Page 781 - Basic _ Clinical Pharmacology ( PDFDrive )

CHAPTER 41 Pancreatic Hormones & Antidiabetic Drugs 767

hyperglycemia after a carbohydrate-rich meal (such as dinner), a form of rapidly absorbed glucose, should be carried by every dia-
short-acting secretagogue before that meal may suffice to control betic person who is receiving hypoglycemic drug therapy.
the glucose levels. Patients with severe insulin resistance may All the manifestations of hypoglycemia are relieved by glu-
be candidates for pioglitazone. Patients who are very concerned cose administration. To expedite absorption, simple sugar or
about weight gain may benefit from a trial of a GLP-1 receptor glucose should be given, preferably in liquid form. To treat mild
agonist, a DPP-4 inhibitor, or an SGLT2 inhibitor, although the hypoglycemia in a patient who is conscious and able to swallow,
average weight loss with these medication is not great. If two dextrose tablets, glucose gel, or any sugar-containing beverage or
agents are inadequate a third agent is added, although data regard- food may be given. If more severe hypoglycemia has produced
ing efficacy of such combined therapy are limited. unconsciousness or stupor, the treatment of choice is 1 mg of
When the combination of oral agents and injectable GLP-1 glucagon injected either subcutaneously or intramuscularly. This
receptor agonists fails to adequately control glucose levels, insulin may restore consciousness within 15 minutes to permit ingestion
therapy should be instituted. Various insulin regimens may be of sugar. Emergency medical services should be called in the event
effective. Simply adding nighttime intermediate- or long-acting of loss of consciousness. The emergency personnel can restore
insulin to the oral regimen may lead to improved fasting glucose consciousness by giving 20–50 mL of 50% glucose solution by
levels and adequate control during the day. If daytime glucose intravenous bolus over a period of 2–3 minutes.
levels are problematic, premixed insulins before breakfast and
dinner may help. If such a regimen does not achieve adequate B. Diabetic Coma
control or leads to unacceptable rates of hypoglycemia, a more 1. Diabetic ketoacidosis—Diabetic ketoacidosis (DKA) is
intensive basal bolus insulin regimen (long-acting basal insulin) a life-threatening medical emergency caused by inadequate or
combined with rapid-acting analog before meals can be instituted. absent insulin replacement, which occurs in people with type 1
Metformin has been shown to be effective when combined with diabetes and infrequently in those with type 2 diabetes. It typi-
insulin therapy and should be continued. Pioglitazone can be used cally occurs in newly diagnosed type 1 patients or in those who
with insulin, but this combination is associated with more weight have experienced interrupted insulin replacement, and rarely
gain and peripheral and macular edema. Continuing with sulfo- in people with type 2 diabetes who have concurrent unusually
nylureas, GLP-1 receptor agonists, DPP-4 inhibitors, and SGLT2 stressful conditions such as sepsis or pancreatitis or are on high-
inhibitors can be of benefit in selected patients. Cost, complexity, dose steroid therapy. DKA occurs more frequently in patients on
and risk for adverse events should be considered when deciding insulin pumps. Poor compliance—either for psychological reasons
which drugs to continue once the patient starts on insulin therapy. or because of inadequate education—is one of the most common
causes of DKA, particularly when episodes are recurrent.
Acute Complications of Diabetes Signs and symptoms include nausea, vomiting, abdominal pain,
deep slow (Kussmaul) breathing, change in mental status (including
A. Hypoglycemia coma), elevated blood and urinary ketones and glucose, an arterial
Hypoglycemic reactions are the most common complication of insulin blood pH lower than 7.3, and low bicarbonate (15 mmol/L).
therapy. It can also occur in any patient taking oral agents that stimu- The fundamental treatment for DKA includes aggressive intrave-
late insulin secretion (eg, sulfonylureas, meglitinide, d-phenylalanine nous hydration and insulin therapy and maintenance of potassium
analogs), particularly if the patient is elderly, has renal or liver disease, and other electrolyte levels. Fluid and insulin therapy is based on
or is taking certain other medications that alter metabolism of the the patient’s individual needs and requires frequent reevaluation and
sulfonylureas (eg, phenylbutazone, sulfonamides, warfarin). It occurs modification. Close attention must be given to hydration and renal
more frequently with the use of long-acting sulfonylureas. status, sodium and potassium levels, and the rate of correction of
Rapid development of hypoglycemia in persons with intact plasma glucose and plasma osmolality. Fluid therapy generally begins
hypoglycemic awareness causes signs of autonomic hyperactivity— with normal saline. Regular human insulin should be used for intra-
both sympathetic (tachycardia, palpitations, sweating, tremulous- venous therapy with a usual starting dosage of about 0.1 U/kg/h.
ness) and parasympathetic (nausea, hunger)—and may progress to
convulsions and coma if untreated. 2. Hyperosmolar hyperglycemic syndrome—Hyperosmolar
In persons exposed to frequent hypoglycemic episodes during hyperglycemic syndrome (HHS) is diagnosed in persons with
tight glycemic control, autonomic warning signals of hypogly- type 2 diabetes and is characterized by profound hyperglycemia
cemia are less common or even absent. This dangerous acquired and dehydration. It is associated with inadequate oral hydration,
condition is termed hypoglycemic unawareness. When patients lack especially in elderly patients; with other illnesses; with the use of
the early warning signs of low blood glucose, they may not take medication that elevates the blood sugar or causes dehydration, such
corrective measures in time. In patients with persistent, untreated as phenytoin, steroids, diuretics, and calcium channel blockers; and
hypoglycemia, the manifestations of insulin excess may develop— with peritoneal dialysis and hemodialysis. The diagnostic hallmarks
confusion, weakness, bizarre behavior, coma, seizures—at which are declining mental status and even seizures, a plasma glucose
point they may not be able to procure or safely swallow glucose- >600 mg/dL, and a calculated serum osmolality >320 mmol/L.
containing foods. Hypoglycemic awareness may be restored by Persons with HHS are not acidotic unless DKA is also present.
preventing frequent hypoglycemic episodes. An identification The treatment of HHS centers around aggressive rehydration
bracelet, necklace, or card in the wallet or purse, as well as some and restoration of glucose and electrolyte homeostasis; the rate of