Pharmacokinetics – Absorption and Distribution

Question 1

What is pharmacodynamics?

Answer 1

Pharmacodynamics refers to ‘what the drug does to the body.’

Question 2

What is pharmacokinetics?

Answer 2

Pharmacokinetics refers to ‘what the body does to the drug’ and involves the study of the time course of drug absorption, distribution, metabolism, and excretion.

Question 3

What are the minimum requirements for clinical efficacy in pharmacokinetics?

Answer 3

The minimum requirements for clinical efficacy include overcoming physiological barriers for absorption and achieving the target with an appropriate concentration for distribution.

Question 4

What are the limitations of pharmacokinetics?

Answer 4

The limitations of pharmacokinetics include drug inactivation through metabolism and elimination through renal, hepatic, or faecal pathways.

Question 5

Why is overcoming absorption, distribution, metabolism, and excretion (ADME) a challenge?

Answer 5

Overcoming ADME is a challenge because if a drug isn’t readily absorbed, its concentration may not reach a therapeutic level. If a drug is distributed to compartments where it’s not needed, it may have limited effects. Poor metabolism can lead to excessive drug levels, while slow excretion can result in dangerous drug accumulation.

Question 6

What is the most common route of drug administration?

Answer 6

The most common route of drug administration is oral (p.o.), which means taking the drug by mouth.

Question 7

What are the advantages of oral administration?

Answer 7

Oral administration is convenient, acceptable, and does not require special skills. Additionally, there is a variety of pharmaceutical solutions available for different patients

Question 8

Name three types of injection routes.

Answer 8

The three types of injection routes are:

Intravenous (IV): directly into a vein
Intramuscular (IM): into a muscle
Subcutaneous (SC): into the tissue layer beneath the skin

Question 9

Which route of administration is commonly used for drugs targeting asthma, such as salbutamol?

Answer 9

Inhalation is the route of administration commonly used for drugs targeting asthma, including salbutamol.

Question 10

What are two other routes of drug administration?

Answer 10

Two other routes of drug administration are:

Sublingual or buccal: placing the drug under the tongue or against the cheek
Rectal: using suppositories inserted into the rectum

Question 11

Besides oral, injection, inhalation, sublingual/buccal, and rectal routes, name three other routes of drug administration.

Answer 11

Besides the mentioned routes, drugs can be administered through other epithelial surfaces such as the skin (topical), cornea (eye drops), vagina (vaginal suppositories), and nasal mucosa (nasal sprays).

Question 12

What is absorption in pharmacology?

Answer 12

Absorption refers to the process of transferring a drug from the site of administration into the general/systemic circulation. It determines the access of the drug to the systemic circulation.

Question 13

What are some factors that influence drug absorption?

Answer 13

Factors influencing drug absorption include pharmaceutical properties (e.g., pharmaceutical form), physicochemical properties (e.g., solubility, pH of the drug, molecular weight), physiological properties (e.g., surface area, contact time, concentration of the drug at the absorption site, absorption site characteristics such as blood flow and pH), interactions (drug-drug, drug-food), and transport systems (e.g., glycoprotein P, specific amino acids and transporters).

Question 14

Define bioavailability.

Answer 14

Bioavailability refers to the fraction or percentage of an administered drug that reaches the systemic circulation in an unchanged form. It reflects the extent and rate at which the drug is absorbed and is available to produce a therapeutic effect.

Question 15

What is distribution in pharmacology?

Answer 15

Distribution refers to the process of a drug moving from the bloodstream to the various tissues and compartments of the body. It determines the spatial and temporal distribution of the drug throughout the body.

Question 16

What is volume of distribution (Vd)?

Answer 16

Volume of distribution is a pharmacokinetic parameter that quantifies the apparent space in the body available to contain a drug. It represents the relationship between the administered dose of the drug and the resulting concentration in the body. It is used to calculate drug doses and predict drug concentrations in different body compartments.

Question 17

What are some factors that influence drug absorption in the oral route?

Answer 17

: Factors influencing drug absorption in the oral route include drug stability in the digestive tract (pH, enzymes), the presence of food or other drugs (interactions), alterations in gastric emptying and intestinal motility, physicochemical properties suitable for crossing membranes, and resistance to drug metabolism (particularly first-pass metabolism).

Question 18

What is the clinical relevance of drug interactions in the oral route?

Answer 18

: Drug interactions in the oral route can be influenced by pH changes (e.g., antacids), the presence or absence of food, and the formation of complexes or chelation. Additionally, gastrointestinal (GI) emptying and motility can affect the absorption of drugs.

Question 19

Define bioavailability.

Answer 19

Bioavailability refers to the fraction of an orally administered drug that reaches the systemic circulation of the patient as an intact drug. It is calculated by comparing the area under the curve (AUC) of the drug after oral administration to the AUC after intravenous (IV) administration. Bioavailability considers both absorption and metabolic degradation by enzymes in the gut wall and liver.

Question 20

How is bioavailability expressed?

Answer 20

Bioavailability is expressed as the oral AUC divided by the IV AUC. For example, if a drug has an oral bioavailability of 20%, the oral dose needed for therapeutic effectiveness would need to be five times higher than the corresponding IV dose.

Question 21

What does the AUC represent?

Answer 21

The AUC, or area under the curve, determines the total amount of drug in systemic circulation. It is a measure of the drug’s exposure over time.

Question 22

What is first-pass metabolism?

Answer 22

First-pass metabolism refers to the metabolism of a drug that occurs after it is swallowed and absorbed from the gastrointestinal tract. The drug travels through the digestive system, enters the hepatic portal system, and undergoes metabolism by liver enzymes before reaching the rest of the body.

Question 23

Define distribution.

Answer 23

Distribution is the process by which a compound, such as a drug, is transferred from the general circulation (bloodstream) to other parts of the body and into the tissues.

Question 24

What are some factors that affect absorption?

Answer 24

Factors that affect absorption include the physicochemical properties of the drug (solubility, pH), presence of food or other drugs, alteration in gastric emptying and intestinal motility, and resistance to drug metabolism (first-pass metabolism).

Question 25

What are some factors that affect distribution?

Answer 25

Factors that affect distribution include blood flow to different tissues, the ability of the drug to cross cell membranes, binding to plasma proteins, tissue-specific characteristics (e.g., pH, lipid content), and the presence of drug transporters.

Question 26

What is the role of the liver in first-pass metabolism?

Answer 26

The liver plays a crucial role in first-pass metabolism by metabolizing drugs that are absorbed from the gastrointestinal tract before they reach systemic circulation. This metabolism can alter the concentration and effectiveness of the drug in the body.

Question 27

What is an example of a compartment with small, water-soluble molecules?

Answer 27

cytoplasm

Question 28

Name a compartment that houses larger, water-soluble molecules.

Answer 28

Extracellular water is a compartment that contains larger, water-soluble molecules. An example of such a molecule is mannitol.

Question 29

Which compartment is known for containing highly plasma protein-bound molecules, very large molecules, and highly charged molecules?

Answer 29

Blood plasma is the compartment that houses highly plasma protein-bound molecules, very large molecules, and highly charged molecules. An example of such a molecule is heparin.

Question 30

Identify a compartment that is associated with highly lipid-soluble molecules.

Answer 30

Adipose tissue is a compartment that contains highly lipid-soluble molecules. An example of such a molecule is diazepam.

Question 31

In which compartments can certain ions, such as fluoride, be found?

Answer 31

Certain ions, like fluoride, can be found in compartments such as bone and teeth.

Question 32

What are the advantages of enteral route administration, such as paracetamol?

Answer 32

The enteral route (e.g., oral administration of paracetamol) offers advantages such as simplicity, affordability, convenience, painlessness, and a low risk of infection.

Question 33

What are the disadvantages of enteral route administration?

Answer 33

Disadvantages of the enteral route include exposure to harsh gastrointestinal (GI) environments, the first-pass effect (metabolism by the liver before reaching systemic circulation), dependency on GI absorption, and slower delivery to the site of action.

Question 34

: What are the advantages of parenteral route administration (intravenous, intramuscular, subcutaneous), like morphine?

Answer 34

The parenteral route (e.g., intravenous, intramuscular, subcutaneous administration of morphine) offers advantages such as rapid delivery to the site of action, high bioavailability, bypassing the first-pass effect and the harsh GI environment.

Question 35

What are the disadvantages of parenteral route administration?

Answer 35

Disadvantages of the parenteral route include the difficulty of reversing the drug’s effects, risk of infection, pain, fear associated with injections, and the requirement of trained personnel for administration.

Question 36

What are the advantages of mucous membrane route administration (e.g., inhalers, suppositories, sublingual), like salbutamol or GTN?

Answer 36

The mucous membrane route (e.g., inhalers, suppositories, sublingual administration of drugs like salbutamol or GTN) provides advantages such as rapid delivery to the site of action, direct delivery, bypassing the first-pass effect and the harsh GI environment. It is often painless, convenient, and carries a low risk of infection.

Question 37

What are the disadvantages of mucous membrane route administration?

Answer 37

Disadvantages of the mucous membrane route include a limited number of drugs available via this route, the requirement of dexterity for inhaler use, and potential irritation caused by certain drugs.

Question 38

What are the advantages of transdermal route administration (e.g., hormone-replacement therapy)?

Answer 38

The transdermal route (e.g., hormone-replacement therapy patches) offers advantages such as simplicity, convenience, painlessness, suitability for long-term use, and bypassing the first-pass effect and the harsh GI environment.

Question 39

What are the disadvantages of transdermal route administration?

Answer 39

Disadvantages of the transdermal route include the requirement of a highly lipophilic drug for effective delivery, slower delivery to the site of action, and the potential for skin irritation.

Question 40

How does distribution of drugs occur in the body?

Answer 40

Most drugs transfer by passive diffusion across capillary walls down a concentration gradient into the interstitial fluid until the concentration of free drug molecules in the interstitium is equal to that in the plasma.

Question 41

Define volume of distribution.

Answer 41

Volume of distribution (Vd) is a measure of how widely a drug is distributed between various body fluids and tissues. It is calculated as the amount of drug in the body (dose) divided by the measured plasma concentration (cp) of the drug.

Question 42

What is the role of drug protein binding in distribution?

Answer 42

Drug protein binding, especially to albumin, can influence drug distribution. Bound drugs are not readily available for distribution to tissues, while unbound (free) drugs can distribute more easily.

Question 43

What are some factors that influence distribution?

Answer 43

Factors influencing drug distribution include drug physicochemical properties, lipid solubility, volume of distribution, drug protein binding, drug particle size, and factors related to blood flow and pH.

Question 44

How does lipid solubility and volume of distribution relate to drug distribution?

Answer 44

Drugs with higher lipid solubility have a higher tendency to distribute widely to various tissues and organs, resulting in a higher volume of distribution (Vd). Water-soluble drugs, on the other hand, are mainly confined to the blood and body water compartments, leading to a lower Vd.

Question 45

What role does blood flow and pH play in drug distribution?

Answer 45

Blood flow to tissues affects drug distribution, as greater blood flow can facilitate the delivery of drugs to various organs. Additionally, pH differences in different tissues can influence the distribution of ionized drugs.

Question 46

Describe the process of plasma protein binding.

Answer 46

Plasma protein binding involves the reversible and saturable binding of drugs to proteins, particularly albumin. The bound and unbound forms of the drug exist in equilibrium.

Question 47

Which fraction of the drug is responsible for the clinical effect?

Answer 47

The unbound or free fraction of the drug is responsible for the clinical effect, as it is available to interact with its target.

Question 48

Why is plasma protein binding important?

Answer 48

Most drugs exist mainly in their bound form, and small differences in protein binding can have significant effects on the concentration of free drug and its clinical effect.

Question 49

What is the most important protein involved in drug binding?

Answer 49

Albumin is the most important protein involved in drug binding. It binds to many different drugs, and competition for binding sites can occur.

Question 50

Name some drugs that are highly protein bound.

Answer 50

Examples of highly protein-bound drugs include warfarin, aspirin, ibuprofen, heparin, and furosemide.

Question 51

When is plasma protein binding clinically relevant?

Answer 51

Plasma protein binding becomes clinically relevant when three criteria are met: high protein binding (>90%), a change in binding, and a low volume of distribution (Vd).

Question 52

What factors can increase the fraction of unbound drug?

Answer 52

Factors that can increase the fraction of unbound drug include saturability of binding sites, displacement from protein binding by other substances, late pregnancy, renal impairment, and low plasma albumin levels.