Aspects Of Pharmacotherapy Question And Answers

Aspects Of Pharmacotherapy

 

Question 1. Write A Short Note On Tolerance
Answer:

Tolerance

Tolerance: Tolerance means a requirement for higher doses of a drug to produce a given response.

Drug Tolerance May Be:

• Natural: The species or individual are inherently less sensitive to the drug, for example, black races are tolerant to mydriatics.
• Acquired: Acquired tolerance develops due to repeated use of a drug, for example, tolerance develops to the sedative action of chlorpromazine.
  Tolerance develops to the analgesic and euphoric action of morphine.

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Mechanism Of Tolerance

• Change in receptors: It is the conformational change in the receptor.
• Loss of receptors: It is due to a gradual decrease in the number of receptors expressed over the cell surface due to their endocytosis or internalization.
• Exhaustion of mediators: It is the depletion of an essential intermediate substance.
• Altered drug metabolism: Increased metabolic degradation or decreased drug metabolism.
• Physiological adaptation: Nullification by the homeostatic response of the body, for Example. antihypertensive action thiazides are lowered because of activation of the renin-angiotensin system.
• Active extrusion of drug from cells: It is seen with anticancer drugs.

Tolerance Can Be Of the Following Subtypes

• Pharmacological tolerance: It is due to pharmacokinetic, i.e. increased elimination, or pharmacodynamic mechanisms, i.e. reduced responsiveness of target tissues.
• Behavioral tolerance: It is the adjustment of an individual to compensate for the presence of drugs. Frequent alcohol drinkers may function better under its influence than first-time drinkers.
• Reverse tolerance: Increased sensitivity leads to the user experiencing the effects with less amount of the same drug.
• Cross tolerance: Tolerance to a drug often leads to tolerance to chemically similar drugs, for Example. alcoholics are relatively tolerant to barbiturates and general anesthetics.

Question 2. Describe The Factors Modifying The Drug Response Giving Suitable Examples.
Or
Describe Various Factors Modifying Drug Action.
Answer:

Factors Modifying Drug Action

Variation in the response to the same dose of the drug, in different patients, and even in the same patient on different occasions is a rule rather than expansion.

The various factors that can be modifying drug effect are:

• Body size: The larger the size more can be the dose required to produce the same effect.
• Age: Infants, children, and elders are more sensitive to drug effects because it depends on the process of metabolism and excretion of the drug and they do have not well-developed systems. While in later they deteriorate with the advancing age.
• Sex: Females have smaller body sizes and require doses of the lower side of the range.
  • Androgens are unacceptable to women and estrogen to men.
  • Gynecomastia is a side effect that occurs only in men not in women.
• Genetic variation: It leads to a change in the rate of drug metabolization which increases or decreases the quantity of metabolizing enzyme.
• Routes of administration: They govern the speed and intensity of drug response, for example, magnesium sulfate given orally acts as a laxative. Applied locally act as an anti-inflammatory and when given IV it produces CNS depression.
• Environmental factors and time of administration: Several environmental factors affect the drug response. Exposure to insecticides, carcinogens, and tobacco smoke induces drug metabolism. Hypnotics taken at night and in quiet, familiar surroundings may work more easily.
• Psychological factors: The efficacy of a drug can be affected by the patient’s beliefs, attitudes, and expectations.
  This is particularly applied to centrally acting drugs, for example, a nervous and anxious patient requires a more general anesthetic.
• Pathological state: Diseases affecting GIT, liver, kidney, and heart can affect the absorption, metabolism, distribution, and excretion of drugs.
• Other drugs: When two drugs are given simultaneously they may modify response to each other by synergism or antagonism.
• Tolerance: When some drugs are given repeatedly, to produce the same response, a higher dose of the drug is required, for Example. morphine and diazepam.

Question 3. Define A Dose Of A Drug. Describe Any Six Factors Modifying The Action Of A Drug.
Answer:

Dose Of A Drug

• The dose of a drug is the quantity needed to be administered to produce adequate concentration in blood so that desired response can be obtained in a given patient.
• It is qualified and quantified in terms of response to be achieved and expressed as a range. Example. analgesic dose of aspirin is 0.3 to 0.6 gm while its dose for producing anti-inflammatory effect in rheumatoid arthritis is 3 to 6 gm.

Factors Modifying Drug Action

Variation in the response to the same dose of the drug, in different patients, and even in the same patient on different occasions is a rule rather than expansion.

The various factors that can be modifying drug effect are:

• Body size: The larger the size more can be the dose required to produce the same effect.
• Age: Infants, children, and elders are more sensitive to drug effects because it depends on the process of metabolism and excretion of the drug and they do have not well-developed systems.
  While in later they deteriorate with the advancing age.
• Sex: Females have smaller body sizes and require doses of the lower side of the range.
  • Androgens are unacceptable to women and estrogen to men.
  • Gynecomastia is a side effect that occurs only in men not in women.
• Genetic variation: It leads to a change in the rate of drug metabolization which increases or decreases the quantity of metabolizing enzyme.
• Routes of administration: They govern the speed and intensity of drug response, for example, magnesium sulfate given orally acts as a laxative.
  Applied locally act as an anti-inflammatory and when given IV it produces CNS depression.
• Environmental factors and time of administration: Several environmental factors affect the drug response. Exposure to insecticides, carcinogens, and tobacco smoke induces drug metabolism.
  Hypnotics taken at night and in quiet, familiar surroundings may work more easily.

Question 4. Write A Short Note On The Advantages And Disadvantages Of Fied Dose Ratio Combination Preparation.
Answer:

Fixed Dose Ratio Combination Preparation

Following are the advantages and disadvantages offered dose ratio combination preparation:

Fixed Dose Ratio Combination Preparation Of Advantages

• Convenience and better patient compliance when all the components present in a formulation are actually needed by the patient. It may also be cost-saving compared to both all the components administered separately.
• Certain drug combinations are synergistic, for Example. sulfamethoxazole + trimethoprim, combination oral contraceptives.
• The therapeutic effect of two components being the same may add up while the side effects being different may not.
  For Example. amlodipine + atenolol as antihypertensive.
• The side effect of one component may be counteracted by the other, for Example. a thiazide + a potassium sparing diuretic. However, the amount of the latter may not be sufficient in all cases.
• The combined formulation ensures that a single drug will not be administered.
  This is important in the treatment of tuberculosis and HIV-AIDS.
• Cost is reduced.

Fixed Dose Ratio Combination Preparation Of Disadvantages

• The patient may not actually need all the drugs present in a combination. He is subjected to additional side effects and expenses.
• The dose of most drugs needs to be adjusted and individualized. When a combined formulation is used, this cannot be done without altering the dose of the other components.
• The time course of action of the components may be different: administering them at the same intervals may be inappropriate.
• The altered renal or hepatic function of the patient may differently affect the pharmacokinetics of the components.
• An adverse effect, when it occurs, cannot be easily ascribed to the particular drug causing it.
• Contraindication to one component contraindicates the whole preparation.
• Confusion of therapeutic aims and a false sense of superiority of two drugs over one is fostered, especially in the case of antimicrobials whose combinations should be avoided.
• Corticosteroids should never be combined with any other drug meant for internal use.

Question 5. Enumerate Factors Modifying Drug Response. Describe Drug Tolerance With Suitable Examples.
Answer:

Enumeration Of Factors Modifying Drug Response

• Body size
• Age
• Sex
• Genetic variation
• Routes of administration
• Environmental factors and time of administration
• Psychological factors
• Pathological state
• Other drugs
• Tolerance.

Drug Tolerance May Be

• Natural: The species or individual are inherently less sensitive to the drug, for example, black races are tolerant to mydriatics.
• Acquired: Acquired tolerance develops due to repeated use of a drug, for example, tolerance develops to the sedative action of chlorpromazine.
  Tolerance develops to the analgesic and euphoric action of morphine.

Question 6. Write A Short Note On Tachyphylaxis.
Answer:

Tachyphylaxis

Tachyphylaxis is also known as acute tolerance. Tachyphylaxis is the rapid development of tolerance after repeated administration of the drug at shorter intervals.

• This is usually seen with indirectly acting drugs, for Example. ephedrine, tyramine, and nicotine.
• These drugs act by releasing catecholamines in the body, i.e. by gradual loss of noradrenaline, and synthesis from adrenergic nerve endings.
  So repeated administration of the drug leads to the gradual depletion of neurotransmitters and there is a reduction in the response.
• Other mechanisms like slow dissociation of the drug from its receptor thereby blocking the receptor, internalization of the receptor, homeostatic adaptation, etc. may also be involved.

Question 7. Write A Short Note On Rational Fixed Dose Drug Combinations (FDCs).
Answer:

Rational Fixed Dose Drug Combinations

Fixed dose combination refers to the combination of two or more therapeutic drugs in the fixed-dose ratio in a single formulation.

Criteria For Choosing Fixed-Dose Drug Combinations

• FDCs must be based on convincing therapeutic rationalization and be carefully justified and clinically relevant.
• They are safe and effective for claimed indications and it cannot be assumed that the benefits of FDC outweigh its risks.
• As for new medicine, the risks and benefits must be defined and compared. Attention should be drawn to the doses of each active substance in FDC.

Examples Of FDCs

• A combination of levodopa and carbidopa is used in Parkinsonism
• Combination of amoxicillin and clavulanic acid as antimicrobial
• Combination of isoniazid and rifampicin and pyrazinamide in tuberculosis
• Combination of estrogen and progesterone as oral contraceptives.

Rational Fixed Dose Drug Combinations  Advantages

• Convenience and better patient compliance when all the components present in a formulation are actually needed by the patient. It may also be cost-saving compared to both all the components administered separately.
• Certain drug combinations are synergistic, for Example. sulfamethoxazole + trimethoprim, combination oral contraceptives.
• The therapeutic effect of two components being the same may add up while the side effects being different may not.
  For Example. amlodipine + atenolol as antihypertensive.
• The side effect of one component may be counteracted by the other, for Example. a thiazide + a potassium sparing diuretic.
  However, the amount of the latter may not be sufficient in all cases.
• The combined formulation ensures that a single drug will not be administered.
  This is important in the treatment of tuberculosis and HIV-AIDS.
• Cost is reduced.

Rational Fixed Dose Drug Combination Disadvantages

• The patient may not actually need all the drugs present in a combination. He is subjected to additional side effects and expenses.
• The dose of most drugs needs to be adjusted and individualized. When a combined formulation is used, this cannot be done without altering the dose of the other components.
• The time course of action of the components may be different: administering them at the same intervals may be inappropriate.
• The altered renal or hepatic function of the patient may differently affect the pharmacokinetics of the components.
• An adverse effect, when it occurs, cannot be easily ascribed to the particular drug causing it.
• Contraindication to one component contraindicates the whole preparation.
• Confusion of therapeutic aims and a false sense of superiority of two drugs over one is fostered, especially in the case of antimicrobials whose combinations should be avoided.
• Corticosteroids should never be combined with any other drug meant for internal use.