Clinical Case 9

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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.

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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.

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Classification of Diabetes Mellitus

• Type I
• Type II
• Others specific type.

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Type I Diabetes Mellitus

• Insulin-dependent diabetes mellitus or
  juvenile-onset diabetes.
• Younger people and usually diagnosis before age
  30.
• lt10 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 ß cell function
  include damage caused by viral such as mumps or
  coxsackie B4 virus and exposure to cows milk
  instead of human milk during infancy.

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• 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.

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Signs and Symptoms

• Polyuria.
• Polydipsia.
• Polyphagia with weight loss.
• Recurrent blurred vision.
• Foot ulcers.
• Will suffer from Diabetic Ketoacidosis (DKA).

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Laboratory Founding

• Fasting serum glucose is gt126 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).

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Type II Diabetes mellitus

• Non-insulin-dependent diabetes mellitus or
  adult-onset diabetes.
• gt80 of diabetes cases which predominantly in gt30
  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 gt90
  (lt50 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.

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Signs and Symptoms

• May be asymptomatic.
• Complication of diabetes, such as a soft tissue
  infection etc.
• Signs of hyperglycemia.
• Increase susceptibility to fungal infections
  (cell-mediated immunity is impaired by acute
  hyperglycemia).
• The nonketotic hyperglycemic hyperosmolar coma
  (NKHC) is also a rare presenting situation.

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Laboratory Founding

• Random glucose gt200 mg/dl.
• Asymptomatic patients require a fasting glucose
  of gt 126 mg/dl on two separate occasions.
• The oral glucose tolerance test is a plasma
  glucose gt200 mg/dl at two hours (or at any time
  up to two hours) after ingesting 75g of glucose
  in solution.

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Treatment

• 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
  1020, and carbohydrate intake of 5560 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.

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Preparation Onset of action Peak action Duration
Regular insulin 3060 min 24 min 68 hr
Rapid-acting (Lispro) 15 min 3090 min 24 hr
Intermediate-acting (NPH and Lente) 13 hr 612 hr 1826 hr
Long-acting (Ultra-lente and PZI) 48 hr 1424 hr 2836 hr
NPH Neutral Protamine Hagedorn. PZI Protamine
Zinc Insulin suspension.
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Mechanisms

• Its major anabolic hormone. Its 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.

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Side effect Hypoglycemia is the most common side
effect that may occur during insulin therapy.

• Numbness around the mouth, tingling in the
  fingers
• Tremors
• Muscle weakness
• Cold temperature
• Excessive yawning
• Irritability
• Loss of consciousness

• Symptoms
• Confusion
• Nausea
• Hunger
• Tiredness
• Perspiration
• Headache.
• Heart palpitations.
• blurred vision

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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.

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• 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 (612 hr), whereas the
  second-generation agent last about 24hr.
• Adverse effects
• Weight gain, hyperinsulinemia, and hypoglycemia
  which delayed excretion of the drug-resulting in
  its accumulation.

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• 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.

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• 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.

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• Thiazolidinediones (glitazones)
• Generic name Pioglitazone, Rosiglitazone
• Mech. Of action
• Binds to peroxisome proliferators-activated
  receptor-? 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

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• a-Glucosidase inhibitors
• Generic name Acarbose, Miglitol
• Mech. Of action
• Decreased glucose absorption.
• Pharmacokinetics
• Acarbose is poorly absorbed. Its 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.

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• 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.

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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.

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• 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.

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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 70120mg/dl.
• Diabetic Ketoacidosis (usually type I).
• Nonketotic hyperosmolar coma (usually type II).
• Retinopathy.
• Stroke, MI.
• Renal insufficiency.
• Neuropathy.
• Infection.

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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)
• Its 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 meals sugar blood level are
  between normal and diabetes mellitus.