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P A R T 6  Drugs acting on the endocrine system

for more information about managing glucose levels during stress. Hyperglycaemia Hyperglycaemia , or high blood sugar, results when there is an increase in glucose in the blood. Clinical signs and symptoms include fatigue, lethargy, irritation, glycosuria, polyphagia, polydipsia and itchy skin (from accumulation of wastes that the liver cannot clear). If the hyperglycaemia goes unchecked, the person will experi- ence ketoacidosis and CNS changes that can progress to coma. Signs of impending dangerous complications of hyperglycaemia include the following: • Fruity breath as the ketones build up in the system and are excreted through the lungs • Dehydration as fluid and important electrolytes are lost through the kidneys • Slow, deep respirations (Kussmaul respirations) as the body tries to rid itself of high acid levels • Loss of orientation and coma This level of hyperglycaemia needs to be treated immedi- ately with insulin. Where available, intravenous insulin will most rapidly reduce blood glucose levels. Hypoglycaemia Hypoglycaemia , or a blood glucose concentration lower than 4.4 mmol/L (40 mg/dL), occurs in a number of clinical situations, including starvation, and if treatment of hyperglycaemia with insulin or oral agents lowers the blood glucose level too far. The body immediately reacts to lowered blood glucose because the cells require glucose to survive, the neurons being among the cells most sensitive to the lack of glucose. The initial reaction to falling blood glucose level is parasympathetic stimu- lation—increased GI activity to increase digestion and

absorption. Rather rapidly, the SNS responds with a “fight-or-flight” reaction that increases blood glucose levels by initiating the breakdown of fat and glycogen to release glucose for rapid energy. The pancreas releases glucagon, a hormone that counters the effects of insulin and works to increase glucose levels and somatosta- tin, which help the body to conserve energy. In many cases, the response to the hypoglycaemic state causes a hyperglycaemic state. Balancing the body’s responses to glucose is sometimes difficult when one is trying to treat and control diabetes. Table 38.1 offers a compar- ison of the signs and symptoms of hyperglycaemia and hypoglycaemia. INSULIN Insulin is the only parenteral hypoglycaemic agent avail- able for exogenous replacement (Table 38.2). It is used to treat type 1 diabetes and to treat type 2 diabetes in adults who have no response to diet, exercise and other agents. (See Box 38.1 for considerations related to the use of insulin based on age.) The types of insulin that are available include insulin analogue or lispro ( Humalog ), insulin aspart ( NovoRapid ), insulin glargine ( Lantus ), insulin glulisine ( Apidra ), insulin detemir ( Levemir ), regular (neutral) insulin ( Actrapid, Humulin R ) and isophane insulin ( Humulin NPH ). Originally, insulin was prepared from pork and beef pancreas. Today, virtually all insulin is prepared by recombinant DNA technology and is human insulin produced by genetically altered bacteria. This purer form of insulin is not associated with the sensitivity problems that many people developed when using the animal products. Animal insulins may still be obtained for people most responsive to them, but they are not generally used. Box 38.5 describes the various forms

■■ TABLE 38.1 Signs and symptoms of hypoglycaemia and hyperglycaemia Clinical effects Hypoglycaemia Hyperglycaemia

Central nervous system

Headache, blurred vision, diplopia; drowsiness progressing to coma; ataxia; hyperactive reflexes Paraesthesias; weakness; muscle spasms; twitching progressing to seizures Tachycardia; palpitations; normal to high blood pressure

Decreased level of consciousness, sluggishness progressing to coma; hypoactive reflexes

Neuromuscular

Weakness, lethargy

Cardiovascular

Tachycardia; hypotension

Respiratory

Rapid, shallow respirations

Rapid, deep respirations (Kussmaul); acetone- like or fruity breath

Gastrointestinal

Hunger, nausea

Nausea; vomiting; thirst

Other

Diaphoresis; cool and clammy skin; normal eyeballs

Dry, warm, flushed skin; soft eyeballs

Laboratory tests Urine glucose negative; blood glucose low

Urine glucose strongly positive; urine ketone levels positive; blood glucose levels high Gradual; person is slow and sluggish; associated with lack of insulin, increased stress

Onset

Sudden; person appears anxious, drunk; associated with overdose of insulin, missing a meal, increased stress