Drugs used for Diabetes Mellitus

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Drugs used for Diabetes Mellitus
2
Introduction

• There are 2 types of diabetes mellitus
• Type 1 Insulin-dependent diabetes mellitus
  (IDDM)
• Destruction of pancreatic beta cells
• Is the result of an autoimmune process
• Type 2 Non-insulin dependent diabetes mellitus
  (NIDDM)
• Results from a combination of insulin resistance
  and altered insulin secretion

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Characteristics of Type 1 Type 2 Diabetes
Mellitus
4
Oral Antidiabetic Drugs

• For the treatment of type 2 (non-insulin-dependent
  ) diabetes mellitus
• Use only after diet modification exercise fail
  to produce glycemic control
• Should be used to augment the effect of diet
  exercise, not to replace them

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Summary of treatment targets for cardiovascular
risk factor intervention in diabetic patients
Evidence-based targets for managing cardiovascular risk factors Evidence-based targets for managing cardiovascular risk factors
Fasting blood glucose lt/ 6mmol/l
HbA1c lt 7
Total cholesterol lt 5mmol/l
LDL cholesterol lt 3 mmol/l
Blood pressure threshold for intervention -Target for treatment -if significant proteinuria 140/90mmHg lt/ 140/80mmHg lt/ 125/75mmHg
Recent guidelines recommend statin and low-dose aspirin treatment where the 10-year coronary heart disease ridk is less than 15 -before adding aspirin ensure blood pressure is controlled -combination antihypertnsive treatment is necessary in the majority of patients to achieve blood pressure targets -other recommendations include HDLgt1.2mmol/l and fasting triglycerideslt1.7mmol/l Recent guidelines recommend statin and low-dose aspirin treatment where the 10-year coronary heart disease ridk is less than 15 -before adding aspirin ensure blood pressure is controlled -combination antihypertnsive treatment is necessary in the majority of patients to achieve blood pressure targets -other recommendations include HDLgt1.2mmol/l and fasting triglycerideslt1.7mmol/l
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Sulphonylureas

• Act mainly by augmenting insulin secretion
• May also increase tissue response to insulin
• Effective only when some residual pancreatic
  beta-cell activity is present
• Considered for patients who are not overweight,
  or in whom Metformin (Glucophage) is
  contraindicated or not tolerated

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Sulphonylureas (Contd)

• Short-acting
• Tolbutamide 0.5-1.5 g daily in divided doses,
  with or immediately after breakfast Max 2 g
  daily
• Gliclazide (Diamicron) 40-160 mg daily in
  divided doses, with breakfast Max 320 mg daily
• Intermediate-acting
• Glipizide (Minidiab) 2.5-15 mg daily in divided
  doses, before breakfast Max 20 mg daily

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Sulphonylureas (Contd)

• Long-acting
• Chlorpropamide (Diabinese) 250 mg daily with
  breakfast Max 500 mg
• Glibenclamide (Daonil) 5 mg daily with or
  immediately after breakfast Max 15 mg daily
• Glimepiride (Amaryl) 1-4 mg daily shortly
  before or with first main meal Max 4 mg daily

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Sulphonylureas (Contd)

• Contraindications
• Severe hepatic and renal impairment
• Breast-feeding and pregnancy
• Elderly (Chlorpropamide, glibenclamide)
• Adverse effects
• Nausea, vomiting, diarrhoea and constipation
• Increased appetite and weight gain
• Hypoglycaemia
• Hypersensitivity

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Biguanides

• Decreasing gluconeogenesis in the liver
• Increase peripheral utilisation of glucose by
  muscle
• Acts only in the presence of endogenous insulin
• Metformin (Glucophage) is the only available
  biguanide
• Is antihyperglycemic, not hypoglycemic
• Recommended for obese or insulin resistant
  diabetic patients

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Biguanides (Contd)

• Metformin
• 500 mg bd-tid Max 3 g, usually limit to 2 g
  daily
• Contraindications
• Hepatic or renal impairment (must withdraw)
• Ketoacidosis
• Predisposition to lactic acidosis severe
  dehydration, which is most likely to occur in
  patients with renal impairment

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Biguanides (Contd)

• Contraindications (Contd)
• Infection, shock, trauma, heart failure,
  respiratory failure, recent myocardial
  infarction, severe peripheral vascular disease
• Hepatic impairment, alcohol dependency
• Use of iodine-containing x-ray contrast media (do
  not restart melformin until renal function
  returns to normal)
• Pregnancy and breast-feeding

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Biguanides (Contd)

• Adverse effects
• Decreased appetite
• Nausea, vomiting and diarrhoea
• Lactic acidosis (rarely)
• Decreased absorption of vitamin B12 and folic
  acid
• Allergic skin reactions

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Biguanides (Contd)

• Nursing alerts
• Take metformin with meals and increase dosage
  slowly to minimise GI adverse effects
• Lactic acidosis, characterised by drowsiness,
  malaise, bradycardia and hypotension is a rare
  but serious adverse effect. Since this is a
  medical emergency, report to the physician
  immediately if suspected

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Alpha glucosidase inhibitor

• Delay the digestion absorption of starch
  sucrose by inhibition of intestinal alpha
  glucosidase in the intestine
• Acarbose (Glucobay)
• 50-100 mg tid Max 200 mg tid

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Alpha glucosidase inhibitor (Contd)

• Contraindications
• Pregnancy and breast-feeding
• Inflammatory or malabsorptive intestinal
  disorders
• Hepatic impairment
• Severe renal impairment

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Alpha glucosidase inhibitor (Contd)

• Adverse effects
• Flatulence, soft stools, diarrhoea, abdominal
  distention and pain
• Liver dysfunction

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Alpha glucosidase inhibitor (Contd)

• Nursing alerts
• Tablets should be taken with first mouthful of
  food
• Absorption of sugar (sucrose) is blocked by
  acarbose. When hypogylcaemia occurs, only glucose
  should be given

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Metglitinides

• Stimulate insulin release
• Rapid onset of action short duration
• Taken shortly before meals

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Metglitinides (Contd)

• Repaglinide (NovoNorm)
• 500 mcg 4 mg daily within 30 min before main
  meals Max 16 mg daily
• Nateglinide
• 60 mg tid within 30 min before main meals Max
  180 mg tid

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Metglitinides (Contd)

• Contraindications
• Ketoacidosis
• Pregnancy and breast-feeding
• Severe hepatic impairment (for repaglinide)

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Metglitinides (Contd)

• Adverse effects
• Hypoglycaemia
• Hypersensitivity reactions including pruritus,
  rashes and urticaria
• Abdominal pain, diarrhoea, constipation, nausea
  and vomiting (repaglinide)
• Nursing alert
• Administration must always be associated with
  meals

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Thiazolidinediones

• Also known as Glitazones
• Reduce peripheral insulin resistance by enhancing
  uptake of glucose by skeletal muscle cells
• Rosiglitazone (Avandia)
• 4 mg daily in combination with metformin or a
  sulphonylurea Max 8 mg daily when with
  metformin
• Pioglitazone (Actos)
• 15-30 mg daily

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Thiazolidinediones (Contd)

• Contraindications
• Hepatic impairment
• History of heart failure, combination of insulin
• Pregnancy and breast-feeding

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Thiazolidinediones (Contd)

• Adverse effects
• GI disturbances, headache, anaemia
• Weight gain
• Oedema
• Hypoglycaemia (less common for Pioglitazone)
• Liver dysfunctions (rare)

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Thiazolidinediones (Contd)

• Nursing Alerts
• Monitor liver function before treatment, then
  every 2 months for 1 year and periodically
  thereafter
• Seek immediate medical attention if symptoms such
  as nausea, vomiting, abdominal pain, fatigue
  dark urine develop
• Discontinue if jaundice occurs
• Monitor closely for oedema other signs of
  congestive heart failure

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Non-oral antidiabetic drugs

• Insulin
• Supplement the insulin secreted by pancreas
• Promote uptake of glucose in muscle
• Facilitate conversion of glucose to glycogen in
  liver, inhibit gluconeogenesis glycogenolysis
  in liver

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Actions of Insulin

• Glucose transport into muscle fat cells.
• Increased glycogen synthesis.
• Inhibition of gluconeogenesis.
• Inhibition of lipolysis increased formation of
  triglycerides.
• Stimulation of membrane-bound energy-dependent
  ion transporters (e.g. Na/K ATPase).
• Stimulation of cell growth

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Insulin (Contd)

• They are divided into short, intermediate
  long-acting preparations
• Short-acting
• Neutral/soluble insulin
• E.g. ActrapidHM, Humulin R
• Insulin Lispro
• E.g. Humalog
• Insulin Aspart
• E.g. NovoRapid

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Insulin (Contd)

• Intermediate-acting
• Isophane insulin
• E.g. ProtaphaneHM, Humulin N
• Insulin zinc suspension
• E.g. Monotard, Humulin L

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Insulin (Contd)

• Long-acting
• Crystalline insulin zinc
• E.g. UltratardHM
• Insulin glargine
• E.g. Lantus

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Insulin (Contd)

• Mixed Insulins
• Biphasic isophane insulin
• 30 soluble insulin/70 isophane insulin
• E.g. Mixtard 30, Humulin 70/30
• 20 soluble insulin/80 isophane insulin
• E.g. Mixtard 20

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Insulin (Contd)

• Dose
• Given through subcutaneous injection
• According to the requirements
• Short-acting
• Usually inject 15-30 min before meals
• Intermediate- long-acting
• Once or twice daily
• Can be given in conjunction with short-acting
  insulin

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Insulin Formulations
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Insulin (Contd)

• Precautions
• may decrease requirements in renal or hepatic
  impairment, some endocrine disorders, coeliac
  disease

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Insulin (Contd)

• Nursing Alerts
• Teach patients how to prepare use the
  subcutaneous (SC) injection, and the usual areas
  used for SC injection including abdomen, thigh
  upper arm
• Rotate the injection site within the general area
  employed. Allow about 1 inch between sites

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Insulin (Contd)

• Nursing Alerts (Contd)
• Storage
• Penfill
• Cartridges not in use should be stored between
  2-8 ?
• Cartridges used in the pen or carried as spare
  can be used for up to one month
• Vial
• Vials not in use should be stored between 2-8 ?
• Vial in use can be kept at room temp for 6 weeks
  (Novo Nordisk)
• Vials in use can be kept at room temp for 28 days
  (Lilly)

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Hypoglycaemia

• Nursing Alerts
• Observe for and teach the patient about signs and
  symptoms of hypoglycaemia
• Tachycardia, palpitations
• Sweating
• Nervousness, headache, confusion, drowsiness
• Fatigue
• Rapid treatment is required
• Patient is conscious oral glucose should be
  given
• Patient is unconscious IV glucose should be used

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BREAK
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Drugs that affect the gastrointestinal system
41
Introduction

• Drugs used in gastrointestinal system or
  digestive disorder primarily exert their action
  by altering GI
• Secretion
• Absorption
• Motility
• They may act systemically or locally in the GI
  tract

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Physiologic and pathologic (i.e. inflammatory)
prostaglandins
Cell activated by physical, chemical, or
hormone stimuli
Arachidonic acid
Traditional NSAIDs Block COX-1 and COX-2 enzymes
COX-2inhibitor NSAIDs Block COX-2 enzyme
Cyclooxygenase-1 (COX-1)
Cyclooxygenase-2 (COX-2)
Physiologic prostaglandins
Pathologic prostaglandins

• Inflammation
• Vasodilation,
• ?Capillary permeability
• Edema
• Pain
• Leukocytosis
• Activatye white blood cells to
• release inflammatory cytokines

• GI protection (?gastric acid,?mucus
• production, maintain blood flow to mucosa)
• Renal protection (help maintain blood flow
• and function)
• Regulate smooth muscle tone in blood
• vessels (e.g., vasodilation) and lungs
• (e.g., bronchodilation)
• Regulate blood clotting

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Antacids Simethicone

• Antacids
• Drugs that neutralize or reduce the acidity of
  stomach duodenal contents by combining with HCl
  producing salt water
• Relieve symptoms in dyspepsia, gastro-oesophageal
  reflux disease (GERD), peptic ulcers
• Simethicone
• Added to antacids as an antifoaming agent to
  relieve flatulence

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Antacids Simethicone (Contd)

• Antacids
• Aluminium Hydroxide (500mg tablet /6 suspension)
• 1-2 tablets chewed qid
• Magnesium trisilicate (Mixture)
• 5 BP Mixture 10ml tid po

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Antacids Simethicone (Contd)

• Antacids combination products
• Triact tablet
• Al(OH)3 Dried Gel 200 mg Mg(OH)2 150 mg
  Simethicone 25 mg
• Chew 1-2 tab q4-6h
• Gastrocaine suspension
• Oxethazaine 10mg, Al(OH)3 Dried Gel 300mg,
  Mg(OH)2 100mg in 5 ml
• Alumag suspension
• Al(OH)3 Mg Trisilicate

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Antacids Simethicone (Contd)

• Antacids combination products (Contd)
• Gelusil tablet
• Mg Trisilicate Dried Aluminium Hydroxide gel
• Mylanta tablet / suspension
• CaCO3 Mg(OH)2
• Simethicone
• Dimethylpolysiloxane (Gasteel 40 mg tablet)

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Antispasmodics

• Relax smooth muscle
• Relieve GI smooth muscle spasm
• Include antimuscarinics others

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Antispasmodics (Contd)

• Antimuscarinics
• Hyoscine Butylbromide (Buscopan)
• Adult 20 mg qid po
• Child 10 mg tid po
• Propantheline bromide
• 15 mg tid at least 1 hr before meals 30 mg at
  night Max 120 mg daily
• Not recommended for children

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Antispasmodics (Contd)

• Side effects
• Constipation
• Urinary urgency and retention
• Dry mouth
• Transient bradycardia

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Antispasmodics (Contd)

• Others
• Mebeverine HCl (Duspatalin)
• Adult child over 10 years 135-150 mg tid
  preferably 20 min before meals
• Peppermint oil (0.2 ml capsule)
• 1-2 capsules tid
• Not recommended for children under 15 years

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Motility stimulants

• Dopamine antagonists
• Stimulate gastric emptying small intestinal
  transit
• Enhance strength of oesophageal sphincter
  contraction
• Sometimes used in non-ulcer dyspepsia
• Useful in non-specific in cytotoxic-induced
  nausea vomiting (NV)

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Motility stimulants (Contd)

• Domperidone (Motilium)
• NV
• adult 10-20 mg q4-8h
• Child 200-400 mcg/kg q4-8h
• Functional dyspepsia
• 10-20 mg tid before food 10-20 mg at night
• Not recommended for children

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Motility stimulants (Contd)

• Metoclopramide (Maxolon)
• Adult 10 mg tid
• 15-19 yrs under 60 kg 5 mg tid
• 1-14 yrs 1 mg bd to 5 mg tid depend on age
• Diagnostic procedures
• Adult 10-20 mg five to ten min before exam
• Child 1-5 mg depends on age

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Motility stimulants (Contd)

• Side effects
• May raised prolactin concentration
• Rashes other allergic reactions
• Acute dystonic
  reaction
  reported
• Extrapyramidal effects (Metoclopramide more
  prominent)

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Motility stimulants (Contd)

• Nursing Alert
• For patients under 20 yrs
• Metoclopramide should be used restricted to
  severe intractable vomiting of known cause,
  vomiting of radiotherapy cytotoxics, aid to GI
  intubation, pre-medication
• Dose based on basis of body-weight

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Ulcer-healing drugs

• Peptic ulceration commonly involves the stomach,
  duodenum lower oesophagus
• Due to imbalance between cell-destructive
  cell-protective effects
• Helicobacter pylori NSAIDs can weaken the
  defences
• Relapse is common when treatment ceases

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Ulcer-healing drugs (Contd)

• Include several groups of drugs
• H2-receptor antagonists
• Chelates complexes
• Prostaglandin analogues
• Proton pump inhibitors

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H2-receptor antagonists

• Histamine acts on receptors located on parietal
  cells to increase production of HCl
• Block histamine H2-receptors
• Heal gastric duodenal ulcers by reducing
  gastric acid output
• Relieve gastro-oesophageal reflux disease
• May occasionally be used for patients with
  frequent severe recurrences for the elderly who
  suffer ulcer complications

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H2-receptor antagonists (Contd)

• Cimetidine
• Adult 400 mg bd Max 2.4 g daily (rarely)
• Child 20-30 mg/kg daily in divided dose
• Famotidine
• 20-40 mg bd
• Not recommended for children
• Nizatidine
• 150-300 mg bd
• Not recommended for children
• Ranitidine
• Adult 150 mg bd
• Child 2-4 mg/kg bd Max 300 mg daily

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H2-receptor antagonists (Contd)

• Side effects
• Diarrhoea other GI disturbances
• Altered liver function tests
• Headache, dizziness, rash

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H2-receptor antagonists (Contd)

• Nursing Alerts
• Cimetidine is a CYP450 inhibitor, avoid in
  patients on warfarin, phenytoin theophylline
• Patients may experience dizziness or drowsiness
  during early therapy, especially in the elderly.
  Assistance may be required for ambulatory
  activities

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Chelates complexes

• Sucralfate
• Complex of AL(OH)3 sulphated sucrose
• Minimal antacid properties
• Protect the mucosa from acid-pepsin attack in
  gastric duodenal ulcers
• 2 g bd or 1 g qid 1 hr before meals at bedtime
  Max 8 g daily
• Not recommended for children

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Chelates complexes

• Side effects
• Constipation, diarrhoea, gastric discomfort
• Dry mouth
• Headache, nausea
• Hypersensitivity reactions

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Prostaglandin analogues

• Misoprostol
• Synthetic prostaglandin analogue (Prostaglandin
  E)
• Antisecretory protective properties
• Inhibit gastric acid secretion
• Increase mucus bicarbonate secretion
• Promote healing of gastric duodenal ulcers

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Prostaglandin analogues (Contd)

• Dose
• 800 mcg daily in 2-4 divided doses
• For prophylaxis of NSAID-induced gastric
  duodenal ulcer
• 200 mcg 2-4 times daily
• Not recommended for children

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Prostaglandin analogues (Contd)

• Side effects
• Diarrhoea (may require withdrawal)
• Abdominal pain, dyspepsia, flatulence, nausea
  vomiting
• Abnormal vaginal bleeding
• Nursing Alerts
• Incidence of diarrhoea may be lessened by taking
  dose right after meals

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Prostaglandin analogues (Contd)

• Nursing Alerts (Contd)
• Manufacturer advises not to be used in women of
  child-bearing age unless the pateint requires
  NASID therapy is at high risk of complications
  from NSAID-induced ulceration
• Patients should take effective contraceptive
  measures be advised the risks of taking
  misoprostol if pregnant

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Proton pump inhibitors

• Inhibit gastric acid by irreversibly blocking the
  hydrogen-potassium adenosine triphosphatase
  enzyme system (proton pump) of gastric parietal
  cell
• Indicated for gastric duodenal ulcers
  gastro-oesophageal reflux disease
• Suppress gastric acid more strongly for a
  longer time than H2-receptor antagonists

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Proton pump inhibitors (Contd)

• Omeprazole
• Adult 10-40 mg daily
• Child over 2 yrs 0.7-1.4 mg/kg daily Max 40 mg
  daily
• IV injection or infusion is not recommended for
  children
• Esomeprazole
• 20-40 mg daily
• Not recommended for children
• Lansoprazole
• 15-30 mg daily
• Not recommended for children
• Pantoprazole
• 20-40 mg daily
• Not recommended for children
• Rabeprazole
• 10-20 mg daily
• Not recommended for children

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Proton pump inhibitors (Contd)

• Side effects
• GI disturbances
• Headache
• Hypersensitivity reactions

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END
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Unawareness of drugs brand name

• Patient has a documented allergy to Zyloric
• Allopurinol was prescribed to this patient
• The doctor prescribing was not aware that
  Zyloric was the brand name for Allopurinol

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Tips

• Check out the contents of the preparation if
  brand name is used before prescribing, dispensing
  or administration

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Improper Drug Abbreviation

• IV Mitoxantrone was prescribed
• The abbreviation MTX was put on the label
• An injection of Methotrexate was prepared instead
  according to the abbreviation on the label
• Methotrexate was administered to the patient as a
  result

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Tips

• Write drug name in full
• Do not use unauthorised abbreviations
• Cross check the dose name of the drug before
  preparation administration

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Repeated Pethidine Injection

• Patient was given a Pethidine injection at AE
  via a verbal order
• Nurse forgot to record this order in MAR
• Prescribing Dr had not confirmed the verbal order
  in the prescription
• A second dose of Pethidine was administered in
  the ward
• Patient collapsed as a result of overdose of
  Pethidine

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Tips

• Pethidine is a Dangerous Drug should not be
  ordered through verbal orders
• For other non-DD, give a verbal order only in
  emergency exceptional circumstances
• Record the verbal instruction in the MAR
  immediately as verbal order
• After writing down the instruction, read back the
  details to the Dr for double checking

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Self-medication of Paracetamol

• Patient was transferred from medical ward to ICU
  with high plasma level of Paracetamol
• Patient was treated with N-acetylcysteine
  infusion as an antidote
• Patient later admitted that she had taken
  approximately 15 tabs of Paracetamol (private
  medications) in the medical ward to relieve her
  leg pain

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Tips

• Put patients brought-in medicines into safe
  custody
• Do not administer the patients own medicines in
  hospital unless they have been positively
  identified, specifically prescribed when
  supplies are not immediately available inside the
  hospitals

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Glibenclamide or Citalopram

• An in-patient presented with severe hypotension
  vomiting
• A review of the MAR revealed that Daonil
  (Glibenclamide) was written right above the
  prescription for Citalopram in pencil
• Upon investigation, it was discovered that some
  nursing staff gave Citalopram to the patient
  whilst others gave Glibenclamide

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Tips

• Familiarise with the medication /or the patient
• If there is uncertainty or confusion about a
  particular prescription, always consult with the
  prescriber
• Adequate communication between staff is the key
  to preventing errors

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Wrong Drug Name

• Martindale 1 drop tds both eyes was prescribed
• Martindale is the name of the drug company that
  makes the eye drops

84
Tips

• Prescribe in generic rather than trade name as
  trade names dont usually give indications of
  their constituents

85
Inappropriate Drug Dosage

• A 10 month old baby was prescribed Cotrimoxazole
  suspension 20mg bd
• Cotrimoxazole is a combination product containing
  Sulphamethoxazole 200mg Trimethoprim 40mg per
  5ml
• 240mg per 5 ml 20mg 0.42ml
• It was later clarified that the dose 20mg refers
  to the Trimethoprim component
• Thus 120mg cotrimoxazole should have been
  prescribed

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Tips

• Should clearly specify drug dosage especially for
  combination product
• Clarify with prescriber if in doubt