Structure of the CNS 

The CNS is a highly complex tissue that controls all of the body activities and serves as a processing center that links the body to the outside world. 
It is an assembly of interrelated “parts”and “systems”that regulate their own and each other’s activity. 

1-Brain                                  
2-Spinal cord 

The brain is formed of 3 main parts: 

I. The forebrain
• cerebrum
• thalamus
• hypothalamus

II. The midbrain
III. The hindbrain
• cerebellum
• pons
• medulla oblongata

Different Parts of the Different Parts of the CNS & their functions CNS & their functions
The cerebrum(cerebral hemispheres):
It constitutes the largest division of the brain. 
The outer layer of the cerebrum is known as the “cerebral cortex”. 

The cerebral cortex is divided into different functional areas: 
1.Motorareas(voluntary movements) 
2.Sensoryareas(sensation) 
3.Associationareas(higher mental activities   as consciousness, memory, and behavior).

Deep in the cerebral hemispheres are located the “basal ganglia” which include the “corpus striatum”& “substantianigra”. 

The basal gangliaplay an important role in the control of “motor”activities

The thalamus:

It functions as a sensory integrating center for well-being and malaise. 
It receives the sensory impulses from all parts of the body and relays them to specific areas of the cerebral cortex.

The hypothalamus:

It serves as a control center for the entire autonomic nervous system. 
It regulates blood pressure, body temperature, water balance, metabolism, and secretions of the anterior pituitary gland.

The mid-brain: 

It serves as a “bridge”area which connects the cerebrum to the cerebellum and pons. 
It is concerned with “motor coordination”.

The cerebellum:

It plays an important role in maintaining the appropriate bodyposture& equilibrium.

The pons:

It bridges the cerebellum to the medulla oblongata. 
The “locus ceruleus”is one of the important areas of the pons.

The medulla oblongata:
 
It serves as an organ of conduction for the passage of impulses between the brain and spinal cord. 
It contains important centers: 
• cardioinhibitory 
• vasomotor 
• respiratory 
• vomiting(chemoreceptor trigger zone, CTZ).

The spinal cord:

It is a cylindrical mass of nerve cells that extends from the end of the medulla oblongata to the lower lumbar vertebrae. 
Impulses flow from and to the brain through descending and ascending tracts of the spinal cord.
 

Insulin
Insulin is only given parenterally (subcutaneous or IV) Various preparations have different durations of action 
 

Mechanism

bind transmembrane insulin receptor
activate tyrosine kinase
phosphorylate specific substrates in each tissue type
liver
↑ glycogenesis
store glucose as glycogen
muscle
↑ glycogen and protein synthesis
↑ K+ uptake 
fat
increase triglyceride storage

Clinical use

type I DM
type II DM
life-threatening hyperkalemia
increases intracellular K+
stress-induced hyperglycemia
 

Toxicity
hypoglycemia
hypersensitivity reaction (very rare)

Insulin Synthesis
first generated as preproinsulin with an A chain and B chain connected by a C peptide. 
c-peptide is cleaved from proinsulin after packaging into vesicles leaving behind the A and B chains

Neomycin

used as a topical preparation

Neomycin is not absorbed from the gastrointestinal tract, and has been used as a preventative measure for hepatic encephalopathy and hypercholesterolemia. By killing bacteria in the intestinal tract, it keeps ammonia levels low and prevents hepatic encephalopathy, especially prior to GI surgery. It is not given intravenously, as neomycin is extremely nephrotoxic (it causes kidney damage), especially compared to other aminoglycosides.

Drugs Used in Diabetes

Goals of diabetes treatment

lower serum glucose to physiologic range
keep insulin levels in physiologic range
eliminate insulin resistance

best initial step in management: weight loss, contractile-based exercise weight loss is more important for insulin sensitivity than is a low-carb diet

Modalities of diabetes treatment

Type I DM

insulin
low-sugar diet

Type II DM
exercise
diet
insulin

6 classes of drugs 

Insulin
Sulfonylureas -    Glyburide
Meglitinides  - Nateglinide
Biguanides    Metformin    
Glitazones (thiazolidinediones)    Pioglitazone
α-glucosidase inhibitors    Acarbose
GLP-1 mimetics (incretin mimetics)    Exenatide
Amylin analog    Pramlintide

Histamine: 

Involved in inflammatory and anaphylactic reactions 
Local application causes swelling redness, and edema, mimicking a mild inflammatory reaction.

Large systemic doses leads to profound vascular changes similar to those seen after shock or anaphylactic origin.

Storage: widely distributed; in tissues, primarily in mast cells; in blood- in basophils, platelets; non-mast cell sites (epidermis, CNS, regenerating cells)

Histamine Stored in complex with:
Heparin
Chondroitin Sulfate
Eosinophilic Chemotactic Factor
Neutrophilic Chemotactic Factor
Proteases

Release: during type I (IgE-mediated) immediate hypersensitivity rxns, tissue injury, in response to some drugs
a.    Process: Fcε receptor on mast cell or basophil binds IgE, when Ag binds → ↑ PLC activity → histamine

Symptoms: bronchoconstriction, ↓ Pa, ↑ capillary permeability, edema

Action

H1 receptors are located mainly on smooth muscle cells in blood vessels and the respiratory and GI tracts. When histamine binds with these receptors producing the following effects.

-Contraction of smooth muscle in the bronchi and bronchioles producing bronchoconstraction.

-stimulation of vagus nerve endings to produce reflex bronchoconstraction and cough.

-Increased permeability of veins and capillaries, which allows fluid to flow into subcutaneous tissues and form edema (little lower blood pressure).

-Increased secretion of mucous glands. Mucosal edema and increased nasal mucus produce the nasal congestion characteristic of allergic rhinitis and the common cold.

-Stimulation of sensory peripheral nerve endings to cause pain and pruritus.

Histamine promotes vasodilation by causing vascular endothelium to release nitric oxide. This chemical signal diffuses to the vascular smooth muscle, where it stimulates cyclic guanosine monophosphate production, causing vasodilation.

H2-receptors present mostly in gastric glands and smooth muscle of some blood vessels. When receptors are stimulated, the main effects are increased secretion of gastric acid and pepsin, increased rate and force of myocardial contraction.

The H3-receptor functions as a negative-feedback mechanism to inhibit histamine synthesis and release in many body tissues. Stimulation of H3 receptors opposes the effects produced by stimulation of H1 receptors.

The H4- receptor is expressed in only a few cell types, and their role in drug action is unclear.

Drugs cause release of histamine: 

Many drugs can cause release of histamine in the body.
-Intracutaneouse morphine injection in humans produced localized redness, localized edema and a diffuse redness. This is due to release of histamine.

-I.V. inj of curare may cause bronchial constriction due to release of histamine.

-codeine , papaverine, meperidine (pethedine), atropine, hydralizine and sympathomimetic amines, histamine releases by these drugs may not be significant unless they are administered I.V in large doses

Pharmacological effects

-  If injected I.V. (0.1 mg of histamine) causes a sharp decline in the blood pressure, flushing of the face and headache. 
- There is also stimulation of gastric acid secretion. 
- If this injection is given to an asthmatic individual, there will be a marked decrease in vital capacity and a sever attack of asthma. 

Circulatory effects of histamine:

The two factors involved in the circulatory action of histamine are:
Arteriolar dilatation and
Capillary permeability
So it leads to loss of plasma from circulation

Effect on gastric secretion:
Histamine is a potent stimulant of gastric Hcl secretion. 

Biguanides

metformin

Mechanism

↓ gluconeogenesis

appears to inhibit complex 1 of respiratory chain

↑ insulin sensitivity
↑ glycolysis
↓ serum glucose levels
↓ postprandial glucose levels

Clinical use

first-line therapy in type II DM

Toxicity

no hypoglycemia
no weight gain
lactic acidosis is most serious side effect 
contraindicated in renal failure