GI/ Heme/ Oncology Review Flashcards
Midgut development
- 6th week
- 10th week
6th week
- midgut herniates through umbilical ring
10th week
- returns to abdominal cavity
- rotates around superior mesenteric artery (270 degrees)
Pyloric stenosis associated with exposure to
Macrolides
Posterior duodenal ulcers penetrate the
gastroduodenal artery
Anterior duodenal ulcer perforate into
the anterior abdominal cavity
Stomach ulcer along lesser curve penetrates the
left gastric
Sites of anastomosis and what vessels involved (3)
1) Esophagus
- Esophageal varices
- L gastric and azygos
2) Umbilicus
- Caput medusae
- Paraumbilical and small epigastric veins of anterior abdominal wall
3) Rectum
- Anorectal varices
- Superior rectal with middle and inferior rectal
Above the pectinate line
- arterial supply
- venous drainage
- innervation
- lymphatic drainage
Above pectinate line
Arterial supply
- superior rectal artery (branch IMA)
Venous drainage
- superior rectal vein –> inferior mesenteric vein –> splenic vein –> portal vein
Innervation
- visceral innervation, not painful
Lymphatic drainage
- Internal iliac lymph nodes
Below Pectinate Line
- Arterial supply
- Venous drainage
- Innervation
- Lymphatic drainage
Below pectinate line
Arterial supply
- Inferior rectal artery (branch of internal pudendal artery)
Venous drainage
- Inferior rectal vein –> internal pudendal vein –> internal iliac vein –> common iliac vein –> IVC
Innervation
- Somatic innervation
- Inferior rectal branch of pudendal n.
- Painful
Lymphatic drainage
- superficial inguinal nodes
Yellow fever affects what zone of liver architecture
Zone II: intermediate zone
Zone affected of liver by viral hepatitis
Zone I: periportal zone
Diaphragmatic hernia
- what side
- due to
Left side due to relative protection of right hemidiaphragm by liver
Congenital defect of pleuroperitoneal membrane
Indirect inguinal hernia
- goes through
- in reference to inferior epigastric vessels
- due to
- covered by
Goes through the internal (deep) inguinal ring, external (superfical) inguinal ring and into the scrotum
Lateral to inferior epigastric vessels
Due to failure of processus vaginalis to close
Can form hydrocele
Covered by all 3 layers of spermatic fascia
Direct inguinal hernia
- goes through
- in reference to inferior epigastric vessels
- due to
- covered by
Protrudes through the inguinal (Hesselbach) triangle. Bulges directly through the parietal peritoneum. Goes through external (superficial) inguinal ring only
Medial to inferior epigastric vessels
(lateral to rectus abdominis)
Due to acquired weakness in the transversalis fascia
Covered by external spermatic fascia
Secreted by duodenum and function
Cholecystokinin
- I cells
- increase pancreatic secretion
- Increase gallbladder contraction
- Decrease gastric emptying
- Increase sphincter of Oddi relaxation
Secretin
- S cells
- Increase pancreatic HCO3 secretion
- Decrease gastric acid secretion
- increase bile secretion
GIP (Glucose-dependent insulinotropic peptide)
- K cells
- Decrease Gastric H secretion
- increase insulin release
Iron, Folate and B12 absorbed where
Iron: duodenum
Folate: Small bowel
B12: terminal ileum
Bile acids conjugated to ____ (2) to make them _____
What catalyzes teh RL step of bile acid synthesis
Conjugated to glycine or taurine to make bile acids water soluble
Cholesterol 7alpha-hydroxylase
Mass in parotid gland, biopsy shows cystic with central mass of pale staining B cells
Papillary cystadenoma lymphomatosum
(Warthin tumor)
Benign cystic tumor with germinal center
Smokers
Birds beak appear on CT
volvulus
Bird beak on barium= achalasia
Esophageal varices located where
Lower 1/3 of esophagus
Plummer-Vinson syndrome
Plumbers DIE
Dysphagia
Iron deficiency anemia
Esophageal webs
Globus sensation
“something is stuck in throat”
Worse w/ swallowing saliva
Alleviated with food and liquid
Associated with anxiety
Functional disorder
Hypertrophied rugae
- disease
- pathogenesis
- results in
Looks like brain gyri
Menetrier disease
Hyperplasia of gastric mucosa –> hypertrophied rugae, excess mucus production
With resultant loss of protein and parietal cell atrophy –> decrease gastric acid production
Enteric protein loss –> hypoalbuminemia –> edema
Precancerous
Gastric cancer
- Intestinal vs Diffuse
Intestinal
- Due to H pylori
- or smoked foods, tobacco smoking, chronic gastritis
- On Lesser curvature
- Looks like ulcer with raised margins
Diffuse
- Signet ring cells
- stomach wall grossly thickened and leathery
(linitis plastica)
Signet ring cells in ovaries
Krukenberg tumor
Gastric cancer spread to ovaries
Zollinger-Ellison syndrome causes what type of ulcers
Tx
Duodenal ulcers
PPI (omeprazole) +/- Octeotide (if hemorrhage)
Common feature of duodenal ulcers (2)
Pain decreases with eating
Hypertrophy of Brunner glands
Test for malabsorption syndromes
- test for fecal fat
Sudan stain
Celiac disease
- intolerance of what protein
- Associated with what HLA
- Assoc w/ condition
- Ab to
- Histology of intestine
- location
Intolerance of gliadin (gluten protein in wheat)
HLA-DQ2 and HLA-DQ8
Dermatitis herpetiformis, decreased bone density
IgA anti-tissue transglutaminase (IgA tTG)
Villous atrophy, blunting
Crypt hyperplasia
Distal duodenum and/or proximal jejunum
Foamy macrophages (distended) in intestinal lamina propria
Confusion Inflamed joints Trouble walking Diarrhea Chest pain WL LAD Hyperpigmentation
Tx
Whipple Disease
Tropheryma whipplei
Tx - Penicillin - Ampicillin - Tetracycline (Takes 1-2 yrs)
Zenker diverticulum location
Between thyropharyngeal and cricopharyngeal parts of the inferior pharyngeal constrictor
Congenital megacolon
- disease
- Lack of
- due to
- Mutation
- Symptoms
Hirschsprung disease
Lack of ganglion cells/ enteric nervous plexuses (Auerbach and Meissner plexuses) in distal segment of colon
Due to failure of neural crest cell migration
RET mutation
Bilious emesis, abdominal distention and failure to pass meconium within 48 hrs
Similar to appendicitis but longer than 1 month
Volvulus
- Children
- Elderly
- pattern
Twisting of bowel around mesentery
Midgut: infants and children
Sigmoid: elderly (coffee bean on xray)
Whirl pattern on CT
Distended loops proximal to volvulus
Abdominal pain
Currant jelly stools
Telescoping
Coiled spring
- Location
- Lead point
- May be associated with
Intussusception
Ileocecal junction
Meckel diverticulum
May be associated with recent viral infection (adenovirus) –> peyer patch hyperplasia –> lead point
Infant
Swollen bowel full of air
Necrotizing enterocolitis
Formula fed infants with immature immune system
- received oral food too soon
Necrosis of intestinal mucosa
Hyperpigmented mouth, lips, hands and genitalia
Numberous hamartomas throught out GI
Peutz-Jeghers syndrome
AD
Man brought into ER after seizure. Has never had one before. Has had intermittent bloody stools for past 4 months. Head CT reveals irregular masses extending from right to left hemisphere. CT of abdomen shows multiple polyploid masses in sigmoid colon
(A) Familial adenomatous polyposis (B) Gardner syndrome (C) Hereditary nonpolyposis colorectal carcinoma (D) Tuberous sclerosis (E) Turcot syndrome
E. Turcot syndrome
FAP/Lynch + Malignant CNS tumors (medulloblastoma, glioma)
Lynch syndrome
- disease
- symptoms
- inheritence
- mutation
- progression
- Location
- Associated with
Hereditary nonpolyposis colorectal cancer (HNPCC)
15-20 polyps, family history of colorectal cancer
AD
Mutation of DNA mismatch repair with microsatellite instability
(Mutation or methylation of mismatch repair genes MLH1)
Progress to colorectal cancer
Proximal colon always involved
Associated with endometrial, ovarian and skin cancers
Apple core lesions on barium enema xray
Colorectal cancer
Main liver cancer
- assoc with
Hepatocellular carcinoma
HCV, alcoholic and nonalcoholic fatty liver disease, alpha 1 antitripsin)
Budd-Chiari
- is what
- due to
- absence
- assoc with
- appearance
Thrombosis or compression of hepatic veins with centrilobular congestion and necrosis
Congestive liver disease
Absence of JVD
Hypercoagulable states (polycythemia vera, postpartum, HCC)
Nutmeg liver (mottled appearance) - Right sided heart failure
Wilson’s disease
- Mutation
- chromosome
- decreased
- symptoms
- Degeneration of
- Tx
ATP7B
Chromosome 13
Decreased ceruloplasmin
Copper accumulates Hepatitis Dysarthria, tremor Moody Yellow eyes (green rings)
Hepatolenticular degeneration
- lenticular nucleus: putamen and globus pallidus
Tx: Penicillamine
Hemochromatosis
- Inheritence
- Mutation
- Chromsome
- HLA
- defect
- Labs
- clinical
- Death due to
Tx
Recessive mutation in HFE gene on Chr 6
Assoc with HLA-A3
Increased iron sensing and intestinal absorption
Increased ferritin, iron, transferrin
Decreased TIBC
Bronze diabetes
Cirrhosis
DM
Hypogonadism
HCC common cause of death
Deferoxamine, Phlebotomy
Acute pancreatitis causes
I GET SMASHED
Idiopathic Gall stones Ethanol Trauma Steroids Mumps Autoimmune Scorpion sting Hypercalcemia/ Hyertriglyceridemia ERCP Drugs (sulfa, NRTIs, protease inhibitors)
Abdominal pain radiating to back
Migratory thrombophlebitis
Obstructive jaundice with palpable non tender gallbladder
Pancreatic adenocarcinoma
Head to pancreas
H2 blockers
- example
- use
- adverse effects
-dine
(cimetidine, ranitidine, famotidine, nizatidine)
Reversible block H2 receptor
Peptic ulcer, gastritis, mild esophageal reflux
Cimetidine
- P-450 inhibitor
- Gynecomastic
- impotence
- Cross BBB (confusion, dizziness)
- Cross placenta
- Decrease methomoglobin levels
Proton pump inhibitors
- example
- MOA
- Uses
-prazole
(Omeprazole, lansoprazole, pantoprazole…)
Irreversibly inhibit H/K ATPase in stomach parietal cells
Peptic ulcer, gastritis, reflux, zollinger ellison,
Stress ulcer prophylaxis
Aluminum hydroxide
Alter gastric and urinary pH
Hypokalemia
Constipation
Hypophospahtemia
Proximal muscle weakness
Seizures
Calcium carbonate
Alter gastric and urinary pH
Hypokalemia
Hypercalcemia
Rebound acid increase
Magnesium hydroxide
Alter gastric and urinary pH
Hypokalemia
Diarrhea
Hyporeflexia
Hypotension
Cardiac arrest
Bind to ulcer base, provide physical protein and allowing HCO3 secretion to reestablish pH gradient
- requires
Bismuth (peptobismal)
Sucralfate
Requires acidic environment (Sucralfate)
PGE1 analog
- MOA
- Use
- adverse effect
Misoprostol
Increase production and secretion of gastric mucous barrier
Decrease acid production
Prevention of NSAID induced peptic ulcers
Off label use for induction of labor (ripens cervix)
Diarrhea
Octreotide
- MOA
- uses
- Adverse effects
Long acting somatostatin analog
Inhibits various splanchnic vasodilatory hormones
Acute variceal bleeds
Acromegaly
VIPoma
Carcinoid tumors
Nausea, cramps
Steatorrhea
Increase risk cholithiasis due to CCK inhibition **
Sulfasalazine
- MOA
- Use
- Adverse
Combo of sulfapyridine (antibacterial) and 5- aminosalicylic acid (anti-inflammatory)
Activated by colonic bacteria
UC and chrons
Nausea, sulfa toxicity
Oligospermia** (reversible)
Loperamide
- MOA
- Use
- Adverse effects
Agonist at mu opoid receptor
Slows gut motility
Poor CNS penetration
Used for diarrhea
AE: constipation, nausea
Ondansetron
- MOA
- Use
- Adverse effects
5-HT3 antagonist (serotonin)
Decrease vagal stimulation
Central- acting aniemetic
Control vomiting post-op and in chemo
Adverse
- Headache **
- Constipation
- QT prolongation **
- Serotonin syndrome
Metoclopramide
- MOA
- Use
- Adverse effects
D2 receptor antagonist
( Stimulates 5-HT, inhibits D2)
Increase resting tone, contractility, LES tone, motility, promotes gastric emptying.
Use: DM and post surgery gastroparesis, antiemetic, persistent GERD
Adverse
- Parkinson effect **
- Tardive dyskinesia
- Seizures **
- Restlessness
- Depression
Orlistat
- MOA
- Use
- Adverse effects
Inhibits gastric and pancreatic lipase
Decrease breakdown and absorption of dietary fats
Use: Weight loss
Adverse
- Steatorrhea
- Decrease absorption of fat soluble vitamins
Laxatives
- Psyllium, methylcellulose
- Magnesium hydroxide, magnesium citrate, polyethylene glycol, lactulose
- Senna
- Docusate
Psyllium, methylcellulose
- Bulk forming
- soluble fibers draw water into lumen
- AE: bloating
Magnesium hydroxide, magnesium citrate, polyethylene glycol, lactulose
- Osmotic laxatives
- Provide osmotic load to draw water into GI lumen
- AE: diarrhea, dehydration
Senna
- Stimulants
- Enteric nerve stimulation –> colonic contraction
- Diarrhea
- Melanosis coli: lumen of gut is pigmented with brown color
Docusate
- Emollient
- Osmotic draw into lumen, increase water absorption by stool
- AE: diarrhea
Aprepitant
- Type
- MOA
- Use
Substance P antagonist
Blocks NK1 receptors in brain
Antiemetic for chemotherapy induced nausea and vomiting
Thrombocyte contains what 2 things
Dense granules
- ADP, Ca
Alpha granules
- vWF, fibrinogen, fibronectin
vWF receptor
GpIb
Fibrinogen receptor
GpIIb/IIIa
Neutrophil chemotactic agents
C5a IL-8 LTB4 kallikrein Platelet activating factor
Target cell seen in
HALT
HbC disease
Asplenia
Liver
Thalassemia
Drugs that target P2Y12 receptor
Inhibit ADP induced expression of GpIIb/IIIa via P2Y12 receptor
Clopidogrel
Prasugrel
Ticlopidine
Drugs that target GpIIb/IIIA
Inhibit directly
Abciximab
Eptifibatide
Tirofiban
Microcytic hypochromic anemia
MCV < 80
Hypochromic (central pallor)
LIST
Lead poisoning
Iron deficiency
Sideroblastic anemia
Thalassemia (Alpha, Beta)
Macrocytic anemia
MCV > 100
Megaloblastic anemia Folate deficiency Vit B 12 deficiency (neurologic symptoms) Orotic aciduria (no hyperammonia)
Non hemolytic, normocytic anemia
Anemia of chronic disease
Aplastic anemia
Pyruvate kinase deficiency
AR
Pyruvate kinase defect
Decreased ATP
Rigid RBCs
Extravascular hemolysis
Increased levels of 2,3 BPG
Decreased hemoglobin affinity for O2
Crystals inside RBCs
Target cells
HbC disease
Glutamic acid –> lyCine (lysine) mutation in beta globin
Causes extravascular hemolysis
Sickle cell vasoocculsion due to
abnormal hemoglobin polymerization
Lead poisoning
- affected enzyme
- accumulated substance
- symptoms
Affected
- ferrochelatase
- ALA dehydratase
Accumulated (blood)
- Protoporphyrin
- ALA
Mental deterioration
HA
Memory loss
Acute intermittent porphyria
- inheritence
- affected enzyme
- Accumulation
- symptoms
- tx
AD
Affected
- porphobilinogen deaminase
(previously known as uroporphyrinogen I synthase)
Accumulation
- Porphobilinogen
- ALA
5 P’s
- Painful abdomen
- Port wine colored urine (reddish urine darkens on exposure to light and air)
- Polyneuropathy
- Psychological disturbances
- Precipitated by drugs (barbiturates, seizure drugs, rifampin, metoclopramide)
Tx Glucose and heme (dextrose)
Porphyria cutanea tarda
- Inheritence
- Affected enzyme
- Accumulation
- symptoms
Affected enzyme
- AD
- Uroporphyrinogen decarboxylase
Accumulation
- Uroporphyrin
Symptoms
- Tea colored Urine
- Blistering to sun
- Hyperpigmentation to sun exposure
Bernard-Soulier
- platelet count
- bleeding time
- defect
Normal or decreased platelets
Increased bleeding time
Defect in platelet plug formation
- Large platelets
- Decreased GpIb
- defect platelet to vWF adhesion
Glanzmann thrombasthenia
- platelet count
- bleeding time
- defect
- blood smear
Normal platelet count
Increased bleeding time
Defect in platelet integrin (GpIIb/IIIa)
- defect in aggreagation
Blood smear shows no clumping
HUS
- platelet count
- bleeding time
- defect
- features
Decreased platelets
Increased bleeding time
Acute renal failure
Children
Diarrhea and E.coli
Immune thrombocytopenia
- platelet count
- bleeding time
- defect
- bone marrow biopsy
Decreased platelets
Increased bleeding time
Anti-GpIIb/IIIa antibodies
Increased megakaryocytes on bone marrow biopsy
Thrombotic thrombocytopenic purpura
- platelet count
- bleeding time
- defect
- increased
- labs
Decreased platelets
Increased bleeding time
Inhibition or deficiency of ADAMTS 13 (vWF metalloprotease) –> decreased degradation of vWF multimers
Increased platelet adhesion, aggregation and thrombosis
Schistocytes, increased lactate dehydrogenase, thrombocytopenia
Owl eyes
- surface marker for this cell type
Reed Sternberg cells
- Hodgkin lymphoma
CD15 and CD 30 B cell
Mandible Mass
Night sweats
Sheets of lymphocytes with interspersed “tingible body” macrophages
- Translocation
- gene
- assoc with
Burkitt lymphoma
t(8;14)
c-myc
EBV
t(8;14)
Burkitt lymphoma
t(14;18)
Follicular lymphoma
BCL-2
t(11;14)
Mantle cell lymphoma
Tranlocation of cyclin D1 (11) and heavy chain Ig (14), CD5+
t(11;18)
Marginal zone lymphoma
Older adult
Rapidly growing mass
Diffuse large B cell lymphoma
Waxing and waning lymphadenopathy
Follicular lymphoma
Cutaneous lesions
Lytic bone lesions
Hypercalcemia
Adult T cell lymphoma
HTLV mutation
Skin patches/ plaques characterized by typical CD4 + cells with cerebriform nuclei and intraepidermal neoplastic ell aggregates
Mycosis fungoides/ Sezary syndrome
Tx multiple myeloma
Proteasome inhibitor
Borteozomib
- boronic acid containing dipeptidase
Rouleaux formation
Multiple myeloma
Multiple myeloma symptoms/ features
CRAB
hyperCalcemia Renal involvement Anemia Bone lytic lesions/ Back pain Monoclonal M protein spike
t(12;21)
ALL
Splenomegaly
Pancytopenia
Marrow fibrosis “Dry tap”
Positive TRAP (tartrate resistant acid phosphatase)
TX
Hairy cell leukemia
- mature B cellt umor
Hair like projections on LM
Treatment
- Cladribine
- Pentostatin
Cell with small amount of purplish clear cytoplasm, large purple nucleus. Small purple particle/ spinter on periphery
- disease
- cell type
- positive for
- translocation
- tx
AML
Auer rods
Myeloperoxidase positive
t(15;17)
TX
- all-trans retinoic acid (vit A)
t (15;17)
AML
t(9;22)
- disease
- lab
- tx
BCL-ABL
Philiadelphia chromosome
CML
Very low LAP
Bcl-abl tyrosine kinase inhibitors
- Imatinib
Myeloproliferative disorders
- examples
- mutation
Polycythemia vera
Essential thrombocythemia
Myelofibrosis
CML
JAK2 mutation
Intense itching after hot shower
- Due to
- Lab
- Tx
Polycythemia vera
Due to episodic blood clots in vessels of the extremities
Decreased EPO
Increased RBC, WBC, Platelets
TX
- Phlebotomy
- Hydroxyurea
- Ruxolitinib (JAK1/2 inhibitor)
Massive splenomegaly
Tear drop RBCs
- Disease
- Due to
- Lab
Myelofibrosis
Obliteration of bone marrow with fibrosis due to increased fibroblast activity
Decreased RBC
Dry tap
Lytic bone lesions
Skin rash
Recurrent otitis media
EM: Tennis racket
- What do cells express
Langerhans cell histicytosis
S-100
CD1a
Heparin
- MOA
- Adverse effects
- Reversal
- Administered
- Site of action
Binds antithrombin III which then inhibits Factor Xa and neutralize thrombin
AE
- Bleeding
- Thrombocytopenia
- Osteoporosis
Protamine sulfate
(binds to heparin)
IV or SQ
Blood
Low molecular weight heparins
Enoxaparin
Dalteparin
Act predominantly on factor Xa
Fondaparinux
- type
- MOA
- 4 features
Low molecular weight heparin
Acts only on Factor Xa
Better bioavailability
Longer half life
Adminstered SQ
Not easily reversible
Heparin induced thrombocytopenia (HIT)
development of IgG antibodies against heparin bound platelet factor 4 (PF4)
Antibody-heparin-PF4 complex activates platelets –> thrombosis and thrombocytopenia
Similar to anticoagulant used by leeches, hirudin
Bivalirudin
Direct thrombin inhibitor
Directly inhibits activity of free and clot associated thrombin
Direct thrombin inhibitors
- examples
- oral one
- MOA
- use
- reversal
Bivalirudin
Argatroban
Dabigatran (only oral)
Directly inhibits activity of free and clot associated thrombin
Use
- venous thromboembolism
- Afib
Dabigatran can be reversed with idarucizumab
Warfarin
- MOA
- Lab
- Adverse effects
- Route of admission
- Site of action
Interferes with gamma-carboxylation of vit K- dependent clotting factors II, VII, IX, X and protein C and S
Inhibits epoxide reductase
Extrinsic pathway
Increase PT
Adverse effects
- Bleeding
- Teratogenic
- Skin/ tissue necrosis ** (due to small vessel microthrombosis)
- Transient hypercoagulability when first use due to Protein C and S
Oral
LIver
Apixaban
- type
- other
- MOA
- Use
Direct Factor Xa inhibitors
-Xaban
Apixaban
Rivaroxaban
Bind to and directly inhibit factor Xa
TX for DVT and PE, stroke prophylaxis in patients w/ Afib
Thrombolytics
- examples
- MOA
- Lab
- Use
Alteplase (tPA), reteplase (rPA), streptokinase, tenecteplase (TNK-tPA)
Directly or indirectly aid conversion of plasminogen to plasmin which cleaves thrombin and fibrin clots
Increase PT, PTT, no change in platelet
Early MI, direct thrombolysis of severe PE
Dont use in patient with active bleeding or history of bleeding issues
Antifibrinolytics
Aminocaproic acid
Tranexamic acid
Clopidogrel
- type
- examples
- MOA
- Prevents
- Use
- Adverse effect
ADP receptor inhibitors
Clopidogrel
Prasugrel
Ticagreolar (reversible)
Ticlopidine
Inhibit platelet aggregation by IRREVERSIBLY block ADP (P2Y12) receptor.
Prevent expression of glycoproteins IIb/IIIa) on platelet surface
Use: Coronary stenting
Adverse effect
- Neutropenia (ticlopidine)
- TTP
Cilostazol
- type
- other example
- MOA
- Use
- Adverse effect
Phosphodiesterase inhibitors
Dipyridamole
Increase cAMP in platelets, resulting in inhibition of platelet aggregation; vasodilators
Use
- Intermittent claudication
- coronary vasodilation
Adverse effects
- Nausea, HA
- Facial Flushing
- Hypotension
- Abdominal pain
Abciximab
- Type
- Other examples
- MOA
- Use
- Adverse
Glycoprotein IIb/IIIa inhibitors
Abciximab
Eptifibatide
Tirofiban
Bind to the glycopreotin receptor IIb/IIIa on activated platelets, preventing aggregation.
Use
- Unstable angina
Adverse
- bleeding
- thrombocytopenia
Dipyridamole
- type
- other example
- MOA
- Use
- Adverse effect
Phosphodiesterase inhibitors
Cilostazol
Increase cAMP in platelets, resulting in inhibition of platelet aggregation; vasodilators
Use
- Intermittent claudication
- coronary vasodilation
Adverse effects
- Nausea, HA
- Facial Flushing
- Hypotension
- Abdominal pain
Eptifibatide
- Type
- Other examples
- MOA
- Use
- Adverse
Glycoprotein IIb/IIIa inhibitors
Abciximab
Eptifibatide
Tirofiban
Bind to the glycopreotin receptor IIb/IIIa on activated platelets, preventing aggregation.
Use
- Unstable angina
Adverse
- bleeding
- thrombocytopenia
Cancer drugs that affect S phase of cell cycle
Antimetabolites
Azathioprine Cladribine Cytarabine 5-fluorouracil Hydroxyurea Methotrexate 6-mercaptopurine
Topoisomerase inhibitors (S and G2)
- Etoposide
- Teniposide
- Irinotecan
- Topotecan
Cancer drugs that affect both S phase and G2 phase
Topoisomerase inhibitors
- Etoposide
- Teniposide
- Irinotecan
- Topotecan
Tirofiban
- Type
- Other examples
- MOA
- Use
- Adverse
Glycoprotein IIb/IIIa inhibitors
Abciximab
Eptifibatide
Tirofiban
Bind to the glycopreotin receptor IIb/IIIa on activated platelets, preventing aggregation.
Use
- Unstable angina
Adverse
- bleeding
- thrombocytopenia
Cancer drugs that affect G2 phase of cell cycle
G2 only
- Bleomycin
Topoisomerase inhibitors (S and G2)
- Etoposide
- Teniposide
- Irinotecan
- Topotecan
Cancer drugs that inhibit M phase of cell cycle
Microtubule inhibitors
- Paclitaxel
- Vinblastine
- Vincristine
Cancer drugs that are independent of cell cycle
Platinum agents (cisplatin)
Alkylating agents
- Busulfan
- Cyclophosphamide
- Ifosfamide
- Nitrosoureas (carmustine)
Cancer drugs that target nucleotide synthesis (4)
MTX, 5-FU
- decrease thymidine synthesis
6-MP
- decrease de novo purine synthesis
Hydroxyurea
- inhibit ribonucleotide reductase
Cancer drugs that target DNA (9)
Alkylating agents, platinum agents
- Cross link DNA
Bleomycin
- DNA strand breakage
Dactinomycin, Doxorubicin
- DNA intercalators
Etoposide/ teniposide
- Inhibit topoisomerase II
Irinotecan/ topotecan
- inhibit topoisomerase I
Use to prevent organ rejection, RA, IBD, SLE
- MOA
- Adverse effects
Azathioprine
6-mercaptopurine
Adverse effects
- myelosuppresion
Use to tx hairy cell leukemia
- MOA
- Adverse effect
Cladribine
Purine analog –> multiple mechanism
- Inhibition of DNA polymerase
- DNA strand breaks
Myelosuppression
Nephrotoxicty
Neurotoxicity
Tx Leukemia (AML) and lymphomas
- MOA
- Adverse effect
Cytarabine (arbinofuranosyl cytidine)
Pyrimidine analog
Inhibition of DNA polymerase
Myelosuppresion with megaloblastic anemia
CYTarabine causes panCYTopenia
Cancer drug can result in hand foot syndrome (palmar-plantar erythrodysesthesia)
- MOA
- Use
5-fluorouracil
Pyrimidine analog
Inhibits thymidylate syntehase
Decrease DNA synthesis
Colon cancer
Pancreatic caner
Basal cell carcinoma
Myelosuppression reversible with
Leucovorin
What drug’s effects are enhanced by leucovorin
5-fluorouracil
Mouth ulcers
Hepatotoxicity
Pulmonary fibrosis
From what drug
Methotrexate
Testicular cancer tx (non-alkylating )
- Drug
- MOA
- Other use
- Adverse effect
Bleomycin
Induces free radical formation –> breaks in DNA strands
Testicular cancer
Hodgkin lymphoma
Pulmonary fibrosis
Hyperpigmentation
Cancer drug causes
1) Pulmonary fibrosis
2) Hyperpigmentation
3) Nephrotoxicity, Neurotoxicity
4) Megaloblastic anemia, myelosuppression
5) Redness, swelling and pain on palms or soles
6) Hepatotoxicty
7) Cardiotoxicity
8) Convulsions, dizziness, ataxia
9) Mouth ulcers
10) Alopecia
11) Neuropathy and hypersensitivity
12) Areflexia, peripheral neuritis, constipation
13) Nephrotoxicity, peripheral neuropathy, ototoxicity
14) Diarrhea and myelosuppression
15) Hemorrhagic cystitis
16) Hemorrhage, blood clots, impaired wound healing
17) Rash only
18) Rash, Elevated LFTs, diarrhea
19) Fluid retention
20) Increased risk of thromboembolic events
1) Methotrexate, Bleomycin, Busulfan
2) Bleomycin, Busulfan
3) Cladribine
4) Cytarabine
5) 5-fluorouracil
6) Methotrexate
7) Doxorubicin, Daunorubicin , Trastuzumab (Herceptin)
8) Nitrosoureas
9) Methotrexate
10) Doxorubicin, Daunorubicin, Etoposide, teniposide
11) Paclitaxel
12) Vincristine, Vinblastine
13) Cisplatin, carboplatin
14) Irinotecan, topotecan
15) Cyclophosphamide, ifosfamide
16) Bevacizumab
17) Erlotinib
18) Cetuximab
19) Imatinib
20) Tamoxifen, Raloxifene
Used to childhood tumors
- Wilms tumor
- Ewing sarcoma
- Rhabdomyosarcoma
MOA
Dactinomycin (actinomycin D)
Intercalates DNA
Doxorubicin
Daunorubicin
MOA
Use
Adverse
- Tx adverse
Anthrocyclines
Generates free radicals
Intercalate in DNA –> breaks DNA –> decrease replication
(Wedge into DNA between base pairs, forms tight bond, DNA cant unwind to replicate)
Solid tumors
Leukemia, lymphomas
Cardiotoxicity (dilated cardiomyopathy)
Alopecia
Dextrazoxane
- iron chelating agent
- prevent cardiotoxicity
Use to prevent cardiotoxicity in patients taking doxorubicin or daunorubicin
Dextrazoxane
Tx CML
MOA
Adverse
Other use
Adverse effects
Busulfan
Cross links DNA
Also used to ablate patient’s bone marrow before bone marrow transplantation
Pulmonary fibrosis
Hyperpigmentation
Alkylating agent that can cross BBB
- Needs
- MOA
- Use
- Adverse effect
Nitrosoureas
- mustine
(carmustine, lomustine, semustine)
Requires bioactivation
Cross BBB
Cross link DNA
Use
- Brain tumors (glioblastoma)
Adverse
- CNS toxicity (convulsions, dizziness, ataxia)
Cisplatin, carboplatin
- MOA
- Use
- Adverse effect
- Prevent adverse with
Cross link DNA
Testicular
Bladder
Ovary
Lung carcinoma
Nephrotoxicity
Peripheral neuropathy
Ototoxicity
Prevent nephrotoxicity with amifostine (free radical scavenger) and chloride (saline) diuresis
Prevent nephrotoxicity with
Amifostine
Free radical scavenger
Aminocapric acid
Tranexamic acid use to reverse
Thrombolytics
Alteplase
Reteplase
Streptokinse
Tenecteplase
Dexarazoxane
Iron chelating agent
Used to prevent cardiotoxity in Doxorubicin, and daunorubicin
Amifostine
Free radical scavenger
Prevent nephrotoxicity in platins
Cyclophosphamide
- MOA
- Other drug
- Uses
- Adverse effect
Cross- link DNA at guanine N-7
Requires bioactivation by liver
Nitrogen mustard
Solid tumors, leukemia, lymphoma
Immunosuppressant
(SLE, Polyarteritis nodosa)
Hemorrhagic cystitis
(Prevented by mesna- thio group of mesna binds toxic metabolites or N-acetylcysteine)
Mesna
Binds toxic metabolites
Prevents Hemorrhagic cystitis
Cyclophosphamide
Hydroxyurea
- MOA
- Use
Inhibits ribonucleotide reductase
Inhibit DNA synthesis in S phase
Myeloproliferative disorders - CML - Polycythemia vera Sickle cells Melanoma
Monoclonal Ab
1) VEGF
- Use
- adverse
2) EGFR
- Use
- Adverse
3) CD20
- Use
- Adverse
4) HER-2
- use
- adverse
1) VEGF monoclonal Ab= Bevacizumab
- Inhibits angiogenesis (blood vessel formation)
- Solid tumors (colorectal cancer, renal cell carcinoma)
- Hemorrhage, blood clots, impaired wound healing
2) EGFR monoclonal Ab= Cetuximab
- Stage IV colorectal cancer (wild type KRAS)
- Head and neck cancer
- Rash, elevated LFTS, diarreha
3) CD20 monoclonal AB= Rituximab
- CD20 on most B cell neoplasma
- Non-hodgkin lymphoma, CLL, ITP, RA
- Increased risk of progressive multifocal leukoencphalopathy
4) Trastuzumab (Herceptin)
- HER2 breast cancer and gastric cancer
- Cardiotoxicity. “Heartceptin” damages the heart
Erlotinib
- Type
- Use
- Adverse
EGFR tyrosine kinase inhibitor
Non-small cell lung carcinoma
Rash
Imatinib
- Type
- Use
- Adverse
Tyrosine kinase inhibitor of BCR-ABL and c-kt
CML, GI stromal tumors (GIST)
Fluid retention
Borteozomib
- type
- MOA
- Other example
- Use
- Adverse
Proteasome inhibitor
Induce arrest at G2-M phase and apoptosis
- Results in accumulation of toxic intracellular proteins excess pro-apoptotic proteins –> induce apoptosis
Boronic acid containing dipeptide
Multiple myeloma
Mantle cell lymphoma
Adverse
- Peripheral neuropathy
- herpes zoster reactivation (shingles)
Carfilzomib
- type
- MOA
- Other example
- Use
- Adverse
Proteasome inhibitor
Induce arrest at G2-M phase and apoptosis
- Results in accumulation of toxic intracellular proteins excess pro-apoptotic proteins –> induce apoptosis
Multiple myeloma
Mantle cell lymphoma
Adverse
- Peripheral neuropathy
- herpes zoster reactivation
Raloxifene
- MOA
- Use
- Adverse effect
Selective estrogen receptor modulators (SERMs)
- antagonist in breast
- agonist in bone
- blocks binding of estrogen to ER + cells
Prevent osteoporosis
(Not direct tx for breast cancer but helps)
Antagonist in endometrial tissue
Increased risk of thromboembolic events
Tamoxifen
- MOA
- Use
- Adverse effect
Selective estrogen receptor modulators (SERMs)
- antagonist in breast
- agonist in bone
- blocks binding of estrogen to ER + cells
Breast cancer treatment and prevention
Partial agonist in endometrium
- increase risk of endometrial cancer “ hot flashes”
Increased risk of thromboembolic events
Vemurafenib
Small molecule inhibitor of BRAF oncogene + melanoma
V600E-mutated BRAF inhibition
VE-MU- RAF-enib is for V600E-MUtated bRAF inhibition
Serine/ threonine kinase
Metastatic melanoma
Tx of cancer
Hyperkalemia
Hyperphosphatemia
Hypocalcemia
Hyperuricemia
Treatment
Tumor lysis syndrome
Agressive hydration
Allopurinol
Rasburicase
Rasburicase
Recombinant uricase that catalyzes metabolism of uric acid to allantoin
Prevention and tx of tumor lysis syndrome
What can trigger toxic megaclon
Antibiotics –> clostridum difficile
Sensation of anterior 2/3 on tongue
Taste
Motor
Sensation: Mandibular branch of trigeminal n. (CN V3)
Taste: facial
Motor: hypoglossal n.
Salivary gland stimulated secretions
Sympathetic
- Thick secretions
- Superior cervical ganglion
Parasympathetic
- Watery
- CN VII and CN IX
What nerve runs through parotid gland and can be damaged with parotid gland surgery
CN VII
Infection common of tonsils and adenoids
S. pyogenes
Infection most common of salivary gland
S. aureus
Viridans group strep
Pleomorphic adenoma
- composed of
Most common salivary gland tumor
Epithelial and mesenchymal cells
Tumor of salivary gland
Double layer of columnar epithelium around cyst. Stroma is lymphoid.
- Can form
Warthin tumor
- Benign cystic tumor
Can form germinal center
Child with immune disorder has recurrent staphylococcal abscess. Found that neutrophils fail to respond because the chemotactic stimuli are deficient. Most likely?
Hyperimmunoglobulin E syndrome (Job syndrome)
- IFN-gamma low
Leukocyte adhesion deficiency
Esophagitis
1) Esophagitis reveals large, pink intranuclear inclusions and host cell chromatin that is pushed to the edge of nucleus
2) Esophagitis reveals enlarged cells, intranuclear and cytoplasmic inclusions and a clear perinuclear halo
3) Biopsy reveals a lack of ganglion cells between the inner and outer muscosal layers
4) Protrusion of mucosa in the upper esophagus
1) HSV esophagitis
2) CMV esophagitis
3) Achalasia
4) Plummer-vinson syndrome
Dark urine
Clay colored stools
Jaundice
Extrahepatic biliary atresia
Incomplete recanalization
Tx Esophageal variceal bleed
Vasopressin
Octreotide
Propranolol or nadolol (beta blocker)
Vagus nerve directly stimulates what in GI
- receptors
- inhibited by
Vagus indirectly stimulates what
- This secretes what
- Inhibited by
Parietal cells to secrete gastric acid
- M3 ACh receptors
- Can be inhibited by atropine
Indirectly stimulates G cells to release Gastrin via Gastrin-releasing peptide
- Gastrin stimulates enterochromaffin like (ECL) cells to secrete histamine
- Stimulates parietal cells to make gastric acid
- Atropine has no effect
- H2 blockers (Cimetidine, Ranitidine)
Upper GI problem
1) Stomach biopsy reveals neutrophils above the basement membrane loss of surface epithelium and fibrin containing purulent exudate
2) Stomach biopsy reveals lymphoid aggregates in the lamina propria, columnar absorptive cells and atrophy of glandular structures
3) Diffuse thickening of gastric folds, elevates serum gastrin levels, biopsy reveals glandular hyperplasia without foveolar hyperplasia
1) Acute gastritis
2) Chronic gastritis
3) Zollinger-Ellison syndrome
Peptic ulcer treatment
Additional tx if hemorrhage
Triple therapy- H. pylori
- PPI + clarithromycin + amoxicillin
- PPI + clarithromycin + metronidazole
Quadruple therapy
- PPI + Bismuth + metronidazole + tetracycline
Hemorrhage= Octreotide (somatostatin)
- decrease splanchnic blood flow
Vasoactive intestinal peptide (VIP)
Smooth muscle cells
Parasympathetic ganglia
Enteric nervous system
Relaxes smooth muscle and sphincters in GI tract
Increase secretion of electrolytes and water
Copious watery diarrhea
Brunner glands
- job
- location
Secretes alkaline mucus
Neutralize gastric acid
Duodenal submucosa
Ligaments that have to be cut to remove spleen
Gastrosplenic lig
Splenorenal lig
Macrolides fxn in GI
Stimulate smooth muscle motilin receptors
Pain out of proportion to physical exam
Ischemic colitis
Downs syndrome GI problems
Dont Have A Clue
Duodenal atresia
Hirschsprung Disease
Annular pancreas
Celiac disease
Preop Tx for appendicitis
Hydration
Cefoxitin
Ampicillin + sulbactam
Stops in Chromosomal instability APC pathway
1) Loss of APC gene
2) KRAS mutation (increased growth stimulus)
3) Loss of tumor suppressor genes
- p53
- DCC (chr 18 q)
Familial adenomatous polyposis
FAP
AD
Lots of polyps
Fatty bulge under skin (fatty tumor)- Lipoma
Bone soft tissue tumors (osteomas)
- Extra bone growth (spur)
Lots of polyps in colon
Retinal hyperplasia (dark black spot in eye)
Gardner syndrome
Tx Crohns
Initial for mild
- 5-ASA agents (5-aminosalicylic)
(Mesalamine, sulfasalazine)
Azathioprine or mercaptopurine
Anti-TNF if arthrtic component (infliximab, adalimumab)
Diverticulitis tx
Metronidazole (anaerobic bacteria)
TMP-SMX or fluoroquinolone
Pancreas derived from
Endocerm
Diabetes Depression Dermatitis DVT Wt loss
Glucoagonoma
Tumor of pancreatic alpha cells
TX: octreotide
Diabetes
Steatorrhea
Gallstones
Achlorhydrdia
Somatostatinoma
Hormones stimulate pancreatic secretion
CCK (pancreas and GB)
Secretin (stimulate bicarb secretion)
Acetylcholine (CN X)
Liver from what germ layer
Endoderm
Metabolic Liver failure can cause an increase in
Increased estradiol levels
- Testicular atrophy
- Gynecomastia
- Spider angioma (telangiectasia)
- Palmar erythema (red palms)
Medications for cirrhosis
- Tx ascites and edema
- Tx varices
- Tx Hepatic encephalopathy
Diuretic (tx ascites and edema)
- Spironolactone
- Furosemide
Beta blockers (varices)
- Propranolol
- Nadolol
Vit K
Lactulose (tx hepatic encephalopathy)
- Trap ammonium in gut so gets excreted in stool
Rifamacin (refractory hepatic encephalopathy)
Tx Hep B
Tenofovir Entacavir Telbivudine Lamivudine Adefovir
Pregnant
- Lamivudinie
Tx Hep D
Pegylated IFN-alpha
Tx Hep C
Ledipasvir-Sofosbuvir
Ombitasvir-paritaprevir-ritonavir + dasabuvir
Anti-smooth muscle ab
Autoimmune hepatitis
Genus and family
1) Hep A
2) Hep B
3) Hep C
4) Hep D
5) Hep E
1) Hep A
- ssRNA
- hepatovirus
- picronavirus
2) Hep B
- dsDNA
- orthohepadnavirus
- Hepadnaviridae
3) Hep C
- ssRNA
- hepacivirus
- Flavivirdae
4) Hep D
- ssRNA
- deltavirdae
5) Hep E
- ssRNA
-
Primary Biliary cholangitis (PBC)
- MOA
- Identifies
- Tx
Autoimmune
T cells attack bile ductules within the liver parenchyma
Granulomas
Cirrhosis
Antimitochondrial antibody (AMA)
Tx: Ursodiol (ursodeoxycholic acid)
- bile acid that decreases the synthesis of cholesterol in the liver
Primary Sclerosing Cholangitis (PSC)
- MOA
- Causes
- Identifier
- Associated with
- Tx
Concentric fibrosis of bile ducts
Irregular ares of stricturing and areas of dilation “Beads on a string”
(+) p-anca
Associated with UC and cholangiocarcinoma
Tx: liver transplant
RL of coagualtion pathway
Factor X
Factor V Leiden
Makes Factor Va resistant to inactivation by protein C
More coagulation
Hypercoagulable
Resistant to Heparin
Antithrombin deficiency
Unable to inactivate thrombin
Protein C deficiency
Unable to inactivate factor V and VIII
PT
Extrinsic
Starts with VII
Monitor Warfarin
PTT
Intrinic
start w/ XII
Monitor heparin
RL step in heme synthesis
delta-ALA synthase
Chipmunk facies
Hair on end appearance X ray
Target cells
Microcytic anemia
Beta thalassemia
Increase Hemoglobin F (2 alpha 2 gamma)
Orotic acid in urine
megaloblastic anemia
No hyperammonemia
Orotic aciduria
Def: UMP synthase
Cold agluttings
Ab against RBC that interact more strongly at low temps
IgM
EBV or mycoplasma
Warm agglutins
Ab react against RBC at body temp
IgG
EBV, HIV
Lupus
Malignancies (CLL, non-hodgkin)
Congenital immune abnormalities
Hereditary spheocytosis defects in
Ankyrin
Spectrin
Band 3
Protein 4.2
Tx Sickle cell
Hydroxyurea (increase HbF)
Order of bands on hemoglobin electrophoresis
A F S C
Ham’s test
Paroxysmal nocturnal hemoglobinuria
Red urine in morning
RBC missing surface markers
-CD55 adn CD59
Increase in PTT and bleeding time
Von Willebrand factor (vWF) deficiency
Von willebrand disease test
Ristsocetin cofactor assay
Causes platelets to aggregate if vWF present
Tx vWF disease
DDAVP
- desmopressin (synthetic ADH)
Increases vWF release from storage sites
Painless non-tender lympadenopathy Low grade fever Night sweats weight loss Pruritis
Hodgkin lymphoma
B cell symptoms
Neutrophils iwth two lobed nucleus connected by thin strand
Neutrophil: lots of light blue/ purple cytoplasm
Pelger-Huet Anomaly
Myelodysplastic syndromes
Small cell lung cancer paraneoplastic syndromes (3)
ACTH –> cushing syndrome
ADH –> SIADH
- Hyponatremia
Lambert-Eaton syndrome
- Ab against presynaptic Ca channels at NMJ
Cancer that secretes PTHrP
Squamous cell lung cancer
Any squamous cell cancer
Tx Actinic keratosis
5-fluorouracil
CA-125 screening
Ovarian cancer
Alpha feto protein screening
hepatocellular carcinoma
Testicular tumors
CA 19-9 screening
Pancreatic cancer
S-100
Melanoma
Schwannoma
Tartrate resistant acid phosphatase (TRAP)
Hairy cell leukemia
Tx testicular cancer (3)
Eradicate Ball Cancer
Etoposide + Bleomycin + Cisplatin
Etoposide + ifosfamide + Cisplatin
Tx choricocarcinoma
Methotrexate
Vincristine
Tx Childhood tumors
- Wilms
- Ewing
VIncristine
Dactinomycin
Tx for philadelphia chromosome
Imantinib
Targets mutant BCR-ABL`
Elevated Liver aminotransferases. Hx of drug use. Panlobular mononuclear cell infiltration taht crooss into adjacent lobules. Occasionally see a intensely Eosinophilic round bodies that are seen scattered amongst the hepatic parenchyma. What could cause this?
Acute viral hepatitis due to drug use
Hepatocytes may undergo cytotoxic T cell mediated apoptosis due to presence of viral antigens on the hepatocyte surface
These apoptotic cells appear as round acidophilic (pink) bodies known as councilman bodies
Epigastric pain, nausea and bloating. Diffuse erythema of antral mucosa. Infiltrate involving the superficial mucosal layers. The underlying cause will lead to
H. pyrloi induced chronic gastritis
–>Gastric lymphoma
Develop resistance to chemotherapy via
P-glycoprotein, a transmembrane protein taht functions as a ATP dependent efflux pump.
Pumps out chemotherapeutic agents
Shrunken liver on autopsy
Drug induced liver injury
- Inhaled anesthetic (halothane)
widespread centrilobular necrosis and inflammation of portal tracts and parenchymas are observed
Elevated AST ALT
Prolonged PT
Leukocytosis and eosinophilia
Gallbladder hypomotility causes waht with bile
Biliary sludge
Hirschsprung disease
Constipation and abdominal distention
Narrow rectum and rectosigmoid area. Rest of colon is dilated.
Failure to pass meconium
Bilious vomiting
Failure of neural crest cells to migrate to intestinal wall or submucosa (meissner) and myenter (auerbach) plexi.
Submucosa of rectum (narrowed segment) should be biopsied
