Antagonists (Drug theory 3), L4

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What do the majority of clinically useful drugs depend on?

antagonists

Define an antagonist

drug that prevents the response of an agonist, efficacy of antagonist = 0

What 5 classes can antagonism be divided into? 

• chemical antagonism

• pharmacokinetic antagonism 

• physiological antagonism

• non-competitive antagonism

• competitive antagonism 

What does the class of an antagonist depend on?

on how they exert their action

Briefly describe chemical antagonism

substances combine in solution so that the effects of the active drug is lost, i.e.the agonist is chemically altered by the antagonism

How are heavy metals inactivated? What type of antagonism is this?

 toxicity is reduced with the addition of a chelating agent (e.g. dimercaprol). 

chemical

How do monoclonal antibodies targeted at cytokine work as a cancer therapy?

essentially, monoclonal antibody bind to cytokine to prevent it from binding to its receptor = blocked inflammatory / signalling pathway that cytokine would abnormally activate in disease state

https://pmc.ncbi.nlm.nih.gov/articles/PMC7551545/

https://www.ncbi.nlm.nih.gov/books/NBK572118/

How would directing monoclonal antibodies to inflammatory mediators be used as a therapy for rheumatoid arthritis?

Briefly describe pharmacokinetic antagonism

reduction in amount of drug absorbed, metabolised or excreted by another

How is warfarin affected by other drugs like antibiotics? Who is this dangerous for? What type of antagonism is this?

some antibiotics stimulate the metabolism of warfarin so reducing its effective concentration in the blood stream - dangerous for older patients taking it to reduce risk of heart attack and stroke

pharmacokinetic antagonism

What are ways in which drugs can interfere with one another in pharmacokinetic antagonism?

• absorption of drug into body

• disruption of drug’s metabolism

• distribution of drug throughout the body

• modify the excretion of another drug

What effect does metabolism usually have on a drug?

typically inactivates drugs, process by which chemical structure of a substance is changed to increase ease by which its excreted from the body

Bonus: define a prodrug

inactive or weakly active drug where metabolites (result of drug metabolism) are pharmacologically active, sometimes even more so than the parent compound

What are the 4 stages of drug metabolism?

absorption, distribution, metabolism, and excretion

Briefly describe physiological antagonism

interaction of two drugs with opposing actions in the body

Considering noradrenaline and histamine are both agonists for receptors in the heart and blood vessels, how can they be considered as being antagonistic? What type of antagonism is this?

NE raises arterial blood pressure through alpha 1 (blood vessels) and beta 1 receptors (heart) // histamine lowers arterial blood pressure by causing vasodilation - both are agonists on their target receptors but have opposing effects on a same system ie are competing for the physiological outcome

physiological antagonism

Dumb down physiological antagonism pls

2 drugs have opposite effects on system, one increases while the other decreases a function so they’re fighting without fighting for same receptor (ie both agonists for their own receptor)

Considering omeprazole (taken for acid reflux/stomach and intestine ulcers) and histamine are both agonists for receptors in the stomach, how can they be considered as being antagonistic? What type of antagonism is this?

omeprazole reduces amount of acid produced by stomach by inhibiting the proton pump // histamine through H2 receptors increases acid secretion in the gut - both are agonists on their target receptors but have opposing effects on a same system ie are competing for the physiological outcome

physiological antagonism

Briefly describe non-competitive antagonism

Blocks some step in the process between receptor activation and response i.e. it does not compete with the agonist for the receptor site and so is termed non-competitive

slide 7 - both examples + comments to be typed up