Random Missed Week 3 Flashcards
What are the 4 major dopaminergic pathways in the brain?
how do anti-psychotics affect these pathways?
- mesolimbic - cognition/behavior; hyperactivity ~ positive symptoms of schizophrenia
[where antipsychotics work to blcok D2 R]
- mesocortical - cognition/behavior; low activity ~ negative symptoms
- tuberoinfundibular - hypothalamus to pitutiary galnd and is responsible for the tonic inhibition of prolactin (arcuate nucleus of the hypothalamus secrete DA and bind to D2 on pituitary lactotrophs –> decrease prolactin secretion) - hyperprolactinemia, galactorrhea, menstrual irregularities
- nigrostriatal - substantia nigra to caudate and putamen; regulates voluntary movements; affected in parkinson’s; antipychotics disrupts this path and cause extrapyramidal effects and drug-induced parkinsonism
What is the hypothalamospinal tract?
Projects from the hypothalamus to the cilispinal center of the intermediolateral cell column (T1-T2) –> provide sympathetic innervation to the ipsilateral eye and face
Disruption of this tract typicall results in ipsilateral Horner Syndrome
Umbilical herninas:
Typical clinical presentaiton
What is one congenital abnormality seen?
Umbilical ring/congenital fascialopening for the umbilical cord, closes and forms the linea alba, a midline band of fibrous tissue
Umbilical hernias are caused by INCOMPLETE CLOSURE of the umbilical ring – allowing protrusion of bowel through the abdominal musculature.
Most are: reducible, asymptomatic, resolve sponteaneous within the first years of live
Associated with: Down’s , hypothyroidism, Beckwith-Wiedemann Syndrome
What part of N. meningitidis correlates with morbidity and mortality, especially in relation with sepsis?
LOS - lipooligosaccharide; acts as an endotoxin, and associated with many of the toxic effects of meningococal disease (LOS plasma levels correlate with disease manifestations and outcomes)
analygous to the lipopolysaccharide of enterig gram negative rods but lacks the repating O antigen of enteric LPS.
Meningococcal growth and lysis leads to release of outer membrane vesicles with membrane-attached LOS (same as LPS release with gram neg infections) –> LOS causes sepsis inducing a systemic inflammatory respones characterized by the production of TNF alpha, IL 1, IL 6, IL 8
What is the Kozak sewuence?
a consensus sequence that helps start translation in eukaryotes (located on mRNA) - helps initiate translation at the metioonine start codon AUG
Analogous to shine-dalgarno sequence in E. coli
(gcc)gccRccAUGG
R - adenin or guanine / purine 3 base pairs from the AUG plays an important role in the initiation process
anti-IgM negative
anti-IgG positive
to hep A
asymptomatic pt with previous infection to hAV
in children <6, HAv infectino is most often silent/subcliinica/anicteric/no jaundice
les freequencly could present as an acute, self-limited illness characterized by jaundice, malaise, fatigue, anorexia, nausea, vomiting and RUQ pain
Hep A- NO asymptopmatic viral carrier state, does not progress to chronic carrier, NO hepatits, no cirrhoss no HCC
What are causes of PKU
Mgmt?
PKU is most commonly caused by a deficiency in phenylalanine hydroxylase – restrict phenylalanine diet, and increase tyrosine diet
Other cause- BH4 cofactor deficiency; most likely due to dihydrobipterin reductance unable to reproduce BH4 (from BH2) after being used as a cofactor
[cofactor BH4 is used in the first 2 steps of phenylalanine metabolism]
What issues could problems with the urea cycle cause?
Mgmt?
What are important players?
Urea cycle is important to remove the extra nitrogen/ammonia from AA catabolism/metabolism;
The cycle takes place in part in the mitochondria and in part in the cytosol. Formation of urea is the final product to be excreted in the urine
Defects in any of the steps –> increase blood concentration of ammmonia –> central nervous system dysfuctnio.
SEvere defects manifest during ealry infancy and childhood, while midler defects may not manifest until adulthood
Tx: balancing dietar protien intake with protien ouput – protein restriction + meds tha provide alternative pathways for the removal of amonia from the blood
Key players: ordinarily, careless crappers are also frivolous about urination
Ornithine, carbomoyl phosphate, citruline, aspartate, arginosuccinate, fumarate, arginine, urea
What is a complication that could be seen with warfarin?
Primary anticoag effect of warfarin- inhibits the vitamin K dependent gamma carboxylation of clotting factors II, VII, IX, X (2,7,9,10)
Warfarin-induced skin necrosis –> transiet hypercoaguable state that occurs duirn ghte first few days of warfarin therapy:
Warfarin inhibits proteins C and S, which are natural anticoagulates present in blood –> vitamin K dependent cofactors continue procoag effect (2,9,10 esp)–> thrombosis and clot formation can interrupt blood flow to skin and lead to skin necrosis –> can lead to skin necrosis, particularly in patients with protein C or S deficiency – this complication is usually seen in the first few days of warfarin therapy
[pt should be given vitamin K and FFP to reverse the effects of coumadin]
*why a heparin bridge is commonly used when warfarin is initiated
H pylori treatment
H. pylri causes infection by downregulating somatostatin, which subsequently increases (through lack of inhibition) gastrin –> parietal cells –> acid release
Treatment given to H pylori to prevent the recurrence of a PUD.
Triple therapy: 2 antibiotics (amoxicillin, clarithromycin) + PPI (omperazole)
metoclopramide?
dopamine antagonist with prokinetic and antiemetic properties that can be used to treat gastrointestinal motility disorders (gastroparesis) and N/V
What are 3 common manifestations of sickle cell disease
most common AR disorder in AA
1. hemolysis- repeated sickling of RBC – permanet deformation and premature destruction; intra and extra vascular hemolysis –> INC indirect bilirubin, lactate dehydrogenase and DEC heptaglobin (binds circulating hb and reduces renal excretion of free hemoglobin, preventing tubular injury)
2. vasooclusive symptoms- pain due to hypoxic tissue injury; microvascular occlusions; dactylitis (hand-foot swelling syndrome! results from small infarctions in the bones of the extremities –> swelling, tenderness and warmth)
3. infections- infections with encapsulated organisms because of repated splenic infarcts cause functional asplenia
Diptheria toxin
Complications-
= AB EXOTOXIN
ADP-ribosylation is inhibited, inactives elongation factor 2
inhibits protein synthesis –> cell death
toxin acts locally, causing respiratory cell necrosis with formation of fibrous, coagulative exudates
(coalescing psedomembrane)
[A= active, active subunit of exotoxin transfers a ribose residue from the NAD to a histidine on the EF2; riboslylation inactivates –> inhibiting protein syntehsis]
Complications:
–> suffocation via obstruction from edema and pseudomembranes
systemically, predilection to brain and heart tissue –> myocarditis/HF and neurologic toxicity
Community acquired pneumo
common bugs-
#1: Strep pneumo (outer polysac cap prevents phagocytosis! no virulence without capsule; others include IgA protease, adhesins, pneumolysin)
H. influezae
Moraxella catarrhalis
Kplebsiella pneumo
S. Aureus
(atypical - C. pneumo, legionella)
What are endotoxins?
who are they produced by and consequnces?
Produced by gram-negative bacteria
consist mainly of LPS - structural component of the gram negative outer membrane, representing the somatic O antigenic determinats
LPS –> fever, hypotension, hemorrhage, DIC due to activation of the clotting system
(LOS in N. menigitis)
Describe the vascular supply of the upper abdomen?
Abdominal Aorta –>
first branch is the celiac truck @ T12
[supplies spleen, stomach, liver abdominal esophagus adn parts of the duodenum and pancreas]
SMA @ L1
IMA @ L3
-see image-
What agents should be used for motion sickness associated emesis?
For chemotherapy-induced emesis?
Motion sickness:
Antimuscarinics/anti-cholinergics such as scopolamine
Antihistamines - diphenyhydramine, meclizine, promethazine
Chemotherapy:
Serotonin (5Ht3) receptor antagonist - ondansetron, granisetron
[5HT3 R are located peripherally in the presynaptic nerve terminals of the vagus nerve in teh GI track, also present centrally in the chemoR trigger zone and the solitary nucleus and tract]
DA receptor antagonist - prochlorperazine, metoclopramine
Neurokinin 1 receptor antagonist - aprepitant fosaprepitant
How does PCP affect the body?
NMDA receptor ANTAGONIST
[can work secondarily to inhibit reuptake of NE, DA, and 5HT, and effects on sigma opiods R]
PCP is known to cause beliligerence, agitation, and loss of coordination, horizontal and vertical nystagmus and a consellation of cognitive sx that includes disorientaiton, poor judgement and memory loss
Can have dissociative and anesthetic effects but may also cause psychosis and server agitaiton leading to violent trauma==ataxia, horizontal and vertigal nystagmus and delirum could also be present
[NMDA agonist = glutamate, aspartate, D-cycloserine]
How would you tell the difference between the following cardiac conditions due to:
Untreated strep A
viral myocarditis/adenovirus, coxasckie B, parvovirus
T. Cruzi/chagas?
Untreated strep A –> acute rheumatic fever – immune-mediated dequela of an untreated group A strep pharyngeal infection; could lead tonew murmur; myocardia biopsy will show interstitial fibrosis with central lymphocytes and macrophages as well as scattered multinucleated giant cells = interstitial myocardial granuloma = ASCHOFF body is pathognomonic for ARF-related myocarditis
Viral myocarditis – lymphocytic interstitial infiltrate with focal necrosis of mycocytes; high in neutrophils??
Chagas – intracellular protozoan parasite will be seen; distension of individual myofibers with intracellular trypanosomes
Describe the development of the testies:
The testicles develop in the fetal abdomen during organogeneisis
between weeks 8 and full term, they shlowly descend into the scrotum by passing from:
the abdomen through the DEEP INGUINAL CANAL –> inguinal canal [transversalis fascia opening, bounded by the trasversus abdominal musc laterally and the inferior epigastric vessels medially] –> passes anteromedially to exit the canal via the SUPERFICIAL INGUINAL RING [opening external oblique muscle aponeurosis above and medial to the pubic tubercle-> then it enters the scrotum
If this does NOT occur = cryptorchidism (increased risk for infertility an dtesticular CA)
If the testis is palpable medial to the deep inguinal ring, then it is already in the inguinal canal
What is achalasia?
motility disorder caused by reduced # of inhibitory ganglion cells in teh esophageal wall –> creates an imbalance favoring excitatory ganglion cells
- normal contraction of the upper esophageal sphincter
- DEC amplitude of peristalsis in the mid esophagus
- increased tone and incomplete relaxation at the LES
barium esophagram typically shows dilation of the esophagus with distal narrowing
What is the most common valve and underlying disease predisposing to IE?
mitral valve is the most commone valve affected by IE, in developed nations
MVP is the most common underlying valvular disease
[Rheumatic heart disease remains a frequent cause of IE in developing nations]
Microscopic deposits of platelets and fibrin occur spontenously in individuals with valvular dz secondary to endocardial injury from turbulent blood flow – deposits the become colonized by micro-organisms during episodes of bacteremi (ie-following dental extraction)
*rheumatic heart disease is the most important form of acquired heart disease in children and young adults in developing countries
what baldder issues could an MS pt see after an acute lesions of the spinal cord?
SPastic bladder – bladder hypertonia
bladder contractility is normal (little to no residual urine after emptying test), but distensibility is poor –> urinary frequency and urge incontinence
the bladder does not distenx/relax properly due to loss of descending inhibitory control from UMN
what could a flaccid bladder indicate?
typically occurs in teh setting of LMN lesion
patient will have large residual volume of urine after attempted emptying and will typically experience urinary incontinence at the end of the day (pressure from a full bladder) becomes greater than urinary sphincter pressure
What is HIV prophylaxis:
Pneumocystis pneumonia <200
TMP-smx
Histoplasma Capsulatum <150
itraconazole
Pneumocystis pneumonia and toxoplasmosis <100
TMP-smx
Mycobacterium avium complex <50
clarithromycin, azithromycin
how to distinguish MAC from extrapulmonary TB?
MAC grows well at high temps and exhibit optimum grow at 41 C
MAC more likely to cause marked anemia, hepatosplenomegaly, elevated alk phos and lactate deydrogenease levels
Explain angioedema in relation with ACE inhibitory therapy
rare and potentially serious side effect
Most commonly involved the tongue, lips or eyelids
laryngeal edema and difficulty breathing may also occur
Due to bradykining accumulation
[normally, ace is responsible for bradykinin breakdown - ACE inhibitors prevent bradykinin degradation, leading to increased levels – bradykinin is a potent vasodilator; and ultimately increases vascular permeability causing significant angioedema]
ACE inhibitors should be discontinued in patients who develop angioedema
The mechanism for clearing lung depends on the size of the particle
10-15 um –> trapped in teh upper respiratory tract
2.5 -10 um –> enter the trachea and bronchi and area cleard by mucocillary transport
finest particles <2 um –> reach the terminal bronchioli and alveoli and are phagocytosed by macrophages
What infection is the most common cause of aplastic crisis, in patients with SCD?
In pt with SCD and other hemolytic disorders, the most common viral cause of an aplastic crisis is infection of erythroid progenitor cells with parvovirus B19 - non enveloped single stranded DNA virus
How is the detrusor muscle regulated?
M3 cholingeric R
stimulation –> contraction
Inhibition –> relaxation and urinary retention
obturator nerve
arises from lumbar plexus and carries fibers from L2-L4 spinal segments
descends posteriormedial to the iliopsoas muslce and courases along the lateral aspect of the lessel pelvins before scending through the obturator canal –? the only major nerve that exits teh pelvis through this canal
supplies the obturator externus muslce and divides into the ant and pos branches supply the rest of the thigh adductor (adductor lungus, brevis, magnus)
ant division of the nerve gives off a aterminal cutaneous branch that provdies sensation over teh sital medial thigh
most comonly injured by compression due to pelvic trauma,surg or tumors (ie-bladder tumor)
pt present with weakness on thigh adduction and sensory loss in teh distal medial thig
What mediates cachexia?
Cachexia is a syndrome that encompasses anorexia, malaise, anemia, wt loss and generalized wasting due to underlying systemic dz
likely a manifesation of the lung neoplasm revealed on his chest symptoms
Tumor necrosis factor alpha (TNFalpha) cytokine that causes necrosis of some tumors in vitro and produces sz of cachezia in experimental animals
also caleld cachectin and is consdered a main mediator of paraneoplastic cachezi along with IL-1b and IL6
produced by macrophages in response to infection and some neoplastic cels
influences hypthalamus, leading to
appetite suppresion
INC BMR
bacterial infections, TNF alpha produces fever along with IL1, mediates sx of septic shock and causes hepatic release of acute phase reactants (C-reactive and fibrinogen)
What are the 4 different types of HTN disorders seen in pregnancy?
Chronic HTN - >140 / 90 prior to conception or before 20 weeks
Gestational HT: new onset HTN at > 20 weeks
NO end-organ damage or proteinuria
Pre-eclampsia: new onset HTN after 20 weeks PLUS
proteinuria or signs of end organ damage
- abnormal placental vasculature leads to placental hypoxia and ishcemia –> release of anti-angiogenic factors into materal circulation; inflammatory factors from hypoxic placenta –> endothelial injury –> endothelial damage increases permeability –> proteinuria*
- dysregulation of vascular tone –> elevated BP, which can cause end-organ damage (brain such as h/a, visual changes, liver - abdominal pain)*
Eclampsia: Preclampsia (htn + proteinuria or end organ damage) + new onset grand mal SEIZURES
what causes drug-induced parkinsonism?
–> extra-pyramidal sx
cogheel rigidity, resting tremor, masked facies adn bradykinesia (within first 3 months)
caused by D2 receptor blocakde in teh nigrostriatal pathway
(occurs more commonly w/first-generation anti-psychotic due to greater D2 blockade but can also occur with second-gen anti-psy)
treat wtih centrally acting anti-muscarinic agent trihexphenidyl, benztropine!
**donot use levopoda as it can precipitate psychosis
What gene is responsible for auto recessive polycycstic kidney disease?
common findings?
PKHD1 - gene for fibrocystin (chrome 16) [or pkd2 on chrom 4]
bilaterally enlarged, cystic fetal kidney, oligohydraminos (low amniotic fluid)
fibrocystin is found in the epithelial cells of both the rental tubule and bile ducts – deficiency leading to characteristic polycystic dilation of both structures
Age of presentaiton is determined by the severity
most severe - prenatal detection
oligohydraminos is present becuase amniotic fluid is composed of fetal urine and renal filtratin is severely impaired in ARPKD –> Potter sequnce; flattened facies, limb deformities, pulmonary hypoplasi
What is VACTERL association?
mesodermal defect
V = vertebral defects
A = anal atresia
C = cardiac defects
T & E = TE fistula
R= renal defects
L = limb defects
Von Hippel-Lindau disease:
rare, AD condition characterized by the presence of capillary hemangioblastomas in the retina and/or cerebellum
and congenital cyst and/or neoplasms in the kindey, liver and pancreas
pt are at risk for RCC - which can be bilateral
Von Recklinghausen’s diseaes is also know as?
NF1
inherited PERIPHERAL nervous system tumor
neurofibromas, optic nerve gliomas, Lisch nodules, cafe au lait spots
Sturge-Weber syndrome
encephalotrigeminal angiomatosis
rare congenital neurocutaneous disorder characterized by the presence of cutaneous facial angiomas as well as leptomeningeal angiomas
skin involvement in V1/V2
associated with mental retardation, seizures, hemiplegia, skull radipacities
“tram track” calcifications of skull radiographs
what is the process of T cell maturation –
Thymocytes are initally produced in the bone marrow but migrate from that location to mature during the FIRST TRIMESTER of genstation in the thymus; this is where TCR gene rearrangement, positive selection, negative selection and expression of exm markers and co-mol occurs
Pro T cells arrive at the thymus as double negatives (lack both CD4 and CD8)
TCR beta gene rearrangement occurs –> CD 4 and CD 8 expression occurs
@ thymic cortex, alpha genes rarrange to produce a functional alpha-beta TCR –> positive then negative selection occurs
positive selection - only T cells expressing a TCR that is able to bind to self MHC are allowed to survive; occurs in the thymic cortex and involved interactions of T cells with thymic cortical epithelial cells expressing self MHC – responsible for development of a T cell reertoire that can recognize self
Negative selection - process by which T cells possessing TCRs that bind with high affinity to self antigen or self MHC I/II, are eliminated by apoptosis.
occurs in thymic medulla, involved interaction with thymic medullary epithelial and dendritic cells
Drug of choice for acute status epilepticus?
IV benzodiazepines (lorazepam)
Work by enhancing the effects of gamma-aminobutyric acid (GABA) at the GABA-A receptor –> increased chloride influx and suppression of action potential firing
ligand-gated ion channel; allosteric attachment of bezos to GABA-A R –> influx of negatively charged chloride ion –> hyperpolarization of postsynaptic neuron and suppression of action potential firing (anticonvulsant effect)
Interferon-gamma
Who secretes it?
whats its role?
Produces primary by activated T lymphocytes and natural killer cells
Critical in immunity against viral and intracellular bacterial infections
Activates macrophages, inc MHC expresison, and promotes T helper 1 lymphocyte differentiation
interferong-gama assays are used for latent TB infection - by measuring the response of T lymphocytes when exosed to antigens uniqe to M. TB
Measure Cell-mediated immunity
can’t be used to distinguis active from latent infection
What enzymes are invovled in glycogen –> glucose-1-p
glycogen phosphorylase a goes form glycogen to glucose 1-p only in its active form
it is activated by phosphorylase KINASE
inactivate by phosphoprotein PHOSPHATASE
*PK is regulated differently in liver than in muscles
-glycogen in liver is used to maintain blood glucose levels during fasting, where as glycogen in muslce is used to provide energy for muscle contraction
IN the liver, PK is activated primaryly through the binding of E and glucago to a Gs protein coupled receptors which increase cAMP concentrations –> phosphorylation of PK (via protein kinase A)
Skeletal m. lacks glucago receptors, but muscle PK can sitll be phosphorylated in response to an E-induced INC in cAMP
Increased Ca2+ is MORE POWERFUL activator of muscle PK – release of SR calcium stores fllowing neuromusculear Ach stimulation allows for synchronization of skeletal muscl contratio and glycogen breakdown, providng eth energy necessary for anerboic m. contraction
riboflavin deficiency
can be seen in chronic alcoholics and severely malnourished
clinical sx: angular stomatitis, cheilitis, glossitis, seborrheic dermatitis, eye changes
Riboflavin = B2
key precursor to key constitutes of TCA and ETC
riboflavin –> FMN –> FAD
FADH –> FADH2
verrucous, skin-colored genital lesions
=condylomata accuminatum
bug?
where does it infect?
HPV, DS-DNA virus >100subtypes
Mostly type 6 and 11
infects basal epithelial cells through small breaks in teh skin or mucosal surfaces
redilection to STRATIFIED SQUAMOUS EPITHELIUM
(anal canal, vagina, cervix)
@ respiratory tract: true vocal cords only
- stratified squamous epithelium, proteicively lines anatomical areas that udnergo frequent friction and abrasion, including true vocal cords, cervix, anus*
- infants can acquire respiratoyr papillomatosis via passage through an HPV-infected birth canal*
Lansoprazole is what drug? MOA?
Proton pump inhibitor (think: omeprazole!)
blocks the final common pathway of gastric acid secretion from parietal cells which is stimulated by ACH, histamine and gastrin
Rentinal artery occlusion, blood traveling to…
internal carotid –> opthalmic artery –> central retinal artery
sx: acute, painless monocular vission loss
thromboembolic complications of atherosclerosis in the internal carotid are the most common cause of rentinal artery occlusion
PTSD first line treatment
trauma-focused cognitive behavioral therapy and anti-depressant medication-
selective serotonin reuptak einhibitor
Treatment for someone wtih dipthriae?
- diptheria antitoxin
- Penicillin or erythromycin
- DPT vaccine
Indirect inguinal hernias
more common than direct
tend to appear on the right side
due to failure of the processus vaginalis to obliterate, allowing abdominal contents to protrude through the deep inguinal ring
Can be detected by deep palpation of the external ring with the tip of the finger
Direct inguinal hernias
protrude through hesselbach’s triangle - weak spot of the anterior abdominal wall
bound by the rectus abdominis, inferior epigastric vessels and inguinal ligament
less prone to incarceration in comparisson to indrection due to their wide neck
uncommon for them to descend
best felt with the pup of the examiners finger on deep palpation
When does excretion of a substance reach its maximum state?
Excretion of a substnace is defined as the filtration plus the secretion minus the reabsorption
once carrier mediated secretion and reabsorption mechanisms are saturated, these processes are at their maximal state
Filtration itself does not require an enzyme or protein, so it does not show a maximal value; thus it cannot be saturated nor excreted
besides gas gangrene, what other symptom may accompany this bug?
Clostridium perfringenes, gram positive bacillus, responsible for 95% of gas gangren (clostridial myonecrosis), abundant in soil and can inoculate penetrating injury sites
sores germinate in ANAEROBIC environment into vegetative cells –> produce phospholipase toxin that attackes cell membranes (alpha toxin) –> extensive tissue damange, necrosis adn reduced blood supply to the affected area results with the diseaes can sometimes be felt on examination (crepitus) and may be visualized on radiographs (help distinguis gas gangrene from other necrotizing infections)
Tx: antibiotics and emergent debridement; overall poor prognosis and tissue loss is often considerable
It can also cause late-onset food poisoning that is characterized by transiet watery diarrhea (toxin formed when large # of clostridial spores are ingested), spores germinate and THEN begin to elaborate toxin (why its late onset)
Between Niemann-Pick and Tay-Sach’s, both cause cherry red spots in the macula, but which one does not have hepatosplenomegaly?
Tay-sach’s = NO hepatosplenomegy
Niemann-Pick - yes hepatosplenomegay
Tay-sach’s is deficient B-hexosaminidase A –> Gm2 accumulation in neurons
Niemann-Pick sphingomyelinase dificiency –> sphingomyelin accumulation within lysosomes results in cells that appear enlarged, foamy and cavuloated on electron microscopy
lip-laden foam cells accumulate in the liver and spleen and cause hepatosplenomegal –> progressive neuronal accumulation is responsible for hypotonia and neurologic degeneration
What is cutis aplasia and what syndrome could this be seen in?
What other clinical presentation is seen in this syndrome?
Cutis aplasia = focal skin defect of the scalp
seen in Patau syndrome
Pataus” trisomy 13 – phenotypic features reflect a defect in the fusion of prechordal mesoderm - an integral embryological structure affecting growth of the midface, eyes and forebrain
- holoprosencephaly, microcephaly, micropthalmia, cleft lip palate, omphalocele; abnl brain development, polydactyl and cutis aplaisa
usually meiotic nondisjunction
What is a fatal cause of hyperbilirubinemia in infants?
ABSENT liver conjucation enzymes (Crigler-Najjar syndrome type 1)
autosomal recessive disorder of bilirubin metabolism caused by a genetic lack of the UGT enzyme needed to catalyze bile glucuronidation
–> unconjugated hyperbilirubineia
Indirect bilirubin levels typically ~10-15
Because it is NOT conjugated - it is HIGHLY INSOLUBLE –> cannot be excreted; it tightly binds albumin and thus cannot be filtered by the glomerulus and not excreted –> deposits can cause kernicterus (bilirubin encephalopathy), potentially fatal condition characterized by severe jaundice and neurologic impairment as a child
substrates of CYP 450:
Anti-epileptics
Theophylline
Warfarin
OCPs
Cyclosporine
Statins
“Can alaways think when outdoors, son”
**be careful when using with either inducers- can increase the metabolism of the drug and thus decrease the therapeutic level - esp careful with warfarin! or inhibitors, that can decrease the metabolism of the drug and thus increase the potential for toxicity**
Inducers of CYP450 (8)
Chronic Alcohol use
St. John’s Wort
Phenytoin
Phenobarbital
Nevirapine
RIfampin
Griseofulvin
Carbamazepine
“chronic alcoholics steal phe-phen and never refuse greasy carbs”
= speed up metabolism
Inhibitors of CYP450
Acute alcohol abuse
Ritonavir
Amiodarone
Cimetidine
Ketoconazole
Sulfanamides
INH/isoniazid
Grapefruit juice
Quiidine
Macrolines (expect azithromycin)
AAA RACKS IN GQ Magazine
**decreaes metabolism of drugs
gliosis =?
proliferation of astrocytes in an area of neuro degeneration
leads to the formation of a glial scar which compensates for the voulme loss that occrs after neuronal death
glial scar
alendronate?
= Fosmax
bisphosphaonates, chemically structure to pyrophosphate and attach to hydroxyapatite binding sites on bony surfaces, preferentially bindg in areas of increased bone turnover
MOA of digoxin
positive inotropic agent
provides SYMPTOMATIC relief in patients with acute decomponsated heart failure due to left ventircular systolic dysfunction
alos has anti-adrenergic effect (via increased parasympathetic tone) with slowing of conduction through the AV node - help improve cardiac function in pt with rapid ventricular rate
Directly INHIBITS NA/K/ATPase pump –> DEC of sodium efflux – increase of sodium inside, then decreases the Na+/Ca2+ exchanger — decreasing efflux of calcium from the cells
INC intracellular calcium –> binding to troponin C and sbsequent actin-myosin cross-bridge formation and myocyte contractino, resulting in imporved myocute contractility and LVSF
antiphospholipid antibody syndrome?
Disorder characterized by the presence of antiphospholipid antibodies in the setting of venous or arterial thromboembolism OR reccurent pregnancy loss.
- may be primary or secondary to other AI dz such as SLE –
suggestive with prolonged aPTT and negative rapid plasma reagin (RPR) -
act to produce hypercoagulable state due to activation of phospholipid dependent coa pathways
these antibodies can cause false-positives results on ontreponemal serologic syphilis test by reacting iwth cardiolipi (dominant antigen used in these test)
