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Pharmacology

Different Systems of the CNS & their functions

These systems are pathways formed of specific parts of the brain and the neurons connecting them. 

They include:
1.The pyramidal system 
2.The extrapyramidal system 
3.The limbic system 
4.The reticular formation 
5.The tuberohypophyseal system

The pyramidal system: 

It originates from the motor area of the cerebral cortex and passes through the spinal cord, therefore it is also known as the “corticospinaltract”. 
It is responsible for the regulation of the fine voluntary movements.

The extrapyramidal system: 

It also controls the motor functionbut involves areas other than the corticospinal tract. 
It is involved in the regulation of gross voluntary movements, thus it complements the function of the pyramidal system. 


The “basal ganglia” constitute an essential part of this system. 

Degenerative changes in the pathway running from the “substantianigra”to the “corpus striatum”(or nigrostriatal pathway) may cause tremors and muscle rigidity characteristic of “Parkinson’s disease”.


The limbic system: 

The major parts of this system are: the hypothalamus, the basal ganglia, the hippocampus(responsible for short term memory), and some cortical areas. 

The limbic system is involved in the control of “behavior”& “emotions”.


The reticular formation:

It is composed of interlacing fibers and nerve cells that run in all directions beginning from the upper part of the spinal cord and extending upwards. 
It is important in the control of “consciousness” and “wakefulness”.


The tuberohypophyseal system: 

It is a group of short neurons running from the hypothalamusto the hypophysis(pituitary gland) regulating its secretions.
 

Operator position

For the right-handed operator, the 8 and 10 o’clock position and for left-handed operators, the corresponding 2 and 4 o’clock position almost always allows for optimal visualization of the injection field.

DIURETICS

The basis for the use of diuretics is to promote sodium depletion (and thereby water) which leads to a decrease in extracellular fluid volume.
An important aspect of diuretic therapy is to prevent the development of tolerance to other antihypertensive drugs.

TYPES OF DIURETICS
A. Thiazide Diuretics examples include     chlorothiazide 
hydrochlorothiazide 
a concern with these drugs is the loss of potassium as well as sodium

B. Loop Diuretics (High Ceiling Diuretics) examples include 
furosemide (Lasix)
bumetanide
these compounds produce a powerful diuresis and are capable of producing severe derangements of electrolyte balance

C. Potassium Sparing Diuretics examples include
triamterene
amiloride 
spironolactone 
unlike the other diuretics, these agents do not cause loss of potassium

Mechanism of Action

Initial effects: through reduction of plasma volume and cardiac output.
Long term effect: through decrease in total peripheral vascular resistance.

Advantages

Documented reduction in cardiovascular morbidity and mortality.
Least expensive antihypertensive drugs.
Best drug for treatment of systolic hypertension and for hypertension in theelderly.
Can be combined with all other antihypertensive drugs to produce synergetic effect.

Side Effects
Metabolic effects (uncommon with small doses): hypokalemia,hypomagnesemia, hyponatremia, hyperuricemia, dyslipidemia (increased total
and LDL cholesterol), impaired glucose tolerance, and hypercalcemia (with thiazides).
Postural hypotension.
Impotence in up to 22% of patients.  

 Considerations
- Moderate salt restriction is the key for effective antihypertensive effect of diuretics and for protection from diuretic - induced hypokalaemia. 
- Thiazides are not effective in patients with renal failure (serum creatinine > 2mg /dl) because of reduced glomerular filtration rate.
- Frusemide needs frequent doses ( 2-3 /day ).Thiazides can be given once daily or every other day.
- Potassium supplements should not be routinely combined with thiazide or loop diuretics. They are indicated with hypokalemia (serum potassium < 3.5 mEq/L) especially with concomitant digitalis therapy or left ventricular hypertrophy.
- Nonsteroidal antiinflammatory drugs can antagonize diuretics effectiveness.

Special Indications

Diuretics should be the primary choice in all hypertensives.

They are indicated in:
- Volume dependent forms of hypertension: blacks, elderly, diabetic, renal and obese hypertensives.
- Hypertension complicated with heart failure.
- Resistant hypertension: loop diuretics in large doses are recommended.
- Renal impairment: loop diuretics

DIAGNOSIS

Affective disorders:
I. unipolar depression – depression alone
bipolar affective disorder – alternating II. bipolar affective disorder – alternating depression and mania

Diagnosis is based on 

At least five of the following for 2 weeks
I. Depressed mood most of the day
II. Markedly diminished interest or pleasureII. Markedly diminished interest or pleasure
III. Significant weight loss or weight
IV. Insomnia or hypersomnia
V. Psychomotor agitation or retardation
VI. Fatigue or loss of energy
VII. Feelings of worthlessness or excessive guilt
VIII. Diminished ability to think or concentrate, 
IX. Recurrent thoughts of death

Underlying biological basis for depression is a deficiency of the monoamine neurotransmitters  norepinephrine and/or serotonin in the brain.

Oxytetracycline

Treats Oxytetracycline is a medicine used for treating a wide range of infections including infections of the lungs, urinary system, skin and eyes. It may also be used to treat sexually transmitted infections, infections caused by lice, rickettsial infections, cholera and plague. It is very occasionally used to treat leptospirosis, gas gangrene, and tetanus.

Fluconazole: an antifungal used orally,  intravenously or vaginally to treat yeast and fungal infections. Side-effects of systemic administration include hepatotoxicity (liver damage).

  • For vaginal candidiasis (vaginal thrush), a once-only oral dose is often sufficient.

Sulfonylureas

1st generation
tolbutamide
chlorpropamide

2nd generation

glyburide
glimepiride
glipizide

Mechanism

glucose normally triggers insulin release from pancreatic β cells by increasing intracellular ATP
→ closes K+ channels → depolarization → ↑ Ca2+ influx → insulin release

sulfonylureas mimic action of glucose by closing K+ channels in pancreatic β cells 
→ depolarization → ↑ Ca2+ influx → insulin release

its use results in

↓ glucagon release
↑ insulin sensitivity in muscle and liver

Clinical use

type II DM

stimulates release of endogenous insulin 
cannot be used in type I DM due to complete lack of islet function

Toxicity

first generation

disulfiram-like effects
especially chlorpropamide

second generation

hypoglycemia
weight gain

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