"Nagging Pests Must Breathe"

• Nocardia
• P. aeruginosa
• M. tuberculosis
• Bacillus spp

Increased Protein with Normal cell count

(Albuminocytologic dissociation)

• Hot as a Hare - fever
• Dry as a bone - mucosal and axillary dryness
• red as a beet - cutaneous flushing
• blind as a bat - mydriasis, cycloplegia
• mad as a hatter - delirium

TCAs (esp. amitriptyline) can mimic Atropine toxicity

Defect/Deficiency of Cystathionine Synthetase

 Requires Vit. B6 as a cofactor

*mcc of elevation is B12 def. (can't from methionine from homocysteine)

Pt w/ Vit. B12 def --> can't from Methycobalamin, results in impaired synthesis of?

Methionine

Homocystinuria/emia occurs in Vit. B12 def. b/c the enzyme homocysteine methyltransferase (converts homocysteine and methy-THF to methionine and THF) requires B12 as a cofactor

Necessary cofactor of synthesis of delta-aminolevulinic acid?

Where might you expect to see delta-aminolevulinic acid elevated?

Cofactor - Pyridoxal Phosphate

Elevated in - Lead Poisoning

-Lead inhibits delta-aminolevulinic acid dehydratase and ferrochetalase (enzymes involved in heme synthesis)

-Pt might present w/ irritability, constipation, and anemia

-Tx: CaEDTA is chelator of choice (dimercaprol another option); use succimer in kids

6 Drugs that Cause

Agranulocytosis

1. Carbamazepine
2. Clozapine
3. Colchicine
4. PTU
5. Methimazole
6. Dapsone

"BCG PQRS"

Barbiturates, Carbamazepine, Griseofulvin, Phenytoin, Quinidine, Rifampin, St. John's Wort

Chronic Alcohol consumption also induces CYP450

Drugs that lower seizure threshold

(CI in epileptic pts)

Metoclopramide

Bupropion

Tramadol

Enflurane

Increased Anion Gap Metabolic Acidosis

Causes:

"MUDPILES"

Methanol (formic acid), Uremia, DKA, Paraldehyde or Phenformin, Iron tablets or Isoniazid, Lactic Acidosis (hypoxia!), Ethylene glycol (oxalic acid), Salicylates (late) and Shock (lactic acidosis)

*Note that salicylate toxicity causes a respiratory alkalosis early, and an AG metabolic acidosis late

"PICK EGgS"

Protease Inhibitors (HIV meds), Isoniazid, Cimetidine, Ketoconazole, Erythromycin, Grapefruit juice, Sulfonamides

*TMP-SMX

*Amiodarone

Glaucoma Meds

(5 classes)

1. alpha agonists (epinephrine & brimonidine) - Do NOT use Epi in closed-angle
2. Beta Blockers (Timolol, betaxolol, cartelol)
3. Diuretics (acetazolamide & mannitol)
4. Cholinomimetics (Direct: pilocarpine, carbachol; & Indirect: physostigmine, echothiophate)
5. Prostaglandins (PGF2alpha - Latanoprost)

"FLAT CHAMP"

FSH, LH, ACTH, TSH, CRH, hCG, ADH (V2 recep.), MSH, PTH

and also Calcitonin, GHRH, and Glucagon

*Notice most of Ant. Pit. hormones (except Prolacting and GH)

ANP & NO (aka EDRF)

"Think Vasodilators"

*ANP receptor has intrinsic GC activity

"GOAT"

GnRH, Oxytocin, ADH (V1 recep.), TRH

*Note Post. Pit. hormones, and its ADH V1 (NOT V2 --> cAMP)

Steroids:

"VET CAP"

Vit. D, Estrogen, Testosterone, Cortisol, Aldosterone, Progesterone

T3/T4

-Nuclear Steroid Receptor

Hormones signaling through receptors w/ Intrinsic tyrosine kinase activity

(MAP kinase pathway - phosphorylation of RAS)

"Think Growth Factors"

Insulin, IGF-1, FGF, PDGF

Hormones that signal through receptors w/ receptor-assoc. tyrosine kinase activity

(JAK/STAT pathway)

GH, Prolactin, IL-2

*and also Colony Stimulating Factors

(M-CSF, GM-CSF for ex.)

Opsoclonus-Myoclonus

(non-rhythmic/chaotic conjugate eye movements and myoclonic jerk)

***Neuroblastoma --> N-myc oncogene overexpression

Pseudohypoparathyroidism Type 1a

Autosomal Dominant; end organ unresponsiveness to PTH (includes proximal tubule not making 1α-hydroxylase)

**Characteristic Sign: shortened 4th/5th digits ("knuckle-knuckle-dimple-dimple" sign);

hypocalcemia, nl to incr. PTH, decr. active Vit. D

"3 P's"

• Parathyroid tumors
• Pituitary tumors (Prolactin or GH)
• Pancreatic Endocrine tumors (Zollinger-Ellison syndrome, Insulinoma, VIPoma, and raely glucagonomas)

**Often presents w/ kidney stones and stomach ulcers

MEN 2a

(tumors and assoc. gene)

"2 P's"

• Medullary Thyroid Carcinoma (secretes calcitonin; amyloid)
• Pheochromocytoma
• Parathyroid Tumors

*ret oncogene; NOTE neural crest origin of these tumors

*All MEN syndromes are autosomal-dominant

MEN 2B

(tumors and assoc. gene)

"1 P"

• Medullary Thryroid Carcinoma
• Pheochromocytoma
• *Oral/intestinal ganglionneuromatosis (aka mucosal neuromas)
• assoc. w/ marfanoid habitus

*ret oncogene

*Auto-Dom. inheritance

Immune cell localization in lymph nodes:

Follicle?

Medulla?

Paracortex?

Follicle (outer cortex) - B cells

Medullary Cords - plasma cells

Medullary sinuses - macrophages/reticular cells

Paracortex (b/t follicles and medulla) - T cells

*How do T and B cells enter from blood? → high endothelial venules

"PAIR"

Psoriasis, Ankylosing spondylitis, Inflammatory Bowel Dz, Reiter's syndrome

Grave's Dz

"Gr8ve's"

DM type I

(Graves too if B8 not an option)

DM type I

Rheumatoid arthritis

Pernicious anemia (-> B12 def.)

Hashimoto's thyroiditis

acute hemolytic transfusion rxns

bullous pemphigoid (anti-hemidesmosome)

pemphigus vulgaris (anti-desmosome)

SLE

Rheumatoid Arthritis

PAN

Hypersensitivity Pneumonitis (ex: Farmer's lung)

MS

Guillain-Barre

Graft v. Host

Type I DM (can have anti-islet abs)

Hashimoto's (can have anti-TPO and Tg abs)

Bupropion (anti-depressant, smoking cessation)

Isoniazid (anti-TB - if given w/o pyridoxine)

Imipenem (abx)

Clozapine (atypical antipsychotic)??

Follicular lymphoma (NHL)

translocation?

change in gene expression?

t(14;18)

Bcl2 overexpression - anti-apoptotic

Plummer-Vinson Syndrome

• triad
• cause
• assoc. malignancy

• atrophic glossitis, esophageal webs, anemia
• iron def.
• squamous cell carcinoma of esophagus (vs. Barrett's esophagus - esophageal adenocarcinoma)

Sulfa drugs w/o Sulfa in their name

(not sulfonamides, sulfasalazine, or sulfonylureas)

Atropine Contraindications

(or other muscarinic antagonists)

• glaucoma
• BPH or urinary obstruction
• GI obstruction or ileus
• delirium, dementia, elderly
• infants w/ fever

Beta2 > Beta1:

Metaproterenol & Albuterol - acute asthma (short-acting)

Salmeterol and Formoterol - long-acting, long-term asthma Tx

Terbutaline - reduce premature uterine contractions

Pure Beta2:

Levalbuterol - use in pts w/ heart dz

Ritodrine - reduce premature uterine contractions

Non-selective α-blockers:

irreversible?

reversible?

Phenoxybenzamine - irreversible (use before removal of pheochromocytoma)

Phentolamine - reversible

α₂-selective antagonist

its use?

its SEs?

Mirtazapine

-used to Tx depression

-SE: sedation, ↑ appetite, ↑ serum cholesterol

*use mirtazapine in an elderly depressed pt who is not sleeping well and has a poor appetite/wt loss

Nebivolol, Acebutolol, Atenolol, Metoprolol, Betaxolol, Esmolol

"Newb Ace Ate MeToo" + Betaxolol & Esmolol

Pindolol and Penbutolol (non-selective)

Acebutolol (β₁ selective)

Good for pts w/ bradycardia/bradyarrhythmias and PVD (periph. vasc. dz)

*Contraindicated in Angina

Chelator of choice for Lead?

in kids?

CaEDTA

-succimer for kids

Dimercaprol

Who needs chelation of gold?  It is used as an Rheumatoid arthritis Tx; blue-gray to purple discoloration of skin

Antidote/Tx for tPA or streptokinase

(fibrinolytics)

Aminocaproic acid

(anti-fibrinolytic)

Binds competitively to plasminogen; blocking the binding of plasminogen to fibrin and the subsequent conversion to plasmin

β-blocker

Si/Sx of acute: vomiting, tremor, tachycardia; hypotension, ventricular arryhthmias and seizures possible

(Theophylline also can be removed by hemoperfusion; as can phenytoin, carbamazepine, & phenobarbital)

• Chloramphenicol
• Benzene
• NSAIDs
• PTU
• Methimazole

Drugs causing hemorrhagic cystitis?

prevention?

Cyclophosphamide, ifosfamide

***coadmin. w/ mesna

• Tinnitus (often accompanied by fullness)
• Vertigo (subjective feeling, often accompanied by N/V and lightheadedness, "room is spinning")
• Sensorineural hearing loss

-incr. vol. and pressure of endolymph in vestibular apparatus of inner ear

Sturge-Weber dz

Si/Sx

congenital vascular disorder affecting capillary-sized blood vessels; manifests w/

-port-wine stain on face, ipsilateral leptomeningeal angiomatosis (intracerebral AVM), seizures, early onset glaucoma, mental retardation, hemiplegia

What effect does ↓ Mg (free serum) have on PTH secretion?

Causes of ↓ Mg?

↓ Mg results in ↓ PTH secretion

-↓ Mg causes include diarrhea, aminoglycosides, diuretics, alcohol abuse

Pot-bellied, pale, puffy-faced child w/ protruding umbilicus and protuberant tongue (macroglossia)

Cretinism (congenital hypothyroidism)

-also are mentally retarded w/ short stature, prolonged jaundice, lethargic and feed poorly; incr. incidence of congenital heart defects

HCTZ (puts electrolytes in urine), indomethacin (↓ RBF), or amiloride (esp. for Li induced)

-adequate fluid intake

2 Rapid acting insulins?

2 long acting insulins?

Rapid: Lispro, Aspart (best for post prandial glycemic control; monomeric forms)

Long: Glargine, Detemir

Glitazones:

-MOA

-SE

Pioglitazone, Rosiglitazone

• MOA: ↑ insulin sensitivity peripherally via binding to PPAR-γ (↑ Adiponection)
• SE: wt gain, edema (can exacerbate CHF), hepatotoxicity, CV toxicity, ↑ MI risk

Volvulus:

MC sites?

usu in what age pop?

cecum and sigmoid colon (areas w/ redundant mesentery)

-usu in elderly

-no fever or leukocytosis

alcohol, hemochromatosis, Wilson's dz

"think metabolic insults"

postinfectious or drug induced hepatitis, primary biliary cirrhosis

"think of significant liver injury"

AST - "A Scotch and Tonic"

opposite for viral hepatitis: ALT > AST