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1- Chemistry
Human insulin
2- Pharmacology
Lansulin® causes a fall in blood glucose concentration. It
facilitates glucose transport into cells and glucose metabolism
within them. It inhibits ketogenesis and glycogenolysis, while
increasing lipid and glycogen synthesis. It reduces amino
acid release from skeletal muscle, and increases amino acid
transport into cells. It causes shifts of potassium and
magnesium from the extracellular fluid into cells.
3- Toxicology
Lansulin® is not proved to cause specific organ damage
separate from its hypoglycemic or lipogenic effects. No
mutagenisis or carcinogenesis has been observed in humans.
4- Clinical pharmacology
Lansulin® causes hypoglycemia in normal subjects when
administered subcutaneously, intra-muscularly or
intravenously. From 15min after starting infusions of 1.0 or
1.7U.h-1, plasma glucose declines by 0.030 or 0.044
mmol.1-1.min-1. When infused at about 1mU.kg-1. min-1 with
somatostatin, which inhibits endogenous insulin output,
Lansulin® increases splanchnic glucose uptake while inhibiting
splanchnic lactate uptake. It does not differ appreciably from
porcine insulin in either respect.
5- Pharmacokinetics
Lansulin® is destroyed in the gut, and virtually none is absorbed
after oral dosing. Absorption after subcutaneous injection
depends on volume of injection, smoking, exercise,
site, and external temperature, as well as on the type of insulin
and on mixing with other insulins. The lag time between
injection and first appearance of Lansulin® is 13min for
Lansulin® R.
For Lansulin® N, maximum concentration is reached about
4h after subcutaneous injections. Lansulin® is eliminated
mainly by metabolic degradation in liver and kidney. Its
pharmacokinetics are complex. Lansulin® has been detected
in cerebrospinal fluid in humans at concentrations about a
quarter of those in serum. As it is destroyed in the gut, any
excretion into breast milk is without clinical significance.
Oral absorption minimal
Presystemic metabolism 100%
Plasma half-life
range 3-5 min
mean 4 min
Volume of distribution 85ml.kg-1
Plasma protein binding ~5%
6- Metabolism
Lansulin® is metabolized in the liver and kidney; small
amounts are metabolized in muscle and fat. It binds to cell
surface receptors, is taken into the cells and is then degraded
by glutathione insulin transhydrogenase to the A and B chains
and by specific intracellular proteases.
Indications
1- Treatment of insulin-requiring diabetes mellitus
All patients with diabetic ketoacidosis require Lansulin® and
in addition, patients with diabetes whose symptoms are not
controlled by other treatment who continue to lose weight or
who have persistent hyperglycemia without symptoms
(especially in pregnancy) may require Lansulin®. In acute
diabetic ketoacidosis, treatment should be started with
Lansulin® given by continuous intravenous infusion at a rate of
6 IU. h-1 initially or by intramuscular injection (20 IU
LANSULIN R
LANSULIN NR
R
Gly lle Val Glu Gln Cys Cys Thr Ser lle Cys Ser Leu Tyr Gln Leu Glu Asn Tyr Cys Asn
Phe Val Asn Gln His Leu Cys Gly Ser His Leu Val Glu Ala Leu Tyr Leu Val Cys Gly Glu Arg Gly Phe Phe Tyr Thr Pro Lys Thr
15
Insulin (Regular)-Human
Insulin Isophane (NPH)-Human
intramuscular initially, then 6 IU intramuscular hourly),
together with potassium chloride and 0.9% sodium chloride
infusions.
Hyperosmolar, non-ketotic diabetic coma is managed similarly,
except that larger volumes of fluid are commonly needed and
hypernatremia may be present when 0.45% sodium chloride
solution is used. Treatment in insulin-requiring diabetics who
are not ketoacidotic may begin with subcutaneous injections
of Lansulin®. Circumstances will dictate the regime used:
commonly two subcutaneous injections a day, one about
30min before breakfast, and one about 30min before the
evening meal, are used. While at first only Lansulin® N may
be needed, it is later necessary to inject both Lansolin R and
Lansulin® N together. Blood glucose concentration therefore
should ideally fall in the range 4-7 mmol.1-1. Usual intravenous
insulin requirements in diabetic subjects are around 0.1-0.4
U.kg-1daily. In states of insulin resistance subcutaneous doses
in excess of 10U.kg-1 daily may have to be used.
2- Acute treatment of hyperkalemia
Life-threatening hyperkalemia may be treated acutely by
intravenous injection of Lansulin® R with glucose (to prevent
hypoglycemia). It is satisfactory to give 5g of glucose for
every international unit administered Lansulin®. This measure
is only temporarily effective in lowering serum potassium
concentration.
Contraindications
1. Hypoglycemia
7- Adverse reactions
Potentially life-threatening effects
Hypoglycemia is the most common adverse effect of treatment
with Lansulin®.
It is more likely when meals are missed, after exercise and
if inappropriately large doses of Lansulin® are used. Symptoms
of hypoglycemia include hunger, unsteadiness and sweatiness.
Signs include sweating, pallor, irrational behavior, aggression,
unconsciousness, focal neurological deficit and convulsions.
If the patient is conscious, treatment of hypoglycemia is by
the administration of rapidly absorbed carbohydrate by mouth.
The traditional carbohydrate to give is warm milk and sugar
(sucrose), but chocolate bars, glucose tablets, raisins or sugary
carbonated drinks are also effective. If the patient is
unconscious, glucose should be given intravenously as 50%
dextrose strong solution. The effects of Lansulin® may also
be counteracted briefly by the intramuscular injection of
glucagon 1mg.
Symptomatic adverse effects
Lansulin® is immunogenic, though probably less so than
highly purified porcine insulin. Urticaria within 30min of
injection, weal reactions 12-24 h after injection and systemic
reactions with demonstrable circulating antihuman insulin
IgE have all been seen with Lansulin®.
8- High risk groups
Neonates
There are no contraindications to the use of Lansulin® in this
age group if it should ever be necessary.
Breast milk. Lansulin® is destroyed in the gut so that breast
feeding is permissible.
Children
There are no contraindications to the use of Lansulin® in
children.
Pregnant women
In pregnant women hyperglycemia is associated with fetal
abnormalities, especially macrosomia, so good diabetic control
is especially important. Insulin requirements tend to fall
during the first trimester, but steadily increase during the
second and third trimesters. Immediately after placental
separation, insulin requirements are markedly reduced, and
the dose of Lansulin®, including that in intravenous infusions,
should then be halved.
The elderly
In the elderly, Lansulin® clearance may be reduced as renal
function declines, and so the duration of action may be
prolonged.
Concurrent disease
Lansulin® clearance is reduced when renal function is impaired
so elimination is slower and the duration of action of standard
preparations is prolonged.
Patients with diabetes secondary to pancreatic disease and
those with Addison’s disease or hypopituitarism in addition
to diabetes, are very insulin sensitive and generally require
very small doses of Lansulin®.
9- Drug interactions
Potentially hazardous interactions
Although several drugs may interact with Lansulin®, such
interactions are often of theoretical rather than practical
importance. The actions of Lansulin® may be augmented by
monoamine oxidase inhibitors, ?-blocking drugs, which also
suppress the tachycardia which accompanies hypoglycemia
(but not the sweating), ganglion-blocking drugs, captopril,
clonidine, and perhaps most importantly,ethanol.
Potentially useful interactions
It has been suggested that sulfonylureas, by their ability to
enhance insulin sensitivity, may be of benefit when given
with Lansulin® to insulin-dependent patients.
Storage
Keep in refrigerator (2-8º C). Protect from light and freezing.
Packaging
Vials of 10 ml
Insulin (Regular)-Human
100 IU/1 ml
(Vials of 10 ml)
R
LANSULIN RR
Insulin Isophane (NPH)-Human
100 IU/1 ml
(Vials of 10 ml)
LANSULIN N
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