Principles of Pharmacology Biochemistry Principles of Pharmacology How drugs work

This presentation explains how drugs work Most drugs act at a molecular level where they mostly bind to proteins to produce their therapeutic effect

How drugs work part I Most drugs bind to proteins There are thousands of different proteins in the body Performing thousands of different tasks Thus there are potentially thousands of different targets for drugs

There are four classes of protein that are targeted by drugs Types of protein There are four classes of protein that are targeted by drugs receptors enzymes ion channels carrier proteins

Receptor proteins Receptors are found on every cell in the body Receptors are very popular targets for drugs Drugs that bind to receptors include Beta blockers Salbutamol Morphine

Agonists and antagonists Some drugs bind to receptors and produce the same effect as the endogenous ligand These are called AGONISTS Some drugs bind to receptors and produce no effect other than preventing the endogenous ligand from binding These are called ANTAGONISTS

Agonists and antagonists

Cell membrane interactions

Enzymes Enzymes are complex proteins that take part in biochemical reactions Many drugs target enzymes and block biochemical reactions Enzyme targeting drugs include… ACE inhibitors NSAIDs Statins

How drugs act on enzymes

Ion channels Ion channels allow ions to cross membranes Neurological functions rely on ion channels Many drugs block ion channels including… Local anaesthetics Anti-arrhythmics Benzodiazepines

Channel blocking drugs

Carrier proteins actively transport molecules across membranes They are popular targets for drugs including… SSRIs (prozac etc.) Tricyclic antidepressants Loop diuretics

Drugs acting on carrier proteins

Similar chemical structure leads to similar function Drugs work by mimicking the chemical structure of a desired target molecule

Damaged and pain-causing cells produce large quantities of an enzyme called cylooxygenase-2. This enzyme in turn produces a chemical called prostaglandin, which sends a message to the brain signaling that a specific part of the body is in pain. The chemical also causes the injured area to release fluids, causing it to swell or become inflamed. ASA (Aspirin) adheres to the cylooxygenase-2 and prevents it from producing prostaglandin. Acetaminophen and ibuprofin also work as an antagonist blocking the production of prostaglandins. As a result, some of the pain signals do not reach the brain and less pain is felt. Also, the inflammation is minimized due to the lack of prostaglandin production.

Acetylsalicylic acid “ASA” Aspirin

Caffeine – 1,3,7-trimethylxanthine, to give it its chemical name – is a member of a group of naturally occurring substances called methylxanthines. These compounds are similar in structure to adenosines, naturally occurring molecules in our bodies which aid the onset of sleep. In its natural context, which is in tea and coffee plants, caffeine can kill or paralyse insects and is thus an effective natural pesticide. Adenosine bonds to receptor cells in the brain to calm the activity of the central nervous system, thus triggering tiredness. There is also evidence to suggest that it decreases blood flow in the brain. Caffeine molecules bind to these receptor cells but have no active effect on the nervous system. However by doing so they take the place of adenosine molecules that could make a difference. This process is known as "competitive inhibition" and effectively delays the onset of fatigue, increases alertness and improves people's ability to sustain attention. Agonist or Antagonist?

Due to the similarity in structure, the caffeine molecule can bind to receptor proteins that would normally bind to an adenosine derived molecule. These receptors produce chemicals which tell an organism it is tired and needs to sleep. Benzodiazepine receptors are also affected by caffeine, these receptors control feelings of panic and anxiety in humans.