PHARMACOLOGY

Mechanisms

A.    Scopolamine

·         Anti-muscarinic

·         Motion Sickness; preoperatively to reduce secretions

·         Anti-muscarinic toxicities (mydriasis & cycloplegia; decreased secretions & sweating; flushing; bradycardia (low doses); tachycardia (high doses); urinary retention; drowsiness, hallucinations, coma)

 

Typical Anti-psychotics (Chlorpromazine, Haloperidol, Thioridazine)

·        Dopamine antagonists

·        Schizophrenia; psychosis

·        Lactation; Extrapyramidal effects (parkinsonism, akathisia (motor restlessness), tardive dyskinesia (lip smacking, jaw movements, etc.)); anti-cholinergic effects (antimuscarinic, alpha-antagonistic (orthostatic hypotension), and anti-histamine (sedation)).  Toxicities are a tradeoff—higher extrapyramidal effects coincide with lower anticholinergic effects and vice-versa.  The higher the extrapyramidal effects, the higher the potency (haloperidol > chlorpromazine > thioridazine)

 

Atypical anti-psychotics (Clozapine)

·         Dopamine antagonist

·         Schizophrenia; psychosis

·         NO extrapyramidal effects or lactation; agranulocytosis (fatal); Neuroleptic Malignant Syndrome (catatonia, autonomic instability, stupor); anti-cholinergic effects as above

 

B.     Opiate Agonists (Morphine, Meperidine, Codeine, Methadone, Heroin, Fentanyl)

·         Act at mu, kappa, delta receptors in CNS

·         Analgesia; Antitussive (Codeine); opiate addiction (Methadone); antidiarrheal (loperamide)

·         CNS depression; nausea; respiratory depression; constipation; urinary retention; dependence

 

Opiate Mixed Agonists-Antagonists (Pentazocine)

·         Same as agonists but will cause withdrawal in those dependent on agonists

 

Opiate Antagonists (Naloxone, Naltrexone)

·         Block opiate receptors

·         Narcotic overdose (no effect if used alone)

 

Erythropoietin

·         Increases RBC production in marrow

·         Anemia associated with renal failure

 

RU486 (Mifepristone)

·         Progestin antagonist

·         Early-term abortion

·         Uterine bleeding, possible incomplete abortion

 

C.    Acarbose

·         Alpha-glucosidase inhibitor—decreases absorption of glucose

·         NIDDM; adjunct to insulin in IDDM

·         Flatulence; diarrhea; abdominal cramping

 

D.    Losartan

·         Angiotensin II antagonist

·         Hypertension

·         Similar to ACE inhibitors but no cough (decreased bradykinin activation)

 

E.     Myasthenia Gravis Drugs

·         Inhibit cholinesterase

·         Diagnosis (edrophonium); long-term treatment (Neostigmine, Pyridostigmine); open-angle glaucoma; reversal of non-depolarizing nm blockade

·         Fasciculations & weakness

 

F.     Leuprolide

·         GnRH analog à desensitization of pituitary receptor à decreased FSH, LH secretion

·         Prostate Cancer

·         Transient excess testosterone production (prevent by combining with flutamide); impotence, hot flashes, tumor flare

 

G.    Flutamide

·         Blocks inhibitory effects of testosterone on GnRH release

·         Combo with leuprolide

 

H.    Aminoglutethimide

·         Inhibits Cholesterol à pregnenelone conversion (like metyrapone)

·         Metastatic breast cancer (decreased estrogen)

·         Induces P450; transient CNS depression; rash

 

I.       Metformin

·         Decreases gluconeogenesis; improves lipid profile (HDL rises, LDL falls)

·         NIDDM – lower risk of hypoglycemia

·         GI side effects; lactic acidosis (rare); long-term interference w B12 absorption

 

J.      Stool Softeners (psyllium, methylcellulose)

·         Absorbs water and softens stool à bulk à peristalsis

·         Constipation

Mechanism, clinical use, and toxicity of dermatologic agents:

CORTICOSTEROIDS:  Synthesized in the zona fascilculata of the adrenal cortex.  Cortisol and Cortisone produced.

1)       Glucocorticoids are catabolic. They influence carbohydrate and fat metabolism to insure adequate delivery of glucose to brain and tissues.

2)       Decrease intestinal uptake of calcium; increase renal excretion of calcium (contribute to osteoporosis).

3)       Supress the inflammatory response – Decrease edema, fibrin deposition, capillary dilatation, leukocyte migration and phagocytic activity.  Inhibit prostaglandin and leukotriene production by inhibiting phospholipase A2.

4)       Include: Cortisone (short acting), Prednisone (intermediate acting), Prednisolone (similar to prednisone but no hepatic metabolism for activity), Methylprednisolone (similar to prednisolone but better anti-inflamatory and less mineralocorticoid effects), Triamcinolone (5x more potent than cortisol), Dexamethasone (long acting)  & Beclomethasone (long acting available as aerosol).

5)       Toxicity:

a)       Skin:   hirsutism, skin thinning, poor wound healing, striae, acne and purpura.

b)       Other: hyperglycemia, hypertension, cataracts, glaucoma, peptic ulcer disease, osteoporosis, and increased susceptibility to infection.

 

RETINOIDS:

1)       Used to treat  the following dermatologic diseases: Acne, psoriasis, icthyosis and has a potential benefit in early skin cancers (actinic keratosis)

2)       Toxicity: in skin it can cause desquamation, dry skin and pruritus, erythema.

 

ANTIFUNGALS:

1)       Polyene antibiotics are fungicidal against both filamentous and yeastlike fungi including Histoplasma, Blastomyces, Coccidioides, Cryptococcus, Candida, Aspergillus and Sporothrix. Polyenes interact with sterols in the cytoplasmic membrane of fungi leading to rapid leakage of small molecules and death.  Sensitive fungi have ergosterol in their membranes.

a)       Amphotercin B: Broad spectrum to treat systemic fungal infections.  Side effects: Fever, chills, impaired renal function, anemia, thrombocytopenia.

b)       Nystatin (Mycostatin): Similar to A but used primarily in topical preparations.  Use in Candida infections and prophylaxis.

2)       Imidazoles: Block the synthesis of fungal cell membrane ergosterols.

a)       Miconazole & Clomitrazole: Miconazole is the only imidazole that can be administered IV; clotrimazole is only used topically.

i)         Intravenous miconazole is rarely used due to toxicity.  Treats ringworm, vulvovaginal candidiasis

b)       Ketoconazole:  Oral administration only. Causes gynecomastia.  

3)       Miscellaneous:

a)       Flucytosine: Administer with amphotercin B in the treatment of cryptococcal meningitis and other systemic infections (synergistic).

b)       Griseofulvin: Binds to keratin, treat Tineas (capitis, corporis etc),

 

Other new pharmacologic agents:

1)       Erythopoietin (EPO): RBC growth factor. Produced in kindneys. Recombinant form available (epoietin alpha).

a)       Use for tx of Anemia 2^nd to renal failure or zidovudine (AZT) use HIV patients.

b)    Use for tx of Anemia 2^nd to chemo, or to stimulate rbc production prior to surgery or to facilitate autologous donation.

c)       Side effects: Clotting of dialysis tubing and hypertension.

2)       RU486 (Mifrepristone): Abortificen. Blocks progesterone receptors and thereby progesterone support of pregnancy.  80% effective, 95% if used with prostaglandins. 

a)       Complications include incomplete abortion (2%), ongoing pregnancy (1%), hemorrhage during D&C (<1%).

Know About......

 

1)       Complications of empiric antibiotic use:

a)       Resistance: Must take into account susceptibility patterns of local settings. Must distinguish between community vs. nosocomial infection, and must take into account the patient's immune status.

b)       Fungal Infections: Due to destruction of normal flora. (candidiasis).

c)       Other complications: C. Diff è Pseudomembranous colitis.  Gentamicinè ototoxicity (must monitor levels), Sulfonamides  and Penicillinè allergic reactions.

2)       Secondary effects of other drugs:

a)        Heparin è osteoporosis with chronic use. Thombocytopenia – usually transient and mild.

b)       Thiazides èHyperlipidemia, hypokalemia.

3)       Drugs that block/increase hepatic drug metabolism:

a)        Cimetidine: Histamine analog that cab reduce hepatic  blood flow and slow clearance of other drugs and also reduces activity of cytochrome p-450

b)       Ethanol: Chronic use induces hepatic microsomal enzymes and may enhance metabolism of other drugs.

c)        Phenobarbital: Increased phenobarbital levels in patients that have ethanol, chloramphenicol or valproic acid on board, since it has microsomal enzyme metabolism.

d)       Phenytoin (Dilantin): same as Phenobarb and ETOH èMetabolized by microsomal enzymes.

e)        Rifampin:  Causes jaundice and hepatotoxicity, also interacts with C p-450 system.

4)       Fundamental Pharmacodinamics:

a)        Partial agonists/agonist: Drugs that bind to receptors and stimulate them.

b)       Antagonists: are drugs that bind to receptors and decrease or block the effect of an agonist. They do not stimulate the receptors.

i)         Competitive antagonist: Reversibly binds to the receptor and prevents binding of the agonist.

ii)       Non competitive antagonist: Usually binds to the receptor irreversibly and prevents any agonist action.

c)        Efficacy: Maximal effect produced by a drug.

d)       Potency: Activity of a drug compared to a reference standard; depends on the drug's ability to reach the receptors and its affinity to the receptor.

5)       Drug efficacy and potency as demonstrated on dose-response curves:

a)        ED50 (effect dose)-  Dose which produces half-maximal response (ie., observed effect seen in 50% of patients); used as a measure of potency (the lower the ED50, the more potent the drug).

b)       TD50 (toxic dose)- Minimum dose which produces a specific toxic effect in 50% of individual (or animals).

c)        LD50 (lethal dose)- Minimum dose which kills 50% of animals.

d)       Therapeutic index- Ratio of dose required to produce a toxic effect to the dose needed for  a therapeutic effect. Used as an indication of drug safety.  Expressed as :

 

TI= TD50        or   TI=  LD50            You want drugs with a high therapeutic index (low

                                       ED 50                      ED50             side effects at usual doses).

 

6)       Pharmacogenetics: drugs whose metabolism is affected by inheritance:

a)       Isoniazid: Most commonly used drug for the treatment of TB.

i)         Inhibits biosynthesis of mycolic acids.

ii)       Metabolized in the liver (acetylated); speed of acetylation and consequently  isoniazid's half life is genetically determined (fast vs. slow acetylators). 

7.       Treatment of Anemia

1. Anemia is due to increased destruction or decreased production.
2. Microcytic anemia

1.       Iron – absorbed in the duodenum and proximal jejunum.  Iron deficiency seen in premature infants, pregnant and lactating women.  Ferrous oral salts can be given; give for 3-6 months to replenish iron stores.  IV iron can also be given.

2.       Iron toxicity

a.       N/V, cramps, constipation, diarrhea – dose-related so decrease the dose

b.       Acute toxicity – seen in kids, necrotizing gastroenteritis followed by shock, lethargy, dyspnea

c.        Chronic iron toxicity - hemochromatosis

3. Megaloblastic anemia – lack of vitamins needed for normal DNA synthesis, so the RBC gets biggger (macrocytic)

1.       Vitamin B12 (normally obtained in meats), requires intrinsic factor for absorption (pernicious anemia decreases absorption), gastrectomy also decreases absorption.  B12 is stored in the body (years supply)

a.       B12 deficiency also shows nervous defects

b.       B12 shots can be given if oral absorption is a problem

c.        Folate will NOT correct neurological features, but WILL help with the anemia

2.       Folic Acid – from green leafy veggies, body stores of folate are lower (1-6 months)

a.       Deficiency doesn't have neurological deficits

b.       Folic acid is well absorbed orally

4. Decreased production

1.       Erythropoietin – used for renal failure, bone diseases, chemotherapy

a.  Toxicity – too rapid increase in hematocrit can lead to HTN, thrombotic complications

2.       Colony stimulating factors (G-CSF, GM-CSF)

a.  Increase recovery after myelosuppressive chemotherapy or BMT

8.       Prevention/treatment of cerebrovascular disease

K.      Aspirin

1.       Irreversibly blocks cyclooxygenase, = inhibits thromboxane (TxA₂) formation from platelets

2.       Only requires a small daily dose

12. Ticlopidine

1.       Inhibits platelet aggregation (inhibits ADP pathway)

2.       Decreases TIAs, completed strokes, unstable angina pectoris

3.       Diarrhea in 20%, leukopenia in 1% (must monitor white count)

13. Thrombolytics – catalyze formation of plasmin, a generalized lytic state in body is produced

1.       Streptokinase – cheap, allergic reactions possible

2.       Urokinase

3.       Tissue plasminogen activators (t-PA) – expensive, from recombinant DNA

9.       Treatment of rheumatoid arthritis

A.  Drugs that alter Pain

1.       Aspirin – 1^st line drug,  GI problems

2.       NSAIDS -

3.       COX-2 inhibitors – less GI problems

2. Drugs that Decrease Progression

1.       Methotrexate and immunosuppressives – more toxic side effects

2.       Gold – dermatitis is common side effect

10.      Vaccines:  indications, potential side effects

1. Indications

1.       Active immunization – antigen is given so host develops antibodies (long protection)

a.  Give to children

2.       Passive – immunoglobins are given (short term protection)

a.  Give to those recently exposed (Tetanus, Botulinum, HBV, Rabies) or to travelers (Polio, tetanus, Measles, diphtheria)

2. Side Effects

1.       Giving live attenuated vaccines may cause the disease (eg. Polio vaccine)

2.       Killed vaccine will not cause the disease

3.       Allergic reactions are possible

11.      Chemotherapeutic agents:  risk of possible secondary cancer

 

ANATOMY

Embryology

Embryonic Period: Weeks 3-8, organ system development simultaneous

I.                    The Heart

A.      Development (MESODERM)

1.       Primitive heart tube

- pair of endocardial heart tubes (mesoderm) form within cardiogenic region

-EHT fuse during lateral folding to form primitive heart tube = endocardium

-surrounding mesoderm develops into myocardium and epicardium

        -PHT forms five dilations (First Aid p. 94)

2.       AP septum (aorticopulmonary)

-divides truncus arteriosus into aorta and pulmonary trunk

-neural crest cells migrate into truncal and bulbar ridges

-grow and twist in spiral, fuse to form AP septum

3.       AV septum (atrioventricular)

-partitions AV canal into right and left AV canals

-dorsal and ventral AV cushions fuse to form AV septum

4.       Atrial septum

-septum primum grows toward AV septum

-foramen primum between edges of septum primum and AV septum; obliterated when SP fuses with AV cushions

-septum segundum (crescent-shaped) forms to right of SP and fuses after birth with SP  to form atrial septum

-foramen ovale is opening between upper and lower parts of SS; shunts blood from right atrium to left atrium

-functional closure soon after birth due to pressure changes; anatomical fusion incomplete in 25% of population; incidental  (Image, see High-Yield Embryo)

 

 

 

5.       IV septum (interventricular)

-muscular IV septum develops into floor of ventricle and grows toward AV septum; stops short to create IV foramen

-membranous IV septum forms following fusion of right and left bulbar ridges and AV septum; closes IV foramen

6.       Aortic Arches (First Aid p. 92)

B.      Congenital Anomalies

1.       AP septal defects

a.       Tetralogy of Fallot

-improper alignment of AP and AV septums

-overriding Aorta, Pulmonary stenosis, VSD (poor AV fusion), right ventricular hypertrophy (right-to-left shunting, cyanosis)

b.       TGA (transposition of great arteries)

-AP septum fails to spiral

-right-to-left shunting, cyanosis

c.        Persistent truncus arteriosus

-abnormal neural crest cell migration, incomplete development of AP septum

-usually accompanied by defect in IV septum

-cyanosis

2.       Atrial septal defects

a.       Patent foramen ovale

-foramen secundum defect, excessive resorption of SP or SS

-symptoms may manifest as late as age 30

-most common ASD

3.       VSDs

a.       Membranous VSD

-most common VSD

-fails to develop

-left-to-right shunting, pulmonary hypertension

-sx: excessive fatigue on exertion

4.       Circulatory anomalies

a.       Coarctation of aorta

-abnormally constricted inf. to ductus arteriosus

-increased BP in upper extremities, lack of femoral pulse, high risk of cerebral hemorrhage and bacterial endocarditis

b.       PDA (patent ductus arteriosus)

-common in premature infants, mothers with rubella during pregnancy

-causes L>R shunting, O2 rich blood back into pulm. circulation

-can treat with indomethacin (prostaglandin synthesis inhibitor; I remember it by saying, Take yo' PDA indo', man! Also used for acute gout, as in stay indo' or go-out)

II.                  The Lungs

A.      Development

-laryngotracheal diverticulum forms in ventral wall of foregut

-tracheoesophageal septum divides foregut into esophagus and trachea

-distal end of LTD enlarges to form lung bud

-lung bud > 2 bronchial buds > primary, secondary, tertiary bronchi = bronchopulmonary segments

-4 stages

1.       Glandular (Weeks 5-17)

-respiration not possible, premature fetuses cannot survive

2.       Canalicular (Weeks 13-25)

-respiratory bronchioels and terminal sacs; vascularization increases

3.       Terminal Sac (Weeks 24-birth)

-Type I and II pneumocytes, respiration possible

-Premature fetuses weeks 25-28 can survive

4.       Alveolar (Birth-year 8)

-resp. bronchioles, terminal sacs, alveolar ducts and alveoli increase in number

B.      Congenital anomalies

1.       Tracheosophageal fistula

-abnormal communication b/t trachea and esophagus; malformation of septum

-sx: gagging and cyanosis after feeding, abd. distention after crying, reflux of gastric contents into lungs

2.       Respiratory distress syndrome

-deficiency of surfactant

-common in premature infants, infants with diabetic mothers, fetuses with prolonged IU asphyxia

-tx: thyroxine and cortisol to mother

3.       Pulmonary hypoplasia

-secondary to congenital diaphragmatic hernia (into pleural cavity) and bilateral renal agenesis

III.               Liver

A.      Development

-hepatic diverticulum (endoderm of foregut) forms in septum transversum (surrounding mesoderm, also plays part in development of diaphragm)

-HD sends hepatic cell cords into ST

-Cell cords surround vitelline veins, which form hepatic sinusoids

IV.                Kidney

A.      Development

-Intermediate mesoderm forms elevation along dorsal body wall = urogenital ridge

-portion of UG ridge, called nephrogenic cord, forms 3 sets of kidneys

1.       Pronephros completely regresses

2.       Mesonephros forms mesonephric (wolffian) duct

3.       Metanephros develops from metanephric mesoderm and ureteric bud (outgrowth of mesonephric duct); becomes definitive adult kidney

-ascends during development from sacral region to adult location at T12-L3

B.      Congenital anomalies

1.       Renal agenesis  - failure of ureteric bud to develop

2.       Horseshoe kidney – inferior poles fuse, kidney trapped behind inf. mesenteric artery

3.       Wilm's tumor – malignant tumor in children, probably of embryonic origin, good prog

4.       Urachal cyst – remnant of allantois, urine drainage from umbilicus

5.       Pheochromocytoma – chromaffin cell tumor, generally along migratory path of neural crest cells

V.                  CNS

A.      Development

1.       Notochord induces overlying ectoderm to differentiate into neuroectoderm to form neural plate; notochord becomes nucleus pulposus

2.       Neural plate folds to form neural tube

-some cells diff. into neural crest cells

-craniocaudal folding

3.       Vesicles

B.      Congenital anomalies

1.       Spina bifida (high AFP levels)

2.       Anencephaly (high AFP levels)

-1/1000 births

-most common serious birth defect in stillborns

3.       Arnold-Chiari – herniation of cerebellum into foramen magnum

4.       Dandy-Walker – hydrocephalus from atresia of foramena of Luschka and Magendie

5.       Hydrocephalus – most commonly from stenosis of cerebral aqueduct

6.       Fetal alcohol syndrome – most common cause of MR; microcephaly, heart disease

7.       Craniopharyngioma – congenital cystic tumor, remnants of Rathke's pouch

VI.                Gut (ENDODERM & MESODERM)

A.      Development

1.       Foregut: celiac artery

-esophagus, stomach, liver, gallbladder, pancreas, upper duodenum

2.       Midgut: superior mesenteric artery

-lower duodenum, jejunum, ileum, cecum, appendix, ascending colon, proximal 2/3 transverse colon

3.       Hindgut: inferior mesenteric artery

-distal 1/3 of transverse colon, descending colon, sigmoid colon, upper anal canal

4.       Lower anal canal = surface ectoderm (think squamous cell carcinoma)

B.      Congenital anomalies

1.       Esophageal atresia – malformed tracheoesophageal septum

2.       Hypertrophic pyloric stenosis – hypertrophy of muscularis externa; projectile vomiting and small, palpable mass at right costal margin

3.       Extrahepatic biliary atresia – incomplete canalization > occlusion of biliary duct; jaundice, pale feces, dark urine

4.       Annular pancreas – ventral and dorsal pancreatic buds form ring around duodenum; obstruction

5.       Duodenal atresia – failed recanalization; polyhydramnios, bile-containing vomit, stomach distention

6.       Omphalocoele – midgut loop fails to return to abd. cavity; light gray sac at base of  umbilical cord

7.       Meckel's diverticulum – remnant of yolk sac b/t umbilicus and ileum; drainage of meconium from umbilicus

8.       Hirschsprung's – failure of neural crest cells to form myenteric plexus in sigmoid colon and rectum; loss of peristalsis, fecal retention, abd. distention

VII.             Other congenital anomalies

A.      Head and neck

1.       First arch syndrome – various facial anomalies

-lack of migration of neural crest cells into pharyngeal arch 1

-Treacher-Collins, Pierre Robin

2.       DiGeorge – pharyngeal pouches 3 & 4 fail to diff. into parathyroids and thymus; "first arch" facial anomalies with cardiovascular anomalies

3.       Cleft palate and cleft lip (First Aid p. 94)

VIII.           Skeletal System

A.      Development

-lateral folding

-three sources: paraxial mesoderm, lateral plate mesoderm, neural crest cells

1.       Paraxial mesoderm

-gives rise to somiteres 1-7 in head region

-gives rise to somites in postcranial region

a.       dermatomes – give rise to dermis

b.       myotomes – give rise to all skeletal muscles below head

c.        sclerotomes – give rise to bones of axial skeleton

-abnormal induction results in spinal defects (scoliosis)

B.      Congenital Anomalies (not any obvious ones relating directly to somite migration)

1.       Caudal dysplasia

-refers to constellation of syndromes ranging from minor lesions of lower vertebrae to complete fusion of lower limbs

-is caused by abnormal gastrulation, in which migration of mesoderm is disturbed

-can be associated with various cranial anomalies:

a.       VATER – vertebral defects, anal atresia, tracheoesophageal fistula, renal defects

b.       VACTERL – similar to VATER, includes cardiovascular defects and upper limb defects

2.       Sacrococcygeal teratoma

-arises from remnants of primitive streak (see below); normally degenerates

-derived from pluripotent cells, develop into various tissue types (hair, bone, nerve)

-more common in female infants, usually malignant, must be removed by 6 months

IX.                Fetal Circulation

A.      Pattern

Aorta > R, L umbilical arteries (deoxy) > Left umbilical vein (oxy) > ductus venosus > Inf. vena cava > Right atrium > foramen ovale > Left atrium > Left ventricle > Aorta

                        Right atrium > Right ventricle > Pulmonary artery > Ductus arteriosus > Aorta

B.      Three main shunts

1.       Ductus arteriosus: pulmonary trunk to aorta

2.       Ductus venosus: bypass liver

3.       Foramen ovale: right atrium to left atrium

C.      Remnants (First Aid p. 92)

D.      After first breath

1.       Alveoli are oxygenated

2.       Decreased pulmonary resistance (lungs expand)

3.       Increased pulmonary blood flow

4.       Increased left atrial pressure

5.       Functional closure of foramen ovale

6.       Ductus arteriosus closes via smooth muscle contraction within a few hours of birth

7.       Ductus venosus closes within a few days, mechanism unknown

X.                  Embryonic Plate: Weeks 2-3 (First Aid p. 91)

A.      Week Two

1.       Embryoblast (bilaminar disk)

a.       Epiblast

b.       Hypoblast

c.        Amniotic cavity

d.       Yolk sac

2.       Trophoblast (Placenta)

a.       Syncytiotrophoblast

b.       Cytotrophoblast

 

B.      Week Three

1.       Gastrulation

-establishes three germ layers: ectoderm, mesoderm, endoderm (trilaminar disk by day 21); give rise to all tissues and organs

-primitive streak first indication

-all derived from epiblast

 

 

Gross Anatomy

1.       Direct hernia: leaves abdominal cavity medial to inferior epigastric vessels

       Indirect hernia: leaves abdominal cavity lateral to inferior epigastric vessels

       Femoral hernia: protrusion of abdominal viscera through femoral ring into femoral canal

       Lumbar puncture: needle into lumbar cistern between spinous processes L3/L4 or L4/L5 Pericardiocentesis: wide bore needle inserted through 5^th or 6^th intercostal space near sternum.  Careful not to puncture internal thoracic artery

 

2.  Thyroid C5                                                                      Duodenum T12-L1

     Sternal notch T2                                                             Kidneys T12-L3

     Bifurcation of trachea T4-T5                                      Conus medularis L1-L2 adult, L3 newborn

     Heart: Base T6-T9                                                         Umbilicus L4

    Apex 5^th left intercostal space

 

3.       Knee:  1. Patellar ligament- damage to femoral nerve or spinal cord L2-L4. Loss of patellar reflex  2. MCL- tear also tears medial meniscus.  Passive abduction of extended leg at knee joint.   3. LCL- passive adduction of extended leg at knee joint. 4.  ACL- anterior drawer sign.  5.  PCL- posterior drawer sign. 6. Terrible triad- MCL, medial meniscus and ACL tears.

 

Hip:   1. Posterior dislocation- head of femur moves posterior to the iliofemoral ligament.  Presents with lower limb that is flexed     at hip joint, adducted, medial rotated and shorter than opposite limb.  2.  Fracture of neck of femur presents laterally rotated and shortened.

 

Shoulder:  1. Dislocation- may be anterior or posterior.  If anterior then axillary nerve may be damaged.  2. Separation- results in a downward displacement of clavicle.

 

Clavicle:  1.  Fracture- most common at medial 1/3.  Results in upward displacement of proximal fraagment and downward displacement of distal fragment

 

4.                   Brachial Plexus:  1. Axillary n- dislocation of shoulder, abduction (deltoid) and lateral rotation (teres minor) are compromised.  2. Long thoracic n- winging of scapula (serratus anterior).  3. Radial n- wrist drop (extensors of forearm).  4. Median n- ape hand (thumb muscles) and flexors of forearm if damage is at elbow or above.  5. Ulnar n-  claw hand and radial deviation of hand,  loss of some flexors if at elbow or above.

 

5.                                           Peripheral nerves: 1. Common peroneal n- foot drop (tibialis anterior m) and inversion (peroneus muscles).  2. Deep peroneal n. entrapment-  Compression of anterior compartment muscles of the lower leg by ski boot or athletic shoes that are too tight.  Causes pain in the dorsum of the foot that radiates to the space between the first two toes.

 

6.                   Hands:  1. Carpel Tunnel Syndrome- compression of median nerve by inflammation, weakend flexion and abduciton and opposition of thumb, loss of extension of index and middle fingers, sensory loss of index, middle and half of ring fingers and palmar part of thumb.  2. Cubital tunnel syndrome- sorry I was not able to find this one. 3. Dupuytren's contracture-  progressive fibrosis of palmar aponeurosis, pulls digits into marked flexion at MCP joints.

 

7.                   Blood-testes barrier: There is a barrier that exists between the blood vessels that supply the testes (branches of the  testicular artery and vein) and the duct system in which spermatozoa are produced and transported.  The testis is derived partly from celomic mesoderm and partly from intermediate mesoderm with the blood vessels migrating in around the duct system.

 

8.                   Abdominal arteries: 1. Celiac trunk(CT)-FOREGUT-left gastric a., splenic a., hepatic a.  2. Superior messenteric a.(SMA)- MIDGUT- part of duodenum through proximal 2/3 of transverse colon. 3. Inferior mesenteric a.(IMA)-HINDGUT- distal 1/3 of transverse colon to upper rectum

 

     Collaterals: 1. Internal thoracic a. to superior epigastric a. to inferior epigastric a.  2. Superior pancreaticoduodenal a.(from CT) to inferior pancreaticoduodenal a. (from SMA)  3. Middle colic a. (from SMA) to left colic artery (from IMA)  4. Marginal a. (from SMA and IMA)  5. Superior rectal a. (from IMA) to middle rectal a. (from internal iliac a.)

 

9.             Bone: 1. Metaphysis: between epiphysis and diaphysis.  2.  Epiphysis: growth plate responsible for linear bone growth.  3.  Diaphysis:  long part of bone responsible for annular bone growth.

 

 

(Add histology and neuroanatomy 1-2)

Neuroanatomy

 

3. Hearing

                -Unlike other sensory systems, the central auditory pathways have bilateral representation of

                  sounds (sound from 1 ear reaches auditory cortex in both hemispheres).

                -Pathway

                                -first neruons in spiral ganglion synapse in cochlear nucleus

                                -second neurons synapse bilaterally in superior olivary nuclei

                                -third neurons travel in the lateral lemniscus to synapse in the inferior colliculus

                                -fourth neurons then synapse in the medial geniculate nucleus

                                -the fibers then go to the transverse temporal gyrus of the cortex

                -Conduction  and nerve deafness

                                -Weber test (forehead)      

                                                -lateralizes to the affected ear with conduction deafness and to the unaffected

                                                 ear with nerve deafness

                                -Rinne test (mastoid process)

                                                -distinguishes between better bone or air conduction of sound

 

4. Extraocular muscles  (see First Aid pg. 111 and table 10.1 pg. 118 in Basic Clinical Neuroanatomy)

                -Movements and innervation

                                -Medial Rectus – CN III – adduction (in)

                                -Superior Rectus – CN III – elevation (after abduction) (up)

                                -Inferior rectus – CN III – depression (after abduction) (down)

                                -Inferior oblique – CN III – elevation and adduction (up and in)

                                -Superior oblique – CN IV – depression and adduction (down and out)

                                -Lateral rectus – CN VI – abduction (out)

                -Lesions

                                -CN III – eye turned down and out, ptosis, mydriasis

                                -CN IV – eye slightly up and in – diplopia going down stairs – tilting head away from the

                                 affected side to correct the diplopia

                                -CN VI – eye deviates medially (abductor paralysis)

 

5 and 6. Chemical synapse, neurotransmitters, receptors, second messengers, effects BRS phys. 13-18

                -Chemical synapse (BRS phys pg. 13-14)

                                -Presynaptic cell

                                                -action potential – depolarization of presynaptic terminal – Ca2+ enters

                                                 presynaptic terminal – release of neurotransmitter into cleft

                                -Postsynaptic cell

                                                -neurotransmitter binds to receptors causing a change in permeability to ion

                                                -inhibitory neurotransmitters hyperpolarize – excitatory depolarize

                -Receptor types (BRS phys pg.35-38)

                                -alpha 1 receptors – excitatory – epi and norepi – IP3 and increase intracellular Ca2+

                                -alpha 2 receptors – inhibatory – inhibit adenylate cyclase and decrease cAMP

                                -beta 1 receptors – excitatory – epi and norepi – activate adenylate cylcase – cAMP

                                -beta 2 receptors –  relaxation – epi and norepi – activate adenylate cyclase – cAMP

 

7. Blood supply to brain (see First Aid pg. 112,  BRS Path pg. 356-357)

                -Embolism – most frequently to middle cerebral artery leading to contralateral paralysis,

                 motor defects, sensory defects, aphasias

                -Thrombosis – from atherosclerosis of carotids, vertebral and basilar aa., and middle cerebral aa.

                -Hemorrhage – hypertension and coagulation disorders – most often in basal ganglia, pons,

                 frontal lobe, cerebellum

 

8. Basal Ganglia (globus pallidus, caudate, putamen) (First Aid pg. 109)

                -initiation of voluntary movements and control of postural adjustments

                -Pathology of the basal ganglia

                                -Negative signs: akinesia, bradydinesia, abnormal postural adjustments

                                -Positive signs (dyskinesia at rest): hypertonicity (rigidity), tremors, chorea, athetosis,

 ballismus

                -Huntington disease – degeneration of striatal neurons (putamen and caudate)

                -Parkinson disease – degeneration of the dopamine neurons in the substantia nigra

                -Tardive dyskinesia – exposure to manganese and drugs – hypersensitivity to dopamine agonists

                -Hemiballismus – lesions in contralateral subthalamic nucleus

 

9. Pituitary associations

                -Optic chiasm sits on top of pituitary – bilateral hemianopsia

                -Sits in the sella turcica - local pressure effects hypopatuitarism

 

10. Brain MRI and CT

                -Abcess or cysticercosis CT and MRI – ring enhancing lesion

                -Multiple sclerosis MRI – multiple focal areas of demyelination (plaques) in brain and spinal cord

                -Huntington's disease – atrophy of the caudate nucleus, putamen, and frontal cortex – looks like

 ventricles have enlarged

 

11. Pupillary light reflex     -  doesn't involve cortex

                -Direct response – afferent pathway is optic nerve of eye tested – efferent pathway is CN III

                 to the eye tested

                -Consensual response – afferent pathway is optic nerve of eye tested – efferent pathway is

                 CN III of opposite eye

                -Accomodation – pupils constrict, eyes converge, lense more convex – depends on CN III

                 and visual association cortex