Drug Interactions of Antidiabetics (Part 1)

1
Drug Interactions of antidiabetics(part 1)

• Dr.P.Naina Mohamed
• Pharmacologist

2
Introduction

• An adverse drug interaction is defined as an
  interaction between one or more coadministered
  medications which leads to alteration of the
  effectiveness or toxicity of any of the
  coadministered medications.
• Drug interactions can be caused by prescription
  and over-the-counter (OTC) medications, herbal
  products or vitamins, foods, diseases, and
  genetics (family history).
• It is estimated that people over 65 take an
  average of seven drugs at any one time to treat a
  variety of illnesses.
• With this amount of medicine use, the probability
  that a person will take two prescribed drugs that
  may interact with one another is very high.

3
Antidiabetic Drugs

• PARENTERAL ANTIDIABETIC DRUGS
• Insulins
• Rapid acting insulins
• Regular insulin (Humulin R, Novolin R)
• Insulin lispro (Humalog)
• Insulin aspart (Novolog)
• Insulin glulisine (Apidra)
• Prompt insulin zinc (Semilente, Slightly slower
  acting)
• Intermediate acting insulins include
• Isophane insulin, neutral protamine Hagedorn
  (NPH) (Humulin N, Novolin N)
• Insulin zinc (Lente)
• Long acting insulins include
• Extended insulin zinc insulin (Ultralente)
• Insulin glargine (Lantus)
• Insulin detemir (Levemir)
• Incretin Mimetics (Glucagon-like peptide
  analogues)
• Exenatide (Exendin-4, Byetta) - First GLP-1
  agonist.
• Liraglutide (Victoza) - once-daily human
  analogue.
• Taspoglutide - Presently in Phase III clinical
  trials.

4
Antidiabetic Drugs

• ORAL ANTIDIABETIC DRUGS
• Secretagogues
• Sulfonylureas
• First-generation agents
• Tolbutamide (Orinase), Acetohexamide (Dymelor),
  Tolazamide (Tolinase), Chlorpropamide (Diabinese)
• Second-generation agents
• Glipizide (Glucotrol), Glyburide or Glibenclamide
  (Diabeta, Micronase, Glynase), Glimepiride
  (Amaryl), Gliclazide (Diamicron), Glycopyramide,
  Gliquidone.
• Meglitinides
• Repaglinide (Prandin)
• Nateglinide (Starlix)
• Insulin sensitizers
• Biguanides
• Metformin (Glucophage)
• Thiazolidinediones (TZDs)
• Rosiglitazone (Avandia)
• Pioglitazone (Actos)

5
Antidiabetic Drugs

• Alpha-glucosidase inhibitors
• Acarbose (Precose/Glucobay)
• Miglitol (Glyset)
• Voglibose
• Dipeptidylpeptidase-4 inhibitors
• Sitagliptin (Januvia)
• Vildagliptin (Galvus)
• Saxagliptin (Onglyza)
• Linagliptin (Tradjenta)
• Aldose reductase inhibitors
• Epalrestat
• Sodium-glucose co-transporter 2 inhibitors
• Dapagliflozin
• Canagliflozin

6
Interactions of insulin

• Insulin Drug Interactions
• Insulin Fluoroquinolones Interaction
• Insulin Beta blockers Interaction
• Insulin Aspirin Interaction
• Insulin Thiazolidinediones Interaction
• Insulin Antipsychotics Interaction
• Insulin Androgens Interaction
• Insulin Antimalarials Interaction
• Insulin Orlistat Interaction
• Insulin CAM interactions
• Insulin Bitter melon Interaction
• Insulin Ginkgo Interaction
• Insulin Ginseng Interaction
• Insulin Gymnema Interaction
• Insulin Fenugreek Interaction
• Insulin Smoking interactions
• Insulin Alcohol interactions

7
Insulin Fluoroquinolones

• Insulin
• Fluoroquinolones
• Elevated risk of Hypoglycemia
• Major and rapid interaction may occur between
  antidiabetics and FQs.
• Closely monitor the blood glucose level and
  adjust the dose of the Insulin as indicated.
• Dose adjustment may be required after
  discontinuation of a fluoroquinolone.
• If a hypoglycemic reaction occurs, discontinue
  the fluoroquinolone, and contact a physician.

8
Insulin Beta blockers

• Insulin
• Beta blockers
• Blockade of beta-2 receptors activity
• Prevention of mobilisation of glucose from the
  liver
• Recovery from hypoglycaemia is delayed
• Rise in BP
• Moderate and delayed interaction may occur
  between antidiabetics and Beta blockers.
• Concurrent use can be uneventful but there are
  some risks.
• The cardioselective beta blockers are probably
  safer than those that are non-selective.
• The risk is greatest with propranolol

9
Insulin aspirin

• Insulin
• Aspirin
• Additive blood glucose lowering effect
• The interaction between the sulfonylureas or
  insulin and the salicylates is established but of
  limited importance.
• Excessive and unwanted hypoglycaemia is very
  unlikely with small to moderate analgesic doses
  of salicylates. Some downward adjustment of the
  dose of the antidiabetic may be appropriate if
  large doses of salicylates are used.

10
Insulin thiazolidinediones

• Insulin
• Thiazolidinediones (Pioglitazone or
  rosiglitazone)
• Thiazolidinediones may potentiate the renal
  effects of insulin on sodium and water retention
• Increased incidence of exacerbation or
  precipitation of heart failure
• As a result of a review, in October 2007 the
  European Medicines Agency concluded that the
  combination of rosiglitazone and insulin should
  only be used in exceptional cases and under close
  supervision, and this recommendation was not
  considered necessary for pioglitazone.
• Similarly, in the US, pioglitazone is licensed
  for use with insulin, and the use of
  rosiglitazone with insulin is not recommended.
• If oedema occurs in a patient taking a
  thiazolidinedione it has been recommended that
  the possible causes be assessed, and that if
  symptoms and signs suggest congestive heart
  failure, a dose change and temporary or permanent
  discontinuance of the thiazolidinedione should be
  considered.
• Concurrent use of insulin and a thiazolidinedione
  also increases the incidence of hypoglycaemia. It
  has been noted that in patients receiving
  insulin, the insulin dose may need to be reduced
  by 10 to 25 if pioglitazone 15 or 30 mg daily
  is given.

11
Insulin Antipsychotics

• Insulin
• Chlorpromazine (Antipsychotics)
• Inhibit the release of insulin induce
  adrenaline release from the adrenals
• Rise in blood glucose levels
• Other classical and atypical antipsychotics
  appear to act similarly.
• Classical antipsychotics (haloperidol,
  pipamperone, levomepromazine, and zuclopenthixol)
  are associated with an increased risk of needing
  insulin.
• Increased monitoring for glycaemic control,
  particularly when starting or stopping any
  classical or atypical antipsychotic in a patient
  with diabetes, is warranted.

12
Insulin anabolic steroids

• Insulin
• Androgens (nandrolone, methandienone,testosterone
  propionate or stanozolol)
• Androgens improve insulin sensitivity
• Enhanced reduction in blood glucose levels
• A reduction in the dose requirements of insulin
  (of an average of one-third) may be expected in
  many patients with the steroids cited.

13
Insulin antimalarials

• Insulin
• Antimalarials (Hydroxychloroquine, chloroquine)
• Inhibition of insulin degradation and induction
  of insulin secretion
• Modest reduction in blood glucose
• Hydroxychloroquine may reduce insulin
  requirements by about 25.
• Similarly, hypoglycaemia has occurred in a
  patient taking chloroquine and insulin.

14
Insulin orlistat

• Insulin
• Orlistat
• Orlistat helps to reduce weight
• Improvement on glycaemic control
• The benefits of orlistat on glycaemic control in
  overweight or obese patients with diabetes are
  established.
• Antidiabetic treatment should be more closely
  monitored in patients taking orlistat, and the
  dose adjusted as necessary.

15
Insulin bitter melon

• Insulin
• Bitter melon
• Bitter melon contains polypeptide P (vegetable
  insulin (v-insulin))
• Insulin-like effects
• Excacerbation of Hypoglycemia (manifested as
  blurred vision, tremor, intense hunger,
  generalized sweating, headache, palpitations,
  piloerection, lethargy, confusion, nervousness,
  and agitation)
• Combination of Insulin and bitter melon may leads
  to rapid and moderately severe interaction.
• Bitter melon is also known as bitter gourd,
  balsam pear, cundeamor and Karela.
• Irregular consumption of Bitter melon as part of
  the diet could possibly contribute to unexplained
  fluctuations in diabetic control.

16
Insulin Ginkgo

• Insulin
• Ginkgo
• May increase pancreatic beta-cell function
• Further reductions of blood glucose
• Combining Insulin with Ginkgo may produce delayed
  and moderately severe interaction.
• Caution is advised if Ginkgo is taken with
  insulin.
• Monitor blood glucose frequently, and monitor for
  signs and symptoms of hyperglycemia or
  hypoglycemia.

17
Insulin ginseng

• Insulin
• Ginseng
• Additive hypoglycemic effect
• Further reductions of Blood glucose
• Combining insulin with ginseng may leads to
  delayed and moderately severe interaction.
• Monitor blood glucose closely in patients taking
  ginseng with antidiabetic agents.
• In patients having difficulty establishing blood
  glucose control, it is recommended to avoid
  concomitant use of ginseng and antidiabetic
  agents.

18
Insulin gymnema

• Insulin
• Gymnema extracts
• Reduced blood glucose and glycosylated hemoglobin
  
• Insulin moderately interacts with gymnema.
• If patients choose to take gymnema with an
  antidiabetic agent, monitor blood glucose levels
  and signs and symptoms of hypoglycemia.

19
Insulin licorice

• Insulin
• Licorice
• Synergistic effect
• Hypokalemia and sodium retention
• Moderate interaction is expected between insulin
  and licorice.
• Caution is advised if licorice is used with
  insulin.
• Advise patients that regular use of even moderate
  amounts of licorice can result in hypokalemia.

20
Insulin fenugreek

• Insulin
• Fenugreek
• Improved peripheral glucose utilization,
• Increased metabolic clearance rate of glucose
  delayed gastric emptying
• Further reductions of blood glucose
• Combining Insulin with fenugreek may cause rapid
  and moderately severe interaction.
• Close monitoring of blood glucose is recommended
  for patients who choose to use fenugreek and
  antidiabetic agents concomitantly.

21
Insulin Smoking

• Insulin
• Smoking
• Peripheral vasoconstriction
• Decreased absorption of Insulin
• Reduced therapeutic efficacy of Insulin

22
Insulin Smoking

• Insulin
• Smoking
• Release of endogenous substances causing insulin
  resistance
• Reduced therapeutic efficacy of Insulin
• Smokers may require an increased insulin
  dosage.

23
Insulin Alcohol

• Insulin
• Alcohol
• Inhibition of gluconeogenesis (formation of new
  glucose from amino acids)
• Exacerbation of hypoglycaemia
• Moderate and rapid interaction may occur between
  antidiabetics and alcohol.
• Diabetes UK (formerly The British Diabetic
  Association) advises diabetics not to exceed 2
  drinks (for women) or 3 drinks (for men) daily.
• Diabetics should not drink on empty stomach.
• Diabetics with peripheral neuropathy should not
  have more than one drink daily.
• Diabetic patients receiving insulin therapy
  should be advised to avoid excessive ethanol
  consumption.

24
Conclusion

• The diabetics should consult their physician and
  pharmacist.
• The diabetics should bring a list of all of the
  drugs they are taking (or simply bring the drugs
  themselves), including prescription drugs,
  over-the-counter drugs, and any supplements,
  herbal or otherwise, during their visit to the
  doctor or pharmacist.
• They are encouraged to ask their doctor or
  pharmacist to look over their list for any
  potentially dangerous combinations.
• It is recommended that people fill all their
  prescriptions at one pharmacy, if possible. In
  addition, they should maintain a list of all of
  their medicines and update it when one is added
  or removed.
• They should review their list with their doctor
  or pharmacist regularly, particularly when they
  begin to take a new medicine.

25
References

• Stockleys Drug Interactions, 9e
• Karen Baxter
• British National Formulary
• June 2013
• Basic Clinical Pharmacology, 12e Bertram
  G. Katzung, Susan B. Masters, Anthony J. Trevor
• Goodman Gilman's The Pharmacological Basis of
  Therapeutics, 12e Laurence L. Brunton, Bruce
  A. Chabner, Björn C. Knollmann

26
References

• http//www.ncbi.nlm.nih.gov/pmc/articles/PMC301938
  7/
• http//spectrum.diabetesjournals.org/content/19/4/
  202.full.pdfhtml
• http//www.fda.gov/cder/consumerinfo/druginteracti
  ons.htm
• http//medicine.iupui.edu/clinpharm/ddis/
• http//www.australianprescriber.com/magazine/24/4/
  83/5
• www.micromedexsolutions.com