Pharmokinetics & pharmodynamics Flashcards
Define pharmokinetics & pharmocogenomics
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
Define pharmacodynamics
Refers to what the drug does to the body e.g., drug interactions, side effects & dose-response relationship
Define a drug
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
Define Medicine
Prescribed for a therapeutic effect, may consist of 1 or more drugs
Define therapeutics
The use of drugs to diagnose, prevent & treat illnesses (and/or pregnancy)
Define formulations
How the drug is formulated/packaged from different substances, including the active drug that is involved in formulating the medication
Define excipients
Substances that are made along side the making of the drug (by-products)
Define a medicinal product
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
Describe the naming of drugs
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
Define a ligand
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
Define a receptor, target agonist & antagonist
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
Define affinity
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
Describe how binding affinity is meaured
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).
Describe what influences the binding of a drug to a receptor
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
Describe the genetic variability of ligand binding
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
What are the effects of ligand variability in a healthcare setting?
- 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
- Minimizing side effects: enables adjustments to be made to maximize treatment of illness with reducing severity of side effects
- Drug efficacy: HP’s can identify the most effective drug for the best outcome
Describe the importance of the molecular structure of a drug
- 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
- 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
- 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.
Describe the importance of the molecular structure of the target
- Type & location: Different drugs act on different cell types, the targets location can affect the drugs action
- Activation/Inhibition: Some drugs acts as agonists/antagonists, so bio response is either promoted/blocked
- 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.
Describe the importance of the molecular target tissues
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
Describe the function of receptors
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
Describe the function of ion channels
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
Describe the function of carrier molecules
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
Describe the function of enzymes
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
Define toxicity
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
Describe drug specificity
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
Describe how drugs that are specific with non-specific effects
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
Describe first pass metabolism
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
Explain the process of drug absorption
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
Describe oral & topical absorption
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
Describe IV, IM, SC, D & DI
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
Describe factors affecting absorption
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
Define bioavailability
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
Describe the distribution of drugs
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.
Describe the metabolism of drugs
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
Define phase 1 in metabolism of drugs
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
Define phase 2 in metabolism of drugs
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
Describe the elimination of drugs from the body
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
Describe the stages in biliary excretion
- 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
- 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
- Excretion: The containing drug/metabolite enters the intestine and is added to faeces to be excreted
Define enterohepatic circulation
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.
Describe factors affecting biliary excretion
- 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.
- 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.
Describe the half-life of a drug
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.
Describe the factors affecting a half-life of a drug
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.
