Brachial Plexus

Just a quick explanation in case it's not clear on the image. I also recommend going through the motions with your hand. It helps! :3

Distal lesions will affect the lumbricals, so the fingers cannot extend.
Proximal lesions will affect the flexors, so the hand cannot make a fist.

A distal lesion of the ulnar nerve will cause the patient to have difficulty uncurling the 4th and 5th digit, but the 2nd and 3rd digit can. A proximal lesion to the medial nerve will cause the patient to have difficulty curling the 2nd and 3rd digit, but the 4th and 5th can. Both will end up looking like the Pope blessing.

A proximal lesion to the ulnar nerve will cause the patient to have difficulty curling the last two digits while a distal lesion to the median nerve will cause the patient difficulty uncurling the 2nd and 3rd digit. Both will end up looking like the OK gesture.

Review Questions

A patient presents to his PCP with a 3 day history of fever, chest pain, and cough. He informs you that he recently went on a trip exploring caves in the midwest. The chronic form of this condition will lead to granulomas and cavitations in the upper lobes of the lungs. What do you expect to find upon histology?
A) pilot's wheel shaped fungus
B) thick walled cells showing broad based budding
C) acid fast bacteria
D) macrophages filled with many yeast-like cells
E) pleural cells showing a biphasic pattern (epithelioid cells and sarcomatoid cells)

A 50yo female with a history of asthma presents to the clinic complaining of white spots in her mouth. She explains that the spots started appearing ever since she started using Fluticasone. She is worried that this may be cancer, but you find that the spots can be scraped off. What does this organism do at 37 degrees Celsius?
A) forms yeast cells
B) unable to grow
C) cause pseudomembranes in the colon
D) leads to changes in vaginal pH
E) forms germ tubes

A 15yo male presents to the clinic with dyspnea. His IgE levels are elevated and CXR reveals bilateral migrating infiltrates. If we were to examine the organism under microscope, we'd see V-shaped branching. The patient has a condition that predisposes him to this condition. What mutation causes this condition?
A) VHL gene chromosome 3
B) COL4A5 gene X chromosome
C) CTFR gene chromosome 7
D) SERPINA1 gene chromosome 14
E) WT1 gene chromosome 11

Paraneoplastic Syndromes

Lung Cancer
1. Small Cell Carcinoma

• SIADH - excess ADH --> hyponatremia
• Cushing Syndrome - excess ACTH
• Lambert-Eaton - antibodies against presynaptic Ca2+ channels --> prevents release of Ach

2. Squamous Cell Carcinoma

• Hypercalcemia - PTHrP, "stones, bones, groans, psychiatric overtones"

Kidney Cancer
1. Renal Cell Carcinoma

• Cushing Syndrome - excess ACTH
• Polycythemia - excess EPO
• HTN - excess renin
• Hypercalcemia - PTHrP, "stones, bones, groans, psychiatric overtones"

Henoch-Schönlein Purpura

HSP is an autoimmune disease that causes vasculitis. It causes blood vessels to leak red blood cells, leading to a bruise-like rash on the arms, legs, and buttocks. The rash is more likely to appear on areas subjected to more pressure. Other symptoms of HSP include abdominal pain and join pain.

Now since our class is having renal pathology on our upcoming exam, we also need to know that HSP can cause nephritic syndrome, specifically IgA nephropathy.

Renal Pathology

Renal Pathology

Here is the complete powerpoint of the following renal pathologies:

• glomerulonephritis
• acute renal failure
• renal cystic disease
• chronic renal disease
• UTIs
• renal tumors
• nephrolithiasis
• incontinence

Notes are from lecture, Pathoma, and First Aid! Anything not high yield is noted in the comments section, so you can use this for the exam and then for board prep. Hope this helps! ^.^

Glomerulonephritis and Acute Renal Failure

Renal Pathology
Many thanks to my awesome study group, Danny, and Jack!

UTIs

Notes from lecture! ^.^ And remember that E. coli gets in via P pili and gal-gal receptors!

Tuberculosis

Pulmonary Infectious Diseases

Pulmonary Infections

Endo-, Myo-, Pericarditis

Coagulation Cascade

For a list of drugs, check out my old post: anticoagulants, fibrinolytics, antiplatelets

Ciliary Dyskinesia

Kartagener Syndrome is an autosomal recessive defect in ciliary genes leading to impaired mucociliary function. This mutation usually affects the dynein arm. As a result, patients with this syndrome present with bronchiectasis and sinusitis because of secretion retention and recurrent infections. This syndrome is also associated with situs inversus, hearing impairment, and male infertility.

Alpha 1 Antitrypsin Deficiency

Alpha 1 Antitrypsin Deficiency can lead to panacinar emphysema. This condition is autosomal recessive (codominant) and caused by SERPINA1 mutations. Normally, alpha-1 antitrypsin is synthesized in the liver and acts in the lungs. It inhibits enzymes like elastase. However when there is an imbalance in antiprotease and protease levels, the elastase in macrophages can destroy basement membranes leading to emphysema. When alpha-1 antitrypsin is not released from the liver, it can cause cirrhosis. The phenotype ZZ is the most severe form of ATT deficiency while the null does not cause hepatitis.

Cystic Fibrosis

One cause of bronchiectasis is cystic fibrosis, an autosomal recessive disease affecting the CFTR gene on chromosome 7. CFTR codes for a Cl- transporter, which leads to lack of Cl- secretion in epithelial cells. As a result, secretions are dry, thick, and difficult to clear. This leads to recurrent sinopulmonary infections and nasal polyps. The most common mutation is delta F508 resulting in a misfolded CFTR protein that is unable to leave the endoplasmic reticulum. This mutation is a missing phenylalanine.

Cystic fibrosis also affects the sweat glands in which the sweat glands are unable to reabsorb the Cl- causing hypertonic sweat. In fact, a pilocarpine test is used to induce sweating in infants if cystic fibrosis is suspected.

Patients with cystic fibrosis also present with pancreatitis, leading to malabsorption of fat soluble vitamins and greasy stools. Patients have meconium ileus (bowel obstruction) because of the thicker mucus secretions in their bowels. This will be seen on radiographs as air fluid levels. In addition, the vas deferens may not be formed. This causes infertility in male patients.

Treatment for patients with cystic fibrosis include Ivacaftor (G551D mutation), antibiotics, pancreatic enzymes, vitamins, and lung transplant.

Asthma Pharmacology

ASTHMA TREATMENT
Step 1: SABA
Step 2: low-dose ICS
Step 3: low-dose ICS + LABA
Step 4: medium-dose ICS + LABA
Step 5: high-dose ICS + LABA
Step 6: high-dose ICS + LABA + oral steroid

consider adding theophylline as alternative for LABA
consider using cromolyn, LTRA, or nedocromil as alternatives for ICS
consider omalizumab for patients with allergies in steps 5 and 6

FOR EMERGENCIES
O2
high-dose SABA
Ipratropium
Oral CST
IV CST
Mg2+

Restrictive Lung Diseases

Restrictive lung diseases come about from poor breathing mechanics or interstitial lung diseases. Poor breathing mechanics result in under-ventilation of lungs. Thus the A-a gradient is normal. Conditions such as ALS, polio, myasthenia gravis, and scoliosis limit the body's ability to take in air. There is no problem with the alveoli. Interstitial lung diseases cause the lungs to become fibrotic and it is the fibrosis and destruction of lung tissue hat leads to less oxygen into the lungs.

Atelectasis, COPD, Asthma

CHF Pharmacology

Cardiomyopathies

Once again...many thanks to my study group!

Congenital Heart Defects

Metabolic Syndrome (Insulin Resistance Syndrome)

A collection of three or more of the following conditions is called metabolic syndrome. It indicates an increased risk of cardiovascular events and diabetes.

Increase waist circumference
Increased glucose
Pre-hypertension
Increased triglycerides
Decreased HDL

Angina Pharmacology

Electrolyte Imbalance

Special thanks to Siu Lam!

Lung Physio

Arrhythmias and EKGs

Notes from Dr. Zhang's and Dr. Shlofmitz's lectures!
Thanks again to my study group for helping to get some of these concepts down!
Arrhythmias and EKGs

DVT, PE, and more...

Submassive PE - without systemic hypotension (>90), RV dysfunction

Massive PE - sustained systemic hypotension (<90) not due to other causes,  pulselessness, bradycardia

Special thanks to my amazing study group!

Timeline of MI

Special thanks to my amazing study group!

Neuroanatomy Part 1

First image is a blank worksheet. Try filling it out before moving on!

Pathology Review

Requested by Krishna! Here are my review powerpoints for Dr. Plummer's lectures! ^.^

Types of Diseases
Necrosis
Inflammation
Tissue Repair
Tumors
Atherosclerosis
Myocardial Infarction

Acid Base Disorders

Special thanks to my amazing study group!

Dyslipidemia

Dyslipidemia

Statin Therapy

ASCVD

LDL > 190

age 40 to 75, DM, LDL 70 to 189

age 40 to 75, 10 year risk ASCVD > or = 7.5%

Special thanks to my amazing study group (Janeah, Deb, Siu Lam, and Abhi)!

Bile Salt Synthesis

Dietary lipids have low solubility. Bile salts act as detergents to emulsify them. Bile salts are synthesized in the liver and stored in the gallbladder. They are reabsorbed in the GI tract and transported back into the liver via enterohepatic circulation.

Cholesterol is modified via hydroxylation and carboxylation to increase solubility. 7 alpha hydroxylase is the rate limiting step. Cholic acid and chenodeoxycholic acid are primary bile acids. In the intestine, they are converted into deoxycholic and lithocholic acid via bacterial enzymes. These secondary acids are less soluble and so are easily excreted.

Bile salts can also be conjugated to glycine or taurine, lowering the pKa and making the bile salts better detergents.

Cholesterol Biosynthesis

Citrate transport system moves acetyl CoA from mitochondria into cytoplasm. Thiolase, HMG CoA synthase, and HMG CoA reductase (rate-limiting) convert it into mevalonate. Mevalonate is then converted into IPP and then cholesterol.

Cholesterol can be esterified and stored in the cell via ACAT, or it can be secreted as a lipoprotein and then converted via LCAT.

Transcriptional Control
If there is a high level of cholesterol, it binds to SCAP and inactivates it. If there is low cholesterol, then SCAP is active. SCAP-SREBP can be transported into the Golgi, where the proteases cleave off the DNA binding domain. That DNA binding domain goes into the nucleus and interacts with SRE. SREBP can then activate the genes for HMG CoA reductase synthesis.

Post-transcriptional control includes proteolysis of the reductase or degradation of the HMG CoA reductase mRNA.

Phosphorylation
Glucagon --> phosphorylation of HMG CoA reductase via kinase like AMPK --> decrease cholesterol synthesis
Insulin --> dephosphorylation of HMG CoA reductase via phosphatase --> increase cholesterol synthesis

Respiratory Control Mechanisms

2,3-BPG

2,3 BPG is produced by erythrocytes when there are low levels of oxygen, like at high altitudes. 2,3 BPG shifts the oxygen dissociation curve to the right so that hemoglobin has reduced affinity for oxygen. This results in an increased in O2 delivery to the tissues.

1,3 BPG, the precursor to 2,3 BPG, is formed during one of the steps in glycolysis. In hypoxic environments, it does not become pyruvate but instead is converted into 2,3 BPG by BPG mutase. As a result, the cell is sacrificing the formation of ATP for increased O2 delivery.

Chiari I and II Malformations

Chiari I malformation is when the lower part of the cerebellum extends into the foramen magnum. Type I may not cause any symptoms. In fact, it may not detected until much later in life.

Chiari II malformation (Arnold-Chiari malformation) is the herniation of the cerebellar vermis and brain stem through the foramen magnum. The herniation can then cause hydrocephalus. Type II is associated with myelomeningocele. During antenatal care, an ultrasound may show a lemon or banana sign. Infants may display symptoms such as stridor (sounds like a seal), dysphagia, hypotonia, and ataxia.

https://rarediseases.info.nih.gov/diseases/9232/chiari-malformation-type-2
https://radiopaedia.org/articles/chiari-ii-malformation

Rib Ligaments

Shock

Special thanks to Siu Lam, Janeah, and Deb!

Wigger's Diagram

Special thanks to my friends, Siu Lam and Janeah, for going through this a third time with me...

Osmotic Diuretics

5. Osmotic Diuretics
Osmotic diuretics, like mannitol (IV), are distributed into the ECF and are freely filtered into the glomerulus. This allows the water to be drawn out from cells. The drug can act on all sites of the nephron permeable to water.

Osmotic diuretics can be used to treat:
-edema
-increased intracranial pressure
-increased intraocular pressure
-adjunct to cisplatin (minimize nephrotoxicity)

Adverse effects of osmotic diuretics include:
-ECF expansion
-headache
-dizziness
-nausea and vomiting
-pulmonary edema
-hyponatremia
-dehydration and hypovolemia
-nephrotoxicity

Contradictions to osmotic diuretics include:
-allergy
-severe dehydration
-severe renal disease
-renal dysfunction
-active cranial bleeding
-progressive heart failure
-pulmonary edema

Potassium Sparing Diuretics

4. Potassium Sparing Diuretics

ENaC Inhibitors
ENaC is a Na+ pump on the apical side of principal cells in the collecting duct. Amiloride blocks Na+ reabsorption causing a decrease in Na+/K+ ATPase activity causing K+ retention. As a result of the reduced K+ electrochemical gradient, there is increased reabsorption of H+, Ca2+, and Mg2+. ENaC polymorphism (T594M) can cause increased sensitivity to the drug.

ENaC inhibitors can be used to treat:
-hypertension
-Li+ induced nephrogenic diabetes
-Liddle Syndrome (pseudohyperthyroidism)

Adverse effects of ENaC inhibitors include:
-hyperkalemia (contradicted in those who have it)

Drug interactions with ENaC inhibitors include:
-ACE inhibitors and ARB (hyperkalemia)
-NSAIDs (hyperkalemia)
-K+ supplements (hyperkalemia)

Mineralocorticoid Receptor Inhibitors
Aldosterone binds to mineralocorticoid receptors, increasing Na+/Cl- reabsorption and K+/H+ secretion. MR inhibitors, such as spironolactone and eplerenone, block ALDO from binding. As a result, there is increased Na+ and Cl- excretion, and increased H+ secretion. Spironolactone can cause antiandrogenic effects like gynecomastia and impotence.

MR inhibitors can be used to treat:
-edema
-hypertension
-primary aldosteronism
-heart failure
-hirsutism (interfere with testosterone)
-hepatic cirrhosis (spironolactone is drug of choice)

Drug interactions with MR inhibitors include:
-Digoxin (decreased clearance with spironolactone)
-CYP3A4 mediated interactions (eplerenone)

Thiazide Diuretics

3. Thiazide Diuretics
Thiazides block the NCC channel in the distal convoluted tubule. This prevents the reabsorption of Na+ and Cl-. Hydrochlorothiazide is a benzothiadiazine derivative while chlorthalidone lacks the benzothiadiazine structure. Chlorthalidone has a longer half-life than hydrochlorothiazide. Thiazides have a moderate diuretic effect. They cause kidney to excrete Na+, Cl-, K+ and titratable acid. However they also cause an increase in Ca2+ reabsorption.

Unlike loop diuretics, the increase in Na+ delivery to the DCT will not cause activation of RAAS. Thus the kidney is unable to compensate for the Na+ excretion, resulting in concentrated urine.

Thiazides can be used to treat:
-congestive heart failure
-hepatic cirrhosis
-nephrotic syndrome
-chronic renal failure
-acute glomerulonephritis
-hypertension
-nephrogenic diabetes

Adverse effects of thiazides include:
-hyponatremia
-hypotension
-hypokalemia
-metabolic alkalosis
-hypomagnesemia
-hypercalcemia
-hyperuricemia (gout)
-hyperglycemia
-hypersensitivity to sulfonamides

Drug interactions with thiazides include:
-Digitalis glycosides (hypokalemia --> arrhythmia)
-Lithium (enhanced Na+ excretion --> lithium toxicity)
-Antihypertensive drugs (hypotension)
-Vitamin D analogs (increase Ca2+)
-Anti-diabetic drugs (hyperglycemia)
-Probenecid (blocks OAT so drug can't get in)
-NSAIDs (block COX-2 --> decreased prostaglandins --> decreased vasodilation --> decreased GFR --> blunted response because not much is filtered)
-Amphotericin B (hypokalemia)
-Glucocorticoids (hypokalemia)
-ACE Inhibitors (increased nephrotoxicity)

Loop Diuretics

2. Loop Diuretics
Loop diuretics block the NKCC channel at the Thick Ascending Loop of Henle. This prevents the reabsorption of Na+, K+, and Cl-. Therefore there is no the potential difference formation, so other solutes (Ca2+ and Mg2+) are also not reabsorbed. In addition to the excretion of Na+, K+, Cl-, Ca2+, Mg2+, there is also increased excretion of titratable acid and decreased excretion of uric acid (gout). Furosemide is a sulfonamide drug. Ethacrynic acid is not. Loop diuretics are highly efficacious as other segments of the nephron are unable to compensate. Furosemide causing venodilation, reducing preload before diuresis occurs. The inhibition of salt transport into the macula densa (low Na+) and the volume depletion (baroreceptor) causes an increase in renin which increases GFR.

Diuretics can evoke compensatory mechanisms such as activation of SNS, RAAS, and decrease BP. These can lead to diuretic resistance or braking phenomenon. For Furosemide, the transporter in the proximal tubule may be blocked so that the drug cannot be secreted into the lumen and travel to the site of action.

Loop diuretics can be used to treat:
-acute pulmonary edema
-congestive heart failure
-nephrotic syndrome
-liver cirrhosis
-chronic kidney disease
-acute kidney injury
-hypertension
-drug overdose
-hypercalcemia

Adverse effects to loop diuretics include:
-hyponatremia
-hypokalemia
-hypomagnesemia
-metabolic alkalosis
-ototoxicity

Contradictions to loop diuretics include:
-pregnancy

Drug interactions with loop diuretics include:
-NSAIDs (block COX-2 --> decreased prostaglandin --> decreased vasodilation --> decreased GFR --> blunted response because not much is filtered)
-ACE inhibitors and ARB (enhanced nephrotoxicity)
-Lithium (enhanced Na+ excretion so lithium toxicity)
-Digitalis glycosides (hypokalemia --> arrhythmia)
-Quinidine (hypokalemia --> torsades de pointe)
-Probenecid (blocks OAT so drug can't get in)
-Aminoglycosides and cisplatin (ototoxicity)
-Amphotericin B (hypokalemia)
-Glucocorticoids (hypokalemia)

Carbonic Anhydrase Inhibitors

1. Carbonic Anhydrase Inhibitors
Carbonic anhydrase converts H2O and CO2 into H+ and HCO3-, allowing Na+ and HCO3- to be reabsorbed into the interstitum. Acetazolamide blocks this conversion and causes HCO3- and Na+ to be excreted. The drug crosses the blood brain barrier and is eliminated in the proximal tubule (site of action). It is a weak diuretic since the Loop and Henle can compensate for the lack of reabsorption. The effects are also self-limiting. Inhibition of carbonic anhydrase will lead to increase solute delivery to the macula densa which will trigger the TGF and decrease GFR. The loss of HCO3- also leads to hyperchloremic metabolic acidosis. The body decreases the amount of HCO3- being filtered leading to enhanced NaCl reabsorption in other parts of the nephron.

Carbonic anhydrase inhibitors can be used to treat:
-open angle glaucoma
-urinary alkalinization
-metabolic alkalosis
-acute mountain sickness (by increasing ventilation)
-epilepsy
-edema
-solubilized uric acid

Adverse effects of carbonic anhydrase inhibitors include:
-metabolic acidosis
-renal stones (calcium phosphate)
-renal K+ wasting
-hypersensitivity with sulfonamide allergies

Contradictions to carbonic anhydrase inhibitors include:
-hypersensitivity with sulfonamide allergies
-acidosis
-renal disease
-cirrhosis (increase ammonium in blood)

Renal Physiology

Anemia

Chapman Points and Visceral Sympathetics 8/8/17

Chapman Points (Anterior)
clavicle and 1st intercostal space - upper respiratory (nasal sinuses, pharynx, tonsils)
2nd intercostal space - bronchi, esophagus, thyroid, heart
3rd and 4th intercostal space - upper and lower lung
1 inch superior and lateral from umbilicus - kidney
umbilicus - bladder
tip of 12th rib - appendix
iliotibial tract - colon

Chapman Points (Posterior)
C2 - upper respiratory (sinuses, pharynx, larynx, tongue)
T2 - bronchi, esophagus, thyroid
T3 - heart
T3 and T4 - upper and lower lung
L3 - kidney
L4 - bladder

Visceral Sympathetics
thyroid T1-T4
lungs T1-T5
heart T1-T6
kidneys T10-T12
bladder T12-L2

TLC Drugs Review

Amoxicillin
-penicillin class
-used with clavulante (beta lactamase inhibitor)
-used for pneumonia
-used for sinusitis
-used for dental abscess
-2nd line for scarlet fever
-2nd line for otitis media
-2nd UTI
-adverse effects include nausea, vomiting, diarrhea, allergic reactions, C. diff infection

Clarithromycin
-used for pneumonia
-used for pertussis (Whooping cough and caused by Bordetella pertussis)
-2nd line for scarlet fever
-2nd line for otitis media

Ciprofloxacin
-fluoroquinolones
-used for otitis externa
-used for dysentery (bloody and mucous stools)
-used for cholera (rice water stools)
-used for UTI
-avoid if tendon problems, muscle disorders, antacids
-not used in children because of deposition

Penicillin V
-scarlet fever

Cefalexin
-2nd line for otitis media

Metronidazole
-used for giardiasis (water and fishy smelling diarrhea )
-2nd line for dysentry

Azithromycin
-used for typhoid fever

H. pylori gastritis
1st line: amoxicillin + metronidazole + omeprazole
2nd line: clarithromycin + metronidazole + omeprazole

Cloxacillin
-used for cellulitis
-used for impetigo
-used for puncture wounds

Vaginal Infection
thrush: flucanozole
bacterial infection: metronidazole
STI: ciprofloxacin + doxycycline
STI (pregnant): cefixime + erythromycin

Conjunctivitis
-cefotaxime + erythromycin

Periorbital/orbital cellulitis
-co-amoxiclav + chloraphenicol

Antacids
-neutralize stomach acid
-used for heartburn, upset stomach, indigestion, GERD
-Mylanta (AlOH2)

Omeprazole
-PPI (proton pump inhibitors)
-used for GERD and gastric ulcers
-adverse affects include risk of fractures

Metformin 
-used for Type 2 DM
-decrease liver glucose production and increase insulin sensitivity
-avoid if kidney problems or ketoacidosis
-overdose can cause lactic acidosis

Amlodipine
-Ca2+ channel blocker
-dilates blood vessels
-used for hypertension
-also used for angina and coronary artery disease
-avoid if liver problems and aortic stenosis

Atorvastatin (Lipitor)
-statin
-decrease production of cholesterol via inhibition of HMG CoA reducatse in liver
-used in dyslipidemia and prevention of CVD

Chlorpheniramine
-1st gen antihistamine

Cetirizine (zyrtec)
-2nd gen antihistamine

SOAP Note Abbreviations

HEENT
normocephalic atraumatic NCAT
extra ocular movements intact EOMI
pupils equal, round, reactive to light, accommodation PERRLA
tympanic membrane intact TMI
septum and turbinates normal

CARDIO
regular rate and rhythm RRR
normal heart sounds S1, S2, no murmurs, gallops, or rubs

LUNGS
clear to auscultation CTA
normal lung sounds no wheezes, rhonchi, or rales

ABDOMEN
positive bowel sounds + BS
distended, non-tender
hepatospenomegaly
masses

BACK
spine
CVA tenderness

MSK
range of motion ROM
5/5 muscle strength
gait

EXTREMITIES
cyanosis
deformities
edema

NEURO
CN 2-12
Romberg
Pronator drift
tandem walking
sensation
deep tendon reflexes DTR

SPECIAL TESTS
straight leg raise SLR
urinary analysis UA
ultrasound US

DRUGS
once a day qd
twice a day bid
every 2 hours q2h
every 12 hours q12h
every night qhs
as needed prn

Beta Lactams, Antifungals, Chemo for Protozoa, Antihelminthics

Beta-Lactams
Antifungals
Chemo for Protozoa
Antihelminthics

Anticoagulants, Fibrinolytics, Antiplatelet

Anticoagulants
1. Unfractionated Heparin
-activates antithrombin III --> degrade thrombin and Xa
-nonspecific binding --> unpredictable and monitor with PTT, Xa assay, platelet count
-prevent progression of existing clots (venous thrombosis, embolism, MI)
-HIT-IgG attack AT III and factor IV complexes-->vascular damage-->thrombocytopenia
-Protamine

2. LMWH
-smaller molecule and more predictable
-degrade thrombin and Xa (more specific for Xa)
-DVT
-monitoring in larger and pregnant patients

3. Fondaparinux
-factor Xa
-DVT and pulmonary embolism

4. Direct Factor Xa Inhibitors (Rivaroxaban CYP3A4/5, Apixaban)
-reversible inhibition of free and bound Xa
-DVT and pulmonary embolism
-nonvalvular atrial fibrillation
-prothrombin complexes

5. Direct Thrombin Inhibitors (Argatroban CYP3A4/5, Dabigatran, Bivalirudin)
-bind to active site of thrombin to prevent fibrinogen --> fibrin and activation of factors V, VIII, XIII

6. Warfarin CYP2C9
-block VKORC1
-inhibit factors X, IX, VII, II, and Protein C and S
-full-thrombotic effect not achieved for several days --> need bridging therapy
-PT and INR monitoring
-bleeding, thrombosis, purple toe syndrome
-contradicted in pregnancy (nasal hypoplasia, hemorrhage, CNS abnormalities)
-Vitamin K, plasma, prothrombin complexes

Fibrinolytics
1. Streptokinase
-binds to plasminogen-->plasmin-->systemic lytic state
-systemic lytic stage-->hemostatic plugs-->concurrent use of heparin increases risk of hemorrhage
2. Alteplase
-activate plasmin in presence of fibrin
3. Tenecteplase
-activate plasmin in presence of fibrin
4. Reteplase
-activate plasmin in presence of fibrin

Antiplatelets
1. Aspirin
-block COX1-->inhibit TXA2
-MI, ischemic stroke, transient ischemic episodes (adjunctive in revascularization)

2. ADP Receptor Antagonist (Clopidogrel CYP2C19, Prasugrel, Ticagrelor)
-P2Y12 receptor inhibitor-->no fibrinogen cross-linking
-STEMI and stent placement
-bleeding, thrombocytpenia

3. Glycoprotein IIb/IIIa Inhibitors (Abciximab, Eptifibatide, Tirofiban)
-fibrinogen cannot bind
-prevention of PCI, STEMI
-used in conjunction with heparin and aspirin
-bleeding

Antimalarials

1. Chloroquine
-large volume of distribution-->need large dose so that drug can be in blood
-sequestered in tissues
-erythrocytic stage
-prevents conversion of heme to hemozoin-->oxidative stress
-K76T PfCRT mutation causes drug to accumulate in parasite's food vacuole
-G6PD deficiency and porphyria->toxic

2. Mefloquine
-widely distributed, including CNS
-neurologic side effects such as vivid dreams, anxiety, sleep disturbance
-disrupt hemozoin polymerization
-associated with amplification of pfmdr1

3. Quinine and Quinidine
-disrupt hemozoin polymerization/DNA intercalation
-short half-life
-cardiotoxic
-cinchonism, hypoglycemia, hypotension, blackwater fever, thrombocytopenia, QTc interval prolongation
-used with doxycycline-->in pregnant women and children, use clindamycin

4. Primaquine
-generation of oxidation-reduction mediators
-prophylaxis to prevent primary and latent hepatic stages
-erythrocytic, primary hepatic, latent hepatic, gametocytes
-pneumonia
-G6PD deficiency and methemoglobinemia-->toxic
-pregnancy contradicted

5. Atovaquone-Proguanil
-inhibit ETC-->collapse mitochondrial membrane
-erythrocytic and primary hepatic

6. Sulfadoxine-Pyrimethamine
-(S) inhibit dihydropteroate reductase
-(P) inhibit dihydrofolate reductase
-high resistance and slow acting

7. Artemisinin
-cleavage of artemisinin endoperoxide bridge-->free radical-->damage to macromolecules
-short half-life
-erythrocytic and gametocytes
-first line
-anemia, hemolysis, hypersensitivity
-combination with Lumefantrine (forms heme complex/decrease synthesis?, risk of QTc prolongation)

8. Doxycycline and Clindamycin
-delayed death mechanism-->impaired apicoplast gene-->death of progeny
-GI problems and photosensitivity

Toxicology

1. Barbiturate Overdose
-alkanize urine-"ion trapping"

2. Benzodiazepine Overdose
-flumazenil-reverses toxicity

3. Alchohol
-intoxication-supportive care
-withdrawal-benzodiazepine, naltrezone, acamprostate, antabuse, clonidine

4. Phencyclidine Overdose
-benzodiazepines

5. LSD Overdose
-benzodiazepines and antipsychotics

6. Cocaine
-rhabdomyolysis-kidney cannot handle myoglobin-->sustained muscle contractions
-overdose-phentolamine and labetalol, acidify urine, supportive care (lorazepam and haloperidol)
-withdrawal-bromocriptine

7. Amphetamine
-overdose-cyproheptadine-serotonin blocker for serotonin syndrome
-withdrawal-bromocriptine

8. Methylxanthines
-toxicity-convulsions, arrhythmias, nausea, vomiting
-treat cardiac with beta-blocker

9. Nicotine
-smoking cessation-buproprion, varenicline

Opioids

1. Morphine
-treats moderate-severe pain
-less anxiety
-hypersensitivity in respiratory disease
-respiratory depression
-increase intracranial pressure

2. Codeine
-treats mild-moderate pain
-"partial activity"
-anti-tussive

3. Meperidine
-less respiratory depression in neonates
-anti-muscarinic
-metabolite can induce seizures
-serotonin syndrome
-MAOI interaction-->coma

4. Diphenoxylate
-antidiarrheal

5. Fentanyl
-more potent than morphine
-lipophilic
-transdermal or transmucosal

6. Levophanol
-treats moderate-severe pain
-D-isomer (dextromethorphan is non-addictive cough suppressant)

7. Methadone
-long duration
-NMDA antagonist
-treats opioid withdrawal

8. Heroin
-no medical use
-collapse of vessels
-HIV + hepatitis
-newborn withdrawal

9. Tramadol
-reuptake inhibitor of NE and 5-HT
-chronic neuropathic pain
-serotonin syndrome

10. Methylnaltrexone
-treats opioid-induced constipation

11. Buprenorphine
-partial agonist
-K receptor block
-precipitate withdrawal in opioid users
-treats opioid withdrawal

12. Naloxone
-treats opioid overdose

Gout Treatment

Gout is an inflammatory arthritis that is caused by the body's immune response to monosodium urate crystals in the joints. Uric acid is the product of purine metabolism and can settle out of solution. Several signs of gout include podagra and tophi. Gout should not be confused for pseudogout which is caused by calcium pyrophosphate. The difference between the two can be seen when observing the crystals. The negative birefringement urate crystals are needle-shaped.

The treatment of gout begins with treatment of symptoms. This includes NSAIDs, corticosteriods, colchicine, and ACTH. Colchicine inhibits inflammatory responses by inhibiting microtubule polymerization and inflammatory mediators.

Patients with gout who present with tophi, frequent attacks, and urolithiasis, may be started on ULT (urate lowering therapy). Allopurinol (hypersensitivity associated with HLA-B allele) is a competitive inhibitor of xanthine oxidase and febuxostat is a non-purine inhibitor of xanthine oxidase. Both will lower the production of uric acid. Uricosuric agents compete with uric acid at the transporters for reabsorption. These include probenecid (reduces excretion of penicillins) and lesinurad.

The transitioning treatment to ULT includes an anti-inflammmatory and a ULT drug.

Plasma Cell Disorders

Blood-borne Pathogens

Palpating Carotids Bilaterally

Why should you not palpate your patient's carotids arteries bilaterally?

I remember being told it could cause less blood flow to the brain. However would that caused by the pressure you place on the vessels? Do you cut off the blood supply?

It is actually because of the carotid body located near the bifurcation of the carotid artery. The carotid body is a bundle of mechanoreceptors that reacts to changes in pressure. If you were to increase the pressure on the carotid body, it would set of the baroreceptor reflex. It signals to the brain that there is an increase in systemic pressure, and then the brain signals the body to lower blood pressure. As a result, there is less blood flow to the brain.

Thanks to Dr. Koehler and Danny!

Orthopedics of Spine

RA Treatment

NSAIDs and glucocorticoids are used to treat the symptoms of rheumatoid arthritis, while traditional and biologic DMARDs are used to treat active RA.


NSAIDs inhibit either COX-1 or COX-2, or even both. In the treatment of rheumatoid arthritis, these drugs inhibit the production of prostaglandins from arachidonic acid leading to a decrease in inflammation. One adverse effect is decrease in cytoprotection in GI via inhibition of COX-1.

Aspirin-irreversibly blocks COX-1 and COX-2, hypersensitivity (bronchospasms), Reye's syndrome, acute and chronic salicylate poisoning (ion trapping)

Acetaminophen-metabolism via sulfation/glucuronidation + CYP2E1+ glutathione detoxification, NAC for toxicity

Traditional NSAIDs
Propionic Acid Derivatives
Ibuprofen-close ductus arteriosus, inhibit aspirin
Naproxen-can be used to treat pain and fever in children>12yo
Acetic Acid Derivatives
Indomethacin-close ductus arteriosus, gout, tocolytic
Ketoroloac-non-selective, seasonal allergies, does not penetrate CSF
Diclofenac-mostly COX-2, hypersensitivity
Enolic Acid Derivative
Meloxicam-OA and RA

Coxib 
Celecoxib-COX-2 selective, no GI effects or bronchospasm but higher risk of CVD


Glucocorticoids interfere with the HPA by acting like cortisol, which then represses transcription. In turn humoral and cellular immunity are suppressed. Glucocorticoids are started and taper down in dose. The adverse effects of glucocorticoids can be summed up as Cushing Syndrome.


Methotrexate (first line traditional DMARD) inhibits DHFH, TYMS, and AICAR formyl transferase. The inhibition of DHFH and TYMS leads to decrease in DNA and RNA synthesis, and so less cell proliferation. The inhibition of AICAR formyl transferase leads to an accumulation in adenosine, which is responsible for MTX's anti-inflammatory effects. MTX can cause GI problems because it is a folate analog, so to treat these adverse effects the patient can take folate (Leucovorin). MTX can also interact with various drugs like penicillin, NSAIDs, aspirin, sulfonamides, probenecid (gout treatment) via competition with OAT. MTX can be displaced by salicylates, doxycycline, phenytoin (prevent seizures).

Other traditional DMARDs include Sulfasalazine (unknown mechanism but is capable of displacing MTX + hypersensitivity), Choloroquine (stabilizes lysosomal membranes and inhibits enzymes responsible for cartilage breakdown), and Leflunomide (inhibits DHODH-->inhibits de novo pyrimidine synthesis). Leflunomide is a teratogen (cause malformation of embryo).


The biologics can be divided into TNF-alpha antagonists and lymphocyte modulating biologics.

TNF-alpha Antagonists (need to screen for exposure to Hep B/C and tuberculosis)
Infliximab-binds to both soluble and membrane cytokine
Etanercept-binds to both soluble cytokine
Adalimumab-human mAb
Golimumab-human mAb
Certolizumab-lacks Fc fragment on antibody-->does not induce complement activation

Lymphocyte Modulating Biologics
Abatacept-inhibit T cell activation
Rituximab-inhibit B cell activation
Tocilizumab-IL-6 antagonist
Anakira-inhibits IL-1 receptor
Tofacitinib-inhibit JAK3 enzyme (cannot phosphorylate STAT-->affects transcription)

Endurance Athlete

Bone Pathology

Unusual Neuro and Factitious Disorders