McKenna's Pharmacology for Nursing, 2e

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P A R T 6  Drugs acting on the endocrine system

has multiple effects on many secretory systems (e.g. it inhibits release of gastrin, glucagon and insulin) and a short duration of action, it is not desirable as a thera­ peutic agent. Analogues of somatostatin, lanreotide and octreotide, are considerably more potent in inhibit­ ing GH release with less of an inhibitory effect on insulin release. Consequently, they are used instead of somatostatin. Bromocriptine, a semisynthetic ergot alkaloid, is a dopamine agonist frequently used to treat acromegaly. It may be used alone or as an adjunct to irradiation. Dopamine agonists inhibit GH secretion in some indi­ viduals with acromegaly; the opposite effect occurs in normal individuals. Bromocriptine’s GH-inhibiting effect may be explained by the fact that dopamine increases somatostatin release from the hypothalamus. Pegvisomant is a GH analogue that was approved in late 2003 for the treatment of acromegaly in individ­ uals who do not respond to other therapies. It binds to GH receptors on cells, inhibiting GH effects. It must be given by daily subcutaneous injection. While registered for use in Australia, this drug is not available under the Pharmaceutical Benefits Scheme (PBS). Table 35.2 shows usual indications for each of these agents. Pharmacokinetics Octreotide must be administered subcutaneously. The drug is rapidly absorbed and widely distributed through­ out the body, and it is metabolised in the tissues with about 30% excreted unchanged in the urine. Lanreotide is administered by either deep subcu­ taneous or intramuscular injection, peaking between 10 and 16 hours after administration. Bromocriptine is administered orally and effectively absorbed from the gastrointestinal (GI) tract. The drug undergoes extensive first-pass metabolism in the liver and is primarily excreted in the bile. Pegvisomant is given by subcutaneous injection and is slowly absorbed, reaching peak effects in 33 to 77 hours. It also clears from the body at a slow rate, with a half-life of 6 days. The drug is excreted in the urine. Contraindications and cautions Bromocriptine should not be used during pregnancy or breastfeeding because of effects on the fetus and because it blocks breastfeeding. There are no adequate studies of effects of octreotide and pegvisomant in pregnancy and during breastfeeding; use of these drugs should be reserved for situations in which the benefits to the mother clearly outweigh any potential risks to the fetus or neonate. Growth hormone antagonists are contra­ indicated in the presence of any known allergy to the drug to prevent hypersensitivity reactions. They should be used cautiously in the presence of any other endocrine

G rowth hormone antagonists GH hypersecretion is usually caused by pituitary tumours and can occur at any time of life. This is often referred to as hyperpituitarism. If it occurs before the epiphyseal plates of the long bones fuse, it causes an acceleration in linear skeletal growth, producing gigan- tism of over 2 metres in height with fairly normal body proportions. In adults, after epiphyseal closure, linear growth is impossible. Instead, hypersecretion of GH causes enlargement in the peripheral parts of the body, such as the hands and feet, and the internal organs, especially the heart. Acromegaly is the term used to describe the onset of excessive GH secretion that occurs after puberty and epiphyseal plate closure. Most conditions of GH hypersecretion are treated by radiation therapy or surgery. Drug therapy for GH excess can be used for those people who are not candi­ dates for surgery or radiation therapy. The drugs include a dopamine agonist (bromocriptine [ Parlodel ]), and the prototype drug (bromocriptine mesylate); somatostatin analogue (lanreotide [ Somatuline ] (not available in New Zealand) and octreotide [ Sandostatin ]); and a GH analogue (pegvisomant [ registered for use in Australia but not readily available ]). Therapeutic actions and indications Somatostatin is an inhibitory factor released from the hypothalamus. It is not used to decrease GH levels, although it does do that very effectively. Because it drug therapy and promote compliance. Instruct a family member or caregiver in the following points: –– Storage of the drug (refrigeration is required) –– Preparation of the drug (the reconstitution procedure varies depending on the brand name product used) –– Administration techniques (sterile technique, need to rotate injection sites and need to monitor injection sites for atrophy or extravasation). Evaluation ■ ■ Monitor response to the drug (return of GH levels to normal; growth and development). ■ ■ Monitor for adverse effects (hypothyroidism, glucose intolerance, nutritional imbalance). ■ ■ Evaluate the effectiveness of the teaching plan (person can name drug, dosage, adverse effects to watch for and specific measures to avoid them; family member can demonstrate proper technique for preparation and administration of the drug). ■ ■ Monitor the effectiveness of comfort measures and compliance with the regimen.