Pharmacy

Thursday, December 16, 2010



It is art and science of compounding and dispensing of drugs  or preparing suitable dosage forms for administration of drugs to man or animals

It includes collection, identification, purification, isolation, synthesis, standardization and quality control of medicinal substances

The large scale manufacture of drugs called pharmaceutics

Pharmacology

It is a  Greek  word .    Pharmacon -----  Drug .       Logos----- discourse in

Drug

French   ---  Drogue  -----   a dry herb

It is single active chemical entity present in medicine that is used for diagnosis, prevention, treatment or cure of disease

Drug nomenclature

  1. Chemical name
  2. Generic name   ( Non- Proprietary name)
  3.  Brand name     ( Proprietary name )


Sources of drugs

Drugs are obtained from different sources

Most of the drugs that are currently used are manufactured synthetically

Recently drugs are synthesized by genetic technologies  like human recombinant gene technology

Ex 
Erythropoietin



Source

Specific source and drugs

Category



Plants
Belladonna- Atropine

Digitalis- Digitoxin

Opium - Morphine
Ant cholinergic

Cardio tonic

Narcotic analgesics


Animals
Pork, Beef – Insulin

Horse – Tetanus anti toxin

Various animals - Heparin
Anti-diabetic

Ant tetanus

Anti- coagulant


Minerals
Charcoal

Magnesium sulfate

Aluminum hydroxide
Antidote

Purgative

Antacid


Microbes
Penicillium Notatum – Penicillin

Actinomycetes – Streptomycin

E. Coli  - L- asparaginase
Antibiotic

Antibiotic

Anti-cancer




Synthetic
Aspirin

Cimetidine

Paracetamol

Phenitoin

Phenobarbitone


Analgesics

Antacid

Anti-pyretic

Anti-epileptic

Hypnotic


Dosage forms

Pharmaceutical companies dispense a drug in a variety of formulations suitable for a single or multiple routes of administration

Some antibiotics are available in tablet, capsules or suspension form for oral administration

So doctor can choose the formulation suitable for the patient

It is important because it influences the bioavailability of drug

For ex

Digoxin when injected intravenously, the bioavailability of that drug is 1.00

But when the same amount of the drug is administered into the body by oral route in tablet form, the bioavailability is about is 0.62

On the other hand, the bioavailability of digoxin elixir administered orally  is 0.80

When a tablet form of drug is swallowed, it is necessary to disintegrate as well as to dissolve before absorption

But in case of capsule, there is no question of disintegration , only dissolution is necessary

In case of suspension, there is no disintegration or dissolution

So, the rate of absorption is greater in suspension than capsule or tablet

Route of administration


To produce a pharmacological effect it is very important for the drug to reach the site of action

This depends on the transfer of drugs across one or more membrane barriers

Drugs after reaching the blood circulation  builds up a therapeutic concentration

The concentration depends on the volume of distribution, biotransformation and excretion

There are some drugs which are not absorbable from one site but get into the circulation from another

Benzyl penicillin is inactivated in the stomach at gastric PH and is not administered orally

Some drugs absorbed from the gastrointestinal tract  pass the intestinal mucosa and  the small  intestine but metabolized  by the gut  wall (such as chlorpromazine , dopamine) or
by  the liver ( such as lignocaine, pethidine, propranolol)

In order to select the route for administration this first-pass biotransformation is considered and on occasions is avoided

Slowly absorbed drug may have delayed onset of effect and may even fail to achieve effective concentration


Route of administration


To produce a pharmacological effect it is very important for the drug to reach the site of action

This depends on the transfer of drugs across one or more membrane barriers

Drugs after reaching the blood circulation  builds up a therapeutic concentration

The concentration depends on the volume of distribution, biotransformation and excretion

There are some drugs which are not absorbable from one site but get into the circulation from another

Benzyl penicillin is inactivated in the stomach at gastric PH and is not administered orally

Some drugs absorbed from the gastrointestinal tract  pass the intestinal mucosa and  the small  intestine but metabolized  by the gut  wall (such as chlorpromazine , dopamine) or
by  the liver ( such as lignocaine, pethidine, propranolol)

In order to select the route for administration this first-pass biotransformation is considered and on occasions is avoided

Slowly absorbed drug may have delayed onset of effect and may even fail to achieve effective concentration


Alcohols

Alcohols are aliphatic hydrocarbons

They contain one or more hydroxyl groups

Classification

1. Mono-hydroxy alcohols

Methyl, ethyl and propyl alcohols

2. Dihydroxy alcohols

Ethylene glycols, propylene glycol

3. Tri-hydroxy alcohols

Glycerol or glycerine

4. Poly-hydroxy alcohols

Mannitol,  sorbitol

Ethyl alcohol

Ethyl alcohol is commonly used alcohol

It is the main constituent of all kinds of alcoholic beverages

It is generally obtained by fermentation of sugars by yeast

The alcohol is separated by simple distillation

It is a colorless, volatile and inflammable liquid

The alcohol content of various beverages varies between 4-55% by volume

Wines containing more than 16%  of alcohol

Beer contains 4-6 % (v/v) of alcohol

Stronger preparation are called Spirit





Mechanism of action

Alcohol produce CNS depression by a generalized membrane action by altering the state of membrane lipids

Alcohol promotes GABAA receptor mediated synaptic inhibition (through chloride channel opening ) as well as inhibits NMDA and type of excitatory amino acid receptors (operating thorough captions channels)

Alcohol can indirectly reduce neurotransmitter release by inhibiting voltage sensitive neuronal calcium channels

Blockade of adenosine uptake by alcohol could also contribute to synaptic depression
The activity of membrane bound enzymes like Na – K ATPase and adenyl cyclase is also altered

The activity and translocation of channel or enzyme proteins in the membrane could be affected by alcohol through protein kinase  C and protein kinase A mediated alteration in the state of their phosphorlation


Pharmacological actions

1. Externally

It evaporates quickly and producing cooling effect and is used for reducing the temperature in fevers

It is used in shaving lotion for producing cooling effect on the skin

In  concentration of  40- 50,  it act as rubifacient and mild irritant action

In concentration of 70% , it acts as antiseptic , the action is seen only against vegetative forms of organism and spores are resistant

Concentrated alcohol , if injected , produces tissue destruction

Higher concentration  denature proteins by partial precipitation and dehydration
In such concentration , it acts as an astringent, a germicidal and an irritant
  
2. GIT

If  taken orally , it increases salivary secretion by reflex action

It has an irritant action on the gastric mucous membrane and act as appetizer
50 ml of 7-10% alcohol increases the gastric secretion ,by releasing histamine and gasstrin  from the antrum of the stomach


Concentration  above 15%  inhibit both motility and secretion and effect may persist for many hours

Concentration above 20% reduce the enzymatic activity of the gastric and the intestinal juices

Concentration above 40% and over have a direct toxic effect on gastric mucosa and may precipitate gastritis, giving rise to pain, nausea, vomiting and other symptoms

Many alcoholics suffer from gastritis and chronic achlorhydria

Many alcoholics suffer from chronic diarrhea as a result of malabsorption from chronic mucosal damage

3. CNS

It is primarily a CNS depressant and acts by enhancing the inhibitory GABA receptor activity or inhibiting NMDA receptors

Proteins are the  primary site of its actions

It  produces initial excitation due to depression of higher inhibitory centers

This is followed by progressive depression, drowsiness, sleep and unconsciousness as the dose is increased

Sudden withdrawal of alcohol causes excitation and hyperactivity of the CNS

4. CVS

Small dose produce only cutaneous and gastric vasodilatation B.P is not affected

Moderate doses cause tachycardia and a mild rise in BP due to increased muscular activity and sympathetic stimulation

Large doses cause direct myocardial as well as  vasomotor centre depression and there is fall in BP
Chronic alcoholism may contribute to hypertension and lead to cardiomyopathy

Atrial fibrillation and other cardiac arrhythmias may occur due to conduction defects and Q-T  prolongation

5. On respiration

Moderate doses produce slight stimulation whereas large doses produce respiratory depression which may be fatal


6. Kidney

Diuresis is often notified after alcohol intake

It is due to depression of ADH production

It does not impair renal function

7. Sax

Alcohol is reputed as an aphrodisiac.

Aggressive sexual behavior is due to loss of inhibitory control

It also provokes the sensation but takes away the performance

Chronic alcoholism can produce impotence, gynaecomastia and infertility


8. Body temperature

Alcohol  produces  a sense of warmth due to cutaneous and gastric vasodilatation , but heat loss is increased in cold surroundings   

High intake of alcohol produces depress temperature regulating centre

9. Liver

It produces fatty liver on chronic administration

It mobilize peripheral fat and increases fat synthesis in liver

Proteins may also accumulate in liver because their secretion is decreased

Acetaldehyde produced during metabolism of alcohol appears to damage the hepatocytes on chronic ingestion of large amounts

Increased lipid peroxidation and glutathione depletion occurs

Regular alcohol intake induces microtonal enzymes

10. Skeletal muscle

Alcohol produces little direct effect.  Fatigue is produced by small doses, but muscle work is increases or decreased

Weakness and myopathy occurs in chronic alcoholism


11. Blood

Regular intake of small to moderate amounts has been found to raise HDL levels and decrease LDL oxidation
 Megaloblastic anemia has been seen in chronic alcoholism due to interference with folate metabolism


Absorption , fate and excretion

Alcohol is absorbed in the stomach (25%) and 75% in small intestine

It is metabolized in the liver as follows

                            Alcohol dehydrogenase
Ethyl alcohol   -------------------------------------------------------Acetaldehyde

                             Aldehyde dehydrogenase
Acetaldehyde-------------------------------------------------------------Acetyl CoA

Acetyl CoA is further metabolized to carbon dioxide and water

Alcohol is eliminated mostly through kidneys and lungs


Toxicity

Side effects of moderate drinking

Nausea, vomiting , flushing, hangover, traffic accidents

Acute alcoholic intoxication

Fall in body temperature

Hypotension

gastritis

hypoglycemia

Collapse, respiratory depression

Coma  and death


Treatment

Gastric lavage maintain patent airway and take steps to prevent aspiration of vomit us

Positive pressure respiration may be needed if it is markedly depressed

Most patients  will recover with supportive treatment, maintenance of fluid and electrolyte balance and correction of hypoglycemia  by glucose infusion  till alcohol is metabolized

Recovery can be hastened by haemodialysis

Insulin + fructose drip has been found to accelerate alcohol metabolism

Chronic alcoholism

On chronic intake, tolerance develops to subjective and behavioral effects of alcohol

It is both pharmacokinetic and cellular tolerance

Psychic dependence often occurs even with moderate drinking

Physical dependence occurs only on heavy and round the clock drinking

Heavy drinking is often associated with nutritional deficiencies, because food is neglected and malabsorption  may occur

Alcoholic cirrhosis of liver, hypertension, cardiomyopathy , CHF, arrhythmias, stroke and skeletal myopathy are complications


Treatment

Psychological and medical supportive measures are needed during withdrawal

Many CNS depressants like barbiturates , phenothiazines, chloral hydrate have been used as substitution therapy in the past to suppress withdrawal syndrome but benzodiazepines like chordiazepoxide, diazepam are the  preferred drugs now

These have a long duration of action and can be gradually withdrawn later


Disulfiram

It is a drug for the treatment of chronic alcoholism

It is a inhibits the enzyme aldehyde dehydrogenaase

So acetaldehyde is not converted into Acetyl CoA

This leads to accumulation of acetaldehyde which  produces nausea and vomiting

It is administered at a dose of 500 mg once daily for a week and alter 250 mg daily as maintenance dose

When alcohol is ingested after taking disulfiram, the concentration of acetaldehyde in tissues and blood rises and a number of distressing symptoms (aldehyde syndrome ) are produced

These are

Flushing 
Burning sensation
Throbbing headache
Perspiration
Uneasiness
Tightness in chest 
Dizziness
Vomiting
Visual disturbances
Mental confusion and circulatory collapse

Duration  of the syndrome (1-4 hours ) depends on the amount of alcohol consumed

Disulfiram is used in chronic alcoholics who are motivated and sincerely desire to leave the habit

Sensitization to alcohol develops after 2-3 hours of first dose and lasts for 7-14 days after stopping it ,because  inhibition of aldehyde dehydrogenase with disulfiram is irreversible
Synthesis of fresh enzyme is required for return  of activity

It should not be used in patients who are physically dependent on alcohol

Side effect of disulfiram are

Drowsiness
Headache
Cramps
Rashes
Metallic taste
Nervousness
Abdominal upset


General anesthetics

Def
General anesthetics are drugs which produce reversible loss of all sensation and consciousness

Conditional feature of General anesthetics are

Loss of all sensation. Specially pain

Sleep ( unconsciousness) and amnesia

Immobility and muscle relaxation

Abolition of reflexes

1. Inhalation anesthetics

A. Gas

Nitrous oxide
Cyclopropane
Ethylene

B. Liquids

Ether
Chloroform
Halothane
Ethyl chloride
Vinyl ether


11. Intravenous anesthetics

Thiopentone
Methohexitone
Ketamine
Paraldehyde
 

Ether ( Di-ethyl ether )

Properties

It is one of the oldest anesthetic agents in use
It is a colorless and volatile liquid with a pungent odour
It is highly inflammable and explosive
It is quickly absorbed and eliminated through lungs

Actions

5-10% of ether is required in the inspired air to induce anesthetic and at least 3-5% to maintain it

It irritates respiratory tract leading to eflex secretion of saliva and mucous from the mouth and respiratory tract

So atropine should be given at least half an hour before to paralyses secretion

The initial stages are more prolonged with ether in the absence of premeditation

Other actions

Ether does little damage to the heart

It increases cardiac output and coronary blood flow

The rate and depth of respiration may be increased

It does not cause any damage to liver

Advantages

It is safest agent . It can be used even by a nurse
It produces analgesia
It produces skeletal muscle relaxation
It produces less inhibition of respiratory centre than other unaesthetic agents   
It does not effect the blood pressure
It dies not interfere with liver or kidney functions
It can be given by all techniques

Dis-advantages

It catches fire
Induction of anesthesia as well as Recovery are slow
Vomiting is likely to occur postoperatively
Generalized convulsions are produced specially in children

  
Chloroform

It is a volatile liquid having a powerful anesthetic property
It is a colorless non-inflammable volatile liquid with a sweetish smell
It produces server toxic effects on the liver and heart
It is not used at present

Action
Anesthesia is induced by the open drop method or by closed circuit method 2%  of chloroform is required in the inspired air to induce anesthesia and about 0.5% for maintenance of anesthesia

Other action
In addition to general an aesthesia, externally it is used as a rubefacint
Internally it is used as a carminative
It is used as a vehicle in mixtures

Advantages

It does not irritate respiratory tract
Muscular relaxation is good
Recovery is accompanied by less nausea and vomiting than with ether
It is non inflammable
Induction is rapid and pleasant

Disadvantages

Chloroform depresses myocardium resulting in slowing down of the heart and even cardiac arrest

It depresses the respiratory centre
Liver function is affected leading to necrosis and hepatic failure and death
Intestinal motility is diminished
Margin of safety is very less
Blood concentration of about 15 mg% is required to maintain anesthesia but about 20-25 mg% is fatal

 
Halothane

Physical properties

It is heavy, colorless liquid, anesthetic agent
It is non inflammable, non toxic fluorinated hydrocarbon
It has sweet , fruity odor and boils
It affects most of metals including stainless steel ,,copper, rubber

Advantages

Induction is very smooth as it has sweet , fruity odor
Recovery is also fast , smooth with low incidences of nausea and vomiting It is not inflammable and hence does not irritate respiratory passage inhibits salivary secretion hence endotracheal intunotion is much easier
It does not produce bronchospasm, and can be used in patients with bronchial asthma

Dis advantages

Muscular relaxation is inadequate
It causes respiratory, cardiovascular depression
Mental recovery is delayed
Shivering during recovery is very common
It is poor analgesic
It is expensive, needs special apparatus for administration