis, Candida
340
echinocandins - toxicity
GI upset, flushing (histamine release)
341
griseofulvin - MoA
interferes with microtubule function
disrupts mitosis
deposits in keratin containing tissue
342
griseofulvin - clinical use
oral treatment of superinfections, inhibits growth of dermatophytes
343
griseofulvin - toxicity
teratogenic, carcinogenic, confusion, headaches, induces CYP450 and warfarin metabolism
344
chloroquine
blocks detoxification of heme into hemozoin
heme accumulates and is toxic to plasmodia
DOES NOT TREAT p.falciparum due to resistance
345
oseltamivir/zanamivir - MoA
inhibit influenza neuraminidase - prevent release of viral progeny
346
oseltamivir/zanamivir - clinical use
treatment/prevention of influenza A and B
347
acyclovir, famciclovir, valacyclovir - MoA
guanosine analogs. monophosphorylated by HSV/VZV thymidine kinase (not phosphorylated in uninfected cells)
preferentially inhibit viral DNA polymerase by chain termination
348
acyclovir, famciclovir, valacyclovir - clinical use
HSV and VZV
weak activity agains EBV
for herpes zoster - used famciclovir
349
acyclovir, famciclovir, valacyclovir - toxicity
obstructive crystalline nephropathy and acute renal failure w/o proper hydration
350
acyclovir, famciclovir, valacyclovir - resistance
mutated viral thymidine kinase
351
ganciclovir - MoA
5'-monophosphate formed by a CMV viral kinase
guanosine analog
preferentially inhibits viral DNA polymerase by chain termination
352
ganciclovir - clinical use
CMV - esp. in immunocompromised
353
ganciclovir - toxicity
leukopenia, neutropenia, thrombocytopenia, renal toxicity
more toxic than acyclovir
354
ganciclovir - resistance
mutate viral kinase
355
Foscarnet - MoA
viral DNA/RNA polymerase inhibitor and HIV reverse transcriptase inhibitor
binds to pyrophosphate binding site of enzyme
does NOT require activation
356
foscarnet - clinical use
CMV retinitis when ganciclovir fails
| acyclovir resistant HSV
357
foscarnet - toxicity
nephrotoxic, electrolyte abnormalities - seizures
358
foscarnet - resistance
mutated DNA polymerase
359
cidofovir - MoA
preferentially inhibits viral DNA polymerase
| does NOT require phosphorylation by viral kinase
360
Cidofovir - clinical use
CMV retinitis
| acyclovir resistant HSV
361
cidofovir - toxicity
nephrotoxic - coadminister with probenecid and IV saline to decrease toxicity
362
interferons - MoA
glycoproteins normally synthesized by virus-infected cells - antiviral and antitumoral properties
363
interferons - clinical use
IFN-alpha: chronic HepB and HepC, Kaposi sarcoma, hairy cell leukemia, condyloma acuminatum, renal cell carcinoma, malignant melanoma
IFN-beta: multiple sclerosis
IFN - gamma: chronic granulomatous disease
364
interferons - toxicity
neutropenia, myopathy
365
ribavirin - MoA
inhibits synthesis of guanine nucleotides by competitively inhibiting inosine monophosphate dehydrogenase
366
ribavirin - clinical use
Chronic HepC
| RSV
367
ribavirin - toxicity
hemolytic anemia; severe teratogen
368
simeprevir - MoA
HCV protease inhibitor, prevents viral replication
369
simeprevir - clinical use
Chronic HepC in combo with ribavirin and peginterferon alfa
370
sofosbuvir - MoA
inhibits HCV RNA dependent RNA polymerase
| acts as chain terminator
371
sofosbuvir - clinical use
chronic HepC w/ ribavirin +/- peginerferon alfa
372
afferent arteriole constriction
dec GFR
dec RPF
no change in FF
373
efferent arteriole constriction
inc GFR
dec RPF
inc FF
374
increase plasma protein concentration (effect of GFR, RPF)
dec GFR
no change in RPF
dec RPF
375
decrease plasma protein concentration (effect of GFR, RPF)
inc GFR
no change in RPF
increase FF
376
constriction of ureter
dec GFR
no change in RFP
decrease FF
377
effect of prostaglandins on glomerulus
prostglandins preferentially dilate the afferent arteriole - increased RPF, increased GFR (no change in FF)
378
effect of NSAIDS on glomeruli
NSAIDS inhibit prostglandins (which preferentially dilate the afferent arteriole) so they cause unopposed constriction of the afferent arteriole - decreased RPF, decreased GFR
379
effects of ACE-inhibitors on glomeruli
ACE-I decrease AT-II (normally constricts efferent arteriole) - vasodilation of efferent arteriole - decreases GFR
380
reabsorptive defect in thick ascending loop of Henle resulting in hypokalemia and metabolic alkalosis with hypercalciuria
Bartter syndrome - affects triple transporter (Na/K/Cl)
| AR
381
reabsorptive defect in DCT - results in hypokalemia, hypomagnesemia, metabolic alkalosis, hypocalciuria
Gitelman syndrome - defective NaCl reabsorption
| AR
382
gain of function mutation leading to increased Na reabsorption in collecting tubules
Liddle syndrome - AD - results in hypertension, hypokalemia, metabolic alkalosis, decreased aldosterone levels
treat with amiloride
383
11 beta hydroxysteroid dehydrogenase deficiency
syndrome of apparent mineralocorticoid excess
enzyme normally converts cortisol to cortisone in mineralocorticoid receptor-containing cells before cortisol can act on receptors
excess cortisol resulting from deficiency - increased receptor activity - hypertension, hyperkalemia, metabolic alkalosis
low serum aldosterone
can acquire from licorice
384
Angiotensin II - actions on kidney
efferent arteriole constriction - increases GFR and FF
compensatory Na reabsorption in proximal and distal nephron
Net effect: increased FF in low-volume state w/ increased Na reabsorption to maintain circulating volume
385
PTH - action on kidney
increased Ca reabsorption from DCT
decreased phosphate reabsorption from PCT
increased D3 production
386
Atrial natriuretic peptide - action on kidney
increased GFR and increased Na filtration with NO compensatory Na reabsorption
Net effect: Na loss and volume loss
387
Aldosterone - effect on kidney
increased Na reabsorption
| increased K and H secretion
388
ADH - effect on kidney
increased aquaporins and H2O reabsorption
389
Potassium shift - out of cell
hyperkalemia
```
Digitalis (blocks Na/K ATPase)
hyperOsmolarity
Lysis of cells
Acidosis
B-blockers
high blood Sugar
```
"DO LABS"
390
potassium shift into cells
hypokalemia
hypo-osmolarity
alkalosis
beta-adrenergic agonists (increase Na/K ATPase)
Insulin (increase Na/K ATPase)
391
RBC casts in urine
glomerulonephritis, malignant HTN
392
WBC casts
tubulointerstitial inflammation, acute pyelonephritis, transplant rejection
393
Fatty casts (oval fat bodies)
nephrotic syndrome
394
granular casts (muddy brown)
acute tubular necrosis
395
waxy casts
ESRD/chronic renal failure
396
Hyaline casts
nonspecific - concentrated urine; can be normal
397
mannitol - MoA
osmotic diuretic - increased tubular fluid osmolarity causing increased urine flow, decreased intracranial/intraocular pressure
398
mannitol - clinical use
drug OD
| elevated ICP/intraocular pressure
399
mannitol - toxicity
pulmonary edema, dehydration,
contraindicated in anuria, heart failure
400
acetazolamide - MoA
carbonic anhydrase inhibitor
| causes NaHCO3 diuresis and decreases total body HCO3 stores
401
acetazolamide - clinical use
glaucoma, urinary alkalinization, metabolic alkalosis, altitude sickness, pseudotumor cerebri
402
loop diuretics - MoA
furosemide, bumetanide, torsemide
inhibit triple transporter in thick ascending limp of loop of Henle
stimulate PGE release (vasodilatory effect on afferent arterioles) - inhibited by NSAIDS
increase calcium excretion
403
loop diuretics - clinical use
furosemide, bumetanide, torsemide
edematous states
HTN
hypercalcemia
404
loop diuretics - toxicity
furosemide, bumetanide, torsemide
Ototoxicity, Hypokalemia, Dehydration, Allergy (sulfa), Nephritis (interstitial), Gout
"OH DANG"
405
ethacrynic acid - MoA
loop diuretic - nonsulfa
| inhibits triple transporter in thick ascending limp of the loop of HENLE
406
ethacrynic acid - clinical use
diuresis in people with sulfa allergies
407
ethacrynic acid - toxicity
can cause hyperuricemia - never use to treat gout
408
thiazide diuretics - MoA
chlorthalidone, hydrochlorothiazide
inhibit Na/Cl reabsorption in early DCT
decreases diluting capacity of nephron
decreases Ca excretion
409
thiazide diuretics - clinical use
chlorthalidone, hydrochlorothiazide
HTN, HF, idiopathic hypercalciuria, nephrogenic diabetes insipidus, osteoporosis
410
thiazide diuretics - toxicity
chlorthalidone, hydrochlorothiazide
hypokalemic metabolic alkalosis (muscle weakness and paralysis), hyponatremia
hyperGlycemia, -Lipidemia, -Uricemia, -Calcemia (hyperGLUC)
sufla allergy
411
potassium sparing diuretics
Spironolactone, eplerenone, triamterene, amiloride
412
Spironolactone, eplerenone - MoA
potassium sparing diuretics
| competitive aldosterone receptor antagonists in cortical collecting tubule
413
triamterene, amiloride - MoA
potassium sparing diuretics - block Na channels in cortical collecting tubule
414
potassium sparing diuretics - clinical use
Spironolactone, eplerenone, triamterene, amiloride
hyperaldosteronism, K depletion, HF
415
potassium sparing diuretics - toxicity
Spironolactone, eplerenone, triamterene, amiloride
hyperkalemia (arrhythmias)
spironolactone - gynecomastia, anti-androgen effects
416
ACE inhibitors - MoA
captopril, enalapril, lisinopril, ramipril
inhibit ACE - decreases ATII - decreases GFR by preventing constriction of efferent arterioles
increased renin due to loss of negative feedback
prevents inactivation of bradykinin - vasodilator
417
ACE-I - clinical use
captopril, enalapril, lisinopril, ramipril
HTN, HF, proteinuria, diabetic nephropathy (dec intraglomerular pressure - slows GBM thickening)
prevent unfavorable heart remodeling as a result of chronic HTN
418
ACE-Inhibitor - toxicity
captopril, enalapril, lisinopril, ramipril
```
cough
angioedema
teratogen
increased creatinine (dec GFR)
hyperkalemia, hypotension
```
"CATCH"
avoid in bilateral RAS - further inhibit GFR leading to renal failure
419
angiotensin II receptor blockers - MoA
losartan, candesartan, valsartan
selectively block binding of AT II to AT1 receptor - similar effect to ACE-inhibitor w/o effect on bradykinin
420
ARB - clinical use
losartan, candesartan, valsartan
HTN, Heart failure, proteinuria, diabetic nephropathy (intol. to ACE-I)
421
ARB - toxicity
hyperkalemia, dec renal function, hypotension, teratogen
422
Aliskiren - MoA
direct renin inhibitor
423
aliskiren - clinical use
HTN
424
aliskiren - toxicity
hyperkalemia, decreased renal function, hypotension
contraindicated in diabetics taking ACE-I or ARBs
425
follicular lymphoma - translocation
t(14;18) - BCL-2
426
mantle cell lymphoma - translocation
t(11;14) - cyclin D1
427
Acute lymphoblastic leukemia/lymphoma - translocation
t(12;21) - kids
| t(9;22) - adults
428
zileuton - MoA
5-lipoxygenase pathway inhibitor
| blocks conversion of arachidonic acid to leukotrienes
429
zilueton - clinical use
asthma
430
zileuton - toxicity
hepatotoxic
431
fluricasone/budesonide - MoA
corticosteroids - inhibit synthesis of cytokines
| inactivate NF-kB - transcription factor that induces production of TNF-alpha and other inflammatory agents
432
fluricasone/budesonide - clinical use
first line, chronic asthma (inhaled)
433
montelukast/zafirlukast - MoA
block leukotriene receptors
| inhibit bronchoconstriction
434
montelukast/zafirlukast - clinical use
aspirin induced asthma
| prophylactic, slow onset
435
omalizumab - MoA
monoclonal anti-IgE antibody
| binds unbound IgE in serum and blocks binding to FceRI
436
omalizumab - clinical use
allergic asthma resistant to beta agonists and corticosteroids
437
theophylline - MoA
bronchodilator via inhibition of phosphodiesterase - increases cAMP by decreasing cAMP hydrolysis
438
theophylline - clinical use
asthma - limited by narrow therapeutic index due to nephro- and cardiotoxicity
439
theophylline - toxicity
blocks action of adenosine
| cardio- and nephrotoxic (increased HR; arrhythmias)
440
cromolyn - MoA
prevents degranulation of mast cells
441
cromolyn - clinical use
asthma - prophylaxis
442
guaifenesin
expectorant, does not suppress cough; thins secretions
443
N-acetylcysteine
expectorant - mucolytic
loosens mucous plugs in CF pts by disrupting disulfide bonds
antidote for acetaminophen OD
444
dextromethorphan
antitussive - antagonizes NMDA glutamate receptors
| synthetic codeine analog
445
Bosetan
endothelin receptor antagonist - decreases pulmonary vascular resistance in pulmonary HTN
hepatotoxic
446
epoprostenol, iloprost
prostacyclin analogs - treat pulmonary HTN
PGI2 w/ direct vasodilatory effects on pulmonary and systemic vascular beds
inhibit platelet aggregation
side effects: flushing, jaw pain
447
acetaminophen - MoA
reversibly inhibit COX
| mostly in CNS (inactivated peripherally)
448
acetaminophen - cliicla use
anti-pyretic and analgesic (not anti-inflammatory)
449
acetaminophen toxicity
OD - hepatic necrosis
metabolite depletes glutathione and forms toxic tissue byproducts
antidote = N acetylcysteine - regenerates glutathione
450
celecoxib - MoA
reversibly inhibits COX2 - spares gastric mucosa and platelet function
451
celecoxib - clinical use
RA, osteroarthritis
452
celecoxib - toxicity
increased risk of thrombosis,, sulfa allergy
453
bisphosphonates - MoA
pyrophosphate analogs - bind hydroxyapatite in bone, inhibit osteoclast activity
454
bisphosphonates - clinical use
osteoporosis, hypercalcemia, Paget disease of bone
455
bisphosphonates - toxicity
corrosive esophagitis
| osteonecrosis of jaw
456
teriparatide - MoA
recombinant PTH - increases osteoblastic activity
457
teriparatide - clinical use
osteoporosis - causes increased bone growth
458
teriparatide - toxicity
transient hypercalcemia, possible inc risk of osteosarcoma
459
allopurinol - MoA
inhibits XO - decreases conversion of xanthine to uric acid (chronic gout)
460
febuxostat
inhibits XO (chronic gout)
461
pegloticase
recombinant uricase - catalyzes metabolism of uric acid to allantoin (chronic gout)
462
probenecid
inhibits reabsorption of uric acid in PCT ( chronic gout)
can precipitate uric acid stones
inhibits secretion of penicillin
463
acute gout treatment
NSAIDS, glucocorticoids, colchicine
464
colchicine - MoA
acute gout
binds and stabilize tubulin to inhibit microtubule polymerization - impairs neutrophil chemotaxis and degranulation
465
entanercept
TNF alpha decoy receptor
RA, psoriasis, ankylosis spondylitis
466
infliximab, adalimumab
anti-TNF-alpha monoclonal antibody
IBD, RA, ankylosing spondylitis, psoriasis
467
azathioprine, 6-MP, 6-TG - MoA
purine (thiol) analogs that decrease de novo purine synthesis
activated by HGPRT
azathioprine metabolized in 6-MP
468
azathioprine, 6-MP, 6-TG - clinical use
preventing organ rejection
RA, IBD, SLE
used to wean pts off steroids and treat steroid refractory chronic disease
469
azathioprine, 6-MP, 6-TG - toxicity
myelosuppression, GI, liver
| azathioprine, 6-MP - metabolized by XO - increased toxicity with allopurinol or febuxostat use
470
cladribine (2-CDA) - mechanism
purine analog - multiple mechanisms including inhibition of DNA poly and DNA strand breaks
471
cladribine - clinical use
hairy cell leukemia
472
cladribine - toxicity
myelosuppression, nephrotoxicity, neurotoxicity
473
cytarabine (arabinofuranosyl cytidine) - MoA
pyrimidine analog - inhibits DNA synthesis
474
cytarabine (arabinofuranosyl cytidine) - clinical use
leukemias (AML), lymphomas
475
cytarabine (arabinofuranosyl cytidine) - toxicity
leukopenia, thrombocytopenia, megaloblastic anemia
476
5-FU - MoA
pyrimidine analog bioactivated to 5F-dUMP - covalently complexes folic acid
inhibits thymidylate synthase - decreases dTMP - decreases DNA synthesis
477
5-FU clinical use
colon cancer, pancreatic cancer, BCC (topical)
478
5-FU toxicity
myelosuppression, not reversible with leuovorin (folinic acid)
479
methotrexate - MoA
folic acid analog that competitively inhibits dihydrofolate reductase - decreases dTMP - decreases DNA synthesis
480
methotrexate - clinical use
leukemia (ALL), lymphomas, choriocarcinoma, sarcomas
ectopic preg, medical abortion, RA, psoriasis, IBD, vasculitis
481
methotrexate - toxicity
myelosuppression, reversible w/ leuvocorin rescue
hepatotoxic, mucositis, pulmonary fibrosis
482
bleomycin - MoA
induces free radical formation - breaks in DNA strands
483
bleomycin - clinical use
testicular cancer, Hodgkin lymphoma
484
bleomycin - toxicity
pulmonary fibrosis, skin hyperpigmentation, mucositis
485
dactinomycin (Actinomycin D) - MoA
intercalates in DNA
486
dactinomycin - clinical use
Wilms tumor, Ewing sarcoma, rhabdomyosarcoma
| childhood tumors
487
doxorubicin, daunoribicin - MoA
generates free radicals
| intercalates DNA - breaks in DNA - decreases replication
488
doxorubicin, daunorubicin - clinical use
solid tumors, leukemias, lymphomas
489
doxorubicin, daunorubicin - toxicity
cardiotoxicity (dilated cardiomyopathy) - prevent with dexrazoxane
myelosupp. alopecia,
toxic to tissues
490
busulfan - MoA
cross-links DNA
491
busulfan - clinical use
CML
| bone marrow ablation
492
busulfan - toxicity
severe myelosupp. pulmonary fibrosis, hyperpigmentation
493
cyclophosphamide - MoA
cross links DNA at guanine N-7
| req's bioactivation in liver
494
cyclophosphamide - clinical use
solid tumors, leukemia, lymphoma
495
cyclophosphamide - toxicity
```
myelosupp.
hemorrhagic cystitis (give mensa)
```
496
nitrosoureas - MoA
req bioactivation
cross BBB - CNS
cross link DNA
497
nitrosoureas - clinical use
CNS tumors
498
nitrosoureas - toxicity
CNS toxicity
499
Taxols (paclitaxel) - MoA
hyperstabilize polymerized microtubules in M phase
| mitotic spindle cannot break down
500
taxols (paclitaxel) - clinical use
breast and ovarian cancer
501
Taxols (paclitaxel) - toxicity
myelosupp. alopecia, hypersensitivity
502
Vinca alkaloids - MoA
Vincristine, Vinblastine - bind beta-tubulin and inhibit it's polymerization into microtubules - prevent mitotic spindle formation (arrested in M phase)
503
vinca alkaloids - clinical use
Vincristine, Vinblastine
solid tumors, leukemias, Hodgkin and non-Hodgkin lymphomas
504
vinca alkaloids - toxicity
Vincristine - neurotoxic, paralytic ileus
| Vinblastine - marrow suppression
505
cisplatin/carboplatin - MoA
crosslink DNA
506
cisplatin/carboplatin - clinical use
testicular, bladder, ovary, lung CA
507
cisplatin/carboplatin - toxicity
nephrotoxic (prevent with amifostine - free rad scavenger; chloride diuresis), ototoxic
508
etoposide, teniposide - MoA
inhibits topoisomerase II - increased DNA degredation
509
etoposide, teniposide - clinical use
solid tumors, leukemia, lymphoma
510
etoposide, teniposide - toxicity
myelosupp.
GI upset
alopecia
511
irinotecan, topotecan - MoA
inhibits DNA topoisomerase I - prevents DNA unwinding and replication
512
irinotecan, topotecan - clinical use
colon cancer, ovarian and small cell lung cancers
513
irinotecan, topotecan - toxicity
severe myelosupp, diarrhea
514
hydroxyurea - MoA
inhibits ribonucleoside reductase - decreases DNA synthesis (S Phase)
515
hydroxyurea - clinical use
melanoma, CML, sickle cell (inc HbF)
516
hydroxyurea - toxicity
severe myelosupp, GI upset
517
bevacizumab - MoA
monocolonal antibody against VEGF
| inhibits angiogenesis
518
bevacizumab - clinical use
solid tumors
519
bevacizumab - toxicity
hemorrhage, clotting, impaired wound healing
520
erlotinib - MoA
EGRF tyrosine kinase inhibitor
521
erlotinib - clinical use
non small cell lung cancer
522
erlotinib - toxicity
rash
523
imantinib - MoA
BCR-ABL and c-kit tyrosine kinase inhibitor
524
imantinib - clinical use
CML - BCR-ABLE
| stromal GI tumors - c-kit
525
imantinib - toxicity
fluid retention
526
rituximab - MoA
monoclonal antibody against CD20 (B-cell neoplasms)
527
rituximab - clinical use
non-Hodgkin lymphomas, CLL, IBD, RA
528
rituximab - toxicity
increased risk of progressive multifocal leukoencephalopathy
529
tamoxifen, raloxifene - MoA
selective estrogen receptor modulators
antagonist in breast, agonist in bone
blocks binding of estrogen to ER+ cells
530
tamoxifen, raloxifene - clinical use
tamoxifen - breast cancer treatment and prevention
raloxifene - prevents osteoporosis
531
tamoxifen and raloxifene - toxicity
tamoxifen - partial agonist in endometrium - increases risk of endometrial CA; hot flashes
532
trastuzumab (Herceptin) - MoA
monoclonal antibody against HER-2 tyrosine kinase receptor
533
trastuzumab (Herceptin) - clinical use
Her-2+ breast cancer and gastric cancer
534
trastuzumab (Herceptin) - toxicity
cardiotoxic
535
vemurafenib - MoA
small molecule inhibitor of BRAF oncogene + melanoma
use to treat metastatic melanoma
536
death cap mushroom
alpha amantinin in amanita phalloides inhibits RNA pol II causing severe hepatotoxicity - causing mRNA synthesis to stop
