Antihypertensives Drugs

CATEGORIES
I.    Diuretics to reduce blood volume 
Chlorothiazide (Diuril)

II. Drugs that interfere with the Renin-Angiotensin System

A. Converting enzyme inhibitors             Captopril , enalapril, Lisinopril

B. Angiotensin receptor antagonists         Saralasin Losartan 

III. Decrease peripheral vascular resistance and/or cardiac output

A. Directly acting vasodilators
1. calcium channel blockers           Nifedipine , Diltiazem,  amlodipine

2. potassium channel activators     Minoxidil 

3. elevation of cGMP                      Nitroprusside 

4. others                                         Hydralazin e

B. Sympathetic nervous system depressants

1. α-blockers                             Prazosin, phentolamine, phenoxybenzamine

2. β-blockers                             Propranolol ,Metoprolol, atenolol

3. norepinephrine synthesis inhibitors     Metyrosine 

4. norepinephrine storage inhibitors     Reserpine
 
5. transmitter release inhibitors         Guanethidine 

6. centrally acting: decrease 
sympathetic outflow                     Clonidine , methyldopa

OXYMETAZOLINE
 

It is a directly acting sympathomimetic amine used in symptomatic relief in nasal congestion which increases mucosal secretion.

It is used:
- As a nasal decongestant in allergic rhinitis, with or without the addition of antazoline or sodium chromoglycate. 
- As an ocular decongestant in allergic conjunctivitis.

Compounds like naphazoline and xylometazoline are relatively selective α2 agonists, which on topical application produce local vasoconstriction.

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.
 

Enflurane (Ethrane) MAC 1.68, Blood/gas solubility ratio 1.9
- Extremely stable chemically.
- Less potent and less soluble in blood than is halothane.
- Respiratory depression is similar to that seen with halothane.
- Cardiac output is not depressed as much as with halothane, and the heart is not sensitized to catecholamines to the same degree.
- Enflurane produces better muscle relaxation than does halothane.
- Metabolism of this agent is very low. Inorganic fluoride is a product of metabolism, but is not sufficient to cause renal problems.
- Enflurane differs from halothane and the other inhalational anesthetic agents by causing seizures at doses slightly higher than those that induce anesthesia. 
- Nausea appears to occur somewhat more often following Enflurane than it does following halothane.

Ofloxacin : It is a quinolone antibiotic and similar in structure to  levofloxacin. It is an alternative treatment to ciprofloxacin for anthrax.

Excretion
Routes of drug excretion
The most important route of drug elimination from the body is via the kidney

Renal Drug Excretion

- Glomerular Filtration

- Passive Tubular Reabsorption: drugs that are lipid soluble undergo passive reabsorption from the tubule back into the blood.

- Active Tubular Secretion

Factors that Modify Renal Drug Excretion

- pH Dependent Ionization:  manipulating urinary pH to promote the ionization of a drug can decrease passive reabsorption and hasten excretion.

- Competition for Active Tubular Transport

- Age:  Infants have a limited capscity to excrete drugs.

Nonrenal Routes of Drug Excretion
Breast Milk
Bile, Lungs, Sweat and Saliva

The kidney is the major organ of excretion. The lungs become very important for volatile substances or volatile metabolites.

Drugs which are eliminated by the kidney are eliminated by:

a) Filtration - no drug is reabsorbed or secreted.

b) Filtration and some of the drug is reabsorbed.

c) Filtration and some secretion.

d) Secretion

By use of the technique of clearance studies, one can determine the process by which the  kidney handles the drug.

Renal plasma clearance = U x V ml/min U  / Cp = conc. of drug in urine

Cp = conc. of drug in plasma

V = urine flow in ml/min

Renal clearance ratio = renal plasma clearance of drug (ml/min) / GFR (ml/min)

Total Body Clearance = renal + non-renal