Page 770 - Basic _ Clinical Pharmacology ( PDFDrive )

756 SECTION VII Endocrine Drugs

injected once or twice a day to achieve a stable basal coverage. are available for reusable pens (Lilly, Novo Nordisk, and Owen
Insulin degludec is available in two concentrations, U100 and Mumford). Disposable prefilled pens are also available for regular
U200, and dispensed in pre-filled disposable pens. insulin (U100, U500), insulin lispro, insulin aspart, insulin gluli-
sine, insulin detemir, insulin glargine, insulin degludec, NPH, 70%
5. Mixtures of insulins—Because intermediate-acting NPH NPH/30% regular, 75% NPL/25% insulin lispro, 50% NPL/50%
insulins require several hours to reach adequate therapeutic levels, insulin lispro, 70% insulin aspart protamine/30% insulin aspart,
their use in patients with diabetes usually requires supplements of and 70% insulin degludec/30% insulin aspart (Table 41–6).
rapid- or short-acting insulin before meals. For convenience, these
are often mixed together in the same syringe before injection. The C. Continuous Subcutaneous Insulin Infusion Devices
regular insulin or rapidly acting insulin analog is withdrawn first, (CSII, Insulin Pumps)
then the NPH insulin and then injected immediately. Continuous subcutaneous insulin infusion devices are external
Stable premixed insulins (70% NPH and 30% regular) are open-loop pumps for insulin delivery. The devices have a user-
available as a convenience to patients who have difficulty mix- programmable pump that delivers individualized basal and bolus
ing insulin because of visual problems or insufficient manual insulin replacement doses based on blood glucose self-monitoring
dexterity. Premixed preparations of rapidly acting insulin analogs results.
(lispro, aspart) and NPH are not stable because of exchange of Normally, the 24-hour background basal rates are prepro-
the rapidly acting insulin analog for the human regular insulin grammed and relatively constant from day to day, although
in the protamine complex. Consequently, over time, the soluble temporarily altered rates can be superimposed to adjust for a
component becomes a mixture of regular and rapidly acting short-term change in requirement. For example, the basal delivery
insulin analog at varying ratios. To remedy this problem, inter- rate might need to be decreased for several hours because of the
mediate insulins composed of isophane complexes of protamine increased insulin sensitivity associated with strenuous activity.
with the rapidly acting insulin analogs were developed (neutral Boluses are used to correct high blood glucose levels and to
protamine lispro [NPL]; aspart protamine). Premixed combina- cover mealtime insulin requirements based on the carbohydrate
tions of NPL and insulin lispro are now available for clinical use content of the food and concurrent activity. Bolus amounts are
(Humalog Mix 75/25 and Humalog Mix 50/50). These mixtures either dynamically programmed or use pre-programmed algo-
have a more rapid onset of glucose-lowering activity compared rithms. When the boluses are dynamically programmed, the
with 70% NPH/30% regular human insulin mixture and can be user calculates the dose based on the amount of carbohydrate
given within 15 minutes before or after starting a meal. A similar consumed and the current blood glucose level. Alternatively, the
70% insulin aspart protamine/30% insulin aspart (NovoLog Mix meal or snack dose algorithm (grams of carbohydrate covered by
70/30) is now available. The main advantages of these new mix- a unit of insulin) and insulin sensitivity or blood glucose correc-
tures are that (1) they can be given within 15 minutes of starting tion factor (fall in blood glucose level in response to a unit of
a meal and (2) they are superior in controlling the postprandial insulin) can be preprogrammed into the pump. If the user enters
glucose rise after a carbohydrate-rich meal. the carbohydrate content of the food and current blood glucose
Insulin glargine or insulin detemir cannot be acutely mixed with value, the insulin pump will calculate the most appropriate dose of
either regular insulin or the rapid-acting insulin analogs. Insulin insulin. Advanced insulin pumps also have an “insulin on board”
degludec, however, can be mixed and is available as 70% insulin feature that adjusts a high blood glucose correction dose to correct
degludec/30% insulin aspart and is injected once or twice a day. for residual activity of previous bolus doses.
The traditional pump (by MiniMed, Animas, Roche, Sooil)—
Insulin Delivery Systems which contains an insulin reservoir, the program chip, the keypad,
and the display screen—is about the size of a pager. It is usually
A. Insulin Syringes and Needles placed on a belt or in a pocket, and the insulin is infused through
Disposable plastic syringes with needles attached are available thin plastic tubing that is connected to the subcutaneously
in 1-mL (100 units), 0.5-mL (50 units), and 0.3-mL (30 units) inserted infusion set. The abdomen is the favored site for the
sizes. The “low-dose” 0.3-mL syringes are popular because many infusion set, although flanks and thighs are also used. The insulin
patients with diabetes do not take more than 30 units of insulin reservoir, tubing, and infusion set need to be changed using sterile
in a single injection except in rare instances of extreme insulin techniques every 2 or 3 days. Currently, only one pump does not
resistance. They are also available in half-unit marking. Three require tubing (OmniPod, Insulet). In this model, the pump is
lengths of needles are available; longer needles are preferable in attached directly to the infusion set (electronic patch pump). Pro-
obese patients to reduce variability of insulin absorption. If the gramming is done through a hand-held unit that communicates
skin is clean it is not necessary to use alcohol. Rotation of sites is wirelessly with the pump.
recommended to avoid problems with absorption due to lipohy- Optimal use of these devices requires responsible involve-
pertrophy from overuse of injection sites. ment and commitment by the patient. Insulin aspart, lispro,
and glulisine all are specifically approved for pump use and are
B. Insulin Pens preferred pump insulins because their favorable pharmacokinetic
The pens eliminate the need for carrying insulin vials and syringes. attributes allow glycemic control without increasing the risk of
Cartridges of insulin lispro, insulin aspart, and insulin glargine hypoglycemia.