Page 767 - Basic _ Clinical Pharmacology ( PDFDrive )

CHAPTER 41 Pancreatic Hormones & Antidiabetic Drugs 753

diagnose diabetes. An HbA1 of 6.5% or greater if confirmed by ■ MEDICATIONS FOR
c
repeat testing is diagnostic of diabetes. Less than 5.7% is normal,
and patients with levels of 5.7–6.4% are considered at high risk HYPERGLYCEMIA
for developing diabetes (Table 41–4).
Insulin Preparations

C. Urine or Blood Ketones Human insulin is dispensed as regular (R) and neutral protamine
Qualitative detection of ketone bodies can be accomplished by hagedorn (NPH) formulations. There are also six analogs of human
nitroprusside tests (Acetest or Ketostix). Although these tests do insulin. Three of the analogs are rapidly acting: insulin lispro, insu-
not detect beta-hydroxybutyric acid, which lacks a ketone group, lin aspart, and insulin glulisine; and three are long acting: insulin
the semiquantitative estimation of ketonuria thus obtained is glargine, insulin detemir, and insulin degludec. Animal insulins
nonetheless usually adequate for clinical purposes. Many laborato- are not available in the United States. Pork and beef preparations
ries now measure beta-hydroxybutyric acid, and meters are avail- (isophane, neutral, 30/70, and lente) are still available in other parts
able (Precision Xtra; Nova Max Plus) for patient use that measure of the world. All the insulins in the United States are available in
beta-hydroxybutyric acid levels in capillary glucose samples. Beta- a concentration of 100 units/ML (U100) and dispensed as 10-mL
hydroxybutyrate levels >0.6 mmol/L require evaluation. A level vials or 0.3-mL cartridges or prefilled disposable pens. Several
>3.0 mmol/L, which is equivalent to very large urinary ketones, insulins are also available at higher concentrations in the prefilled
will require hospitalization. disposable pen form: insulin glargine 300 units/mL (U300); insulin
degludec (U200); insulin lispro 200 units/mL (U200); and regular
D. Self-Monitoring of Blood Glucose insulin 500 units/mL (U500) (Tables 41–5, 41–6).
Capillary blood glucose measurements performed by patients
themselves, as outpatients, are extremely useful. In type 1 A. Short-Acting Insulin Preparations (Tables 41–5, 41–6)
patients in whom “tight” metabolic control is attempted, they The short-acting preparations include regular human insulin
are indispensable. Several paper strip methods and a large and the three rapidly acting insulin analogs. All are clear solu-
number of blood glucose meters are now available for measur- tions at neutral pH. The insulin molecules exist as dimers that
ing glucose on capillary blood samples. All are accurate, but assemble into hexamers in the presence of two zinc ions. The
they vary with regard to speed, convenience, size of blood hexamers are further stabilized by phenolic compounds such as
samples required, reporting capability, and cost. Some meters phenol and meta-Cresol. The mutations engineered into the rap-
are designed to communicate with an insulin pump. A number idly acting insulin analogs are designed to disrupt the stabilizing
of continuous glucose monitoring (CGM) systems are also avail- intermolecular interactions of the dimers and hexamers, leading
able for clinical use. The systems utilize a subcutaneous sensor to more rapid absorption into the circulation after subcutaneous
that measures glucose concentrations in the interstitial fluid injection.
for 3–7 days. Studies show that adult type 1 patients who use
continuous systems have improved glucose control without an 1. Regular insulin—Regular insulin is a short-acting, soluble
increased incidence of hypoglycemia. There is great interest in crystalline zinc insulin whose hypoglycemic effect appears within
using continuous glucose monitoring systems to automatically 30 minutes after subcutaneous injection, peaks at about 2 hours,
deliver insulin by continuous subcutaneous insulin infusion and lasts for 5–7 hours when usual quantities (ie, 5–15 U) are
pump. The first artificial pancreas system has been approved by administered. For very insulin-resistant subjects who would oth-
the U.S. Food and Drug Administration (FDA) and will become erwise require large volumes of insulin solution, a U500 prepara-
available in 2017. With this system, the continuous glucose tion of human regular insulin is available both in a vial form and
monitor readings are used to automatically adjust the basal insu- a disposable pen. If the vial form is used, it is necessary to use
lin dosing by the insulin pump. a U100-insulin syringe or tuberculin syringe to measure doses.

TABLE 41–5 Summary of bioavailability characteristics of the insulins.

Insulin Preparations Onset of Action Peak Action Effective Duration
Insulins lispro, aspart, glulisine 5–15 min 1–1.5 h 3–4 h
Human regular 30–60 min 2 h 6–8 h
Technosphere inhaled insulin 5–15 min 1 h 3 h
Human NPH 2–4 h 6–7 h 10–20 h
Insulin glargine 0.5–1 h Flat ~24 h
Insulin detemir 0.5–1 h Flat 17 h
Insulin degludec 0.5–1.5 h Flat >42 h