Download Clinical Case 9

Clinical Case 9
G. V., a 42-year-old male showbiz personality was
known to have “Juvenile-onset” diabetes. For one
week, he complains of feeling bloated or full despite
minimal food intake, nausea and vomiting. His blood
sugar level is poorly controlled.
Question:
1.What is your diagnosis and proper therapeutic
management of this case?
2.What are prokinetic agents?
3.Give the pharmacokinetics, clinical uses and side
effects of the different prokinetic drugs.
Diagnosis: Diabetes mellitus with
hyperglycemia.
 Diabetes
mellitus is a chronic disorder of
carbohydrate, fat, and protein metabolism. A
relative or absolute deficiency in insulin
secretory response, which translates into
impaired carbohydrate (glucose) use, is a
characteristic feature of diabetes mellitus, as
is the resulting hyperglycemia.
Classification of Diabetes Mellitus
 Type
I
 Type II
 Others specific type.
Type I Diabetes Mellitus






Insulin-dependent diabetes mellitus or juvenile-onset
diabetes.
Younger people and usually diagnosis before age 30.
<10% of all DM cases.
Definition is hyperglycemia resulting from autoimmune
destruction of the insulin-producing beta cells of pancreas.
80% have HLA (HLA-DR3 and DR4) phenotypes
associated with anticytoplasmic antibodies directed toward
pancreatic beta cells (islet cell antibodies) and to glutamic
acid decarboxylase (GAD anti bodies).
Extrinsic factors that affect β cell function include damage
caused by viral such as mumps or coxsackie B4 virus and
exposure to cow’s milk instead of human milk during
infancy.
Recent studies indicate there are two
subgroups of type I diabetes:
1. Type 1A DM (immune-mediated type)
results from autoimmune beta cell
destruction, which leads to insulin deficiency.
2. Type 1B DM (idiopathic type) lack
immunologic markers indicative of an
autoimmune destructive process of the beta
cells. However, they develop insulin
deficiency by unknown mechanisms and are
ketosis prone.
Signs and Symptoms
 Polyuria.
 Polydipsia.
 Polyphagia
with weight loss.
 Recurrent blurred vision.
 Foot ulcers.
 Will suffer from Diabetic Ketoacidosis (DKA).
Laboratory Founding
 Fasting
serum glucose is >126 mg/dl.
 Glucosuria (causes an osmotic diuresis that
leads to the dehydration).
 HbA1c is a measure (it can provides an
index of the average blood glucose levels
over the 120 day life span of erythrocytes).
Type II Diabetes mellitus
Non-insulin-dependent diabetes mellitus or adultonset diabetes.
 >80% of diabetes cases which predominantly in
>30 age adults, but occasionally in adolescents
and children due to incidence of obesity and
sedentary lifestyle.
 Epidemiologic data indicate strong genetic
influences, since in monozygotic twins is >90%
(<50% type I).
 Definition is hyperglycemia due to insulin
resistance. The syndrome of insulin resistance
involves hyperglycemia leading to obesity,
hypertension, hyperlipidemia, and coronary artery
disease.

Signs and Symptoms
May be asymptomatic.
 Complication of diabetes, such as a soft tissue
infection etc.
 Signs of hyperglycemia.
 Increase susceptibility to fungal infections (cellmediated immunity is impaired by acute
hyperglycemia).
 The nonketotic hyperglycemic – hyperosmolar
coma (NKHC) is also a rare presenting situation.

Laboratory Founding
 Random
glucose >200 mg/dl.
 Asymptomatic patients require a fasting
glucose of > 126 mg/dl on two separate
occasions.
 The oral glucose tolerance test is a plasma
glucose >200 mg/dl at two hours (or at any
time up to two hours) after ingesting 75g of
glucose in solution.
Treatment
1.
2.
3.
4.
Education for when to seek medical attention, side
effects of medications, proper foot care, ophthalmology
visits, and symptoms of hyperglycemia and
hypoglycemia.
Diet recommendations for limit cholesterol to 300 mg
daily, advise a daily protein intake of 10~20%, and
carbohydrate intake of 55~60% of total calories. And
Insoluble fiber diet which tend to retard nutrient
absorption rates so that glucose absorption is slower and
hyperglycemia may be slightly diminished.
Exercise.
Medication therapy.
For the type I diabetes the mainstay of therapy is insulin
injection.
Preparation
Onset of action
Peak action
Duration
Regular insulin
30~60 min
2~4 min
6~8 hr
Rapid-acting
(Lispro)
15 min
30~90 min
2~4 hr
Intermediateacting (NPH
and Lente)
1~3 hr
6~12 hr
18~26 hr
Long-acting
(Ultra-lente
and PZI)
4~8 hr
14~24 hr
28~36 hr
NPH – Neutral Protamine Hagedorn.
PZI – Protamine Zinc Insulin suspension.
Mechanisms:

1.
2.
3.
4.
5.

It’s major anabolic hormone. It’s necessary for
Transmenbrane transport of glucose and amino
acids.
Glycogen formation in the liver and skeletal
muscles.
Conversion of glucose to triglycerides.
Nucleic acid synthesis.
Protein synthesis.
Because insulin is a polypeptide, it is degraded
in the gastrointestinal tract if taken orally. It
therefore is generally administered by
subcutaneous injection.
Side effect: Hypoglycemia is the most common
side effect that may occur during insulin therapy.
 Numbness around the
Symptoms
mouth, tingling in the
 Confusion
fingers
 Nausea
 Tremors
 Hunger
 Muscle weakness
 Tiredness
 Cold temperature
 Perspiration
 Excessive yawning
 Headache.
 Irritability
 Heart palpitations.
 Loss of consciousness
 blurred vision
For the type II diabetes is oral hypoglycemic
agents:
 First-generation
sulfonylureas
Generic name: Tolbutamide
 Second-generation sulfonylureas
Generic name: Glipizide, Glyburide,
Glimepiride
Mech. Of action:
Stimulate insulin secretion.
Pharmacokinetics:
 Given orally, these drugs bind to serum
proteins, are metabolized by the liver, and
are excreted by the liver or kidney.
Tolbutamide has the shortest duration of
action (6~12 hr), whereas the secondgeneration agent last about 24hr.
Adverse effects:
 Weight gain, hyperinsulinemia, and
hypoglycemia which delayed excretion of
the drug-resulting in its accumulation.
Meglitinide analogs
Generic name: Nateglinide, Repaglinide
Mech. Of action:
Stimulate insulin secretion.
Pharmacokinetics:
 These drugs are well absorbed orally after being
taken one to thirty minutes before meals. Both
meglitinides are metabolized to inactive products
by CYP3A4 in the liver and are excreted through
the bile.
Adverse effects:
 Although these drugs can cause hypoglycemia,
the incidence of this adverse effect appears to be
lower than with the sulfonylureas.

Biguanides
Generic name: Metformin
Mech. Of action:
Decreased endogenous hepatic production of
glucose.
Pharmacokinetics:
 Metformin is well absorbed orally, is not bound to
serum proteins, and is not metabolized. The
highest concentrations are in the saliva and
intestinal wall. Excretion is via the urine.
Adverse effects:
 Nausea.

Thiazolidinediones (glitazones)
Generic name: Pioglitazone, Rosiglitazone
Mech. Of action:
Binds to peroxisome proliferators-activated receptor-γ
in muscle, fat and liver to decrease insulin resistance.
Pharmacokinetics:
 Both pioglitazone and rosiglitazone are absorbed very
well after oral administration and are extensively
bound to serum albumin. Both undergo extensive
metabolism by different cytochrome P450. The
metabolites are primarily excreted in the urine, but the
parent agent leaves via the bile.
Adverse effects:
 Weight gain and risk of heptotoxicity


α-Glucosidase inhibitors
Generic name: Acarbose, Miglitol
Mech. Of action:
Decreased glucose absorption.
Pharmacokinetics:

Acarbose is poorly absorbed. It’s metabolized primarily by
intestinal bacteria, and some of the metabolites are
absorbed and excreted into the urine. On the other hand,
miglitol is very well absorbed but has no systemic effects. It
is excreted unchanged by the kidney.
Adverse effects:

The major side effects are flatulence, diarrhea, and
abdominal cramping. Patient with inflammatory bowel
diease, colonic ulceration, or intestinal obstruction should
not use these drugs.
 The
first and scond-generation sulfonylureas
and meglitinide have risk of hypoglycemia.
 The classification, or type, of diabetes is
determined by the underlying cause of the
diabetes, not the type of therapy that is used
to treat the diabetes. Many patients with
type 2 diabetes will progress insulin to
control of blood glucose levels, but these
patients are still type 2 diabetics.
Note:
1. Hyperglycemia
A condition in which an excessive amount of glucose
circulates in the blood plasma. Caused by :
 Impaired secretion of insulin.
 Decreased insulin effectiveness at glucose uptake.
 Impair inhibition of hepatic gluconeogenesis.
Sign and Symptom







Extreme thirst.
Hunger.
Headache.
Blurred vision.
Dry skin.
Feeling drowsy.
Feeling sick with stomach.
2. Diabetic Ketoacidosis (DKA)
It is metabolic acidosis due to ketoacid accumulation due to
severely depressed insulin levels. Blood sugar levels
exceed 240 mg/dl for an extended period of time the
diabetic is at risk of going into diabetic ketoacidosis. Cause
by:
 Severe insulin deficiency so lead the body to switch from
metabolizing carbohydrates to metabolizing and oxidizing
lipids.
 Precipitated by lapse in insulin treatment, acute infection,
or major trauma.
Sign and Symptom
 Polyuria, nausea, vomiting.
 Signs of dehydration and hypotensive and tachycardic.
 Kussmaul respirations (rapid deep breaths).
 Aceton (fruity) odor breath.
Complications of Diabetes (Types
I and II)
Hypoglycemia may be cause by injecting too much
insulin (overdose) or not eating enough food
during a daily diet regimen so lead blood sugar
level below the normal which is 70~120mg/dl.
 Diabetic Ketoacidosis (usually type I).
 Nonketotic hyperosmolar coma (usually type II).
 Retinopathy.
 Stroke, MI.
 Renal insufficiency.
 Neuropathy.
 Infection.

Others Specific Type of Diabetes
Mellitus
1. Maturity-onset diabetes of the young (MONDY)
 This subgroup is a relatively rare monogenic
disorder characterized by non-insulin-dependent
diabetes with autosomal dominant inheritance and
an age at onset of 25 years or younger.
2. Gestational diabetes mellitus (GDM)
 It’s happen during pregnancy. But in the serum,
the HbA1c detect is normal and it will become
normal after delivery of six-week.
3. Impaired glucose tolerance (IGT)
The before and after meal’s sugar blood level are
between normal and diabetes mellitus.