Pharmokinetics & pharmodynamics

Question 1

Define pharmokinetics & pharmocogenomics

Answer 1

Pharmokinetics: what the body does to the drug, e.g., metabolizes, absorption, distribution & elimination
Pharmocogenomics: Pharmacogenomics analyzes how the genetic makeup of a patient affects their response to drugs. It deals with the influence of acquired and inherited genetic variation on drug response

Question 2

Define pharmacodynamics

Answer 2

Refers to what the drug does to the body e.g., drug interactions, side effects & dose-response relationship

Question 3

Define a drug

Answer 3

A known chemical substance that can change the normal functioning of the body. It produces biological effects and can be used for medicinal or recreational purposes

Question 4

Define Medicine

Answer 4

Prescribed for a therapeutic effect, may consist of 1 or more drugs

Question 5

Define therapeutics

Answer 5

The use of drugs to diagnose, prevent & treat illnesses (and/or pregnancy)

Question 6

Define formulations

Answer 6

How the drug is formulated/packaged from different substances, including the active drug that is involved in formulating the medication

Question 7

Define excipients

Answer 7

Substances that are made along side the making of the drug (by-products)

Question 8

Define a medicinal product

Answer 8

A substance or combination of substances that have properties of treating/preventing illness. it can be given to restore physiological function. It can exert a pharmacological, metabolic or immunological effect

Question 9

Describe the naming of drugs

Answer 9

Drugs have a chemical, generic & proprietary name
Chemical: this describes the chemical structure of the drug e.g., N-methyl-3-phenyl etc
Generic: the class of which the drug belongs to e.g., antidepressants (fluoxetine)
Proprietary: the name of the drug from the manufacturer

Question 10

Define a ligand

Answer 10

a molecule that binds to a receptor e.g., a hormone, these can act on different receptors (muscarinic/nicotinic). They can be natural or synthesized ligands
Ligand binding is often reversible as the ligand associates/ dissociates from the target

Question 11

Define a receptor, target agonist & antagonist

Answer 11

Receptor: a molecular target for the drug
Target: a molecule, normally a protein that is accessed via a drug to produce a therapeutic effect
Agonist: a molecule that activates a receptor
Antagonist: a molecule that blocks or reduces agonist responses

Question 12

Define affinity

Answer 12

Refers to how well a ligand binds to a receptor

High Affinity: will bind to receptor tighter & more readily, requires a lower concentration of the ligand to achieve an effect, this means the ligand stays bonded to a receptor to a greater duration.
Low Affinity: A ligand will not bind as tightly, requires a higher conc to produce same effect, these ligands tend to dissociate from their target more easily

Question 13

Describe how binding affinity is meaured

Answer 13

It is measured by the dissociation constant (Kₖ), this represents how easily the ligand dissociates from the target. A lower Kₖ indicates higher affinity (stronger binding), and a higher Kₖ indicates lower affinity (weaker binding).

Question 14

Describe what influences the binding of a drug to a receptor

Answer 14

Drugs are structurally specific as they bind to receptors via lock and key mechanism, drug & receptor must be complimentary to on another to initiate ligand binding

Drugs also have electrostatic charges that affect how it binds to a receptor, e.g., a negative drug needs to bind to positively charged receptor

Question 15

Describe the genetic variability of ligand binding

Answer 15

Genetic variability refers to differences in the DNA sequence which can influence a persons response to drugs
1. structure of target: Variation may cause the receptor to change its shape, making the drug more or less likely to bind to the receptor, makes more/less effective
2. Altered metabolism: Different people have different metabolisms and this can alter how quickly the drug is broken down & used by the body

Question 16

What are the effects of ligand variability in a healthcare setting?

Answer 16

1. Tailored treatment: By looking at a persons genetic makeup, doctors can predict their response to a certain drug, allowing the correct drug, dose & duration for a patient in order to minimize side effects
2. Minimizing side effects: enables adjustments to be made to maximize treatment of illness with reducing severity of side effects
3. Drug efficacy: HP’s can identify the most effective drug for the best outcome

Question 17

Describe the importance of the molecular structure of a drug

Answer 17

1. Affinity: A drug’s shape needs to fit with its target (lock & key), the better the fit the stronger the binding therefore the greater the efficacy of the drug
2. Receptor specificity: This structure determines where the drug will bind to, e.g., a drug designed to treat one condition (like pain) may have a structure that specifically binds to opioid receptors
3. Pharmacokinetics: the molecular structure of the drug affects how it is absorbed, metabolized etc, e.g., a drug with a small, lipophilic (fat-soluble) structure may pass through cell membranes more easily, allowing it to reach its target faster.

Question 18

Describe the importance of the molecular structure of the target

Answer 18

1. Type & location: Different drugs act on different cell types, the targets location can affect the drugs action
2. Activation/Inhibition: Some drugs acts as agonists/antagonists, so bio response is either promoted/blocked
3. Target variability: genetic variation within a target can influence the efficacy of the drug, . For example, variations in a receptor’s gene could make the receptor more or less sensitive to a drug.

Question 19

Describe the importance of the molecular target tissues

Answer 19

Cell type: Different cells/ tissues have different receptors or proteins, the effectiveness of the drug depends on the tissue’s ability to respond
Tissue permeability: some tissue are more selective about what molecules can pass through, this will determine if the drug passes through and at what concentrations
Tissue environment: The chemical environment of the tissue such as pH & blood flow can also affect how the drug behaves

Question 20

Describe the function of receptors

Answer 20

Receptors are the molecular site in which the drug binds to, when a drug binds its alters the receptor structure & triggers a 2nd messenger, creating a chain of reactions
Agonist: some drugs bind & cause activation to produce a biological response
Antagonist: other drugs block the activation of ligands & prevent a reaction e.g., blocks binding of a hormone

Question 21

Describe the function of ion channels

Answer 21

They are proteins found in the CM that control the passage of ions in/out of the cell, it establishes an electrochemical gradient
Ion channels are selective only allowing passage of specific substances.
Blockers: some drugs bind to a IC and block ion flow therefore altering cellular activity, e.g., controlling Heart arrhythmias
modulators: Other drugs bind to IC to allow ions to flow more freely

Question 22

Describe the function of carrier molecules

Answer 22

These are protein molecules that act as transporters to move molecules across cell membrane. Drugs can bind to these and influence the likelihood of a molecule entering or blocking the movement into the cell membrane.
This works via active transport & facilitated diffusion.
Inhibition: some drugs inhibit transporters, preventing a substance from entering a cell
Blocking or increasing: some drugs block specific molecules and some enable passage of specific molecules into cell membrane

Question 23

Describe the function of enzymes

Answer 23

Enzymes are functional proteins that catalyze biochemical reactions in the body, drugs can speed up or slow down enzymes

Inhibition: drugs may act as inhibitors by binding to an enzyme active site, preventing binding of substrate, blocking a reaction.
Example drugs:
Aspirin inhibits the COX enzymes to reduce pain and inflammation.

Activation: Some drugs can enhance enzyme activity in conditions where there may be a deficiency

Question 24

Define toxicity

Answer 24

Refers to drugs that produce abnormal metabolites that can lead to harmful side effects or organ toxicity, especially if metabolites accumulate or cause unwanted reactions

Question 25

Describe drug specificity

Answer 25

This refers to how selectively a drug binds to a relevant target and how it affects it, leading to desired therapeutic effects. There is a greater chance of non-specific effects with higher doses Non-specific drugs refers to drugs that interact with multiple targets or have secondary effects due to chemical properties e.g., side effects

Question 26

Describe how drugs that are specific with non-specific effects

Answer 26

Drugs that are highly specific in binding tend to have fewer non-specific effects as they interact only with the intended target and produce minimal interference with other tissues Less specific drugs are more likely to interact with multiple targets and cause a widespread effect, leading to a higher chance of non-specific effects which could lead to side effects or toxicity, these could be potentially harmful

Question 27

Describe first pass metabolism

Answer 27

This refers to the initial metabolic processing of a drug by the liver after it is absorbed from the GI, but before it reaches systemic circulation. It is important for dosing regiments and route of administration, drugs may be more effective if they bypass the liver e.g., intravenous, dosing regiments may be required for drugs that undergo 1st pass metabolism

Question 28

Explain the process of drug absorption

Answer 28

The process in which the drug enters the bloodstream, this can occur through different routes which can influence effectiveness of absorption common routes: oral, intravenous, intramuscular, subcutaneous, topical & inhalation

Question 29

Describe oral & topical absorption

Answer 29

Oral: drug is inserted into mouth, passes through digestive system, absorbed in stomach or SI, lower risk of infection, simple to give and fast to absrob Topical: cream with drug is applied to skin surface to be absorbed, low systemic effects, low infection risk, however risk of direct systemic absorption Drug must be lipid soluble, have a small molecular size and have a carrier molecule

Question 30

Describe IV, IM, SC, D & DI

Answer 30

IV: intravenous, drug injected into blood stream IM: intramuscular, drug injected into skeletal muscle SC: subcutaneous, drug injected & absorbed from subcutaneous tissue ID: Dermal, injected into dermal vascular layer DI: depot injection, given for slow-release drugs Injections allow rapid bioavailability, could pose a risk for infection, but avoids 1st pass metabolism

Question 31

Describe factors affecting absorption

Answer 31

Drug properties: size, solubility & chemical structure impact how well a drug can cross a cell membrane Blood flow: areas with greater blood flow often have higher absorption rates pH: acidity & alkalinity of stomach & intestines can affect how drug is absorbed

Question 32

Define bioavailability

Answer 32

The proportion of drug that reaches systemic circulation and is free to bind to target, this is affected by route of administration or if it has an enteric coating Bioavailability is not a measure of drug effectiveness

Question 33

Describe the distribution of drugs

Answer 33

This refers to the movement of the drug from the bloodstream into the organs/tissues, influenced by: Blood flow: organs with high blood flow e.g., heart will receive the drug earlier than areas with less blood flow Plasma protein binding: Many drugs bind to proteins in the blood e.g., albumin, Only unbound drugs are active, so the extent of protein binding of drugs can influence drug action Tissue permeability: Some tissues e.g., brain that has a blood-brain barrier, are more selective with what they allow to pass through Volume distribution: This is a parameter in which describes the extent to which the drug is distrubuted through the body, Drugs with a high Vd tend to accumulate in tissues, while those with a low Vd stay in the bloodstream.

Question 34

Describe the metabolism of drugs

Answer 34

This is a process where the body chemically alters the drug, e.g., to make it water soluble allowing it to be eliminated This process produces active metabolites which can influence a drugs therapeutic effects or side effects. Metabolism tends to inactive the drug, a person's metabolic rate can influence how quickly the drug is broken down and used by the body

Question 35

Define phase 1 in metabolism of drugs

Answer 35

Involves hydrolysis, oxidation & reduction reactions. It involves enzymes that add or expose functional groups to the drug making it more polar & reduce it's pharmacological activity. This produces toxic metabolites

Question 36

Define phase 2 in metabolism of drugs

Answer 36

Stage of conjugation reaction where drug/metabolite combines with a molecule e.g., acetylation/methylation to increase water solubility, this converts toxic metabolites to allow them to be soluble & biologically inactive and be excreted Phase 2 can occur before & in the absence of phase 1

Question 37

Describe the elimination of drugs from the body

Answer 37

This refers to the removal of drugs from the body e.g., through kidneys/ sweat, Kidneys: kidneys filter drugs from the blood into urine, only unbound drugs can be eliminated by glomerular filtrate Biliary excretion: some drugs/metabolites are excreted in the bile & eliminated through faeces Half-life: the time taken for the concentration of the drug in the blood to decrease by 50%, useful to know for dosing schedules

Question 38

Describe the stages in biliary excretion

Answer 38

1. Liver processing: drugs that are fat soluble are metabolized via hepatocytes to from water-soluble conjugates, the drug is then transported into the bile canaliculi which leads to common bile duct 2. Transport into bile: Active transporters in hepatocytes help move drug/metabolite from liver to bile, this needs ATP to occur, it then enters the gallbladder or directly to the duodenum 3. Excretion: The containing drug/metabolite enters the intestine and is added to faeces to be excreted

Question 39

Define enterohepatic circulation

Answer 39

Some drugs may undergo enterohepatic circulation, where they are reabsorbed in the intestines, transported back to the liver, and then secreted into the bile again, prolonging the drug’s presence in the body and extending its effects.

Question 40

Describe factors affecting biliary excretion

Answer 40

1. Drug conjugation: phase 2 where drugs are conjugated. Often make the drug more water-soluble. Drugs that are not efficiently conjugated may not be excreted efficiently through bile. 2. The gut microbiome can influence how biliary excreted drugs are metabolized. Some metabolites might be deconjugated by gut bacteria, allowing the drug to be reabsorbed and prolonging its action.

Question 41

Describe the half-life of a drug

Answer 41

The half-life (t½) of a drug is the time it takes for the concentration of the drug in the bloodstream to decrease by 50%. Most drugs follow first-order elimination kinetics, meaning that the rate of drug elimination is proportional to the concentration of the drug in the body. The half-life of a drug helps determine how frequently it should be administered. Drugs with shorter half-lives need to be taken more often to maintain therapeutic levels, while drugs with longer half-lives may only need to be taken once daily or even less frequently.

Question 42

Describe the factors affecting a half-life of a drug

Answer 42

Liver function: The liver is the primary organ for drug metabolism, so impaired liver function (e.g., in cirrhosis or hepatitis) can increase a drug's half-life because the drug is metabolized more slowly. Kidney function: Renal excretion is another important route of drug elimination. Kidney disease or impaired renal function can prolong the half-life of drugs excreted through the urine. Age: In the elderly, liver and kidney functions often decline, which can result in prolonged drug half-lives.