Shared Flashcard Set

Details

GI/Pulmonary EXAM 4 - Vogler Cirrhosis
GI/Pulmonary EXAM 4 - Vogler Cirrhosis
37
Pharmacology
Graduate
04/26/2011

Additional Pharmacology Flashcards

 


 

Cards

Term
Jaundice:
yellow discoloration of scleras and skin
darkening of the urine

inability of liver cells to conjugate and excrete bilirubin leads to build up of bilirubin in the blood
Definition
pathophysiology of jaundice secondary to cirrhosis
Term
Portal HTN: increased gradient between the portal venous and central venous pressure (inferior vena cava)

hepatocellular injury grogresses -> fibrous material develops within the hepatic lobules -> desrupts normal blood flow through the liver
fibrous tissue accumulates -> resistance to portal blood flow increases -> persistent and progressive elevations in portal blood pressure
also increases in endothelin (vasoconstrictor) and decreases in nitric oxide (vasocilator) attenuate increases in portal venous pressure
Definition
pathophysiology of portal HTN secondary to cirrhosis
Term
varices:
portal-to-systemic shunting -> alternative routes of blood flow fromt he portal system to the systemic circulation
deoxygenated blood goes around the liver b/c the portal vein is blocked

blood "backs up" from portal HTN and finds an alternative route back to the systemic circulation
varices decompress the portal system and return blood to the systemic ciculation
varices can occur at any level of the GI tract

most clinically significant route is the gastric vein and development of esophageal varices

risk of variceal bleeding begins when portal venous pressure reaches 12 mmHg > inferior vena cava pressure
Definition
pathophysiology of varices secondary to cirrhosis
Term
rupture of varices into the GI tract leading to blood loss -> can progress to hypovolemic shock
hemorrhage is complicated by the hypocoaguable state that accompanies liver disease
Definition
pathophysiology of acute variceal hemorrhage secondary to cirrhosis
Term
ascites: pathological accumulation of lymph fluid within the peritoneal cavity

earliest and most common presentation of cirrhosis
portal HTN coupled with arterial vasodilation (compensation for increased pressure in the poral vein) and Na/water retention via activation of the renin-angiotensin system (body thinks it is hypotensive b/c of arterial vasodilation and activates RAAS) -> plasma volume expansion -> translocation of lymph fluid from the hepatic sinusoids and splanchnic capillaries into the peritoneal cavity
Definition
pathophysiology of ascites secondary to cirrhosis
Term
SBP: infection of ascetic fluid in absence of primary intra-abdominal source of infection

overall not well understood - likely result from seeding of ascetic fluid via blood, lymph, or bacteria crossing GI tract wall

most common pathogen = gram-negative enterobacteriaceae, especially E. coli
Definition
pathophysiology of spontaneous bacterial peritonitis
Term
HE: neuropsychiatric syndrome with broad spectrum of neurological impairment; waxing and waning alterations in mental status that occurs as a consequence of hepatic failure or portal-to-systemic shunting

accumulation of gut-derived nitrogenous substances (specifically ammonia) bypass the liver via portal-to-systemic shunting -> enter the CNS and alter neurotransmission
elevated arterial ammnoia levels are the most commonly cited causative agent although there is poor correlation with ammonia levels and severity of HE
clinical symptoms range from subtle mental status changes to deep coma
can progress over any time period (hours to days)
Definition
pathophysiology of hepatic encephalopathy
Term
reduced synthesis of clotting factors

decrease absorption of vitamin K
vitamin K activated clotting factors II, VII, IX, and X
Definition
pathophysiology of coagulopathy secondary to cirrhosis
Term
yellow discoloration of scleras and skin

darkening of the urine
Definition
clinical manifestations of jaundice
Term
may lead to varices
Definition
clinical manifestations of portan HTN
Term
upper GI bleed - variceal hemorrhage

hemorrhoids

caput medusa - on the abdomen, veins branch out (like medusa) on the surface of the skin
Definition
clinical manifestations of varices
Term
hematemesis or melena

decrease ini hemoglobin (Hgb) or hematocrit (Hct)

possible hypotension, dizziness
Definition
clinical manifestations of acute variceal hemorrhage
Term
serum ascites albumin gradient (SAG):
determines if ascites is result of portal HTN
requires diagnostic paracentesis (stick needle into peritoneal space, look at albumin level in the serum and in the peritoneal space)
SAG = serum albumin - ascetic albumin
if SAG > 1.1 g/dL = portal HTN present with 97% accuracy

clinical manifestations:
increased abdominal girth
fluid wave
shifting dullness
shortness of breath
hyponatremia - extra water being retained causes hyponatremia
Definition
clinical manifestations of ascites
Term
fever
increased WBC count (leukocytosis)
abdominal pain
gaurding
hypoactive/absent bowel sounds
rebound tenderness
SOME PATIENTS ASYMPTOMATIC
Definition
clinical manifestations of spontaneous bacterial peritonitis (SBP)
Term
cognitive changes:
confusion (ranging from mild to severe)
agitation
euphoria
restlessness, insomnia
reversal of day/night sleep pattern
somnolence, coma

motor changes:
fine tremor
slowed coordination
asterixis - patients hold up hands; most people can do this steadily; people with HE will flap their hands
posturing and flaccidity

increased serum ammonia levels
Definition
clinical manifestations of hepatic encephalopathy
Term
bleeding
increased PT/INR
Definition
clinical manifestations of coagulopathy
Term
low protein levels in the ascetic fluid (< 1 g/dL)

high bilirubin (2.5 mg/dL)

variceal hemorrhage

prior SBP
Definition
risk factors for development of SBP
Term
low ascetic protein levels (< 1 g/dL)

variceal hemorrhage
Definition
indications for primary prophylaxis for SBP
Term
previous SBP, prophylaxis is lifelong
Definition
indications for secondary prophylaxis for SBP
Term
GI bleed
infection
excessive dietary protein intake
constipation
electrolyte abnormalities
electrolyte abnormalities
azotemia/dehydration/overdiuresis
sedative medications
non-compliance
portosystemic shunts
acute or chronic liver failure
Definition
precipitating factors for hepatic encephalopathy
Term
NON-SELECTIVE BETA BLOCKER = FIRST LINE

mechanism:
inhibit beta1 and beta2 receptors and allows unopposed alpha1 vasoconstriction
beta1 receptor inhibition leads to a decrease in cardiac output and beta2 receptor inhibition decreases splanchnic blood flow
the combined effects produce a decreased portal pressure

agents and dosing:
PROPRANOLOL 10 mg po tid
NADOLOL 20 mg po daily
titrate doses to decrease in resting HR or ~25%, an absolute HR or 55-60 bpm, or development of ADRs

NITRATES

mechanism:
smooth muscle vasodilation -> decrease portal pressure

place in therapy:
as ADD-ON THERAPY to patients that have inadequate response to beta blockers as monotherapy

agents and dosing:
isosorbide mononitrate 20 mg po bid
titrated to 20 mg po tid after 1 week if tolerated
Definition
treatment of portal HTN
Term
ENDOSCOPIC BAND LIGATION (EBL)

place in therapy:
for patients with contraindications or intolerance to non-selective beta blockers
***superior to both beta blockers and nitrates for preventing first bleed - BUT since not proven to improve survival and long term benefits are still uncertain, therapy is reserved for those intolerant to beta-blockade***

mechanism:
draw in veins and snap on rubber band; cuts off circulation to abnormal veins and reduces risk of future bleeds; areas that are banded slough off
Definition
treatment of varices
Term
supportive measures
vasoactive therapy
antibiotics
endoscopic interventions
surgical interventions
Definition
treatmet of acute variceal hemorrhage
Term
adequate fluid resuscitation - PRBCs, crystalloids
monitor for presentation or progression to hypovolemic shock

correction of coagulopathies and thrombocytopenia
fresh frozen plasma (FFP), platelets, vitamin K
Definition
supportive measures for an acute variceal hemorrhage
Term
smoatostatin, OCTREOTIDE, vasopressin (ADH), terlipressin

OCTREOTIDE = preferred agent
mechanism: naturally occurring somatostatin analog; inhibits vasoactive intestinal peptide -> mesenteric vasoconstriction -> decreased splanchnic blood flow -> decreasing portal and variceal pressure
ADRs: bradycardia, hyperglycemia, GI disturbances

other vasoactive therapies:
vasopressin - non-selective vasoconstrictor witn the vasoconstricting effects not restricted to the splanchnic vessel; ADRS - coronary ischemia, AMI, arrhythmias
terlipressin - analog of vasopressin with longer half-life; allows for q4h dosing rather than continuous infusion; not available in the US; drug of choice in Europe
Definition
vasoactive therapy for acute variceal hemorrhage
Term
place in therapy:
ALL PATIENTS WITH A VARICEAL HEMORRHAGE SHOULD BE ON ANTIBIOTICS
active bleeding places patients at high risk of infection

increased risk due to:
aspiration
placement of multiple IV access devices
sclerotherapy
translocation
defects in immune function

ANTIBIOTICS REDUCE THE RISK OF SEPSIS -> REDUCES THE RISK OF REBLEEDING AND INCREASE SHORT-TERM SURVIVAL

screen for infection (spontaneous bacterial peritonitis)
Definition
Antibiotics use in acute variceal hemorrhage
Term
place in therapy:
guidelines recommend as PRIMARY DIAGNOSTIC AND TREATMENT STRATEGY for upper GI tract hemorrhage secondary to portal HTN and varices

sclerotherapy:
inject EPI into varices causing vasoconstriction and decreased blood flow to the area

band ligation:
placement of rubber bands around each varix
after placement the varix will slough off after 48-72 hours
Definition
endoscopic interventions for an acute variceal hemorrhage
Term
place in therapy:
if standard therapy fails (salvage)

transjugular intrahepatic portosystemic shunt (TIPS):
placement of one or more stents between the hepatic vein and portal vein
DECOMPRESSES PORTAL SYSTEM BY SHUNTING BLOOD AROUDN THE LIVER

complications of TIPS:
hepatic encephalopathy (ammonia would normally be broken down by the liver, but is being shunted away and goes to the brain causing encephalopathy)
shunt malfunction
Definition
surgical interventions for an acute variceal hemorrhage
Term
any of below alone or in combination:

endoscopic management:
endoscopic band ligation (EBL) or endoscopic injection sclerotherapy (EIS) q 2 weeks until varices are gone, then re-endoscope at 3 and 6 months

non-selective beta blockers

non selective beta blockers + nitrates

TIPS procedure
Definition
secondary prophylaxis against an acute variceal hemorrhage
Term
therapeutic paracentesis:
if tense ascites is present - 4-6 L removal of ascetic fluid prior to institution of diuretic therapy

sodium restriction:

diuretics:
slow diuresis - max daily weight loss of 0.5 kg/day to avoid hypotension
agents and dosing - SPIRONOLACTONE 100 MG DAILY + FUROSEMIDE 40 MG DAILY
rationale for combo - spironolactone has ~14 day delay in onset of action
titrate diuretic using 100mg:40mg ratio up to max combo dose of 400 mg spironolactone:160 mg furosemide
rationale for ration = usually maintains normokalemia

diagnostic paracentesis:
much smaller volume that therapeutic paracentesis
rule-out spontaneous bacterial peritontitis
determine if ascites is a result of portal HTN (SAG)
Definition
initial treatment of ascites
Term
serial, therapeutic paracentesis:
on PRN or scheduled basis

albumin infusion post paracentesis is recommended if > 5 L removed
give 8-10 g of albumin for every L of fluid removed above 5 L to replace oncotic pressure
Definition
refractory treatment of ascites
Term
ANTIBIOTICS + ALBUMIN

antibiotic therapy:
3rd generation cephalosporin - cefotaxime 2 g IV q8h; ceftriaxone 2 g IV q24h
fluoroquinolones - ciprofloxacin 400 mg IV q12h or 500 mg po bid; levofloxacin 750 mg PO/IV q24h
duration of therapy - 5 days if repeat paracentesis at 48 hours reveals sterile ascetic fluid; 10-14 days if no follow up paracentesis performed; primary prophylaxis (for variceal bleed) x 7 days

albumin therapy
Definition
primary prophylaxis and treatment of spontaneous bacterial peritonitits
Term
SMX/TMP 800/160 mg po bid
ciprofloxacin 750 mg po q week

DURATION OF TREATMENT IS LIFELONG, ONCE THE PATIENT HAS HAD SBP

concerns:
development of resistant organisms
fungal infections
Definition
secondary prophylaxis for spontaneous bacterial peritonitis
Term
treat underlying and/or precipitating factors - KEY
avoid and/or discontinue CNS depressants
avoid loop diuretics -> hypovolemia can aggravate problems
dietary protein management
pharmacological - aimed at decreasing ammonia production

INTESTINAL CLEANSING
ANTIBACTERIALS
Definition
treatment of hepatic encephalopathy
Term
LACTULOSE = FIRST LINE

mechanism:
remove nitrogen containing compounds from the GI tract
lower GI pH -> bacteriostatic effect reduces number of ammonia-producing bacteria
decreases ammonia content in GI tract leading to diffusion of additional ammonia into the GI tract from serum and then subsequent GI removal

dose:
acute - start with 30-60 ml/dose q2h until catharsis begins then scedule 15-30 ml po qid - titrated to produce 2-4 soft stool per day
acute with no PO access - retention enema of 300 ml lactulose in 700 ml water or NS - held for 30-60 minutes
chronic - most patients require 30-60 ml per day - titrate to 2-4 stools/day
Definition
agents used for intestinal cleansing in hepatic encephalopathy
Term
mechanism:
inhibit activity of urea producing bacteria

place in therapy:
patients refractory to lactulose
can use in combo with lactulose or substitution

agents:
neomycin - ADRs ototoxicity and nephrotoxicity
metronidazole - ADRs GI, metallic taste, disulfram-like reaction with alcohol intake
rifaximin - ADRs GI
Definition
antibacterials used for hepatic encephalopathy
Term
vitamin K IV/SQ/PO daily for 3-5 days

fresh frozen plasma (FFP) for prolongation of PT/INR - give if patient is actively bleeding or before invasive procedure to decrease bleeding
Definition
treatment of coagulopathy
Supporting users have an ad free experience!