Читать книгу Fundamentals of Pharmacology for Paramedics - Группа авторов - Страница 30

Ion channels represent the only means for ions to cross cell membranes, and all cells contain multiple species of ion channel in their membranes. These channels can be gated in a number of ways, and drugs which can bind to specific channels can alter cellular activity profoundly by altering the passage of ions across the membrane, thereby altering the cell’s membrane potential. Most drugs that act in this way block ion channels rather than open them.

The local anaesthetic lidocaine, for example, acts by binding to and inhibiting voltage‐gated sodium channels in neuronal cell membranes, preventing the generation of action potentials by the affected neurons. Sensory neurons detecting touch, pressure and pain stimuli therefore become less responsive to those stimuli, resulting in anaesthesia.

The benzodiazepine class of drugs, including agents such as midazolam and diazepam, act by binding to a chloride ion channel in neuronal membranes.

Figure 1.1 Drugs which act at receptors. (a) A cell has receptors for a specific signalling compound (e.g. a neurotransmitter or hormone) located on the cell membrane. (b) The endogenous signalling molecule binds to its receptors, fitting the receptor perfectly. (c) The binding triggers a series of actions inside the cell. These actions would be the normal response to that signalling compound. (d) If the molecular structure of a drug is sufficiently similar to that of the endogenous signalling compound, the drug will also be able to bind to the receptor and produce the same actions in the cell. This drug would be known as an agonist at this receptor. (e) If a drug has a molecular structure vaguely similar to that of the endogenous signalling compound, it may still be able to bind to the receptor, but not fit it perfectly enough to produce the same actions in the cell. This drug could prevent the endogenous signalling compound (and the agonist) getting to the receptor, thereby blocking their actions. This drug would be known as an antagonist at the receptor.

Figure 1.2 Enzymes operate by binding reacting substances (a) and accelerating their reaction – in this case the reaction is a combination of two molecules (b), then releasing the product from the enzyme’s binding site (c). A drug which can also bind to this site can prevent the catalytic function of the enzyme, thereby reducing the level of product (d).

This channel is opened normally by the inhibitory neurotransmitter GABA (gamma‐aminobutyric acid). Opening a chloride channel in the membrane allows the influx of negatively charged chloride ions to the cell, which hyperpolarises the cell, making it less likely to produce action potentials. The benzodiazepine class of drugs also act at this ion channel, albeit at a different site to GABA, but when they bind, they enhance the inhibitory actions of GABA, and add to the hyperpolarisation of neurons and the resulting nervous system depressant effect (Figure 1.3).