ODISHA STATE BOARD OF PHARMACY
D. Pharm - II Examination - 2017 (I)
PHARMACEUTICS - II (THEORY)
Time - 3 Hours Full Marks - 80
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1.(a) Define the following:
[2×8]
(i) Posology(ii) Syrup & Elixir
(iii) Depilatories
(iv) Poultices
(v) Displacement Value
(vi) Cracking of Emulsion
(vii) Idiosyncrasy
[1x4]
(i) Si opus sit(ii) Collunarium
(iii) Secundum artem
2. Define the term 'Incompatibility'. Classify it. Discuss chemical incompatibilities which occur due to alkaloidal salts.
[3+4+8]
3.(a) Explain various adjuvants used in the formulation of mixtures.
[7
(b) Define Suspension. Differontiate between flocculated & non-floculate suspesion.
[2+6
4.(a) Discuss in brief:
(i) Dentrifices
(ii) Shampoos
[4×3.5
(b) Write essential qualities of an ideal ophtalmic product.
[7.5
5.(a) Write the requirements of Ideal suppository base.
[4
(b) Write Advantage & Disadvantages of coca butter as suppository base.
[5
(c) Write classification of ointment bases with its examples, advantages & disadvantages.
[6
6. What are parenteral Preparations ? Describe various steps involved in processing of parenteral preparations. Write a note on Isotonic solution.
[2+12+1]
7. Explain the term dose. Discuss various factors which affect the dose of a drug. Write the formula of young's rule.
[2+10+3]
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ANSWER TO 2017 (I)
1.(a) Define the following:
(i) Posology
Ans.
(i) The word posology is derived from the Greek words 'posos' meaning how much and 'logos' meaning science.
(ii) So posology is a branch of medical science which deals with dose or quantity of drugs which can be administered to a patient to get the desired pharmacological actions.
(ii) Syrup & Elixir
Ans.
Syrup :
(i) It is a concentrated or nearly saturated solution of sucrose in purified water.
(ii) The conc. of sugar is 66.7% w/w
(iii) The syrups containing medicinal substances are called medicated syrup and those containing aromatic or flavoured substances are known as flavoured syrups.
Elixirs :
(i) These are clear, sweetened, aromatic, hydroalcoholic liquids intended for oral use.
(ii) The main ingredients of elixirs are ethyl alcohol (5-40%), water, glycerin or propylene glycol, flavouring agent, colouring agent and some suitable preservative. The medicated elixirs usually contain a potent drug such as, antibiotics, antihistamines or sedatives.
(iii) Depilatories
Ans.
Depilatories : These are the chemicals used to remove the hair without injury to the skin. Example- Calcium sulphide.
(iv) Poultices
Ans.
This is a soft, viscous wet mass of solid substances applied to the skin for their fermentation action in order to provide relief from pain or reduce inflammation or to act as a counter irritant.
(v) Displacement Value
Ans.
Displacement value is the quantity of the drug which displaces one part of the base in a suppository.
(vi) Cracking of Emulsion
Ans.
Cracking of Emulsion - it is the separation of two lyaers of disperse and continuous phase of an emulsion which in difficult to redisperse by shaking.
(vii) Idiosyncrasy
Ans.
(i) Idiosyncrasy: An extraordinary response to a drug which is different from its characteristic pharmalogical action is called idiosyncracy.
(ii) The word idiosyncrasy has now been replaced by the term drug allergy. For example, small quantity of aspirin may cause gastric haemorrhage and a small dose of quinine may produce ringing in the ears. Some persons are sensitive to penicillin and sulphonamide because they produce severe toxic symptoms.
(viii) Pessaries
Ans.
These are the conical, wedge shaped or rod shaped semisolid dosage form meant for introduction into the vagina
(b) Define the following terms into English:
(i) Si opus sit
Ans.
When required a when necessary
(ii) Collunarium
Ans.
A medicated solution for instillation into the nostrils as a wash or spary or as drops.
(iii) Secundum artem
Ans.
According to the practice
(iv) Unguentum
Ans.
An ointment
2. Define the term 'Incompatibility'. Classify it. Discuss chemical incompatibilities which occur due to alkaloidal salts.
Ans.
- Incompatibility occurs as a result of mixing of two or more antagonistic substances and an undesirable product is formed wich may affect the safety, efficacy and appearance of the pharmaceutical preparation.
- The interaction of a drug with another drug or of a drug with additives or adjuncts; dosage errors etc. comes under incompatibility.
- Incompatibility may occur not only during compounding and dispensing but also at any stage during formulation, manufacturing, packaging or administration of drugs.
Types of Incompatibilities :
The incompatibilities are of three types:
(A) Physical incompatibility
(B) Chemical incompatibility
(C) Therapeutic incompatibility
Physical incompatibility :
- When two or more than two substances are combined together, a physical change take place and an unacceptable product is formed.
- Physical incompatibility is usually due to immiscibility, insolubility, precipitate formation or liquefaction of solid materials.
Chemical incompatibility:
- Chemical incompatibility may be as a result of chemical interactions between the ingredients of a prescription and a toxic or inactive product may be formed.
- Chemical incompatibilities often occur due to oxidation-reduction, acid base hydrolysis or combination reactions.
Therapeutic incompatibility:
- Therapeutic incompatibility may be as a result of prescribing certain drugs to a patient with the intention to produce a specific degree of pharmacological action, but the nature or intensity of the action produced is different from that intended by the prescriber.
- This occurs due to the following reasons:-
1. Error in dosage;
2. Wrong dose or dosage form;
3. Contra-indicated drugs;
4. Synergistic and antagonistic drugs; and
5. Drug interactions.
Chemical Incompatibility due to alkaloidal salts :
Most alkaloidal salts are soluble in water but alkaloidal bases are practically insoluble in water and are freely soluble in organic solvents. When an alkaline substance like aromatic spirit of ammonia, solution of ammonia, ammonium bicarbonate, sodium bicarbonate, potassium bicarbonate, borax, etc., is added to an alkaloidal salt solution the free alkaloid may be precipitated.
Alkaloidal salts with alkaline substances :
- Alkaloids are weak bases. They are almost insoluble in water but alkaloidal salts are soluble in water. If these salts are dispensed with alkaline preparations, such as strong solution of ammonium acetate, aromatic spirit of ammonia, solution of ammonia, ammonium bicarbonate, sodium bicarbonate, the free alkaloid may be precipitated.
- However, they are not always precipitated, because all alkaloids are slightly soluble in water.
Alkaloidal Salts with Soluble Iodides :
- Potassium iodide is generally prescribed as an expectorant in some of the cough mixtures also containing alkaloids but the quantity of alkaloids present(e.g. emetine from ipecacuanha tincture) is usually so low that the precipitation of hydriodide is unlikely to take place.
- Strychnine when combined with soluble iodides forms a very insoluble hydriodide, the precipitates of which are diffusible hence follow method A for precipitate-yielding combinations.
Alkaloidal Salts with Tannins :
- When an alkaloidal salt is combined with a drug containing tannins, the alkaloidas form tannates which are insoluble in water and the precipitates so formed are usually diffusible in nature therefore follow method A for precipitate-yielding combinations.
- Since most alkaloids form insoluble tannates therefore this fact is frequently used in the treatment of alkaloidal poisoning in which case a strong solution of tannic acid or strong tea is administered which will precipitate the alkaloid and render it less harmful.
Alkaloidal Salts with Salicylates :
Generally quinine compounds are prescribed with salicylates in the treatement of malaria. When quinine is combined with salicylates it forms indiffusible precipitates of quinine salicylate therefore follow method B for precipitate-yielding combinations
3.(a) Explain various adjuvants used in the formulation of mixtures.
Ans.
Adjuncts :
The following adjuncts are generally used to improve the stability, colour and flavour of the mixtures :
(a) Chemical stabilisers :
- Certain chemicals having antioxidants or reducing properties are used to improve the chemical stability of the mixtures.
- For example, ascorbic acid (0.1%) is prescribed in ferrous sulphate mixture to prevent oxidation of ferrous to ferric ions.
- The ferric salts are relatively ineffective in haemoglobulin formation.
- Similarly sodium metabisulphite (0.1%) is included in mixtures containing sodium salicylate to prevent the darkness of mixture due to atmospheric oxidation.
(b) Colouring agents :
- No special colouring agents are added but many mixtures contain coloured medicaments.
(c) Flavouring agents :
The following flavouring agents are commonly used in mixtures :-
- Aromatic water such as anise water.
- Syrup and glycerol for sweeting children's preparation
- Liquid extract of liquorice to mask the saline taste of certain mixtures.
- Spirit lemon to cover the taste of alkaline citrates.
- Orange syrup and compound orange spirit to mask the metallic and astringent tastes of iron salts in paediatric's mixtures.
(d) Preservatives :
- Diluted vegetable extract and favouring agents are the source of growth of bacteria and fungi in mixture. Hence chlorofom (0.25% v/v/) and benzoic acid (0.1% w/v) is used to preserve such mixtures.
(b) Define Suspension. Differentiate between flocculated & non-foculated suspension.
Ans.
- Suspensions are the biphasic liquid dosage form of medicament in which the finely divided solid particles ranging from 0.5 to 5.0 micron are suspended or dispersed in a liquid or semi-solid vehicle.
- The solid particles constitutes the discontinuous phase whereas the liquid vehicle constitutes the continuous phase.
Qualities of Good Suspension
A well formulated suspension should have the following properties :
1. The dispersed particles should not settle readily and the settled particles should redisperse immediately on shaking.
2. The particles should not form a cake on settling.
3. The viscosity should be such that the preparation can be easily poured.
4. It should be chemically stable.
5. Suspensions for internal use must be palatable and suspensions for external use must be free from gritty particles and possess other characteristics required for external preparations.
Flocculated
1. Particles form loose aggregates and form a network like structure.
2. Rate of sedimentation is high
3. Sediment is rapidly formed.
4. Sediment is loosely packed and does not form a hard cake.
5. Sediment is easy to redisperse.
6. Suspension is not pleasing in appearance
7. The floccules stick to the sides of the bottle.
Non-flocculated
1. Particles exist as separata entities.
2. Rate of sedimentation is slow.
3. Sediment is slowly formed
4. Sediment is very closely packed and a hard cake is formed.
5. Sediment is difficult to redisperse.
6. Suspension is pleasing in appearance.
7. They do not stick to the sides of the bottle
4.(a) Discuss in brief : (i) Dentrifices, (ii) Shampoos
Ans.
Dentrifices:
Dentifrices are the preparations meant to be applied to the teeth with a tooth brush for the purpose of cleaning the accessible surface of the teeth.
Dentifrices are used in the following cases:
(i) Cleaning of tooth
(ii) Polishing of the tooth
(iii) Removal of strains from the teeth
(iv) reduce incidence of tooth decay
(v) Reduction of mouth odours.
(vi) Reductionof periodontal disease (disease of the gun)
(vii) prevention of formation of removal of dental plaque.
(viii) Prevention of formation of calculus
The common dentifrices are available in the form of tooth powders, tooth pastes and liquid preparations
Qualities of a Good Dentifrice :
Tooth paste or tooth powder should have the following qualities:
(i) It should be economical
(ii) It should be non-toxic
(iii) It should be properly sweetened and flavoured.
(iv) it should give fresh and clean sensation.
(v) it should be efficient in removing food substances, plaque and other foreign particles.
(vi) It should clean the teeth.
In the formulation of dentifrices the following ingredients are used:
(i) Abrasives: these are also known as polishing agents and are used to remove debris and residual strains from the teeth surface without damaging it.
(ii) Binders : Binders are used to keep the solids and liquids in the united form and to maintain the consistency. The commonly used binders are gum tragacanth, sodium alginate, methyl cellulose, etc.
(iii) Detergents : These are surface active agents which are used to enhance the action of abrasives.
(iv) Flavouring agents : There are included in the preparation to impart flavour to the preparation.
(v) Humectants : These are used in tooth paste to retain moisture and will not allow the paste to become dry,
(vi) Preservatives : The preservatives are included in dentifrices formulation to prevent the growth of bacteria in tooth paste.
(viii) Sweetening agents : These are included in dentifrices to impart sweet taste to the preparation. Saccharin in the ratio of 0.005 to 0.25% is the most commonly used sweetening agent for this purpose.
(viii) Therapeutic agents : These are included only in medicated tooth pastes in order to check dental diseases and to remove bad smell. The commonlt used therapeutic agents are antibiotics, fluorides, proteolytic enzymes inhibitors, crystal growth inhibitors, chlorophyll and essential oils etc.
Method of Preparation :
Tooth powders are prepared in big blending and mixing tanks.
The solid ingredients are weighed and mixed thoroughly in ascending order of their weights.
Flavoring agents are sprayed during the course of mixing.
The stainless steel containers are used while preparing tooth paste.
A mixture of binder and humectant is dispersed in a liquid containing saccharin and preservative.
It is then allowed to swell to form a homogenous gel. The homogenous gel is then pumped into suitable mixing tank.
Add slowly the abrasive agent with agitation in order to form a smooth and uniform paste.
Flavouring agent and detergent is then incorporated.
Tooth pastes are finally packed in collapsible tubes
Types of Dentifrices
(a) Liquid dentifrices :
- These preparations are not much popular, but still they are used for tooth cleaning purpose.
- They are basically aqueous or hydroalcoholic solutions of surfactants in which thickening agent, sweeteners, flavour etc. are incorporated.
(b) Tooth powders :
- These are oldest, cheapest and simple preparations meant for cleaning the teeth.
- The main ingredients in tooth powders are abrasives, surfactants, sweeteners and flavours.
- Tooth powders are having very fine particle size.
(c) Tooth pastes :
- These are most popular and widely used preparations for cleaning the teeth.
- They are more expensive as compare to tooth powders but still they are more preferred.
- The main ingredients in tooth pastes are abrasives, foaming agents, sweetening agents, flavours, binding agents, humectants, preservation and therapeutic agents.
Shampoos:
- Shampoos may be defined as a preparation containing surface active agents which are used to remove dirt, grease and debris from the hair,
- scalp and other parts of the body without affecting the natural gloss of hair.
- Shampoo also helps to keep the hair fragrant, lustrous, soft and manageable.
- In majority of the cases, shampoos are water soluble solutions or suspensions prepared by dissolving cleansing agents in suitable liquid to which other agents are added to improve the functions of the shampoo.
- The majority of modern shampoos are prepared by using synthetic detergents.
Qualities of an ideal shampoo
(1) It should be capable of removing grease, dirt, and skin debris from the hair and scalp.
(2) It should be non-toxic
(3) It should be non-irritant.
(4) It should provide sufficient fragrance to the hair after its use.
(5) It should be effective in small amounts.
(6) It should get easily removed by washing with water.
(7) It should produce sufficient foam, both in hard and soft water.
(8) It reduces the fluffiness and smoothens the hair shafts. It make the hair soft and shiny.
Types of shampoos
The shampoos are available in market in different forms which are as under:-
(1) Medicated dandruff shampoos
(2) Powder shampoos
(3) Clear liquid shampoos
(4) Gel shampoos
(5) Soap shampoos
(6) Cream or paste shampoos
(7) Liquid cream or lotion shampoos
(8) Baby shampoos
(9) Aerosol shampoos
Formulation of shampoos
The various types of additives are required to be included in the formulation of shampoos. These are as under:-
1. Conditioning agents : These are used in lubricating the hair and improves the texture of the hair. It reduces the fluffiness and smoothen the hair shafts. It makes the hair soft and shiny.
Lanolin and its derivatives, glycerin and propylene glycol are used as hair conditioners.
2. Thickening agents : These are used to increase the viscosity of the shampoos and provide the desired consistency to the preparation. Polyvinyl alcohol, methyl cellulose, sodium alginate and sodium stearate are used as thickening agent.
3. Solubilizing agents : These are used to solubilize poorly soluble substances so as to get a clear shampoo. Ethyl alcohol, glycerol, propylene glycol and diethylene glycol, monoethyl ether are commonly used as solubilizing agents.
4. Opacifying agents : These are used to make the shampoo opaque. Glycol, glyceryl stearate, cetyl alcohol and stearyl alcohol, stearic amides are some of the commonly used opacifying agents.
5. Preservatives : These are required to preserve the shampoos against bacteria or mould contamination by adding preservatives. Methyl paraben and propyl paraben are commonly used preservatives in shampoos.
(b) Write essential qualities of an ideal ophtalmic product.
The thickening agents are not included in the formulation of eye drops and eye lotions which are required to be used during or after surgery due to some possible adverse effects on the interior of the eye.
3. Tonicity : Ophthalmic products must be isotonic with lachrymal secretions to avoid discomfort and irritation. It has been observed that eye can tolerate a range of tonicity from 0.5 to 2% sodium chloride. There are certain isotonic vehicles which are used to prepare ophthalmic products like 1.9% boric acid, sodium acid phosphate buffer.
4. pH of the preparation : pH plays an important role in therapeutic activity, solubility, stability and comfort to the patient. Tears have a pH of about 7.4. Eye can tolerate solution having wide range of provided they are not strongly buffered, since the tears will rapidly restore the normal pH value of the eye. Alkaloidal salt solutions are stable at pH 2 to 3 but this pH is irritant to the eye. The alkaloids precipitated at pH above 7 and creates a number of formulation problems.
5. Sterility : Ophthalmic preparation must be sterile when prepared. Pseudomonas aeruginosa is very common gram negative bacteria which is generally found to be present in ophthalmic products. It cause serious infection of cornea. It can cause complete loss of eyesight in 24-48 hours. To maintain sterility in multidose container containing ophthalmic products, a suitable preservative is added. The preservative should be non-toxic, non-irritant and should be compatible with medicaments. The ophthalmic products are generally sterilised by autoclaving, filtration, through bacteria proof filters and addition of bactericide at low temperature.
6. Surface activity : Vehicles used in ophthalmic preparation must have good wetting ability to penetrate cornea and other tissues. Certain surfactants or wetting agents are added which are found suitable for ophthalmic products. It should not cause any damage to tissues of eye. Benzalkonium chloride, polysorbate 20, polysorbate 80, dioctyl sodium sulpho-succinate, etc., are some of surfactants, which are commonly used.
5.(a) Write the requirements of Ideal suppository base.
Ans.
An ideal suppository base should have the following properties :
1. It should melt at body temperature of dissolve or disperse in body fluids.
2. It should keep its shape when being hendled.
3. It should release the medicament readily.
4. It should be non-toxic and non-irritant to the
mucous membrane.
5. It should be stable on storage.
6. It should be compatible with large number of durgs.
7. It should be stable if heated above its melting point.
8. It should be easily moulded and it should not
adhere to the mould.
9. It should be good in appearance.
10. It should be easily mouldable by pouring or cold compression.
(b) Write Advantage & Disadvantages of coca butter as suppository base.
Ans.
Advantages :
Theobroma oil melts at body temperature and release the medicament for rapid absorption.
It is considered a most suitable base for rectal suppositories but not suitable for pessaries, nasal and urethral bougies because after melting it has a tendency to leak out of the cavities and also it is immiscible with mucous secretions.
It is readily liquefy on warning and quickly settle on cooling
Disadvantages :
Cocoa butter has most of the qualities of an ideal suppository base but still, it has a number of serious disadvantages which are as follow:
(a) It shows the phenomena of polymorphism i.e., when theobroma oil is melted and cooled, it gets solidified into different crystaline forms depending upon melting temperature, rate of cooling and size of the mass.
(b) It bocomes rancid and melts in warm weather.
(c) It has a tendency to stick to the sides of the mould when solidified.
(d) The leakage from body cavities on melting can take place.
(e) It is relatively costly.
(f) It is immiscible with body fluids.
(g) Certain drugs such as chloral hydrate, lactic acid etc. When incorporated with cocoa butter,
liquefaction take place. To maintain the desired consistency, the beeswax can be added.
(c) Write classification of ointment bases with its examples, advantages & disadvantages.
Ans.
The ointment base is that substance or part
of an ointment, which serves as carrier or vehicle for the medicament. An ideal ointment base should possess the following properties:
(i) It should be inert, odourless and smooth.
(ii) It should be physically and chemically stable.
6. What are parenteral Preparations ? Describe various steps involved in processing of parenteral preparations. Write a note on Isotonic solution.
Ans.
i. Parenteral preparations are those pharmaceutical products that are given by other than oral routes, e. g. Transfusion fluids and injections.
ii. Injections are the sterile solutions or suspension of drugs in aqueous or oily vehicle meant for introduction into the body by means of an injectable needle under or through one or more layers of the skin or mucous membrane.
iii. Injections should be sterile, isotonic and free from foreign particles, such as dust, fibres etc.
iv. They should be introduced through the same route for which they are intended. For example, an oily suspension meant for intramuscular injection may be very dangerous if it is administered by intravenous injection.
Processing of Parenteral Preparation :
The following steps are involved in the processing of parenteral preparations:
(1) Cleaning of containers, closures and equipment
(ii) Collection of materials
(iii) Preparation of parenteral products
(iv) Filtration
(v) Filling the preparation in final containers
(vi) Sealing the containers.
(vii) Sterilisation
(viii) Evaluation of parenteral preparations
(ix) Labelling and packaging.
(i) Cleaning of containers, closures and equipment: All the containers, closures and equipment which are required during the preparation of parenteral products are thoroughly cleaned with detergents and washing is done with tap water, followed by clean distilled water and finally rinsed with water for injection. Rubber closures are washed with hot solution of 0.5% sodium pyrophosphate in water. The closures are then removed from the solution, washed with water followed by rinsing with filtered water for injection. On a small scale washing is done manually but on a large scale automatic washing machines are used.
(ii) Collection of materials: The various ingredients of the formulation of parenteral preparations are weighed and collected in the preparation room. The raw materials required in the preparation of parenteral products should be pure. Water for injection free from pyrogens and microorganisms are used in the preparation of parenteral products.
(iii) Preparation of parenteral products: The pharmacist should decide the order of mixing and exact method of preparation to be followed before preparing the parenteral products. The parenteral preparations must be prepared under strict aseptic conditions. The ingredients are accurately weighed separately and dissolved in the vehicle as per method of preparation to be followed.
(iv) Filtration: The parenteral solution so formed is passed through bacteria proof filter, such as, filter candle, seitz filter, membrane filter, and sintered glass filters. The primary objective of filtration is to clarify the solution by removing foreign particles. If the parenteral preparations are required to be sterilised by means of bacteria proof filters, filtration should be done under strict aseptic condition to avoid contamination of filtered solution, before it is finally transferred into final container and sealed.
(v) Filling the preparation in final containers: The filtered product is filled into final containers such as, ampoules, vials and transfusionbottles, which are previously cleaned and dried. Ampoules are used for filling single doses whereas, vials are used for filling multidoses. Bottles are meant for filling transfuson fluids. On small scale, filling is done manually by using hypodermic syringe and needle. On large scale, filling is done by automatic filling machine.
The sterile powders are filled into containers bby individual weighing or by using automatic or semi automatic devices. The filling operation is carried out under strict aseptic precautions.
During the filling of ampoules, the care should be taken that the solution should be filled below the neck of ampoules and the solution should not touch the neck of the ampoules. This will prevent the cracking and staining of the neck of ampoules at the time of sealing.
(vi) Sealing the containers: Sealing should be done immediately after filling. Ampules are sealed manually on a small scale by rotating the neck of the ampule in the flames of Bunsen burner. But on a large scale ampoule sealing machine is used in which tip of ampoule is fused to seal it. The vials and transfusion bottles sra sealed by closing its opening with a rubber closures. The rubber closures are held in place by crimping the aluminium caps which is done manually or by mechanical means.
(vii) Sterilisation: The parenteral preparations should be immediately sterilised after sealing in its final containers. The sterilisation is done by any one of the methods of sterilisation which depends on the nature of medicament(s) present in parenteral preparations.
For thermostable medicament, the parenteral products are sterilised either by autoclaving at a temperature of 115°C to 116°C for 30 minutes or 121°C for 20 minutes or in hot air oven at 160°C for two hours. The thermolabile preparations are sterilised by filtration through a suitable bacteria-proof filters. Parenteral preparations which are sterilised by filtration method may contain a suitable bacteriostatic agent to prevent the growth of microorganisms. When the solutions are used for intravenous or intrathecal injection in doses exceeding 15 ml, the becteriostatic agent should not be used. The sterilised product is filled into the final containers and The process of filtration, filling and sealing are done under aseptic conditions.
Isotonic Solutions:
Solutions having the same osmotic pressure are called iso-osmotic. It is not necessary that solutions which are iso-osmotic will also be isotonic. If a red blood cell is in contact with a solution that has the same osmatic pressure as that of blood plasma, the cell wall will neither swell nor shrink i.e. it will retain its tone and therefore the solution is said to be "isotonic".
A solution containing 0.9% of sodium chloride is, therefore, practically isotonic with blood plasma and is regarded as standard. A solution containing more than 0.9% sodium chloride is called 'hypertonic' and one containing less than that is called 'hypotonic'.
7. Explain the term dose. Discuss various factors which affect the dose of a drug. Write the formula of young's rule.
Ans.
i. Dose is the quantity of drugs which can be administered to a patient to get the desired pharmacological actions.
ii. The dose of a drug cannot be fixed rigidly because there are so many factors which influence the doses.
iii. These factors are age, condition of the patient, severity of the disease, tolerances both natural and acquired, idiosyncrasy, route of administration, formulation used, drug interactions and rate of elimination. Posology is the study of dose.
Factors Influencing Dose:
The following are some of the factors which influence the dose :
(i) Age: The pharmacokinetics of many drugs changes with age. Children and old people need lesser amount of drug than the normal adult dose, because they are unable to excrete drugs to that extent as adults. Children can tolerate relatively larger amounts of belladona, digitalis and ethanol, whereas, elderly patients are more sensitive to some drug effects e.g. hypnotics and tranquillizers which may produce confusion states in them.
(ii) Sex: Women do not always respond to the action of drugs in the same manner as it is done in men. and barbiturates may produce more excitement before sedation in women. Special care should be taken when drugs are administered during menstruation, pregnancy and lactation. The strong purgatives such as aloes should be avoided during menstruation. Similarly the drugs which may stimulate the uterine smooth muscle e.g. drastic purgatives, antimalarial drugs and ergot alkaloids are contra indicated during pregnancy. There are certain drugs which on administration to the mother are capable of crossing the placenta and affecting the foetus e.g.alcohol, barbiturates, narcotic and non narcotic analgesics etc. During lactation, the drugs like antihistamines morphine and tetracycline which are excreted in milk should be avoided or given very cautiously to the mothers who are breast feeding the babies.
(iii) Body weight: The average dose is mentioned either in terms of mg per kg body weight or as a total single dose for an adult weighing between 50-100 Kg. However, the dose expressed in this fashion may not apply in cases of obese patients, children and malnourished patients. It should be calculated according to body weight.
(iv) Route of administration: Intravenous dose of drugs are usually smaller than the oral doses, because the drugs administered intravenously enter the blood steam directly. Due to this reason the onset of drug action is quick with intravenous route and this might enhance the chances of drug toxicity. The effectiveness of drug formulation is generally controlled by the route of administration.
(v) Time of administration: The presence of food in the stomach delays the absorption of drugs. The drugs are more rapidly absorbed from the empty stomach. The irritating drugs are better tolerated if administered after meals e.g. iron, arsenic and cod-liver oil should always be given after meals. (vi) Environmental factors Hypnotics are more effective at night. The amount of barbiturate required to produce sleep during day time is much higher than the dose required to produce sleep at night. Alcohol is better tolerated in cold environments than in summer.
(vii) Emotional factors: The personality and behaviour of a physician may influence the effect of drug or especially the drugs which are intended for use in a psychosomatic disorder. Inert dosage forms called placebos which resemble the actual medicament in the physical properties are known. to produce therapeutic benefit in diseases like angina pectoris and bronchial asthma.
(viii) Presence of disease: Drugs like barbiturates and chlorpromazine may produce unusually prolonged effect in patients having liver cirrhosis. Streptomycin is excreted mainly by the kidney may prove toxic if the kidney of the patient is not working properly.
(ix) Accumulation: The drugs which are slowly excreted may built up a sufficient high concentration in the body and produce toxic symptoms if it is repeatedly administered for a long time e.g. digitalis, emetine and heavy metals. This occurs due to accumulative effect of the drug. The cumulative effects are usually produced by slow excretion, degradation and rapid absorption of drugs.
(x) Additive effect: When the total pharmacological action of two or more drugs administered together is equivalent to sum of their individual pharmacological action, the phenomena is called as an additive effect. For example, combination of ephedrine and aminophylline in the treatment of bronchial asthma.
(xi) Synergism: When two or more drugs are used in the combination form, their action is increased. The phenomena is called synergism. Ex: Co trimoxazde
(xii) Antagonism: When the action of one drug is oppsed by the other drug on the same physiological system is known as drug antagonism. The use of antagonistic responses to drugs is valuable in the treatment of poisoning e.g. milk of magnesia is given in acid poisoning where alkaline effect of milk of magnesia neutralise the effect of acid poisoning. When adrenaline and acetylcholine are given together, they neutralise the effect of each other due to antagonism because adrenaline is vasoconstrictor and acetylcholine is vasodilator.
(xiii) Idiosyncrasy: An extraordinary response to a drug which is different from its characteristic phramacological action is called idiosyncrasy. The word idiosyncrasy has now been replaced by the term drug allergy. For example, small quantity of aspirin may cause gastric haemorrhage and a small dose of quinine may produce ringing in the ears.
(xiv) Tolerance: When an unusually large dose of a drug is required to elicit an effect ordinarily produced by the normal therapeutic dose of the drug, the phenomenon is termed as drug tolerance, e.g., smokers can tolerate nicotine, alcoholic can tolerate large quantity of alcohol. The drug tolerance is of two types.
(a) True tolerance, which is produced by oral and parenteral administration of the drug.
(b) Pseudo tolerance, which is produced only to the oral route of administration.
(xv) Tachyphylaxis: When certain drugs are administered: eatedly at short intervals, the cell receptors get blocked up and pharmacological response to that particular drug is decreased. The decreased response cannot be reversed by increasing the dose. The phenomenon is known as tachyphylaxis or acute tolerance. For example, ephedrine when given in repeated doses at short intervals in the treatment of bronchial asthma may produce very less response due to tachyphylaxis.
(xvi) Metabolic disturbances : Changes in water electrolyte balance and acid base balance, body temperature and other physiological factor may modify the effects of drugs. Salicylates reduce body temperature only in case an individual has rise in body temperature. They have no antipyretic effect if the body temperature is normal.
Young's Formula :
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