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
- Chemical name
- Generic name ( Non- Proprietary name)
- 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
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
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
