Download Drugs used for Diabetes Mellitus

Drugs used for Diabetes
Mellitus
1
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
2
Characteristics of Type 1 & Type 2
Diabetes Mellitus
Age of onset
Acuteness of onset
Presenting features
Body habitus
Control of diabetes
Ketoacidosis
Insulin requirement
Control by oral agents
Control by diet alone
Complications
Type 1
Type 2
Usually < 25 years
Usually sudden
Polyuria, polydipsia,
polyphagia, acidosis
Often thin
Difficult
Frequent
Always
Never
Never
Frequent
Usually > 40 years
Usually gradual
Often asymptomatic
Usually overweight
Easy
Seldom, unless under stress
Often unnecessary
Frequent
Frequent
Frequent
3
Oral Antidiabetic Drugs
For the treatment of type 2 (non-insulindependent) 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

4
Summary of treatment targets for cardiovascular risk factor
intervention in diabetic patients
Evidence-based targets for managing cardiovascular risk factors
Fasting blood glucose
</= 6mmol/l
HbA1c
< 7%
Total cholesterol
< 5mmol/l
LDL cholesterol
< 3 mmol/l
Blood pressure threshold for intervention 140/90mmHg
-Target for treatment
</= 140/80mmHg
-if significant proteinuria
</= 125/75mmHg
Recent guidelines recommend statin and low-dose aspirin treatment where the 10year 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
5
-other recommendations include HDL>1.2mmol/l and fasting
triglycerides<1.7mmol/l
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

6
Sulphonylureas (Cont‘d)

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
7
Sulphonylureas (Cont‘d)

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

8
Sulphonylureas (Cont‘d)

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

9
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
10
Biguanides (Cont’d)

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
11
Biguanides (Cont’d)

Contraindications (Cont’d):
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

12
Biguanides (Cont’d)

Adverse effects:
Decreased appetite
 Nausea, vomiting and diarrhoea
 Lactic acidosis (rarely)
 Decreased absorption of vitamin B12 and folic
acid
 Allergic skin reactions

13
Biguanides (Cont’d)

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

14
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
15
Alpha glucosidase inhibitor
(Cont’d)

Contraindications:
Pregnancy and breast-feeding
 Inflammatory or malabsorptive intestinal
disorders
 Hepatic impairment
 Severe renal impairment

16
Alpha glucosidase inhibitor (Cont’d)

Adverse effects:
Flatulence, soft stools, diarrhoea, abdominal
distention and pain
 Liver dysfunction

17
Alpha glucosidase inhibitor (Cont’d)

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

18
Metglitinides
Stimulate insulin release
 Rapid onset of action & short duration
 Taken shortly before meals

19
Metglitinides (Cont’d)

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
20
Metglitinides (Cont’d)

Contraindications:
Ketoacidosis
 Pregnancy and breast-feeding
 Severe hepatic impairment (for repaglinide)

21
Metglitinides (Cont’d)

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
22
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
23
Thiazolidinediones (Cont’d)

Contraindications:
Hepatic impairment
 History of heart failure, combination of insulin
 Pregnancy and breast-feeding

24
Thiazolidinediones (Cont’d)

Adverse effects:
GI disturbances, headache, anaemia
 Weight gain
 Oedema
 Hypoglycaemia (less common for
Pioglitazone)
 Liver dysfunctions (rare)

25
Thiazolidinediones (Cont’d)

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

26
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

27
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 energydependent ion transporters (e.g. Na/K
ATPase).
 Stimulation of cell growth

28
Insulin (Cont’d)
They are divided into short, intermediate &
long-acting preparations:
 Short-acting:


Neutral/soluble insulin
 E.g. Actrapid®HM,

Insulin Lispro
 E.g.

Humulin R®
Humalog®
Insulin Aspart
 E.g.
NovoRapid®
29
Insulin (Cont’d)

Intermediate-acting:

Isophane insulin
 E.g.

Protaphane®HM, Humulin N®
Insulin zinc suspension
 E.g.
Monotard®, Humulin L®
30
Insulin (Cont’d)

Long-acting:

Crystalline insulin zinc
 E.g.

Ultratard®HM
Insulin glargine
 E.g.
Lantus®
31
Insulin (Cont’d)

Mixed Insulins:

Biphasic isophane insulin
 30%

E.g. Mixtard ®30, Humulin ®70/30
 20%

soluble insulin/70% isophane insulin
soluble insulin/80% isophane insulin
E.g. Mixtard ®20
32
Insulin (Cont’d)

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
33
Insulin Formulations
Duration of action Examples
Peak effect (h)
Duration of action (h)
Short
Insulin Injection
(soluble insulin)
2h-4h
6h-12h
Intermediate
Isophane insulin
Insulin zinc suspension
(amorphous)
5h-12h
3h-6h
12h-24h
12h-16h
Long
Insulin zinc suspension
(crystalline)
5h-14h
24h-30h
Mixed
Variable portions of
soluble & isophane
insulins
2h-10h
3h-8h
18h-20h
16h-24h
34
Insulin (Cont’d)

Precautions:

may decrease requirements in renal or
hepatic impairment, some endocrine
disorders, coeliac disease
35
Insulin (Cont’d)

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

36
Insulin (Cont’d)

Nursing Alerts (Cont’d):

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)
37
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
38
39
Drugs that affect the
gastrointestinal system
40
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
41
Physiologic and pathologic (i.e. inflammatory) prostaglandins
Cell activated by
physical, chemical,
or hormone stimuli
Traditional NSAIDs
Block COX-1 and
COX-2 enzymes
Arachidonic acid
COX-2inhibitor NSAIDs
Block COX-2 enzyme
Cyclooxygenase-1 (COX-1)
Cyclooxygenase-2 (COX-2)
Physiologic prostaglandins
Pathologic prostaglandins
•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
•Inflammation
Vasodilation,
↑Capillary permeability
•Edema
Pain
•Leukocytosis
•Activatye white blood cells to
release inflammatory cytokines
42
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, gastrooesophageal reflux disease (GERD), peptic
ulcers


Simethicone

Added to antacids as an antifoaming agent to
relieve flatulence
43
Antacids & Simethicone (Cont’d)

Antacids

Aluminium Hydroxide (500mg tablet
/6% suspension)
 1-2

tablets chewed qid
Magnesium trisilicate (Mixture)

5% BP Mixture: 10ml tid po
44
Antacids & Simethicone (Cont’d)

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
45
Antacids & Simethicone (Cont’d)

Antacids combination products (Cont’d):
 Gelusil

tablet
Mg Trisilicate+ Dried Aluminium Hydroxide gel
 Mylanta


tablet / suspension
CaCO3 & Mg(OH)2
Simethicone

Dimethylpolysiloxane (Gasteel® 40 mg tablet)
46
Antispasmodics
Relax smooth muscle
 Relieve GI smooth muscle
spasm
 Include antimuscarinics &
others

47
Antispasmodics (Cont’d)

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
48
Antispasmodics (Cont’d)

Side effects:
Constipation
 Urinary urgency and retention
 Dry mouth
 Transient bradycardia

49
Antispasmodics (Cont’d)

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
50
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 cytotoxicinduced nausea & vomiting (N&V)

51
Motility stimulants (Cont’d)

Domperidone (Motilium®)

N&V:
 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
52
Motility stimulants (Cont’d)

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
53
Motility stimulants (Cont’d)

Side effects:
 May
raised prolactin concentration
 Rashes & other allergic reactions
 Acute dystonic
reaction reported
 Extrapyramidal effects
(Metoclopramide more prominent)
54
Motility stimulants (Cont’d)

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
55
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

56
Ulcer-healing drugs (Cont’d)

Include several groups of drugs
H2-receptor antagonists
 Chelates & complexes
 Prostaglandin analogues
 Proton pump inhibitors

57
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

58
H2-receptor antagonists (Cont’d)

Cimetidine



Famotidine



20-40 mg bd
Not recommended for children
Nizatidine



Adult: 400 mg bd; Max: 2.4 g daily (rarely)
Child: 20-30 mg/kg daily in divided dose
150-300 mg bd
Not recommended for children
Ranitidine


Adult: 150 mg bd
Child: 2-4 mg/kg bd; Max: 300 mg daily
59
H2-receptor antagonists (Cont’d)

Side effects:
Diarrhoea & other GI
disturbances
 Altered liver function tests
 Headache, dizziness, rash

60
H2-receptor antagonists (Cont’d)

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

61
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

62
Chelates & complexes

Side effects:
Constipation, diarrhoea, gastric
discomfort
 Dry mouth
 Headache, nausea
 Hypersensitivity reactions

63
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
64
Prostaglandin analogues (Cont’d)

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
65
Prostaglandin analogues (Cont’d)

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
66
Prostaglandin analogues (Cont’d)

Nursing Alerts (Cont’d):
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

67
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
68
Proton pump inhibitors (Cont’d)

Omeprazole




Esomeprazole




15-30 mg daily
Not recommended for children
Pantoprazole



20-40 mg daily
Not recommended for children
Lansoprazole


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
20-40 mg daily
Not recommended for children
Rabeprazole


10-20 mg daily
Not recommended for children
69
Proton pump inhibitors (Cont’d)

Side effects:
 GI disturbances
 Headache
 Hypersensitivity reactions
70
71
Unawareness of drug’s 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
72
Tips

Check out the contents of the preparation if brand name
is used before prescribing, dispensing or administration
73
74
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
75
Tips

Write drug name in full

Do not use unauthorised abbreviations

Cross check the dose & name of the drug before
preparation & administration
76
Repeated Pethidine Injection

Patient was given a Pethidine injection at A&E 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
77
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
78
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
79
Tips

Put patients’ brought-in medicines into safe custody

Do not administer the patient’s own medicines in hospital
unless they have been positively identified, specifically
prescribed & when supplies are not immediately
available inside the hospitals
80
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
81
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
82
Wrong Drug Name

Martindale 1 drop tds both eyes was prescribed

Martindale is the name of the drug company that
makes the eye drops
83
Tips

Prescribe in generic rather than trade name as trade
names don’t usually give indications of their constituents
84
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
85
Tips

Should clearly specify drug dosage especially for
combination product

Clarify with prescriber if in doubt
86