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    Pharmacotherapy of Diabetes Mellitus: Matrikulasi PSPA STIFAR RIAU Angkatan V Senin, 15 Februari 2021

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    Sulastari Cahyani II
    Pharmacotherapy of Diabetes Mellitus involves treatment with insulin or oral medications to manage blood glucose levels. The document discusses classification of diabetes, mechanisms of insulin and other drugs, and treatment of conditions like diabetic ketoacidosis. It provides an overview of insulin preparations and analogs, oral antidiabetic drugs like sulfonylureas and metformin, and newer classes of drugs like thiazolidinediones that work by sensitizing tissues to insulin.

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    Pharmacotherapy of Diabetes Mellitus: Matrikulasi PSPA STIFAR RIAU Angkatan V Senin, 15 Februari 2021

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    Sulastari Cahyani II
    26 views50 pages
    Pharmacotherapy of Diabetes Mellitus involves treatment with insulin or oral medications to manage blood glucose levels. The document discusses classification of diabetes, mechanisms of insulin and other drugs, and treatment of conditions like diabetic ketoacidosis. It provides an overview of insulin preparations and analogs, oral antidiabetic drugs like sulfonylureas and metformin, and newer classes of drugs like thiazolidinediones that work by sensitizing tissues to insulin.

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    diabetesmellitus-ADRIANISUSANTY

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    Pharmacotherapy of Diabetes Mellitus involves treatment with insulin or oral medications to manage blood glucose levels. The document discusses classification of diabetes, mechanisms of insulin and other drugs, and treatment of conditions like diabetic ketoacidosis. It provides an overview of insulin preparations and analogs, oral antidiabetic drugs like sulfonylureas and metformin, and newer classes of drugs like thiazolidinediones that work by sensitizing tissues to insulin.

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    © All Rights Reserved
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    Download as pptx, pdf, or txt
    26 views50 pages

    Pharmacotherapy of Diabetes Mellitus: Matrikulasi PSPA STIFAR RIAU Angkatan V Senin, 15 Februari 2021

    Uploaded by

    Sulastari Cahyani II
    Pharmacotherapy of Diabetes Mellitus involves treatment with insulin or oral medications to manage blood glucose levels. The document discusses classification of diabetes, mechanisms of insulin and other drugs, and treatment of conditions like diabetic ketoacidosis. It provides an overview of insulin preparations and analogs, oral antidiabetic drugs like sulfonylureas and metformin, and newer classes of drugs like thiazolidinediones that work by sensitizing tissues to insulin.

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    © All Rights Reserved
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    of 50

    Pharmacotherapy of Diabetes Mellitus

    Matrikulasi PSPA STIFAR RIAU Angkatan V

    Senin, 15 Februari 2021

    Dr. apt. Adriani Susanty, M.Farm


    *Diabetes
    • Diabetes is a group of metabolic
    disorders characterized by
    chronic hyperglycemia associated with
    disturbances of carbohydrate, fat and protein
    metabolism due to absolute or relative
    deficiency in insulin secretion and/or action
    • Diabetes causes long term damage,
    dysfunction & failure of various
    organs
    *Diagnosis of diabetes
    • Fasting Plasma Glucose ≥ 126 mg / dl
    • Symptoms of DM and a random blood
    glucose level of ≥ 200 mg/dl
    • Oral glucose tolerance test
    – 2 hr after 75 gm glucose load ≥ 200 mg /
    dl
    *Classification of Diabetes
    Proposed by ADA - 1997.
    • Type I:
    – Absolute Insulin Deficiency due to
    islet cell destruction
    • Either immune mediated or idiopathic
    • Type II:
    – Relative insulin deficiency due to impaired -cell
    function
    – Marked ↑ peripheral insulin resistance
    • Type III: Other Specific types
    • Type IV: Gestational Diabetes
    *Other specific types
    A) Genetic defects of Beta cell function (MODY syndromes)

    B) Genetic defects in Insulin action (Lipo atrophic Diabetes)

    C) Diseases of the Exocrine Pancreas (pancreatitis)

    D) Secondary to Endocrinopathies (Acromegaly, Cushings syndrome)

    E) Drugs / Chemical induced (Steriods, thiazides)

    F) Infections (Congenital Rubella )

    G) Uncommon form of Immune Mediated Diabetes. (Anti insulin receptor


    antibodies)

    H) Other Genetic Syndromes associated with Diabetes (Down’s syndromes,


    Turners syndromes, Klinefelters syndrome)
    * Type 2
    Diabetes
    β cells : insulin 65-70 %

    cells : glucagon 25 % δcells

    : somatostatin 10 %

    PP (or F cells): pancreatic


    polypeptide 2 %
    *Insulin
    • Glucose transporters –

    • GLUT 1
    Non insulin mediated glucose uptake
    • GLUT 3

    • GLUT 2 – Beta cell – Glucose sensors

    • GLUT 4 – Insulin mediated glucose uptake in


    muscle & Adipose tissue
    * Cell at rest
    *Secretion of insulin
    > 70 mg/ml

    GLUT 2
    *Regulation of insulin secretion
    • Direct stimulation
    • Plasma glucose or Amino Acids , ketones
    • Hormonal regulation
    • Gastrointestinal hormones (GIP, CCK) directly
    stimulate β cells
    • Neural regulation
    • Parasympathetic stimulates insulin release
    through IP3/ DAG
    • Sympathetic NS inhibits insulin release
    through 2 receptor activation
    *Carbohydrate metabolism
    • Over all action of insulin is to ↓ glucose level
    in blood
    – ↑ Transport of glucose inside the cell
    – ↑ Peripheral utilization of glucose
    – ↑ Glycogen synthesis
    – ↓ Glycogenolysis
    – ↓ Neoglucogenesis
    *Lipid metabolism
    • ↓ Lipolysis
    • ↑ Lipogenesis
    • ↓ Ketogenesis
    • ↑ Clearance of VLDL & chylomicrons from
    blood through enzyme Vascular Endothelial
    Lipoprotein Lipase
    *Protein metabolism
    • Protein synthesis
    • ↑ entry of amino acids in cells

    Electrolyte metabolism
    • ↑ transport of K+, Ca++, inorganic phosphates
    *Other actions
    • Vascular actions:
    – Vasodilation ? Activation of endothelial NO
    production
    • Anti-inflammatory action
    – Especially in vasculature
    • Decreased fibrinolysis
    • Growth
    • Steroidogenesis
    *Mechanism of action of insulin
    *Conventional insulin
    Type preparations
    Onset
    (Hr)
    Peak DOA
    (Hr) (Hr)
    Regular 0.5 -1 2-4 6-8
    Short acting insulin 1 3-6 12-16
    Semilente
    Intermedia Lente
    te acting Isophane 1-2 8-10 20-24
    (NPH)
    Long acting Ultra lente
    Protamine 4-6 14-18 24-36
    Zinc Insulin
    (PZI)
    *Newer Insulin analogs
    Type Onset Peak DOA
    (Hr) (Hr)

    Lispro 5-15 min 1 3-5


    Rapid Aspart 10-15 min 1 3-5
    acting Glulisine 5-15 min 1 5-6

    Long acting Glargine 1-2 hrs No peak 24 hr


    Detemir 2-3 hrs 6-8 hr 24 hr
    *Action Profiles of Insulins
    Aspart, glulisine, lispro 4–5 hours
    Plasma Regular 6–8 hours
    insulin NPH 12–16 hours
    levels
    Detemir ~14 hours
    Ultralente 18–20 hours
    Glargine ~24 hours

    0 1 2 3 4 5 6 7 8 9
    10 11 12 13 14 15 16 17 18 19 20 21 22 23 24
    Hrs
    Danne T et al. Diabetes Care. 2003;26:3087-3092
    *Indications of insulin in type
    II DM
    • Primary or secondary failure of oral
    hypoglycemics
    • Pregnancy
    • Perioperative period
    • Steroid therapy
    • Fasting > 300 mg HbA1c
    • Unintentional wt loss with or with
    out ketosis
    • Type 2 with DKA ( severe beta cell
    *Pathogenesis of DKA
    Insulin deficiency Absolute / relative
    +
    Counter hormone excess
    ↓ Anabolism ↑catabolism
    ↑ Glycogenolysis
    ↓Peripheral utilization ↑ Glycolysis
    of Glucose ↑Gluconeogenesis

    Hyperglycemia Dehydration
    ↓ Fluid intake
    Heavy glucosuria Loss of water
    (osmotic diuresis) & electrolytes Hyperosmolarity
    *Pathogenesis of DKA
    (How ketoacidosis occurs)
    ↑ Lipolysis Hyperketonemia

    ↑ FFA to liver ↓ Alkali reserve

    ↑ Acetyl coA
    Acidosis

    ↑ Acetoacetyl coA

    Acetoacetate -Hydroxy butrate


    Acetone
    *Treatment of DKA
    • Fluid therapy
    • Rapid acting regular insulin
    • Potassium replacement
    • Bicarbonate replacement
    • Phosphate replacement
    • Antibiotics
    • Treatment of precipitating cause
    • General measures
    *Fluid therapy
    • Adequate tissue perfusion is necessary insulin
    action
    • Normal saline is fluid of choice for initial
    rehydration
    – 1 litre in first hour
    – Next 1 L in next 2 hours
    – 2 litres in next 4 hours
    – 2 litres in next 8 hours
    • i.e 4 to 6 litres in 24 hours
    • When BSL reaches 300 mg% fluid should be
    changed to 5 % dextrose with concurrent insulin
    *Insulin in DKA
    • Regular/ short acting insulin IV treatment of
    choice
    • Loading dose = 0.1-0.2 U/kg IV bolus
    • Then 0.1 U /kg/hr IV by continuous infusion
    • Rate doubled if no significant fall in BSL in 2 hr
    • 2-3 U/hr after BSL reaches 300mg%
    • If patient becomes fully conscious encouraged to
    take oral food & SC insulin started
    *Potassium replacement
    • In initial stage of treatment potassium not
    administered because in DKA it remains
    normal or ↑
    • In presence of insulin infusion Sr potassium ↓
    hence 10 mEq/L potassium can be added with
    3rd bottle of normal saline
    • Sr K+ < 3.3 mEq/L : 20 -30 mEq/hr
    *Bicarbonates & phosphates
    • Bicarbonates
    – If blood pH > 7.1 no need of sodium
    bicarbonate
    – In presence of severe acidosis 50 mEq of sodium
    bicarbonate added to IV fluid
    • Phosphates
    – Non availability of ideal preparation
    – Replacement not very essential unless < 1 mEq/L
    – potassium phosphate 5-10 m mol/hr
    *Insulin resistance
    • State in which normal amount of insulin
    produces subnormal amount of insulin
    response
    – ↓ insulin receptors
    – ↓ affinity for receptors
    • May be acute or chronic
    • Requirement of > 200 Units of insulin per day in
    absence of stress
    • Common in type II diabetics & obese
    *Oral antidiabetic drugs
    • Sulfonylureas:
    • Meglitinides:
    • Biguanides :
    • Thiazolidinediones:
    • -glucosidase inhibitors:
    *Sulfonylureas
    I.Generation
    – Tolbutamide
    – Chlorpropamide
    II.Generation
    – Glipizide
    – Gliclazide
    – Glibenclamide (Glyburide)
    – Glimepiride
    *Adverse effects
    • Hypoglycemia:
    • GI disturbances: Nausea, vomiting, metallic
    taste, diarrhoea & flatulence
    • Weight gain
    • Hypersensitivity
    • Not safe in pregnancy
    • Chlorpropamide:
    – cholestatic jaundice, dilutional hyponatremia,
    antabuse reaction
    *Contra indications
    1. Allergy to SU
    2. Renal failure:
    3. Significant hepatic dysfunction
    4. Severe infections, stress, trauma, major surgery
    5. Pregnancy (except Glibenclamide)
    6. T1DM
    *METFORMIN - INDICATIONS
    • Obese Type 2 Diabetes.

    • Secondary Sulfonylurea Failure state.

    • To reduce Insulin requirements.

    • Can be combined with Sulfonylureas,


    Glitazones, Insulin.
    *Thiazolidinediones (Glitazones)
    Rosiglitazone & pioglitazone Selective agonists of PPAR

    Bind to nuclear PPAR

    Activate insulin responsive genes - regulate


    carbohydrate & lipid metabolism

    Sensitize the peripheral tissues to insulin

    ↓blood glucose by

    Inhibit hepatic
    ↑ Glucose transport into
    gluconeogenesis Promote
    muscle & adipose tissue
    lipogenesis
    • Pioglitazone:
    – 15 to 45 mg once daily orally
    • Rosiglitazone:
    – 4 to 8 mg once daily orally
    • Pt who benefit most are type II DM with
    substantial amount of insulin resistance
    • Monotherapy – Hypoglycemia rare
    • Add-on Therapy – readjust dosage.
    • Takes one month to act
    *Alpha glucosidase inhibitors
    • Acarbose
    • Miglitol
    • Voglibose
    *Voglibose
    • Advantages over Acarbose and Miglitol
    – 20-30 times more potent then acarbose
    – Does not affect digoxin bioavailability unlike
    acarbose
    – No dosage adjustment required in renal
    impairment patients unlike miglitol
    – Superior tolerability
    – Dose: 0.2 to 5 mg

    43
    *Newer drugs for Type II DM
    • GLP-1 Analogues
    • Amylin analog:
    –Exenatide
     Pramlintide
    –Liraglutide
    • DPP-IV Inhibitors

    –Sitagliptin
    –Vildagliptin
    –Alogliptin
    * Principles of treatment of Type 2 DM

    Grade Diabetes Mellitus as mild, moderate or severe NB: (150


    -200 ---mild ) HbA1c < 8
    ( 200-250 --- Moderate) HbA1c 8 - 9
    ( more than 250 severe) HbA1c 9 - 10
    For severe DM start on insulin if there is wt loss & ketosis
    For mild & moderate DM use metformin if obese &
    sulfonylureas if not obese
    If diabetes not controlled

    Look for SU failure

    Occult infection – TB – UTI

    Drug history and compliance

    Food history – hypoglycaemia

    and compliance
    cardiac problem – avoid
    glitazones
    if in failure
    avoid metformin
    Renal problem
    – avoid
    metformin
    * Liver problem avoid
    – glitazone
    and
    metformin

    In general

    patients with complication

    Short acting SU or insulin


    Be ware of other drugs

    - Diuretics

    - Corticosteroid

    - Other hormones

    - ACE inhibitors

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