Pharmacology for Anaesthesia and Intensive Care

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Section IVOther important drugs

Hypothalamus TSH

TSH

T 3 /T 4

Pituitary

Thyroid

Figure 25.2.Feedback loops affecting thyroid hormone production.−→,Stimulates;

, inhibits.

controlled by the hypothalamic thyrotropin-releasing hormone (TRH) and thy-

rotropin (TSH), which are inhibited in the presence of T 3 and T 4 (Figure25.2).

Uses

Replacement hormone is required to treat hypothyroidism, which may be due to

thyroid, hypothalamic or pituitary disease. Synthetic T 4 is the mainstay of oral

replacement therapy butl-triiodothyronine (T 3 ) may be given intravenously (5–

50 μg according to response) in hypothyroid coma as it has a faster onset. T 3 may

also be given orally.

Mechanism of action

Free T 4 enters the cell via a carrier mechanism where most is converted to the more

active T 3. Their main intracellular targets are receptors on the mitochondria and cell

nucleus to which they bind inducing a conformational change.

Effects


Cardiovascular – thyroid hormones exhibit positive inotropy and chronotropy. The

cardiac output increases, while a reduced peripheral vascular resistance often

leaves the mean arterial blood pressure unchanged. The increased myocardial

oxygen demand may cause ischaemia in those with ischaemic heart disease.


Respiratory – owing to an increased metabolic rate the minute volume increases.


Central nervous system – they act as central stimulants and may evoke tremor.

They also act to inhibit TSH and TRH by negative feedback.


Metabolic – T 3 affects growth, development, lipid metabolism, intestinal carbohy-

drate absorption and increases the dissociation of oxygen from haemoglobin by

increasing red blood cell 2,3-diphosphoglycerol (2,3-DPG).