UW 06-04-12

TCA - work by blocking reuptake of NE and seratonin
- Toxicity = the Tri-C's: Convulsions, Coma, Cardiotoxicity

- N-oligosaccharide modification = Asparagine
- Mannose-6-phosphate on Lysosomal proteins
- O-oligosaccharides added to = Serine & Threonine
in the vietnam war, NAM LOST, but Golgi lost his EYE

Mitral regurge

Via the Left Gastric Vein

MLF syndrome d/t lesion in the medial longitudinal fasciculus (MLF)
Medial rectus palsy when attempting a lateral gaze
seen in MS (think Ann Romney is a MiLF w/ MS)

Amphotericin B is drug of choice
VERY Nephrotoxic (↓GFR & directly toxic to lumenal epithelium) → electrolyte abnormalities (palpitations; ↓K, ↓Mg lost in DT) & anemia (weakness)

d/t Bartonella henselae (cat scratch)
found in Immunocompromised/HIV patients
Prz: Red-purple papular skin lesions (vascular proliferation); also found in viscera; can be fatal
- B. henselae → Cat Scratch (low fever, LA), bacillary angiomatosis, and endocarditis (culture negative)

Pirmary Hyperparathyroidism

1) ↑ fluid (flow rate)
2) Citrate (will bind Ca and prevent it from ppt'ing)

Neural pathway of limbic system involved in cortical control of emotion and memory; damaged in Wernicke encephalopathy (especially the mammillary bodies)

B6 = Pyridoxal phosphate

1) Secxually active young adults = Gonorrhea
2) Kids/>50 y/o /IVDA = Staph aureus

ToRCHHeS
- Toxo
- Rubella
- CMV
- HIV
- HSV2
- Syphilis

1) GBS (agalactica - vaginal flora)
2) E. coli (vaginal flora)
3) Listeria monocytogenes

Either Rubella (German measles/Togavirus) or CMV (Herpesvirus)

HSV2 - can also give the same herpetic lesions

It's chorea d/t Rheumatic Fever (AI sequela of GAS pharyngitis or impetigo)
- anti-neuronal Ab's attack the caudate and subthalamic nucleus

Scarlet = Toxigenic (Sandpaper, Strawberry tongue)
Rheumatic = immunologic (ab's to M-Protein → Myocardium, Myelin, Marginatum, Polyarthritis)

Causes:
1) Antipsychotics
2) Reserpine (Huntington's Drug - prevents loading of DA/EPI/NE into vesicles)
3) Metoclopramide (D2 R antagonist; tx's gastroparesis in DM and post-sx)

Tx = Antimuscarinics like Benztropine & Trihexyphenidyl (CONTRA = BPH and Angle Closure Glaucoma)

High solubility in blood (e.g. blood/gas partition)
High A/V concentration gradient [reflects the solubility in the tissue - so more needed to SATURATE the tissue and get your effect]

It's a COMT inhibitor used in Parkinson tx
- Prevents PERIPHERAL degradation of L-DOPA (just like carbidopa, a DDI, prevents the transformation to DA peripherally as well)
- Increases the amount of L-DOPA that reaches the brain untouched

Like entacapone, it's a COMT inhibitor used in Parkinson tx.
UNLIKE entacapone:
- it acts CENTRALLY and PERIPHERALLY
- is a/w Hepatotoxicity

1) COMT Inhibitors = Entacapone (periph) and Tolcapone (CNS/Periph)
2) MAO Inhibitors = Selegiline (CNS) prevent breakdown of DA

It's a specific type of Ca-channel blocker = Ryanodine R blocker
Prevents release of Ca into the cytoplasm of muscle fibers from the SR
Used in Tx of Malignant Hyperthermia (Halothane induced massive release of Ca into muscle cytosol by sensitive Ryanodine R's; results in massive ATP use and production → Heat → Rhabdomyolysis → ↑ K+, Myoglobin, Creatine Kinase

LT B4

It's a Thymidine analog used in the grading of brain tumors
High uptake would indicate lots of cells undergoing S-phase and therefore ready to proliferate - this would indicate high grade tumor and poor prognosis

GLUTAMATE = glutamic acid
- in HbS - substitute VALINE (neutral)
- in HbC - substitute LYSINE (positive)

Plasma protein that binds free Hb so it's not renally excreted
Levels are decreased in patients w/ hemolytic anemia

Direct Tissue Toxicity
- High TG's (>1000 mg/dL) → High FA's & overwhelm the ability of albumin to bind
- High [FA] injures acinar cells and pancreatic capillaries

It's responsible for G1 → S transition
- in Go it is ACTIVE (unphophorylated) so it binds up E2F transcription factor
- When growth factor stimulates the cell, CDK4 is activated, which phosphorylates Rb (making it inactive) thus releasing E2F to transcribe

It's a Thiazolidinedione (TZD) used to improve insulin sensitivity
- Major SE is hepatotoxicity

Chronic Respiratory Alkalosis
- drop in O2 increases respiratory drive (peripheral sensors) thus blowing off more CO2
- w/in 48 hours, kidney compensates for alkalosis by excreting HCO3 and making the body a little more acidotic
- pH mildly elevated; PaO2 ~ 60; PaCO2 ~ 20; HCO3 ~ 15

Osteopetrosis

Rickets (vitamin D deficiency)

Receptor activates Janus Kinase (JAK) which activates Signal Transducers and Activators of Transcription (STATs);
- Cytokines
- hGH
- PRL
- IL-2

RTK's stimulate MAP Kinase which activates Ras protein:
- Insulin
- EGF
- PDGF

2nd Generation Anti-H1

1st Generation Anti-H1
like diphenhydramine, chlorpheniramine, and hydroxyzine

It is the apex of the cochlea (near the end) that picks up low-frequency sounds
- high frequency is picked up closer to the base of the cochlea, near the round and oval windows

MS = the murmur → LA hypertrophy and enlargement → impinging (and leading to neurapraxia) of the recurrent laryngeal nerve = Ortner syndrome

TZD's like pioglitazone → complex increases transcription of adiponectin → increased insulin sensitivity

HSP = Henoch-Schonlein purpura (IgA-complexes)
- palpable purpura on the butt
- GI → Upper and lower bleeding (hematemesis/bloody diarrhea)
- Renal = IgA (Berger)
- Joints = mirgratory arthralgias/arthritis

Bugs and Reticulocytes: Borrelia, Chlamydia, Plasmodium, and Trypanosomes

A TCA Antidepressant

1) Virus = Rabies (rhabdovirus)
2) Fungus = Histoplasmasmosis

1) ß-blockers (like atenolol)
2) Non-DHP Calcium Channel Blockers (Verapamil, Diltiazem)

1) DHP's (Nifedipine) are anti-hypertensives acting primarily on vasculature (↑Peripheral dilation) -- NOTE: leads to reflex Tachycardia
2) Non-DHP's (Verapamil/Diltiazem) slow conduction thru the AV node (useful for AFib w/ a rapid ventricular response)

It's an ADP antagonist used to prevent platelet aggreagation; Usually you would use clopidogrel + aspirin (blocks TXA2 release) because it can cause neutropenia (manifests as fever and mouth ulcers)

Metronidazole
Cephalosporins
Procarbazine (Hodgkins)
Sulfonylureas (DM - First generation)

1) Exophthalmos
2) Pretibial myxedema
3) Edema of the Eye = Periorbital and Conjuctival

SPANS:
Staph aureus
Pseudomonas cepia
Aspergillus
Nocardia
Serratia marcenescens

Sulfhydryl groups, as in cystine
- Cyanide converts Cystine → CystEine
- Nitroprusside binds CystEine rutning it purple

It's a drug that is used to test for vWB factor dysfunction. If present, it will catalyze vWF to bind w/ platelet Gp1b-IX

Intracellular iron
- Can differentiate b/w lipofuscin or hemosiderin (both golden yellow/brownish cytoplasmic granules)

ANCA-associated RPGN

1) Hydrochlorothizides (result in ↑Na resorption in PT - and lithium along w/)
2) ACE-I's
3) NSAIDS

HNPCC = DNA Mismatch Repair gene mutations (MLH1, MSH2, MSH6, PMS2)
Sporadic Colon Adenocarcinoma = Proto-Oncogenes & Tumor Suppressors (APC, K-ras, p53, and DCC)

NO
Cholinergic receptors on endothelia promote the release of NO → muscle cells where they activate Guanylate Cyclase (↑cGMP) → activates Ca pumps and causes Ca efflux from cells → muscle relaxation w/o Ca

KETOGENIC = Leucine & Lycine
KETO & GLUCOGENIC = Isoleucine, Phenylalanine, Tryptophan

Von Gierke's = Type 1
- will have SEVERE fasting hypoglycemia, ↑↑ glycogen in liver, ↑ lactate in blood, hepatosplenomegaly

ABCDE:
- A = shig-A like (SLT) of E. coli (E157:H7)
- B = Botox
- C = Cholera
- D = Diphtheria
- E = Erythrogenic toxin (GAS)

It's a Corticosteroid (inhaled) used in the LONG TERM treatment of chronic asthma

CMV is treated w/ Ganciclovir which interferes w/ host cell DNA synthesis (leading to neutropenia, anemia, thrombocytopenia, and↓ renal fx)
Zidovudine (ZDV aka AZT) binds/inhibits some DNA polymerases too, leading to possible bone marrow suppression (anemia, granulocytopenia)

They both can impair hematopoiesis, so this combo increases risk of neutrorpenia and anemia

Selective IgA deficiency
- Recurrent sinopulmonary infections (HiB and S. pneumonia)
- GI (diarrhea) d/t viral, bacterial, and G. lamblia
- Anaphylactic response to transfusions (recognize IgA's as foreign)

Niacin administration leads to flushing, warmth, and itching d/t Prostaglandins. Prophylactic ASA can be used beforehand to prevent these SE's.

Increased sensitivity to sound d/t paralysis of the stapedius muscle (d/t stapedius (CN VII) injury)
The stapes can then oscillate more widely.
Commonly seen in Bell's palsy = peripheral facial nerve palsy

Laboratory culturing technique used to test for Listeria monocytogenes b/c it can multiply at 4ºC (thus it can contaminate refrigerated foods: dairy, undercooked meats, and unwashed veggies)

D/t mixing w/ the deoxygenated bronchial veins that empty in to the LA - drops from 104 (equilibrated w/ the alveoli) to about 100 mm Hg

Aortic stenosis (most commonly d/t degenerative (senile) calcification of the aortic valve leaflets)

ACE-I's - prevent the A-II mediated LV hypertrophy and remodeling
For acute, symptomatic relief, then use a diuretic

Radial nerve (goes through the radial groove)
Deep Brachial artery (runs w/ radial n)

Microsomal monooxygenase aka Cytochrome P450

It is basically "trapped" in the plasma compartment (3 L) d/t to:
- HIGH molecular weight
- HIGH protein plasma binding
- HIGH charge
- HYdrophilicity

Dermatitis herpetiformis

It's a purine analog used in HCL
Special b/c it resists ADA breakdown

TNF-α, Catecholamines, Glucocorticoids, and Glucaon activate Serine & Threonine Kinase activity.
These serine kinases inactivate the IRS (insulin receptor substrates) as well as directly affect the intracellular tyrosine kinase portion of the insulin receptors

Melanoma (melanocyte proliferation) Mutation = V600E (valine replacing glutamate)

Type I = probablity of seeing a difference when there is no difference
Type II = probability of not seeing a difference when there really is one