Pharmacokinetic and Pharmacodynamic Interactions

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Questions and Answers

Which mechanism of tolerance involves a genetic disorder resulting in rapid drug metabolism?

Tachyphylaxis

Cross tolerance

Congenital tolerance (correct)

Acquired tolerance

What type of drug interaction occurs during the preparation or mixing of drugs resulting in physicochemical incompatibilities?

In vivo interactions

Pharmacodynamic interactions

Metabolic interactions

In vitro interactions (correct)

What is the main strategy to prevent antimicrobial resistance when prescribing antibiotics?

Use antibiotics only when necessary (correct)

Switch antibiotics every week

Administer lower doses than prescribed

Use antibiotics as growth promoters

What is tachyphylaxis?

Rapid decrease in drug response after repetitive short-term use Signup and view all the answers

Which of the following is NOT a recommended strategy to prevent tolerance?

Gradually increase the drug dosage Signup and view all the answers

Which term describes the phenomenon where microorganisms can resist the effects of antibiotics they've been exposed to previously?

Antimicrobial resistance Signup and view all the answers

What type of drug interaction occurs inside the body that alters the overall response to the drugs?

In vivo interaction Signup and view all the answers

What effect does probenecid have on the renal excretion of penicillin?

It decreases the renal excretion of penicillin. Signup and view all the answers

What is the best approach to manage and prevent drug cumulation effects?

Monitor drug levels regularly Signup and view all the answers

When two drugs have a combined effect that is greater than the sum of their individual effects, this is referred to as:

Synergism Signup and view all the answers

What is one potential cause of drug cumulation in the body?

Slow metabolism Signup and view all the answers

Which of the following is an example of pharmacological antagonism?

Succinylcholine and acetylcholine Signup and view all the answers

Which mechanism characterizes the effect of barbiturates on other drugs?

Increased metabolism Signup and view all the answers

The prolonged effect of a drug due to its binding to tissue or plasma proteins is known as:

Drug accumulation Signup and view all the answers

Which of the following represents a potentiation effect?

Probenecid and penicillin Signup and view all the answers

In cases of antagonism, what effect does adrenaline have in combination with histamine?

Inhibits bronchoconstriction Signup and view all the answers

Which factor does NOT affect drug dosage?

Environmental conditions. Signup and view all the answers

What is the definition of the therapeutic dose of a drug?

The safe amount of a drug that induces the desired effect. Signup and view all the answers

What does a higher therapeutic index indicate?

Wider safety margin for drug usage. Signup and view all the answers

What is meant by 'potency' in the context of a drug?

The amount of drug required to induce a given response. Signup and view all the answers

What is the minimal effective dose?

The smallest amount that initiates a response. Signup and view all the answers

Which of the following receptors would likely interact with an antagonist?

Receptors with a higher affinity for agonists. Signup and view all the answers

What describes the maximal effective dose of a drug?

The largest quantity that can be administered without toxicity. Signup and view all the answers

What is the purpose of dosage regimens?

To provide a structured plan for medication administration. Signup and view all the answers

Study Notes

Pharmacokinetic Interactions

Absorption:
- Calcium can interfere with tetracycline absorption by forming an insoluble chelate.
- Antacids can decrease the absorption of acidic drugs.
Distribution:
- Diuretics can reduce the distribution of aminoglycosides, leading to increased toxicity.
Biotransformation:
- Barbiturates can increase the metabolism of other drugs, shortening the duration of their action.
Excretion:
- Probenecid can decrease the renal excretion of penicillin, extending its duration of action.

Pharmacodynamic Interactions

Addition: The combined effect of two drugs with the same action is equal to the sum of their individual effects.
- Example: Paracetamol and caffeine as pain relievers.
Synergism: The combined effect of two drugs with the same action is greater than the sum of their individual effects.
- Example: Penicillin and streptomycin as antibiotics.
Potentiation: One drug enhances the effect of another drug with different properties.
- Example: Probenecid and penicillin, or streptomycin and succinylcholine.
Antagonism: One drug opposes the effect of another drug when administered together.
- Physiological: Examples include histamine (bronchoconstrictor) and adrenaline (bronchodilator).
- Chemical: Examples include protamine and heparin, which form an inactive product.
- Pharmacological:
  - Competitive: Example is tubocurarine and acetylcholine competing for cholinergic receptors.
  - Depolarizing: Example is succinylcholine and acetylcholine competing for cholinergic receptors.

Drug Cumulation

Drugs can accumulate in the body due to slow metabolism or excretion or binding to tissue or plasma proteins.
- Slow metabolism or excretion can occur when the rate of administration exceeds the rate of elimination.
- Binding to tissue or plasma proteins can result in a prolonged effect and increased toxicity.
The full therapeutic response can be achieved by a summation of doses, often involving an initial dose, a period of cessation, and resumption of the drug.

Route of Administration

The route of administration can alter a drug's action.
- For example, magnesium sulfate can be used orally as a purgative, locally to reduce swelling, or intravenously to induce CNS depression.
The intravenous dose is typically one-fourth the oral dose.
The intramuscular dose is typically one-third the oral dose.
The subcutaneous dose is typically one-half the oral dose.
The rectal dose is typically twice the oral dose.

Time of Administration

Stomachic drugs: Administered before meals.
Digestants: Administered during meals.
Irritant drugs: Administered after meals.
Hypnotics: Administered before sleep.

Pathological State

The pathological state of an individual can affect drug action and doses.
- Consider factors such as:
  - Inflamed intestine
  - Diseased liver or kidney
  - Immunocompetence (very young or very old)

Intolerance

Intolerance is an extraordinary response to a drug at therapeutic or sub-therapeutic doses, increasing the risk of toxicity.
- Genetic deficiency of metabolizing enzymes (poor metabolizer):
  - Example: Warfarin can lead to hemorrhage in individuals who are poor metabolizers.
  - Solution: Reduce the initial dose.
- Sudden stopping of some drugs (blockers) after prolonged administration:
  - This can lead to a "rebound action".
  - Example: Beta blockers can lead to severe tachycardia and arrhythmia if stopped abruptly.
  - Solution: Gradual withdrawal is recommended.

Tolerance

Tolerance is the unusual resistance to the therapeutic drug dose, requiring an increased dose to obtain the initial response.
- Congenital:
  - Occurs without prior drug exposure due to genetic disorders.
  - Example: Ruminants tolerate barbiturates, and rabbits tolerate atropine.
- Acquired:
  - Develops with repeated drug use.
  - Cross Tolerance: Occurs between two pharmacologically related drugs (e.g., barbiturates).
  - Tachyphylaxis (acute tolerance): Rapid decrease in drug response with repeated use at short intervals (e.g., ephedrine).
  - Antimicrobial resistance: Microorganisms can resist antibiotics after previous exposure (e.g., aminoglycosides).

Preventing Tolerance

To prevent tolerance:
- Use the lowest effective dose.
- Avoid prolonged drug use.
- Take breaks from the drug.
- Shift to a different medication (e.g., a corticosteroid instead of ephedrine).
To prevent antimicrobial resistance:
- Use antibiotics only when prescribed.
- Administer the full course.
- Limit the use of antibiotics as growth promoters.
- Follow withdrawal time instructions.

Drug Interaction

Drug interaction occurs when two or more drugs are administered together, resulting in an altered response.
- Outside the body (in vitro):
  - Can occur during drug preparation or mixing, leading to physicochemical incompatibilities.
  - Example: Oil and water are immiscible.
    - Gentamicin (basic drug) and penicillin (acidic drug) can neutralize each other.
- Inside the body (in vivo):
  - Can occur through various mechanisms, such as affecting drug absorption, distribution, metabolism, or excretion.

Dose and Dosage of Drugs

Therapeutic (Effective) dose: The safe amount of a drug that induces the desired effect.
Minimal effective dose: The smallest amount that initiates a response.
Maximal effective dose: The largest amount safely administered without causing toxicity.
Maintenance (Ongoing) dose: The regular amount required to keep the therapeutic blood level by replacing the eliminated amount.
Toxic dose: The sufficiently large amount to induce toxic symptoms.
Lethal dose: The sufficiently large amount to induce death.
Dosage (drug regimen): A set of instructions for how to take a medication, including dose, route, frequency, time, and duration.

Dose/Response Relationship (DRC)

The dose/response relationship is a plot of dose versus response.
Efficacy (Emax): The maximal possible effect induced by a drug regardless of the dose.
- More efficient drugs have a higher plateau on the dose/response curve.
Potency (ED50): The amount of drug required to induce a given response (usually 50% response).
- More potent drugs require lower doses to induce the given effect.

Therapeutic Index (Window)

The therapeutic index measures a drug's safety margin.
Therapeutic Index (TI) = LD50 / ED50
- ED50 (median effective dose): The dose that induces a therapeutic effect in 50% of the tested lab animals.
- LD50 (median lethal dose): The dose that kills 50% of the tested lab animals.
- A higher value indicates a wider safety margin.

Factors Affecting Drug Action and Doses

Age:
- Young and older animals often require reduced doses compared to adults.
Body Weight:
- Dosage is generally proportional to body weight. Heavier patients typically require higher doses.
Gender:
- Females may require altered doses due to smaller organ size, hormonal differences, and factors like pregnancy and lactation.
Species:
- Physiological and metabolic variations exist between species.
  - For example, emetics are not used in horses or cattle, and ivermectin can be toxic to cats and dogs.
Time of Administration:
- The optimal time for drug administration depends on the specific drug and its intended effect.
Pathological State:
- An individual's health status can influence drug action and required doses.
Route of Administration:
- The method of drug delivery influences how quickly and effectively the drug reaches its target.
Drug Interactions:
- The presence of other drugs can alter the effectiveness or safety of a given medication.
Individual Variability:
- Individual differences in metabolism, receptor sensitivity, and disease states can influence drug response.

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Description

This quiz explores pharmacokinetic and pharmacodynamic interactions between drugs. It addresses how various factors such as absorption, distribution, biotransformation, and excretion affect drug efficacy and toxicity. Test your understanding of synergism, addition, and potentiation in drug interactions.