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Pharmacology

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.
 

Class IV Calcium Channel Blockers
• Block the movement of calcium into conductile and contractile myocardial cells 
• Treatment: treatment of supraventricular tachycardia 
– Diltiazem 
– Verapamil 

Adverse Effects 
• Adverse effects associated with vasodilation of blood vessels throughout the body. 
• CNS – dizziness, weakness, fatigue, depression and headache, 
• GI upset, nausea, and vomiting. 
• Hypotension CHF, shock arrhythmias, and edema 
 

Neurolept Anesthesia
An antipsychotic agent such as droperidol plus an opiate analgesic agent such as fentanyl or sufentanil. This latter agent is approximately eight to ten times more potent than fentanyl.

Phenoxymethylpenicillin (penicillin V) Phenoxymethylpenicillin, commonly known as penicillin V, is the orally-active form of penicillin. It is less active than benzylpenicillin

Indications:

infections caused by Streptococcus pyogenes, tonsillitis, pharyngitis, skin infections, prophylaxis of rheumatic fever, moderate-to-severe gingivitis (with metronidazole)

Treatment modifications to consider if there are concerns regarding vasoconstrictors

- Monitor blood pressure and heart rate preoperatively

- Minimize administration of epinephrine or levonordefrin

- Monitor blood pressure and heart rate 5 min after injection

- May re-administer epinephrine or levonordefrin if blood pressure and heart rate are stable

- Continue to monitor as required

- Consider limiting epinephrine to 0.04 mg, levonordefrin to 0.2 mg

- Avoid epinephrine 1:50,000

- Never use epinephrine-impregnated retraction cord

Thrombolytic Agents:

Tissue Plasminogen Activator (t-PA, Activase)

t-PA is a serine protease. It is a poor plasminogen activator in the absence of fibrin. t-PA binds to fibrin and activates bound plasminogen several hundred-fold more rapidly than it activates plasminogen in the circulation.

Streptokinase (Streptase)

Streptokinase is a protein produced by β-hemolytic streptococci. It has no intrinsic enzymatic activity, but forms a stable noncovalent 1:1 complex with plasminogen. This produces a conformational change that exposes the active site on plasminogen that cleaves a peptide bond on free plasminogen molecules to form free plasmin.

Urokinase (Abbokinase)

Urokinase is isolated from cultured human cells.Like streptokinase, it lacks fibrin specificity and therefore readily induces a systemic lytic state. Like t-PA, Urokinase is very expensive.

Contraindications to Thrombolytic Therapy:

• Surgery within 10 days, including organ biopsy, puncture of noncompressible vessels, serious trauma, cardiopulmonary resuscitation.

• Serious gastrointestinal bleeding within 3 months.

• History of hypertension (diastolic pressure >110 mm Hg).

• Active bleeding or hemorrhagic disorder.

• Previous cerebrovascular accident or active intracranial bleeding.

Aminocaproic acid:

Aminocaproic acid prevents the binding or plasminogen and plasmin to fibrin. It is a potent inhibitor for fibrinolysis and can reverse states that are associated with excessive fibrinolysis.

ANTICHOLINERGIC DRUGS
Blocks the action of Ach on autonomic effectors.

Classification
Natural Alkaloids - Atropine. Hyoscine

Semi-synthetic deriuvatives:- Homatropine, Homatropine methylbromide, Atropine methonitrate.

Synthetic compounds 

(a) Mydriatics - Cyclopentolate. Tropicamide.
(b) Antisecretory - Antispasmodics - Propantha1ine. Oxy-phenonium, Pirenzipine.
c) Antiparkinsonism- Benzotopine, Ethopropazine, Trihexyphenidyl, Procyclidine, Biperiden 
Other drugs with anticholinergic properties • Tricyclic Antidepressants • Phenothiazines • Antihistaminics • Disopyramide

MUSCARINIC RECEPTORS SUBTYPES & ANTAGONISTS 
• M 1 Antagonists – Pirenzepine, Telenzepine, dicyclomine, trihexyphenidyl 
• M 2 Antagonists – Gallamine, methoctramine 
• M 3 Antagonists – Darifenacin, solifenacin, oxybutynin, tolterodine

Pharmacological Actions
CNS - stimulation of medullary centres like vagal. respiratory. vasomotor and inhibition of vestibular excitation and has anti-motion sickness properties.
CVS - tachycardia.
Eye - mydriasis
Smooth muscles - relaxation of the muscles receiving parnsympathetic motor innervation.
Glands - decreased secretion of sweat and salivary glands
Body Temperature - is increased as there is stimulation of  temperature regulating centre.
Respiratory System- Bronchodilatation & decrease in secretions. For COPD or Asthma - antimuscarinic drugs are effective
GIT - Pirenzepine & Telenzepine - decrease gastric secretion with lesser side effects.

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