Insulin22
Upcoming SlideShare
Loading in...5
×
 

Insulin22

on

  • 4,157 views

ALL ABOUT INSULIN FROM HISTORY TO PRESENT TRENDS OF USE...

ALL ABOUT INSULIN FROM HISTORY TO PRESENT TRENDS OF USE...

Statistics

Views

Total Views
4,157
Slideshare-icon Views on SlideShare
4,157
Embed Views
0

Actions

Likes
4
Downloads
219
Comments
0

0 Embeds 0

No embeds

Accessibility

Upload Details

Uploaded via as Microsoft PowerPoint

Usage Rights

© All Rights Reserved

Report content

Flagged as inappropriate Flag as inappropriate
Flag as inappropriate

Select your reason for flagging this presentation as inappropriate.

Cancel
  • Full Name Full Name Comment goes here.
    Are you sure you want to
    Your message goes here
    Processing…
Post Comment
Edit your comment

    Insulin22 Insulin22 Presentation Transcript

    • INSULIN
      Dr.Nagula Praveen
    • Insulin is not a cure for diabetes; it is a treatment. It enables the diabetic to burn sufficient carbohydrates, so that proteins and fats may be added to the diet in sufficient quantities to provide energy for the economic burdens of life. 
      — Sir Frederick Grant Banting'Diabetes and Insulin', Nobel Lecture, 15 September 1925. In Nobel Lectures: Physiology or Medicine, 1922-1941 (1965), 68. 
    • Laughter is the best medicine - unless you're diabetic, then insulin comes pretty high on the list. Jasper Carrott 
    • Introduction
      Is a protein
      Synthesised from the beta cells of islets of langerhans.
      Deficiency causes DIABETES MELLITUS.
      Gene located on chromosome 11.
      Name 'insulin'by J de meyer .-1907.
      Insulin –first hormone for which radioimmunoassay was developed.
      Name ''insulin'' is derived from word insula—meaning island---a latin word.
      Connaught initial name
      Novo nordisk –since 1923
    • History
      1869---Paul Langerhans–two distinct group of cells in pancreas –acinar cells ,islets.
      1889---Minkowski---pancreactomized dogs—diabetes mellitus.
      1921—Frederick Grant Banting–insulin secreted was destroyed by proteolytic digestion
      Charles .H.Best, a fourth year medical student –ligated the pancreatic ducts
      Leonard Thompson, a 14 yr old was the first person to receive insulin .---11 JAN 1922
      J.M.Collip-who purified epinephrine,purified insulin also.
      Purified and crystallized –Abev
      Aminoacid sequence by Sanger—1960
      Complete synthesis of protein-1963
      3 dimensional structure—Hodgkins-1971
      NOBEL PRIZE in medicine or physiology-1923-Banting and Best,Mcleod and Collip
    • Best and Banting
    • BANTING AND BEST
    • Leonard thompson
    • V.SHESHAIH
    • Secretion of insulin
      Β cells of islets of langerhans in the pancreas—secrete 110 AA chain ,single chain—PREPROINSULIN.
      Rough endoplasmic reticulum---24 AAterminal( NH2)of preproinsulin is cleaved off—PROINSULIN
      During formation of PROINSULIN,the molecule folds,disulfide bonds are formed
      Converted to INSULIN-golgi complex.
      During conversion –4 basic AA are removed,remaining connector or C peptide removed byproteolysis.
      Insulin formed is stored in vesicles.
      Bound to zinc atoms.
      Exist in hexamer form.
    • Structure of insulin
      51 amino acids
      5808 daltons
      2 peptide chains A and B
      One intrasubunit and two intersubunit disulphide bonds
      A-21 AA,B-30 AA
      Slight difference in structure in species
      Porcine-one AA
      Bovine—3 AA
      C peptide differs in all.
    • Equimolar amounts of C peptide,insulin are released into the circulation.
      C peptide has no biological function.
      It is useful index of insulin secretion.
      Proinsulin-insulin by 2 Ca endopeptidases
      PC2 lysine arginine—C-A
      PC3 argininearginine –C-B
    • Structure of insulin
      Conserved portions of insulin—3 disulfide bonds
      Both ends of A chain
      C terminal residues of B chain
    • INSULIN STRUCTURE
    • Genetics of insulin
      Single insulin gene –chromosome 11
      Close to IGF-1
      Single protein product in most species
      2 genes encode—rat,mice---two molecules differ from each other by 2 AA residuesin B chain.
      Several  helical regions in both A and B chains.
      Proinsulin –INS gene
    • Existence of insulin
      Isolated chains of insulin are inactive.
      In acid solution –dimers
      At neutral Ph—exist as hexamers and with Zn.
      Insulin in solution exists as monomer,dimer,hexamer
      Intermediate,long acting insulins have hexamers are common
      2 molecules of zn are incorporated in hexamer .
      Zn plays a role in crystallization.
      Monomer is active.
    • Pharmacology of insulin
      Introduction of insulin of human insulin,proinsulin gene into organisms—e.coli,yeast-recombinant DNA technology.
      Insulin ppt at ph—5.4—soluble at 2-3
      1 U of insulin -38.5 ug of substance
      40 U and 100 U –40u/ml,100u/ml
      10 U for infants
      T1/2—40 min
    • NN= SaccharomycesCerevisiae
      Eli lilly= non-disease producing strain of E.Coli
      Sanofi= non-disease producing strain of E.Coli
    • Insulin receptor
      Insulin binds to N and C terminal of  subunit of the receptor.
      cysteine rich region in alpha subunit.
      Affinity towards receptor-effect on glucose metabolism.
      Insulin is a member of IGF s.
      IGF1,IGF2 –are similar to proinsulin ,concerned with growth,Cpeptides are not removed.
      IGF1 –somatomedin,growth promoting actions of insulin.
      Proinsulin has 2% metabolic potency of insulin,50% as potent for mitogenesis---atherosclerosis
    • hexamer
    • After injection
    • Regulation of insulin secretion
      Prinicipal stimulus for insulin secretion is the glucose.
      Sugar is more effective in provoking insulin secretion when taken orally than when taken IV –inc vagal activity.
      Stimulants—various nutrients-glucose,AA,FA,ketones.
      GI hormones
      pancreatic hormones
      autonomic neuro transmitters
      2 adrenergic receptor—inhibits insulin receptor.
      Β2 adrenergic receptor,vagal—release.
      Hypoxia,hypothermia,surgery,severe burns—suppress insulin secretion.
      2 antagonists—increases insulin
      B2 antagonists—decreases insulin
      HORMONES—GLP-1,GIP-inc insulin
      Similarly gastrin,secretin,cholecystokinin,VIP,GRP,enteroglucagon
    • Insulin secretion is BIPHASIC.
      First phase—peak at 1-2 min,short lived.
      Second phase-delayed onset,long duration.
      Depends on intracellular calcium
      Intracelular Ca—increased by phospholipase C by Ach,cholecystokinin
      Inc c AMP-b adenylcyclase---GLUCAGON.
      Insulin circulates in blood as monomer.
      Distributed in ECF..
      Aminoacid which causes secretion of insulin –arginine.
      Glucokinase acts as glucose sensor.
      Glucose conc <90mg/dl—no insulin release
    • Rate of secretion in fasting—1U of insulin /hr into portal vein
      Conc of insulin 2-4 ng/ml.50-10031U/ml-portal vein
      Peripheral circulation—0.5ng/ml,12U/ml.
      Goal of insulin therapy is to mimic this pattern –diificult to achieve with SC injection.
      T1/2-insulin 5-6 min in normal subjects
      Increased in diabetes
      Proinsulin -17 min
      C peptide -30 min serves as a marker of insulin secretion
    • degradation
      Liver,kidney,muscle
      50% insulin that reaches liver is destroyed.
      It is filtered by glomeruli-reabsorbed by tubules –degrade it
      Renal function impairement appears to affect the rate of disappearance of circulating insulin to a greater extent than hepatic disease
      Degraded in endosomes of liver.
      Thiolmetalloproteinases in liver,muscle,kidney,brain
      insulinase
    • Functions of insulin
      Globally—
      Control of cellular intake of certain substance-glucose in muscle,adipose tissue.
      Increase of DNA replication and protein synthesis
      Modification of activity of numerous enzymes.
    • Cellular level
      Increased glycogen synthesis.
      Increased fatty acid synthesis.
      Increased esterification of fatty acids
      Decreased proteolysis
      Decreased lipolysis
      Decreased gluconeogenesis
      Decreased autophagy
      Increased aminoacid uptake
      Increased potassium uptake
      Relaxes arterial muscle tone,increases blood flow-micro arteries
      Increases HCL secretion in stomach.
    • Types of insulin
      20types of insulin products available in four basic forms,each with a different time of onset and duration of action.
      Which to choose is individulaised
      Choosing insulin depends on
      Onset-how soon it starts working
      peak time-when it works the hardest
      Duration-how long it lasts in the body.
      Obesity affects the work of insulin in the body.extra fat tissue –more resistant to insulin.
    • Types of insulin
      Five different types
      Some are clear in appearance .,some are cloudy
      RAPID ONSET-FAST ACTING INSULIN-novo rapid (insulin Aspart)
      humalog (Lispro)
      SHORT ACTING INSULIN—actrapid,Humulin,hypurin neutral(bovine)
      INTERMEDIATE ACTING INSULIN-cloudy—protamine or zinc added
      Protamine—protaphane,humulinNPH.hypurinisophane
      MIXED INSULIN—RAPID/INTERMEDIATE—novomix 30,humalog mix 25,mixtard 30/70,mixtard 20/80
      30/70—30% is short acting,70% long acting
      LONG ACTING INSULIN-lantus-(glargine).levemir(detemir)
    • Insulin sliding scale
      Not recommended for subcutaneous injection
      50U -50 ml NS
      Every one hour until the blood glucose level stabilises
      Rate of infusion adjusted as per blood sugar.
      <120mg/dl-no insulin
      120-200---2U/hr
      200-300—3U/hr
      300-500---5U/hr
      >500---7U/hr
      -JAPI october 2007
    • Somoygi phenomenon
      Somogyi effect is a rebounding high blood sugar that is a response to low blood sugar.
      It is due to counteracting hormones release –glucagon,adrenaline,cortisol
      Frequent monitoring of blood glucose
      Night dose to be low compared to morning dose.
    • Dawns phenomenon
      Early morning hyperglycemia without nocturnal hypoglycemia.
      It is due to counter regulatory hormones
      No need of insulin dose change.
    • Increasing requirements
      Infection,stress,puberty,pregnancy,acromegaly,cushings syndrome.
      Lipohypertrophy at the site of injection
      Malignancies
      Compliance of the patient
    • Decreaesing requirements
      Impending renal failure
      Honeymoon phase in type 1
      Hypothyroidism
      Addisons disease
      Hypopituitarism
      Remission of diabetes
    • In renal disease
      Half of the sliding scale of insulin dose to be given
      As insulinase enzyme does not function
      The duration of insulin action increases.
    • Indications for insulin therapy
      Type 1 diabetes
      Women with diabetes who become pregnant or are breastfeeding
      Transiently in type 2 diabetes in special situations- renal & hepatic disease, pancreatitis, HHS, during surgery, infections etc.
      In type 2 diabetes, inadequately controlled on OADs
    • Side effects of insulin use
      Hypoglycemia
      Weight gain
      Locally-allergy
      infection
      abscess
      anaphylaxis
    • Insulin devices
      Insulin syringes
      Delivery pens
      Insulin pumps
      Insulin syringes—10ml insulin vials
      30 unit—0.3 ml,50 unit-0.5 ml,100 unit-1ml
      Needles -8mm to 13mm
      Use each syringe only once.
      Insulin pen-insulin catridge-3ml-300units fits into the device
      Disposable, reusable
      Durable pens are—Novopen3,Novopen demi,Innovo and HumaPen
      Pre filed disposable devices –innolet,flexpen and Novolet.
    • Insulin pumps-reservoir of insulin-infusion set
      worn outside the body—abdomen
      Only short or rapid acting insulin are used—mimics physiological pattern
      Inhaled insulin
    • Mode of administration
      Subcutaneous
      Intravenous
      Inhaled
      Intramuscular
    • Subcutaneous injection
    • Sites
      Rotation of injection site to prevent lipohypertrophy.
      Within one area.
      Abdomen has fastest rate of absorption
      Exercise increases
      lipohypertrophydecreasees
      Rate of absorption after IM is faster.
    • Sites of injection
    • syringes
      1ml most common
      26-31 guage needle
      30 or 31 bend in single use
      No sharing of needles
      Reuse is widely practiced
      Infection---poor hygeine,concurrent illness
    • Insulin syringe and vial
    • Timing of insulin
      30 min prior to meals
      Not to exceed 30 min in case of rapidly acting insulins
      Intermediate acting insulin –bed time.
    • Insulin injection
      Cloudy insulin gently rolled in between
      Pen needs to be rotated upside down for at least ten times before using
      Air of volume equal to dose of insulin should be injected in vial.
      No use of alcohol may destroy silicon coating.
      90 angle—thin 45 
      Routine aspiration not needed
      Embedded for 5 sec after complete depression--pens
    • Alternative routes—failed
      Jet injectors—deliver high pressure stream of insulin.
      Useful in lipoatrophy.
      Transdermal
      Iontophoresis
      Low frequency ultra sound
      Transferomes—phosphatidylcholine vesicles
      50% SC efficiency
    • Intranasal
      Bioavailability is 8-15%
      Nasal irritation is common
      High rates of treatment failure.
      Gelified nasal insulin
      Oral
      Enteric—limited bioavailability
      Too large,hydrophilic
      Only 0.5% reaches circulation
      Buccal—aerosol solution
      • Pulmonary—large surface area—premeal delivery
      Lung cancer risk
    • Thank you
    • Types of insulin
    • Types of insulin and action
    • Regular insulin
      Clear solution at neutral pH
      0.4% zinc added-hexamers
      Phenol or cresol-prevent growth of microorganisms
      Onset of action within 15-30 min after SC
      max activity-120 -150 min
      Action -6-8 hrs
      Insulin to be given 30-40 min prior to meals
    • indications
      In case of type1 DM ,type 2 DM –DKA,HONK,Pregnancy,patients being taken up for surgery,acute illness.
      Controls post prandial blood glucose levels when used with long acting insulins.
    • NPH or isophane insulin
      At hagedorn university in 1940.
      Protamine added in 1:6 ratio to regular insulin
      Phosphate buffer for neutral ph
      Zinc ,cresol.
      Peak of action at 5-7 hrs
      Action lasts for 12-15 hrs.
      Bed time to control FBS.
      Cloudy.
    • Lente insulin
      Zinc in amounts 10 times to NPH
      Acetate as buffer
      Insoluble zinc insulin complexes
      Semilente---amorphous,biphasic absorption
      Ultralente—long acting crystalline suspension
      Can’t be mixed with regular insulin.
    • Premixed formulations
      30:70
      50:50
      25:75
      Regular and NPH insulin
    • Rapidly acting insulins—insulin analogues
      Analogous to keep insulin in monomeric form
      Only change in aminoacid sequence at a particular point.
      Action starts within 15 min after SC injection.
      Peaks at 60-90 min
      Over by 4 hrs
      Post prandial excursions curtailed
      No delayed hypoglycemia.
    • Aspart
    • Aspart
      by Novo Nordisk as Novolog or Novorapid
      B28 ---proline is substituted by aspartic acid residue.
      Increased charge repulsion—no hexamers
      Components-
      zinc-metal ion19.6g/ml
      buffer-disodium hydrogen phosphate dihydrate1.25 mg/ml
      Preservative-- m cresol 1.72mg/ml Phenol 1.50mg/ml
      Isotoncity agent –glycerin and Nacl
      ph 7.2-7.6
    • NovoRapid (Insulin Aspart )
      Pro
      Phe
      Gly
      Arg
      Phe
      Asp
      Tyr
      Glu
      B20
      Thr
      Gly
      Asp
      Cys
      Lys
      B28
      B30
      Thr
      Val
      Asn
      Cys
      A21
      Tyr
      Leu
      A1
      Gly
      Asn
      Tyr
      Ile
      Glu
      Leu
      Val
      Leu
      Ala
      Glu
      Gln
      Glu
      Gln
      Tyr
      Val
      Leu
      Cys
      Ser
      Cys
      Leu
      Ile
      Ser
      Thr
      Cys
      His
      Ser
      Gly
      Cys
      Leu
      B1
      His
      Gln
      Asn
      Val
      Phe
    • Lispro
    • Lispro
      Marketed by Eli Lilly—HUMALOG
      First insulin analogue.
      Penultimate lysine and proline residues on the Cterminal end of B chain are reversed---no change in receptor binding.
      No formation of hexamers
      Post prandial excursions are controlled.
    • Glulisine
    • Glulisine
      Marketed by sanofiaventis. APIDRA
      Asparagine is replaced by lysine at B3
      Lysine replaced by glutamic acid at B29
      3B-lysine-29B-glutamic acid-human insulin
    • Long acting insulin analogues
      Steady basal insulin levels
      Glargine –isoelectric at 7.4
      Clear and soluble at acidic ph
      Ppt after SC injection
      Action >24 hrs
      Detemir—fatty acid chain attached to it.
    • Glargine
    • Glargine
      Marketed by sanofiaventis—Lantus
      Resembles basal insulin secretion of non diabetic pancreatic beta cells.
      Controls fast blood glucose.
      Glycine for asparagine at A21 and two arginine added to carboxy terminal of B chain.
      Formulated at acid pH—4.0
      Hexamers at pH-7.4
      Can be injected with I port
    • Glargine
      In 2009 there was conflicting and confusing data regarding the link of glargine insulin and cancer developing risk.
      ADA –the avaailable data does not provide a cause for concern and that changes to the prescribing advice are therefore not necessary.
    • Detemir
    • C14 fatty acid chain
      (Myristic acid)
      Phe
      Gly
      Phe
      Arg
      Glu
      Tyr
      Thr
      Gly
      Pro
      Cys
      Lys
      Val
      Thr
      Lys
      Cys
      Asn
      A21
      B29
      Leu
      Tyr
      Gly
      A1
      Asn
      Tyr
      Ile
      Glu
      Leu
      Val
      Leu
      Ala
      Glu
      Glu
      Gln
      Gln
      Tyr
      Val
      Cys
      Leu
      Leu
      Cys
      Ser
      Ser
      Thr
      Cys
      Ile
      His
      Ser
      Gly
      Cys
      Leu
      Gln
      His
      Asn
      Val
      Phe
      B1
      Design of Insulin Detemir - 1
      LysB29(N-tetradecanoyl)des(threonine)human insulin
      Des-threonine myristic(mir) acid
    • Detemir
      Marketed by Novo Nordisk –LEVEMIR
      Fatty acid myristic acid is bound to lysine aminoacid at B29.
      quickly absorbed—binds to Albumin—complex
      Better control of blood glucose levels
      Appreciable decrease in HbA1c levels--
    • levemir
      Albumin binding: Makes Levemir therapy with a smooth and peakless profile throughout the day
    • Time-action profile
      Up to 24 hours
      Predictability
      lower within-patient variability than NPH and glargine
      Glycaemic control
      Better glycaemic control
      Hypoglycaemia
      Lesser hypoglycaemia compared with NPH & glargine
      Weight
      No undesirable weight gain shown in all studies
    • Premixed analogue
      Protamine insulin +rapidly acting analogues.
    • Strength of insulin
      40 U /ml –most widely used
      WHO—all insulin across the globe to be U 100.
      Storage
      Refrigerated
      <2 and >30 C
      Excess agitation avoided
      Used for > 1 month –may lose potency.
      Away from sunlight.
    • Mixing insulins
      glargine is not mixed with any other insulin.
    • Problems with syringes / vials
      Cumbersome procedure
      Difficult to transport and carry around
      Inaccuracy in withdrawing the correct amount of insulin
      Difficulty in mixing insulin
      Insulin wastage
      Stigma of injections and hence suggestion of ill-health
      Needle passes a rubber membrane and losses sharpness-more pain
    • Advantages with Devices
      Simplicity - Simple to operate and inject
      Accuracy - A new superior standard in dose accuracy
      Reliability - High quality materials and finish
      Discreeteness - Non-medical, non-syringe design
      All-in-one - Pen + insulin cartridge + needles
      Portability - Small & compact, robust carrying case - with space for extra needles and cartridge
    • Device vs. Syringe
    • Prefilled pen
      Contain a built-in, single-use insulin cartridge
      Loading
      Require no loading by patient
      Ease of use
      Portable, durable, & lightweight delivery systems
      patients who have difficulty handling the
      cartridges in reusable pens
      persons with busy schedules
      short - term therapy = GDM, Post-Surgery
      Ease of disposal
      are made of non-polluting plastic
      it breaks down into naturally occurring substances when burned industrially
      it can be safely landfilled
    • FlexPen®
      Easy to use
      • dialling dose; accurate / reliable
      • good control during injection
      • ‘can hear clicks’
      • minimal pressure required
      • can be administered with one hand
      Easy to read (white font on black)
      • numbers clearly visible
      • safer because mistakes less likely
      Convenient; pre-filled / no re-loading
      • easy to attach needles
      • easy to teach
      Portable and discreet
      • comes in carry case
    • FlexPen®
      FlexPen® is a unique dial-a-dose insulin pen. You can dial doses from 1 to 60 units inincrements of 1 unit
      • Single unit increment
      • Easy dial back
      • Large & easy to ready display
      • Max single dose-60 U
      • Virtually painless 31G needle
      FlexPen- Easy to use and teach
    • Design Characteristic of FlexPen
      The FlexPen is a disposable, prefilled insulin delivery device— there is no insulin cartridge to change.
      The FlexPen is simply thrown away when the last of the insulin has been used, or at the end of the in-use time.
    • FlexPen Prefilled syringes are available with three insulin analog preparations: Levemir, NovoRapid, and NovoMix 30.
      Each FlexPen is named for the insulin it contains and is color branded for easy identification.
      • LevemirFlexPen = identified by green push button
      • NovoMix 30 FlexPen = identified by Blue push button
      • NovoRapidFlexPen = identified by orange push button
    • Durable pen
      Patient has to insert an insulin cartridge into pen's delivery chamber
      Flexibility
      Allows greater flexibility for some patients
      Changing types of insulin without needing to buy another pen if prescription changes
      Ease of use
      Durable and easy to use
      Designed for longer duration of use.
      With individual use - risk of infection is minimized
    • NOVO NORDISK
    • Insulin dose calculation
      Calculate total daily insulin TDI
      0.5 *WEIGHT (KG) or sum of current doses
      Ex—60 kg---30U.
      Total meal time insulin—lispro,aspart,regular
      60% 0f TDI
      18U-----three divided doses—breakfast,lunch.dinner
      Total basal insulin—NPH,glargine,ultrlente
      40% of TDI
      12U---bed time insulin
    • Insulin dosage
      DKA
      Bolus dose—IV 0.1U/kg
      IM-0.3U/kg
      Then 0.1U/kg/hr
      Mild episodes of DKA—short acting insulin analogues
      IV regular insulin to be used in infusion until acidosis resolves
      0.05-0.1U/kg/hr.
    • Pre prandial insulin dose
      INSULIN /CARBOHYDRATE ratio
      1-1.5 U/10 gm of carbohydrate
      Supplemental or correcting insulin—1Uof insulin for every 50mg/dl of glucose over the preprandial glucose target.
      Ex
      A 60kg male has FBG 0f 250 mg/dl,desired is 100mg/dl,the insulin dose is 60*(250-100)/1500
      60(150/1500-----60*150/1500----6U
    • Twice daily regimens
      Long acting insulinNPH.regular insulin –morning,bed time.
      2/3 of insulin in the morning
      1/3 of insulin at bed time
      To prevent nocturnal hypoglycemia.
      FBG-prior evening long acting insulin
      Pre lunch glucose—morning short acting insulin
      Pre supper glucose-morning long acting insulin’
      Bed time—pre supper short acting insulin.
      Not an optimal regimen for 1 DM
    • Continuous subcutaneous insulin infusion CSII
      Very effective insulin regimen for type 1 DM
      To the basal infusion,,a pre prandial insulin bolus is delivered by the device based on instructions from the patient—who uses an individualized algorithm incorporating the preprandial plasma glucose and anticipated carbohydrate intake.
      Sophisticated device
      Advantages:
      programmed dose
      basal infusion rates altered during exercise
      different doses of insulin can be matched based on meals
      reqiures education of the patient and frequent interactions
      Disadvantages---infection,hyperglycemia,DKA
      Short acting insulin analogues are used.
      SBMG
    • EXUBERA
    • SEP 2006-OCT 2007
      Powdered form of recombinant human insulin
      Effective but no better than short acting insulin.
      Discontinued because of poor sales.
      Marketed by pfizer.
      1mg-3U
      Increment is not linear
      1mg given subsequently is more insulin than 3 mg given once.
      3mg—8U
      May be associated with lung cancer
      not Cost effective
      Mannkind --AFREZZA
    • Drug interactions
      Enhances blood glucose lowering effect---OAD,ACEI,disopyramide,fibrates,fluoxetine,MAOI,pentoxyfilline,propoxyphene,salicylates,sulphonamides.
      Reduces blood glucose lowering effect—corticosteroids,danazol,diazoxide,diuretics,glucagon,isoniazid,etrogens,phenothiazine,somatropin,salbutamol.
    • Thank you
      sagittarian