Renin (half-life 80 minutes) splits the decapeptide angiotensin I from the circulating plasma protein angiotensinogen, which is synthesised in the liver and is present in the α2-globulin fraction of plasma proteins. Angiotensin-converting enzyme (ACE) converts angiotensin I to the active octapeptide angiotensin II, and also inactivates bradykinin. Angiotensin II is broken down in the kidney and liver to inactive metabolites and angiotensin III, which retains some activity (Figure 17.1).

Pharmacokinetics is the study of the way in which the body handles administered drugs. The use of mathematical models allows us to predict how plasma concentration changes with time when the dose and interval between doses are changed, or when infusions of a drug are used. Because there is an association between plasma concentration of a drug and its pharmacodynamic effect, models allow us to predict the extent and duration of clinical effects. Mathematical models may therefore be used to programme computers to deliver a variable rate infusion to achieve a predetermined plasma level and hence a desired therapeutic effect.

Isomerism is the phenomenon by which molecules with the same atomic formulae have different structural arrangements – the component atoms of the molecule are the same, but they are arranged in a different configuration.

BDZs modulate the effects of GABA at GABAA receptors. The specific α-subunit type determines the BDZ pharmacology – anxiolytic or sedative. Two BDZ receptor subtypes have been identified: BZ1, found in the spinal cord and cerebellum – responsible for anxiolysis; and BZ2, found in the spinal cord, hippocampus and cerebral cortex – responsible for sedative and anticonvulsant activity.

Interactions occur when one drug modifies the action of another. This interaction may either increase or decrease the second drug’s action. Sometimes these interactions result in unwanted effects, but some interactions are beneficial and can be exploited therapeutically.

Drug interaction can be described as physicochemical, relating to the properties of the drug or its pharmaceutical preparation, pharmacokinetic due to alterations in the way the body handles the drug or pharmacodynamic where the activity of one drug is affected. The chance of a significant interaction increases markedly with the number of drugs used and the effects of any interaction are often exaggerated in the presence of disease or coexisting morbidity.

Antacids neutralise gastric acidity. They are used to relieve the symptoms of dyspepsia and gastro-oesophageal reflux. They promote ulcer healing but less effectively than other therapies.

α-Adrenoceptor antagonists (α-blockers) prevent the actions of sympathomimetic agents on α-adrenoceptors. Certain α-blockers (phentolamine, phenoxybenzamine) are non-specific and inhibit both α1- and α2-receptors, whereas others selectively inhibit α1-receptors (prazosin) or α2-receptors (yohimbine). The actions of specific α-adrenoceptor stimulation are shown in Table 14.1.

Individual nerve fibres are made up of a central core (axoplasm) and a phospholipid membrane containing integral proteins, some of which function as ion channels.

This has three elements: platelets, the coagulation cascade and fibrinolysis. The first two are involved in preventing haemorrhage by thrombus formation, while fibrinolysis is an essential limiting mechanism.

The neuromuscular junction (NMJ) forms a chemical bridge between the motor neurone and skeletal muscle. The final short section of the motor nerve is unmyelinated and comes to lie in a gutter on the surface of the muscle fibre at its mid-point – each being innervated by a single axonal terminal from a fast Aα neurone (en plaque appearance). However, for the intra-ocular, intrinsic laryngeal and some facial muscles the pattern of innervation is different with multiple terminals from slower Aγ neurones scattered over the muscle surface (en grappe appearance).

Antimicrobial agents are used to kill or suppress the growth of microorganisms and are used widely both to treat and prevent infection. In order to understand how antimicrobial drugs work it is necessary to understand the anatomy and structure of microorganisms.

Sodium nitroprusside is usually administered as a 0.005–0.02% (50–200 μg/ml) intravenous infusion, the dose of 0.5–6 μg.kg−1.min−1 being titrated to effect.

The kidney is a complex organ maintaining fluid, electrolyte and acid–base balance. It also serves an endocrine function by secreting renin and erythropoietin.

Structure–activity relationships (SAR) describe how the structure of related drugs influences their behaviour, for example whether they are agonists or antagonists. In order to understand how differences in drug structure can affect activity it is necessary to appreciate drug development methods and some basic organic chemistry. Once the properties of the contributing groups are understood, then it becomes easier to predict the likely behaviour of a drug molecule compared with the parent drug. In addition, knowledge of the structural properties of a drug may help us appreciate some of their physicochemical properties, such as their solubility in oil and water, their pKa values and whether they are weak acids or bases.