NEET MDS Synopsis
Catecholamines Agonists
Pharmacology
Catecholamines Agonists :
Epinephrine
A and B receptors - B1, A1, B2
- Good for emergency bronchospasm treatment (acute asthma or anaphylactic shock) and open-angle glaucoma
- Also gives longer duration of anesthetic action via vasocontriction and reducing systemic absorption
- Increases sBP lowers dBP
Norepinephrine
- A and B in therapeutic doses, most A receptor influence
- Good to increase peripheral resistance (A1)
- Good for shock treatment (increase TPR and BP); increases sBP and dBP
Isoproterenol
- Synthetic: B1 and B2, little A stimulation
- Strong cardiac stimulation (b1), dilation of skeletal vessels (b2), and bronchodilation (b2)
- Increases sBP lowers dBP
Dopamine
- Precursor to NE; A and B activity and dopamine receptors in renal and mesenteric vasculature causing vasodilation
- B1 stimulation of the heart
- Therapeutic: choice drug for shock as it increases BP via cardiac stimulation and also increases kidney blood flow (increased GFR and Na diuresis)
Dobutamine
- Synthetic B1 agonist
- To increase CO in CHF
- Watch out in Afib as it may increase AV conduction
Phenylephrine - Synthetic A1 agonist – for nasal decongestion
Methoxamine - Synthetic A1 agonist – for hTN in surgery
Clonidine - A2 agonist- - Used to lower pressure in essential HTN (via CNS effect, diminishing sympathetic outflow)
Factors affecting onset and duration of action of local anesthetics
Pharmacology
Factors affecting onset and duration of action of local anesthetics
pH of tissue
pKa of drug
Time of diffusion from needle tip to nerve
Time of diffusion away from nerve
Nerve morphology
Concentration of drug
Lipid solubility of drug
Fibrous and Fibro-Osseous Tumors
General Pathology
Fibrous and Fibro-Osseous Tumors
Fibrous tumors of bone are common and comprise several morphological variants.
1. Fibrous Cortical Defect and Nonossifying Fibroma
Fibrous cortical defects occur in 30% to 50% of all children older than 2 years of age; they are probably developmental rather than true neoplasms. The vast majority are smaller than 0.5 cm and arise in the metaphysis of the distal femur or proximal tibia; almost half are bilateral or multiple. They may enlarge in size (5-6 cm) to form nonossifying fibromas. Both lesions present as sharply demarcated radiolucencies surrounded by a thin zone of sclerosis. Microscopically are cellular and composed of benign fibroblasts and macrophages, including multinucleated forms. The fibroblasts classically exhibit a storiform pattern. Fibrous cortical defects are asymptomatic and are usually only detected as incidental radiographic lesions. Most undergo spontaneous differentiation into normal cortical bone. The few that enlarge into nonossifying fibromas can present with pathologic fracture; in such cases biopsy is necessary to rule out other tumors.
2. Fibrous Dysplasia
is a benign mass lesion in which all components of normal bone are present, but they fail to differentiate into mature structures. Fibrous dysplasia occurs as one of three clinical patterns:
A. Involvement of a single bone (monostotic)
B. nvolvement of multiple bones (polyostotic)
C. Polyostotic disease, associated with café au lait skin pigmentations and endocrine abnormalities, especially precocious puberty (Albright syndrome).
Monostotic fibrous dysplasia accounts for 70% of cases. It usually begins in early adolescence, and ceases with epiphyseal closure. It frequently involves ribs, femur, tibia & jawbones. Lesions are asymptomatic and usually discovered incidentally. However, fibrous dysplasia can cause marked enlargement and distortion of bone, so that if the face or skull is involved, disfigurement can occur.
Polyostotic fibrous dysplasia without endocrine dysfunction accounts for the majority of the remaining cases.
It tends to involve the shoulder and pelvic girdles, resulting in severe deformities and spontaneous fractures.
Albright syndrome accounts for 3% of all cases. The bone lesions are often unilateral, and the skin pigmentation is usually limited to the same side of the body. The cutaneous macules are classically large, dark to light brown (café au lait), and irregular.
Gross features
• The lesion is well-circumscribed, intramedullary; large masses expand and distort the bone.
On section it is tan-white and gritty.
Microscopic features
• There are curved trabeculae of woven bone (mimicking Chinese characters), without osteoblastic rimming
• The above are set within fibroblastic proliferation
Individuals with monostotic disease usually have minimal symptoms. By x-ray, lesions exhibit a characteristic ground-glass appearance with well-defined margins. Polyostotic involvement is frequently associated with progressive disease, and more severe skeletal complications (e.g., fractures, long bone deformities, and craniofacial distortion). Rarely, polyostotic disease can transform into osteosarcoma, especially following radiotherapy.
Non-barbiturate sedatives
Pharmacology
Non-barbiturate sedatives
1- Chloral hydrate is trichlorinated derivative of acetaldehyde that is converted to trichlorethanol in the body. It induces sleep in about 30 minutes and last up to 6 hr. it is irritant to GIT and produce unpleasant taste sensation.
2- Ramelteon melatonin receptors are thought to be involved in maintaining circadian rhythms underlying the sleep-wake cycle. Ramelteon is an agonist at MT1 and MT2 melatonin receptors , useful in patients with chronic insomnia with no rebound insomnia and
withdrawal symptoms
3- Ethanol (alcohol) it has antianxiety sedative effects but its toxic potential out ways its benefits.
Ethanol is a CNS depressant producing sedation and hypnosis with increasing dose.
Absorption of alcohol taken orally is rapid, it is highly lipid soluble, presence of food delayed its absorption, maximal blood concentration depend on total dose, sex, strength of the solution, the time over which it is taken, the presence of food and speed of metabolism.
Alcohol in the systemic circulation is oxidized in the liver principally 90% by alcohol dehydrogenase to acetaldehyde and then by acetaldehyde dehydrogenase to products that enter the citric cycle.
Alcohol metabolism by alcohol dehydrogenase follows first order kinetics in the smallest doses. Once the blood concentration exceeds about 10 mg/100 ml, the enzymatic processes are saturated and elimination rate no longer increases with increasing
concentration but become steady at 10-15 ml/ 1 hr. in occasional drinkers.
Thus alcohol is subject to dose dependant kinetics i.e. saturation or zero order kinetics.
Actions
- Ethanol acts on CNS in a manner similar to volatile anesthetic.
- It also enhances GABA so stimulating flux of chloride ions through ion channels.
- Other possible mode of action involve inhibition of Ca-channels and inhibition of excitatory NMDA receptors.
- Ethanol has non selective CNS depressant activity.
- It causes cutaneous vasodilatation, tachycardia and myocardial depression
HEART DISORDERS
Physiology
HEART DISORDERS
Pump failure => Alters pressure (flow) =>alters oxygen carrying capacity.
Renin release (Juxtaglomerular cells) Kidney
Converts Angiotensinogen => Angiotensin I
In lungs Angiotensin I Converted => Angiotensin II
Angiotensin II = powerful vasoconstrictor (raises pressure, increases afterload)
stimulates thirst
stimulates adrenal cortex to release Aldosterone
(Sodium retention, potassium loss)
stimulates kidney directly to reabsorb Sodium
releases ADH from Posterior Pituitary
Myocardial Infarction
Myocardial Cells die from lack of Oxygen
Adjacent vessels (collateral) dilate to compensate
Intracellular Enzymes leak from dying cells (Necrosis)
Creatine Kinase CK (Creatine Phosphokinase) 3 forms
One isoenzyme = exclusively Heart (MB)
CK-MB blood levels found 2-5 hrs, peak in 24 hrs
Lactic Dehydrogenase found 6-10 hours after. points less clearly to infarction
Serum glutamic oxaloacetic transaminase (SGOT)
Found 6 hrs after infarction, peaks 24-48 hrs at 2 to 15 times normal,
SGOT returns to normal after 3-4 days
Myocardium weakens = Decreased CO & SV (severe - death)
Infarct heal by fibrous repair
Hypertrophy of undamaged myocardial cells
Increased contractility to restore normal CO
Improved by exercise program
Prognosis
10% uncomplicated recovery
20% Suddenly fatal
Rest MI not fatal immediately, 15% will die from related causes
Congenital heart disease (Affect oxygenation of blood)
Septal defects
Ductus arteriosus
Valvular heart disease
Stenosis = cusps, fibrotic & thickened, Sometimes fused, can not open
Regurgitation = cusps, retracted, Do not close, blood moves backwards
Specific Agents
Pharmacology
Specific Agents
Hydralazine [orally effective]
MOA: Not completely understood. Seems to be partially dependent on the release of EDRF and perhaps partially due to K+-channel activation
- in clinical doses action is manifest primarily on vascular smooth muscle (non-vascular muscle is not much affected).
- Re: Metabolism & Excretion. In cases of renal failure the plasma half life may be substantially increased (4-5 fold). One mode of metabolism is
via N-Acetylation (problem of slow acetylators)
Side Effects
- those typical of vasodilation = headache, nasal congestion, tachycardia etc.
- chronic treatment with high doses > 200 mg/day may induce a rheumatoid-like state which may resemble lupus erythematosus.
Minoxidil (Loniten) [orally effective]
MOA: K+-channel agonist
- very effective antihypertensive. Used primarily to treat life-threatening hypertension or hypertension resistant to other agents.
Side effects - growth of hair
Diazoxide (Hyperstat) [used only IV]
MOA: K+-channel agonist
- Administered by rapid IV injection; action appearing after 3-5 min; action may last from 4 to 12 hours.
Nitroprusside (Nipride) [used only IV]
MOA: increase in cGMP
- unlike the other vasodilators, venous tone is substantially reduced by nitroprusside.
- rapid onset of action (.30 sec); administered as an IV-infusion.
- particularly useful for hypertension associated with left ventricular failure.
Oxyphenbutazone
Pharmacology
Oxyphenbutazone: one of the metabolites of phenylbutazone. Apazone. Similar to phenylbutazone, but less likely to cause agranulocytosis
Dermatomes of the lower limb
Anatomy
Dermatome
Area supplied
L1
Inguinal area (over inguinal canal).
L2
Anterior and Lateral part of Upper 2/3rdof thigh.
L.3
Anterior, Lateral & Medial part of Lower 1I3'd of thigh and knee.
L4
Medial side of leg.
L5
Lateral side of leg, Medial half of dorsum of foot, first web space.
SI
Posterior surface of ankle, and lateral half of dorsum of foot.
S2
Posterior of thigh and leg.
S3
Gluteal area around perianal region, Groin.
S4
Perianal skin &Groin.