Therapeutics:

Hypertension, Diabetes
Mellitus & Dyslipidaemia
Group B
Topics:
B1+ B2a - Young Hypertension
B3 + B2b - Essential Hypertension
B5+ B4a - Diabetes Mellitus
B6 + B4b - Dyslipidaemia

Link for TBL guidelines:

https://elearn.imu.edu.my/pluginfile.php/166718/mod_folder/content/0/TBL%20Guide%20-
Therapeutics%20for%20Hpt%2C%20DM%20%20Hyperlidimia.pdf?forcedownload=1
Young Hypertension
N, 32-year-old lady with underlying hypertension for 5 years, presented with

1. Giddiness for 1 day

a. Sudden onset, happened when resting
2. Central chest pain for 1 day
a. 1 episode, sudden onset, when resting
b. Pressing in nature, not radiating
3. Frontal headache for 1 day

Associated with palpitation, shortness of breath, sweating, bilateral upper and lower
limbs numbness

Denies of orthopnoea, PND, bilateral lower limbs swelling. Urination and bowel
movement normal
Went to Klinik Kesihatan Nilai. BP: 204/160mmHg and was given Captopril 25mg. She
was then referred to HTJS.

Past Medical History:

She was diagnosed with hypertension 5 years ago but had defaulted medication and
follow up. She had 2 LCSC in 2012 (26 weeks) and 2014 (34 weeks) due to pre-
eclampsia. She was given hypertensive medication during pregnancy and after delivery.
However, she defaulted medication and follow up.

Family History:
Mother diagnosed with hypertension in 20+ years old
Father died at 56 years old due to heart attack.

Social History:
No smoking, no alcohol.
In the ED, her BP was 200-219/101-124mmHg. She was given T. amlodipine 10mg and
T. aspirin 300mg.
ECG showed ST depression in leads 1,2, V5 and V6.
Chest X-Ray showed cardiomegaly.
Troponin I: <0.04
Physical Examination:
Patient is well, obese.
Vital signs: BP 151/78mmHg, PR: 98bpm, RR: 18bpm

Cardiovascular examination:
Apex beat at left 6th intercostal space
S1 S2 heard, no murmur
No parasternal heave
No bibasal crepitaiton

Respiration, abdominal, and neurological examinations are unremarkable

Impression: Hypertension emergency with ACS

Medication
In ward,
1. S/C Fondaparinux 2.5mg OD for 3 days
2. T. Perindopril 4mg OD
3. T. Amlodipine 10mg OD
4.. T. Simvastatin 20mg ON
5. T. Cardiprin 100mg OD

On day 3 of admission, the dosage of perindopril was increased to 8mg OD.

She was discharged with:

1. T. Amlodipine 10mg OD
2. T. Perindopril 8mg OD
3. T. Cardiprin 100mg OD
4. T. Simvastatin 20mg ON
Amlodipine

Drug Name Amlodipine

Drug Dosage Adult: Initially 5mg OD. Increase to 10mg OD if needed

Indication Hypertension, stable angina

Contraindication Severe hypotension, shock, haemodynamically unstable heart failure after

acute MI, obstruction of the outflow tract of left ventricle (aortic stenosis)

Adverse Effect Ankle swelling, flushing, somnolence, fatigue, abdominal pain, nausea.
Rarely, confusion, rash, gingival hyperplasia, muscle cramp

Rationale Hypertension

Prescribing Writing T. Amlodipine 10mg OD 2/ 52

Aspirin
Drug Name Aspirin (Cardiprin 100)

Drug Dosage 100mg

Indication Conditions where modification of platelet behaviour is considered beneficial

- transient ischemic attacks
- secondary prevention of myocardial infarction
- prophylaxis against stroke, vascular occlusion and deep vein thrombosis

Contraindication - active peptic ulceration

- hemophilia
- known to be allergic to aspirin.
Use in pregnancy: safe, but it may prolong labour and contribute to maternal and
neonatal bleeding, best avoided in 3rd trimester of pregnancy

Adverse Effect May precipitate bronchospasm, induce attacks of asthma, gastrointestinal

haemorrhage

Rationale For secondary prevention of myocardial infarction

Prescribing Writing T. Aspirin 100mg OD X 2/ 52

PERINDOPRIL (ACEON)
Drug Name Perindopril

Drug Dosage 4mg in ward; discharge with 8mg.

(4-8mg orally per day in 1 or 2 divided dose
Max : 16mg/ day)

Indication Hypertension, Heart Failure, Ischemic

Heart Disease

Contraindication Pregnancy, Hepatic impairment, renal

artery stenosis, angioedema

Adverse Effect Hypotension, Dizziness, Renal Dysfunction

Rationale Hypertension

Prescribing Writing T. Perindopril 8mg BD 2/ 5 2

Simvastatin
Drug Name Simvastatin

Drug Dosage 10mg ON

usually start with 10-20mg . Adjust dose @ interval of 4 weeks
Max80 mglday

Indication Dyslipidemia
CV risk reduction

Contraindication acute liver disease, transaminase, pregnancy , lactation, dose adjust in renal disease

Adverse Effect rhabdomyolysis, Hepatitis, G1 symptoms

Rationale Dyslipidemia & very high Cv Risk

Prescribing Writing T. Simvastatin 10mg ON x 2 / 52

Essential Hypertension
J, 67-year-old Malay gentleman with underlying hypertension and dyslipidemia for
more than 20 years presented with chest pain one day prior to admission.

Patient has a sudden onset of central chest pain at 7am when he was driving his car.
The pain was tightening in nature and radiated to left shoulder. It was accompanied
with minimal sweating as well.

Patient denies of any palpitation, shortness of breath, nausea, vomiting, or loss of

consciousness.

He was subsequently sent by his lao po to the Emergency Department and pain was
relieved by sublingual GTN.
Past Medical History: He has been diagnosed with hypertension and dyslipidemia for
more than 20 years but has not been fully compliant with his medications and follow
ups. This is his 3rd admission which his first two admissions were due to acute chest
pain similarly to this episode.

Family history: Father had hypertension passed away at the age of 78. His mother lives
with his sister and is well according to patient.

Social History: He is a retired peneroka at FELDA. Does not smoke nor consume
alcohol.

Drug & Allergy History: No known drug allergy or food. Previous medications include
simvastatin, bisoprolol, amlodipine, and perindopril

Systemic review: No fever, headache, cough, abdominal pain or discomfort. Bowel

habits and urination are normal.
Clinical Examination

Patient Vital signs: BP 158/78 PR: 75 RR: 20 T: 37

Height: 1.70m Weight: 62kg BMI: 21.5 kg/m2 Waist circumference: 88cm
Cardiovascular examination: apex beat felt 1cm lateral to midclavicular line at 5th
intercostal space. S1, S2 appreciated with no additional murmurs.

Other systems were insignificant.

ECG: T-wave inversion present on V2-V6

Trop I: 0.1
ECHO: Ejection fraction of 65% (55-70%)
Stress test normal
Renal Profile normal
Risk stratification: Medium risk (10-20% risk of major CV event in 10 years)
Impression: unstable angina CAD
Medication
Upon admission, patient was given sublingual GTN and subcutaneous fondaparinux
2.5mg OD for 3 days.

Day 2 patient was stable and continued anticoagulation therapy with aspirin and
clopidogrel.

Patient was discharged with:

1. T. Cardiprin 100mg OD
2. T. Simvastatin 20mg ON
3. T. Bisoprolol 5mg OD
4. T. Amlodipine 10mg OD
5. T. Perindopril 4mg OD
Bisoprolol
Drug Name Bisoprolol

Drug Dosage 5-10 mg once daily. Max: 20mg/day

Indication Hypertension, Angina pectoris

Contraindication Cardiac failure, cardiogenic shock,

symptomatic bradycardia and hypotension,
severe bronchial asthma or COPD

Adverse Effect Bradycardia, worsening of heart failure,

hypotension, dyspnea

Rationale Hypertension and angina

Prescribing Writing T. Bisoprolol 5mg OD

Diabetes Mellitus
Diabetes Mellitus
NB, a 59-year-old married Malay woman with underlying Type 2 DM, HPT &
Dyslipidaemia, came to KK Nilai on 1/11/2017 for a routine follow-up.

Ever since her last follow up on 31/7/2017, she experienced 3 episodes of

hypoglycaemic attacks after taking S/C Novomix (Insulin): profuse cold sweating
and feeling funny, 15 minutes after taking insulin during lunch time. Claimed to
be having her lunch when that happened. No tremors or fainting episodes.
Relieved by resting and eating keropok.
Gained 5 kg over the last 3 months. Claimed to be eating well in normal portions.
Currently not experiencing polydipsia, polyuria, polyphagia, nocturia, tingling
sensation or numbness on hands and feet, headache, palpitations, fever, chest
pain, orthopnoea, paroxysmal nocturnal dyspnoea, shortness of breath, calf pain
or foot ulcers.
 Last blood sugar reading recorded that morning was 6.6 mmol/L (random blood
sugar); last HbA1C reading (April 2017): 14.6%
On S/C Novomix 20/20/20 and T. Metformin 250mg BD
She takes her insulin injections on time everyday however she is not compliant to
Metformin, Perindopril & Simvastatin. Not experiencing any side effects from any
of them.
Does not monitor capillary blood glucose or blood pressure at home
No macrovascular complications like chest pain, palpitations, dyspnoea at rest or
on exertion, swelling on lower extremities, or claudication
No microvascular complications like blurring of vision, feeling fatigue, dyspnoeic
or numbness on extremities.

2) Hypertension

Last BP reading: 120/80 mmHg

Past Medical History:

Been having Type 2 DM for 14 years since 2003. Initially presented with
persistent vomiting, abdominal pain & fatiguability. Admitted to hospital due to
Diabetic Ketoacidosis with Random Blood Sugar of 19 mmol/L.
Also has Hypertension in for 13 years, diagnosed during follow-up, and
Dyslipidaemia for 4 years

Medication History:

S/C Novomix 20/20/20 (previously took S/C Mixtard 30/20 BD)

Metformin 250mg BD
Perindopril 4mg OD
Simvastatin 10mg ON
 Family history:

Both parents and younger sister have diabetes mellitus. No history of ischaemic
heart disease.

Allergies:

No allergies towards food or medications

Diet History:

Takes home-cooked food regularly. Does not take sweet drinks. All meals are
taken on time.

Social history:

Non-smoker and does not take alcohol.

Housewife, lives with her husband who's retired, has 5 children.
Physical Examination
Blood pressure: 150/80 mmHg
Pulse rate: 64 beats/min
Respiratory rate: 14 breaths/min
Temperature: 36.8 degrees Celsius
Cardiovascular, peripheral
vascular, and neurological
examinations were unremarkable
Mild lipodystrophy on injection
sites around umbilicus

Body weight: 70 kg

BMI: 26 kg/m2

Waist circumference: 94 cm
INVESTIGATIONS
31/7/2017 1/11/2017

WEIGHT 65 KG 70 KG

BMI 26 27

WAIST CIRCUMFERENCE 89 CM 94CM

BLOOD PRESSURE 120/80 MMHG 130/92 MMHG

RBS 13.8 6.6

SYMPTOMS HYPOGLYCEMIC
 2008 2009 2010 2014 2016 2017 2017

HBA1C 9.9 9.5 9.2 9.3 11.5 10.6 14.3

TOTAL 5.3 5.2 6.5 5.8 5.9 4.8

CHOLEST
ROL

TG 1.0 2.3 2.06 1.49 2.25 1.19

LDL 3.1 2.2 3.6 3.4 3.25 2.5

HDL 1.79 1.91 2.0 1.88 1.66 1.85

UREA 4.6 5.9 4.0 5.0 10.1 4.5

NA 139 136 135 132 135 133

K 4.5 4.0 3.9 3.8 3.6 3.2

CL 101 101 102 98.3 95.5

CR 72 85 72 78 107 81

URIC ACID 280 274 306 402

This patient is under SC Novomix, Metformin, Perindopril and Simvastatin.

NAME NOVOMIX (ASPART AND PROTAMINE IN 30/70 RATIO)

DOSAGE 100 U/ML 20/20/20

INDICATION DM TYPE 2 REQUIRING INSULIN

CONTRAINDICATION HYPERSENSITIVITY TO THE ACTIVE SUBSTANCE

ADVERSE EFFECTS HYPOGLYCEMIA, URTICARIA, PERIPHERAL

NEUROPATHY, ANAPHYLACTIC REACTION

RATIONALE INTENSIFYING TREATMENT FOR UNCONTROLLED

DIABETES

PRESCRIPTION WRITING SC NOVOMIX 20/20/20

Oral Anti-diabetic agents
a) Biguanides

Drug name Metformin

Dosage Initial dose : 500 mg OD

Usual dose : 1500 mg OD
Max dose : 2g/day

Indication Diabetes Mellitus, as first line therapy.

Contraindication Renal disease/ dysfunction, diabetic

ketoacidosis

Adverse Effects Metallic taste, GI disturbances, nausea

Rationale Type 2 Diabetes Mellitus, as add-on

therapy for insulin

Prescription writing T. Metformin HCl 500mg OD x (duration)

b) Sulphonylureas
Drug name Gliclazide

Dosage 40-80 mg OD
Max dose: 320mg /day

Indication Type 2 DM. Use only in patient under 65

y/o

Contraindication Type 1 DM, pregnancy, diabetic metabolic

decompensation

Adverse Effects Increased appetite, weight gain, pruritus, GI

disturbances

Rationale

Prescription writing Tablet Gliclazide 40 mg OD x (duration)

c) Alpha-Glucosidase Inhibitors (AGIs)
Drug name Acarbose

Dosage Initial dose : 50 mg OD

Max: 200mg TDS

Indication Non-insulin dependent DM in combination

with conventional oral therapy where
glycemic control is inadequate

Contraindication Less than 18 years old, chronic intestinal

disorders, cirrhosis, DKA, pregnancy,
lactation, severe renal impairment

Adverse effects Flatulence, abdominal distension, diarrhea

Rationale Type 2 DM

Prescription writing Tablet Acarbose 50 mg OD

d) Thiazolidinediones (TZD)

Drug name Pioglitazone

Dosage Initially 15 - 30mg OD, max 45mg OD

Indication Diabetes Mellitus as monotherapy or in

combination with metformin and SUs

Contraindication DKA, Congestive Cardiac Failure, acute

liver disease

Adverse effects URTI, headache, sinusitis,myalgia, fluid

retention

Rationale Type 2 DM

Prescription writing T. Pioglitazone 15mg OD

e) Dipeptidyl Peptidase-4 Inhibitors (DPP-4)

Drug name Sitagliptin

Dosage Initial dose: 25 mg OD

Max dose: 100mg OD

Indication As add-on therapy for those who failed

therapy and/or contraindicated to
metformin/ sulphonylureas

Contraindication Pregnancy, lactation, ketoacidosis

Adverse effects Pancreatitis, allergic reactions, worsening

renal function, URTI

Rationale Type 2 DM unresponsive/ contraindicated

to metformin

Prescription writing Tablet Sitagliptin 25 mg OD

f) Sodium-glucose Cotransporter 2 Inhibitors (SGLT2)

Drug name Dapagliflozin

Dosage 5 mg OD, max dose: 10mg/ day

Indication 1) Adjunct therapy to diet & exercise as

monotherapy in T2DM above 18 y/o
2)add-ons to metformin/ SUs/ Insulin

Contraindication DKA, Type 1 DM, severe renal impairment,

lactation

Adverse effects Hypoglycemia, thrush, UTI, polyuria, painful

urination

Rationale Type 2 DM

Prescription writing Tablet Dapagliflozin 5mg OD

Injectable agents
Glucagon-like Peptide-1 Receptor Agonist

Drug name Exenatide IR / XR

Dosage Exenatide IR 5 g BD
Exenatide XR 2 mg weekly

Indication Monotherapy or add-on to metformin /

sulphonylureas/ TZD/ Insulin glargine

Contraindication Hypersensitivity

Adverse effects Injection site reaction, nausea, vomiting,

diarrhea , flatulence. May cause
hypoglycemia if used w SUs

Rationale Type 2 DM not controlled on conventional

oral therapy

Prescription writing SC Exenatide XR 2mg weekly

Insulin
Drug name Actrapid (short acting), insulatard (intermediate), glargine
(long acting), novomix (premixed insulins)

Dosage Personalised units according to plasma glucose level,

given subcutaneously

Indication - Inadequate glucose control despite optimal dose

and number of OAD
- Short term use in:
- Acute illness/ surgery
- Pregnancy, breastfeeding
- Severe metabolic decompensation

Contraindication Allergy, intravenous administration

Adverse effects Hypoglycemia, injection site reaction

Rationale Type 2 DM not controlled on conventional oral therapy

Prescription writing Subcutaneous Novomix 20|20|20

Dyslipidemia
Case - Klink Kesihatan
S, 57 years old Malay male, retired teacher (known DM, HPT, Dyslipidemia >10yrs)

- Polyuria, polydipsia, urinary incontinence

- Occasionally, dizziness, tremor, sweating take sweets
- Denied headache, chest pain, blurred vision, numb/tingling sensation hands/feets

Past medical hx

- Hypertension (Amlodipine 10mg OD, Perindopril 8mg OD)

- DM (Metformin 500mg BD, Insulin 28 units ON)
- Dyslipidemia (Simvastatin 10mg ON)

Family Hx - dad, mother, siblings (DM, HPT, Dyslipidemia)

Social Hx - diet uncontrolled (3 heavy meals; 3in1 nescafe, nasi briyani+kambing)

-gardening; no smoke/alcohol
Physical Examination Investigations
Height: 162 cm Lipid profile

Weight: 90 kg LDL: 2.5

BMI: 31.9 kg/m2 HDL: 1.8

BP: 134/74 mmHg ECG - previous MI; incidental finding

RBS: 19.1 mmol/L (Right axis deviation; left circumflex artery

affected)
No significant examination
findings
Management
- Advice on diet
- Dietitian referral
- Increased insulin dose to 30 units ON; advice possible need of 2 dosage/day
- Follow up 3 months clinic visit
Principles of management
A. Therapeutic lifestyle changes
- Medical nutrition therapy - diet high in saturated fatty acids and trans fatty acid
raise LDL levels, high intake of monounsaturated and polyunsaturated fatty acids
lower LDL, reduce CV risk. High intake of carbohydrates reduces HDL, raises TG
- Weight reduction - lower TG, raise HDL. waist circumference <90cm males,
<80cm females
- Physical activity
- Stop smoking - major risk factor for CVD
- Restrict alcohol - alcohol increases TG levels
- Lipid profile should be measured after 6-12 weeks before considering drug
therapy
 B. Drug therapy

1. Statins (HMG CoA Reductase Inhibitors)

2. Fibrates (Fibric acid derivatives)
3. Resins (Bile acid sequestrants)
4. Niacin (Nicotinic acid)
5. Cholesterol absorption inhibitors

- Statins are drug of choice for reducing LDL

- fibrates and nicotinic acid may be considered for increasing HDL and reducing TG
AFTER LDL treatment goal is achieved.
 C. LDL apheresis

It is indicated in patients with homozygous familial hypercholesterolemia who do not

respond satisfactorily to maximum multiple drug therapy.

Can also be considered in severe heterozygous familial hypercholesterolemia and

progressive coronary artery disease who do not achieve target lipid levels with
maximal drug therapy.
Anti lipidemic drugs
1. Statins (HMG CoA Reductase Inhibitors)
2. Fibrates (Fibric acid derivatives)
3. Resins (Bile acid sequestrants)
4. Niacin (Nicotinic acid)
5. Cholesterol absorption inhibitors
Statins - HMG CoA Reductase Inhibitors
Drug dosage: simvastatin 10-80mg

Indication: first line agents for familial hypercholesterolemia, primary and secondary
prevention of CVD

Contraindication: pregnancy, breastfeeding, active or chronic liver disease

Adverse effects: myopathy-myalgia, myositis, rhabdomyolysis, increased liver

enzymes, slight increased risk for new onset DM, increased frequency of proteinuria

Rationale: treatment of choice for reducing LDL

Prescription writing: simvastatin 10mg ON x 1/12

 Fibric-Acid Derivatives (Fibrates)
Drug dosage: Fenofibrate 100mg TDS; Gemfibrozil 600-1200mg daily; Bezafibrate 200 mg daily;
ciprofibrate 100mg OD
Indication: very high TG levels who do not respond to non-pharmacological measures, diabetes
already on maximally tolerated statins, and who have low HDL-C (0.88 mmol/L) and high TG (2.3
mmol/L), fibrates may be considered to reduce CV events
Contraindication: Absolute- Severe hepatic disease, Severe renal disease; relative-Concomitant use of
certain drugs (gemfibrozil and repaglinide)

Adverse effects: dyspepsia, cholelithiasis, myopathy

Rationale: reduce serum Tg , Increase HDL-C

Prescription writing: Fenofibrate 100mg TDS daily; Gemfibrozil 600-1200mg daily doses before meal;
Bezafibrate 200 mg daily increasing (gradually over 5-7 days) to a maximum dose of 200 mg tds
(regular) or 400 mg daily (sustained release);ciprofibrate 100mgOD
PCSK 9 inhibitors (proprotein convertase subtilisin kexin type 9
inhibitors)
Drug Names Evolocumab
Drug Dosage 140mg SC every two weeks or 420mg SC every
monthly

Indication High CV risk who have persistently elevated LDL-C

level despite optimum lipid modifying therapy,
Familial hypercholesterolemia, very high risk or high
risk patients with true statin tolerance and
persistently high LDL-C

Contraindication History of serious evolocumab hypersensitivity

reaction

Adverse effects Injection site swelling, flu-like symptoms, nausea,

joint pain

Rationale

Prescribing Writing SC evolocumab 140mg every 2 weeks / SC

evolocumab 420mg monthly
Nicotinic acid
Drug Name Nicotinic acid (Niacin)
Drug Dosage Initial dose: 150-300mg daily in divided dose
Usual dose: titrated up to 2g/day
Max : 6g/day

Indication Dyslipidemia, treatment and prophylaxis of

pellagra,

Contraindication Absolute: hepatic disease, severe gout

Relative: DM, hyperuricemia, peptic ulcer
disease

Adverse effects Cutaneous flushing, hypertriglyceridemia,

hepatotoxicity, gastritis

Rationale elevated TG and not responsive to

nonpharmacological intervention (lowers TG
and increase HDL)

Prescription Writing T. Nicotinic acid 2g OD(taken with meals)

Bile Acid Sequestrants (Anion exchange resins)
Drug dosage: Cholestyramine 4 g/d increased by 4g at weekly intervals to 12-24 g/day in 1-4 divided doses, Max: 24
g/day

Indication: High LDL-C

Contraindication: Absolute: Dysbetalipoproteinemia, TG >4.5 mmol/L; Relative: TG >2.3 mmol/L

Adverse: GIT distress, Constipation. Reduce absorption of folic acid and fat-soluble, vitamins (A, D & K),
***Decreased absorption of certain drugs

Rationale: dyslipdenia

Prescription writing: Cholestyramine 1g qid x 1/52

***Paracetamol, NSAIDs, anticoagulant, valproate, digitalis, thiazides, thyroxine, raloxifene, propranolol and
tricyclic antidepressants.