The billion dollar pill Flashcards
What are agonist drugs?
Drugs that stimulate biological responses
What are antagonist drugs?
Drugs that inhibit biological responses.
What are the 3 tenets of pharmaceutical science?
- All drugs must bind to a biological target in order to achieve a desired biological effect.
- Magnitude of the response depends on the dose.
- Every drug is a potential poison.
What are the general biological targets of a drug?
- Targets that are overexpressed.
- Targets that are underexpressed.
- Targets that control a critical process that affects the biology that you are trying to manipulate.
What is the largest class of drug targets?
Enzymes.
What are exogenous molecules?
Molecules originating from outside the organism
What is pharmacokinetics and pharmacodynamics?
pharmacokinetics: study of how the body affects the drug
Pharmacodynamics: study of how the drug affects the body
Where are HER2 receptors overexpressed?
on the cell surface of breast tumours
Why are enzymes the largest class of drug targets?
because of the presence of the active site, which can be exploited as binding sites for pharmaceutical enzyme inhibitors
How does potency relate to EC50?
higher potency = lower EC50
Why is higher potency of a drug sometimes bad?
the chance of the drug binding to other targets is higher, causing side effects
What are the 2 ways in which a drug can become a poison?
- Too much action on the target
- Loss of selectivity, where the drug binds to other targets
What is the first step in the process of drug discovery?
Identification and validation of a target.
What are the criteria for a good target?
- The target’s 3D structure is accessible
- Effects of altering the target is measurable
- It is not evenly distributed throughout the body
What are the criteria during target validation?
- Is the effect of the target reproducible?
- Can the target be modulated?
After identifying a target, how is the drug chosen?
Start with a endogenous molecule that is known to bind to the target and go from there
What is an endogenous molecule?
A molecule originating from inside the organism
What is a pharmacological assay?
An investigative procedure to measure the presence, amount or functional activity of a drug
What are the 4 processes of pharmacokinetics?
- Absorption
- Distribution
- Metabolism
- Elimination
Why might drugs not be absorbed into the bloodstream?
- poor solubility
- degradation prior to absorption
- cannot be transported well across the cellular barrier
What is paracellular transport?
Transport of molecules in between 2 cells
How do you use logP to determine hydrophobicity?
- Negative log P = hydrophilic
- Positive log P = hydrophobic
Why are some drugs taken with food or milk?
- They are poorly soluble in water, so the food/milk allows the drug to be absorbed into the bloodstream
- To delay the absorption of some drugs
What is the bioavailability of a drug administered through IV injection? Why?
1
because there is no pre-absorption losses
What is the first pass effect?
A phenomenon in which a drug gets metabolised at a specific location in the body that results in a reduced concentration of the active drug upon reaching its site of action or the blood.
Why are some drugs taken before meal?
- Food may inhibit metabolism of the drug
- Speeds up gastric emptying so there’s quicker exposure to the drug
What is the most water soluble area of the body?
Blood
What is the most lipid soluble area of the body?
bone marrow
What does volume of distribution measure?
It approximates how well a drug binds to different tissues
What are instances where a drug’s poor oral absorption is a good thing?
Poor absorption means the drug will stay in the gut longer, which is good if you want a localised effect in the gut
What is the goal of metabolism?
- To convert a foreign substance into a more water soluble entity so that it can be readily excreted from the system
- To convert a substance into something less reactive so that it causes less harm to the system
What happens if the metabolism of a drug is too fast or too slow?
- Too fast: The effect of the drug may be too little
- Too slow: The effect of the drug may become toxic
What is biotransformation?
Chemical modification of the compound made by an organism usually through an enzymatic process
What are xenobiotics?
Chemicals found in the body which are not normally produced or present within the organism
What is bioactivation?
Enzymatic conversion of a substance into a reactive species
What are the general characteristics of metabolism?
- It is an enzymatic process
- One enzyme can metabolise many subtrates
- Targets are mostly xenobiotics
- They exhibit genetic differences
What are some organs that carry out metabolism?
- liver
- kidneys
- gastrointestinal mucosa
- skin
- lung
What is the primary organ for metabolism?
Liver
How are water soluble substances secreted?
Secreted by the kidneys in urine
How are fat soluble substances secreted?
Secreted by liver into bile and then in faeces
What is clearance?
It reflects the intrinsic ability of the body to clear the specific drug
What is the main organ that eliminates drugs from the body?
Kidney
What is enterohepatic recirculation and how is it significant?
- It is the process by which bile gets reabsorbed back into the blood from the small intestine
- It prolongs the half life of the drug
What is bioavailability?
It provides an indication of the proportion of the
administered dose that will be taken into the circulatory system.
What are the main categories of toxicity testing?
- general toxicity
- safety pharmacology
- developmental and reproductive toxicity
- immunotoxicity
- phototoxicity
- genotoxicity and carcinogenecity
What are the limitations of toxicity testing?
- Many toxicities are hard to pick up from trials
- We do not fully understand the mechanism of toxicities
- All models are imperfect (computer based, animal models, human studies)
