What is Alpha Blockers? Side effects of alpha blockers? Alpha blockers

     

 ALPHA ADRENERGIC RECEPTOR  BLOCKING AGENTS

              (ALPHA BLOCKERS)

Drugs with diverse chemical structures block alpha adrenergic receptors and inhibit their responses.The blockade is reversible except in case of  phenoxybenzamine which causes irreversible blockade  due to its covalent biding to alpha receptors.
  These drugs differ regarding their capability of blocking the two subtypes of alpha receptors i.e. postsynaptic alpha 1 receptors and presynaptic alpha 2 receptors. Prazosin is a selectoive blocker of postsynaptic alpha 1 receptors.Phenoxybenzamine is more potent in blocking postsynaptic alpha 1 receptors than in blocking presynaptic alpha 2 receptors. Phentolamine and tolazoline are nonselective blockers of alpha receptors. On the other hand yohimbine is a selective alpha 2 blocker.

CLASSIFICATION OF ALPHA BLOCKERS:

1. CHEMICAL CLASSIFICATION:

• BETA-Halokylamines

           Phenoxybenzamine
           Dibenamine

• Substituted Imidazolines

           Phentolamine

           Tolazoline

• Phenoxyalkylamines

          Thyroxamine

• Ergot alkaloids

           Ergotamine

           Dihydroergotamine

• Dibenzapines

           Azapetine

• Benzodioxans

           Piperoxan

• Indolealkylamines

           Yohimbine

• Phenothiazines

           Chlorpromazine

• Miscellaneous

           Prazosin

           Indoramine

           Labetalol

   
      2.  CLASSIFICATION BASED  ON DURATION OF ACTION:

• Reversible 

           Phentolamine

           Tolazoline

           Prazosin

• Irreversible

           Phenoxybenzamine

           Dibenamine

      3..CLASSIFICATION BASED ON SELECTIVITY OF ACTION:

• Selective alpha 1 Postsynaptic blocking agent

           Prazosin

• Predominantly aplha 1 Postsynaptic blocking agent

           Phenoxybenzamine

• Selective alpha 1 Presynaptic blocking agent

          Yohimbine

• Non-selective( Blocks both alpha 1 and alpha 2)

          Phentolamine

 PHARMACOLOGICAL ACTIONS OF ALPHA BLOCKERS

    These drugs bind to alpha adrenergic receptors and interfere with the capacity of sympathomimetic amines to initiate action at these sites.They prevent the response of effector organs to adrenaline,nonadrenaline and other sympathomimetic amines whether released in the body or injected. Circulating catecholamines are antagonized more readily than are the effects of sympathetic nerve stimulation. Phenoxybenzamine binds covalently to the alpha receptors and produce irreversible blockade. Other drugs bind reversibly and antagonize the action of sympathomimetic amines competitively.

Vasodilation:

  The principal action of all alpha blackers is to produce peripheral vasodilation, with the exception of ergotamine which possesses a direct vasoconstrictor action.

Vasomotor Reversal:

   Alpha blockers reverse the pressor effect of adrenaline due to the unmasking of beta effects producing vasodilation of skeletal muscle vessels and hypotension. These drugs abolish the pressor effect of nonadrenaline which possesses mainly alpha effects.

Miosis:

  These drugs constrict pupil of eyes by blocking the action of fibres of iris.

THERAPEUTIC USES OF ALPHA BLOCKERS:

Peripheral Vascular Spastic Disease:

   With the exception of the ergot alkaloid,alpha blockers have been used in the treatment of peripheral vascular spastic diseases for such conditions as thromboangitis obliterans(Buerger's disease) and Raynaud's syndrome. It is assumed that sympathetic hyperactivity contributes in part to these conditions and that this component is eliminated by alpha receptors blockade. Alpha blockers are used for treatment of chillblains and intermittent claudication.

Phaeochromocytoma:

   Alpha blockers are used in the investigation and in the preoperative treatment of phaechoromocytoma which is a rare hyperfunctioning tumour of adrenal medulla. It is composed of chromaffin tissue and secreates large quamtutues of adenaline and nonadrenaline, alpha adrenergic blockade transiently lowers the elevated arterial pressure that is characteristic of this tumour.

Hypertension:

  Treatment of hypertension with alpha blockers except prazosin has been rather disappointing due to reflex tachycardia and palpitation produced by them. Usefulness of prazosin in hypertension may be due to its lack of potency in inhibiting presynaptic alpha 2 receptors. Phenoxybenzamine and phentolamine have been used successfully to control acute hypertensive episodes due to symparhomimetics,amd to certain foods and drugs in the presence of MAO inhibition.

Autonomic Hyperreflexia:

   It follows high spinal cord transection and is associated with paroxysmal elevation in blood pressure. These pressor episodes and associated signs ans symptoms are well controlled by relatively small oral doses of phenoxybenzamine,

Glaucoma:

    Alpha blockers may be use in glaucoma.

Migraine:

   Ergotamine is of particular value in migraine due to its direct vasoconstrictor effects.

Shock:

 In certain types of shock when reflex neurogenic vasoconstriction due to hyperactivity of compensatory mechanisms is a prominent feature, the judicial use of alpha blockers can increase local blood flow in important areas, kidney and mesenteric bed, where local anoxia is relieved and recovery facilitated. These drugs should not be given unless the central venous pressure has been elevated by fluid administration without an adequate circulatory response. However use of dopamine is preferred in such situations.

ADVERSE EFFECTS OF ALPHA BLOCKERS:

• Postural Hypotension
• Tachycardia
• Nasal Stuffiness
• Sedation
• Diarrhoea
• Failure of ejaculation

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what is posology(doses of drugs) and its types?posology

POSOLOGY

It the branch of pharmacology which deals with the study of the dosage of drugs is called posology.
  Dose is the quantity of drug given to the patient at one time.The quantity should be adequate to produce certain therapeutic effects.It should not be too small or too large.If too large, undesirable effects will appear.However there are individual variations and the same drug in the same doses may show marked differences in response.Some persons may be highly sensitive and respond to a very small dose, while others are more resistant and fail to respond except in very large doses.This is known as “normal biological variation”.

posology (doses of drug)

  The British Pharmacopoeia gives two doses, one a minimum and the other a maximum dose. By “minimum dose” is meant the minimum amount which is expected to produce some therapeutic effects. By “maximum dose” is meant the largest amount which one can use without risk of producing toxic effects.These doses are meant for oral administration unless otherwise stated, and are for adults i.e. for persons between 18 and 60 years. When a drug is meant for administration by any other route, the dose to be used as well as the route of administration by any other route, the dose to be used as well as the route of administration is specifically mentioned.
The United States Pharmacopoeia gives only an “average dose”. It is for the prescriber to adjust the dose according to the requirements of the patient.

Daily dose:

   It is the total amount of the drug which can be given in the day either as a single dose, as with emetine hydrochloride, or the total amount is to be divided into three or four doses.The total daily dose of sodium amino salicylate is 10 to 15 g and it should be given in divided doses.

Total dose:

     It is the amount of the drug to be given to the patient during the full course of treatment. It should not be exceeded on account of toxicity. Thus the dose of colchicine is 1/2 to 1mg. Total dose is 8 mg.

Single dose:

     Means that only one dose should be given during the day. Single dose of Emetine is 30 to 60mg.
      For the treatment of certain diseases it is necessary to use a large dose initially to produce an effective concentration as quickly as possible and then to use small dose to maintain the effect. The former is known as “initial or loading dose” and the latter as “maintenance dose”. The initial dose of sulphadiazine is 3 g and subsequent dose is 1 g. Initial dose of digoxin is 1 to 1.5 mg and the maintenance dose is 0.25 mg once or twice daily.
    For certain drugs the British Pharmacopoeia does not prescribe any dose and expects the physician to select the dose according to the requirements of the patients; for example, no dose is given for insulin and some of the antibiotics.

Median Lethal Dose(LD50):

         It is the amount of drug which is fatal to 50 percent of experimental animals. It is the measure of acute toxicity of the drugs.

Median Effective Dose(ED50):

     It is the amount of the drug which produces the desired therapeutic effect in 50 percent of experimental animals. It is the measure of effectiveness of the drug.

Therapeutic Index(Therapeutic Ratio):

       It is the ratio of median lethal dose to the median effective dose. The higher is the ratio the safer is the drug.

Toxic Dose:

   It is the amount of drug which produces undesirable harmful effects of serious nature and liable to endanger the life of the patient.

Fatal Dose:

   It is the amount of drug which is liable to cause death due to toxic effect of the drug in a normal person.

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What is Pharmacology? History of Pharmacology?pharmacology

PHARMACOLOGY

pharmacology is the branch of science which deals with the study of drugs, including their origins, history, uses, toxicity and other properties
The main focus is on the action of drugs on the body
Pharmacology comes from the Greek word PHARMAKON means drug or medicine and logos means study

pharmacology     

General History of Pharmacology

Like other disciplines of science pharmacology is quite young as it emerged as a discipline in the 19th Century but the knowledge of drugs and their application in disease is as old as mankind history

In ancient times the idea-disease of disease has been conceived as an evil spirit to harm a person physically or mentally hence religion have been brought in the healing.
Hippocrates did not believe in magic remedies. so a  reaction has been started against these myths and more emphasis was given to drugs.

Theophratus discovered about 500 drugs he had a good knowledge of plants and their use in the disease. Hindus had their medical text SUSRUTA in which 760 herbs were mentioned

In ancient Chinese medicine, the Emperor SHAN NUNG was known as the father of Chinese materia medicine he was the author of Pen Taao which describes 265 drugs of which 240 were vegetable substances.
The Chinese employed Iodine, Rhubarb, Aconite, iron, sulphur, mercury, and other drugs some of which contain ephedrine or camphor

In Ancient Roman period Celsus wrote a book in which 28 chapters were related to therapentics 

Pliny wrote seven books on remedies derived from plants and trees. Galen wrote 30 books on drugs they introduced the method of preparing pure drugs from their crude sourcesand such preparation like tinctures found extracts etc are still used Caued Galenicals

Arabs ultimate saurce of medical knowledge was Dioscorides. They introduced castoroil which was used as Catnartic. The Arabs also introduced musk for cerebral and Ophthalmic discauses Ambergris was used in the treatment of cramps, heart diseases, brain disorders Camphor for vertigo, cholera, haemorrhage and inflammation of brain
Nux vonica as emetic during Arab period great schools of learning had been established at Baghdad.

Although the main advances in 18th century were due to the progress of chemistry.Digitalis and Foxglove became popular in 18th century.The first pharmacopoeia of US in 19th century listed purple foxglov,ether known as chemical agent from 19th century was used for toothache in 19th century.Chloroform made in 1831 was used as general anaesthetic much later.
The great achievement in the century was the introduction of chemotherapeutic agents against the bacterial infection by Paul Ehrlich(1854-1915).The compounds killing the microorganisms were also injurious to the host.However advances in the subject brought in sulphonamide compounds and then the antibiotics which have made true the dreams of Ehrlich.
In early 19th century morphine was isolated from opium and was followed by isolation of quinine.A new phase of modern pharmacology was started by Oswald Schmied-Berg(1838-1921) with consideration of fate of drugs in the body.Now in the 21st century the effects of drugs on sub-cellular level and molecular level has put pharmacology amongst the advanced sciences.

FIELDS OF PHARMACOLOGY:

MAIN FIELDS:

1)Pharmacodynamics:
              It is the study of the physiological and biochemical effects of drugs as well as their mechanisms of action.It is also defined as the response of the drug to the body i.e.,onset,peak and duration of action etc.

2)Pharmacokinetics:
              It deals with the study of response of the body to the drug i.e.absorption,distribution,biotransformation and excretion of drugs and their relationship to the onset,duration and intensity of drug effects.

OTHER FIELDS:

1)Therapeutics:
              It is the art and science of treatment of disease.It includes drug treatment.

2)Pharmacotherapeutics:
              it is also called Medical pharmacology which deals with the proper selection and use of drugs for the prevention and treatment of disease.

3)Chemotherapy:
              it deals with the effect of drugs upon microorganisms and parasites,living and multiplying in a living body,without damage to the host.

4)Clinical pharmacology:
              It is the scientific study of drugs in man.It includes pharmacodynamic and pharmacokinetic investigations of drugs in man and their therapeutic evaluations.

5)Toxicology:
             It deals with the adverse effects of drugs.Also concerned with other chemicals responsible for household,environmental or industrial poisonings.

6)Pharmacognosy:
             It is the science of identification of drugs.

7)Pharmacy:
            It is the science which deals with the preparation,compounding and dispensing of medicines.

8)Posology:
           It is the branch of pharmacology which deals with doses of drugs.


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                           What is posology( Doses of drugs) ?
                            What are Alpha blockers? side effects of alpha blockers?