cardio pharmacology

Question 1

Complications of chronic HTN

Answer 1

Major risk factor for:
Stroke – ischaemic and haemorrhagic
Myocardial infarction
Heart failure
Chronic renal disease
Cognitive decline
Premature death

Increases the risk of:
Atrial fibrillation (independent stroke risk)

Question 2

how to diagnosis of HTN and stages

Answer 2

People with suspected hypertension are offered ambulatory blood pressure monitoring (ABPM) to confirm a diagnosis of hypertension.

The 4 stages of hypertension are:
Elevated blood pressure levels between 120-129/less than 80. …
Hypertension stage 1 is 130-139/80-89 mmHg.
Hypertension stage 2 is 140/90 mmHg or more.
Hypertensive crisis is higher than 180/120 or higher.

Question 3

mechanisms of BP control

Answer 3

the targets for therapy are:

1.Cardiac output and Peripheral Resistance

2. Interplay between:
   a. Renin-Angiotensin-Aldosterone system
   b. Sympathetic nervous system (noradrenaline)
3. Local vascular vasoconstrictor and vasodilator mediators

Question 4

summary or Renin system

Answer 4

angiotensin 2:
increases vascular growth ( hyperplasia and hypertrophy,
salt retention ( aldosterone release and increases tubular sodium reabsorbtion
angiotensin 2 can act on sympathetic nerve end to increase peripheral resistance and cardiac output

Question 5

actions of SNS on BP

Answer 5

Alpha receptors - peripheral resistance
beta receptors - cardiac output
sns also acts to potentiate renin activity

Question 6

potential drug targets of BP

Answer 6

RENIN system:
ACE inhibitors
ARB - angiotensin receptor blocker
Renin Inhibitor
Aldosterone antagonist

SNS:
Alpha blocker,
Beta Blocker
calcium channel blocker

Question 7

Clinical indications - ACE Inhibitors, state examples

Answer 7

Main clinical indications

Hypertension
Heart failure
Diabetic nephropathy

examples: ramipril, perindopril, enalapril

Question 8

Adverce effects of ACEi

Answer 8

Main adverse effects

1. Related to reduced angiotensin II formationa. Hypotension
   b. Acute renal failure
   c. Hyperkalaemia
   d. Teratogenic effects in pregnancy - CANT GIVE TO PREGGOS
2. Related to increased bradykinin production
   Bradykinin is involved in plasma extravasation, bronchoconstriction, nociception, vasodilation, and inflammation Burch et al (1990)
   ACE breakdown bradykinin into inactive products
   a. Cough
   b. Rash
   c. Anaphylactoid reactions

Question 9

clinical indications of ARB angiotensin 2 receptor blocker

Answer 9

Main clinical indications

Hypertension
Diabetic nephropathy
Heart failure (when ACE-I contraindicated)

e.g cadesartan, valsartan, losartan, irbesartan, telmisartan

Question 10

side effects of ARB

Answer 10

Symptomatic hypotension (especially volume deplete patients)
Hyperkalaemia
Potential for renal dysfunction
Rash
Angio-oedema

Contraindicated in pregnancy - NO PREGGOS
Generally very well tolerated

Question 11

indication for CCB and E.G

Answer 11

Hypertension
Ischaemic heart disease (IHD) – angina
Arrhythmia (tachycardia)

Question 12

difference in groups of CCB

Answer 12

Effect: L-type calcium chanel blocker

1. Dihydropyridines: nifedipine, amlodipine, felodipine, lacidipinePreferentially affect vascular smooth muscle
   Peripheral arterial vasodilators
2. Phenylalkylamines: verapamilMain effects on the heart
   Negatively chronotropic (rate), negatively inotropic (force of contraction)
3. Benzothiazepines: diltiazemIntermediate heart/peripheral vascular effects

Question 13

Adverse Effects of CCB

Answer 13

Due to peripheral vasodilatation (mainly dihydropyridines)
Flushing
Headache
Oedema
Palpitations

Due to negatively chronotropic effects (mainly verapamil/diltiazem)
Bradycardia
Atrioventricular block

Due to negatively inotropic effects (mainly verapamil)
Worsening of cardiac failure so cant use for heart failure obviously

Verapamil causes constipation

Question 14

clinical indications for beta blockers

Answer 14

Ischaemic heart disease (IHD) – angina
Heart failure
Arrhythmia
Hypertension

e.g bisoprolol, propranolol , metoprolol

Question 15

Drug selection of beta receptors: B1 vs B2

Answer 15

there is no cardioselective beta blocker, but BB have different affinities. this can be affected by the concentration of the drug. relative to some factors.

B1 receptors are found in the heart
B2 recepotrs are found in the lungs, but 40% of hearts are b2

BB in asthmatic contradictions can worsen condition

Question 16

adverse effects of BB

Answer 16

Fatigue - worsen effects in active people who regularly have adrenaline boosting activities
Headache
Sleep disturbance/nightmares

Bradycardia
Hypotension
Cold peripheries
Erectile dysfunction

Worsening of:
Asthma (may be severe) or COPD
PVD – Claudication or Raynaud’s
Heart failure – if given in standard dose or acutely, if heart failure is chronic BB should be given slow and dosage should be titrated

Question 17

Diuretics Clinical Indication and Types with examples

Answer 17

Hypertension
Heart failure

Classes

Thiazides and related drugs (distal tubule):
Bendroflumethiazide, hydrochlorothiazide
these are more commonly used for HTN

Loop diuretics (loop of Henle)
furosemide (fast acting), bumetanide
These are more commonly used for Heart failure

Potassium-sparing diuretics:
AMILORIDE

Aldosterone antagonists these swapped potassium sparing diuretics. also as acting on RENIN sysem can eb considered Disease MODIFYING AGENTS
spironolactone,

Question 18

Adverse effects of diuretics

Answer 18

Hypovolaemia (mainly loop diuretics)
Hypotension ( “ )

Low serum potassium (hypokalaemia)
Low serum sodium (hyponatraemia)
Low serum magnesium (hypomagnesaemia)
Low serum calcium (hypocalcaemia)

Raised uric acid (hyperuricaemia – gout)

Erectile dysfunction 		(mainly thiazides)
Impaired glucose tolerance	(             “              )

Question 19

other hypertensive

Answer 19

Alpha 1 Adrenorecptors - Doxazosin
centrally acting anti-HTN - MOXONIDINE
Direct renin inhibitor - Aliskiren

Question 20

treatment rubric for HTN

Question 21

what is and Types of Heart Failure

Answer 21

Heart failure is a complex clinical syndrome of symptoms and signs that suggest the efficiency of the heart as a pump is impaired.
It is caused by structural or functional abnormalities of the heart. Most common cause is coronary artery disease

Heart failure due to left ventricular systolic dysfunction - LVSD

Heart failure with preserved ejection fraction (diastolic failure) – HFPEF

Acute heart failure
Chronic heart failure

Question 22

why is it bad to use heart performance drugs with heart failure

Answer 22

when the heart is impaired, feedback system works to try to perserve circulation. these resposne such as sympathetic responses are needed. thus treatment looks at modifying this sympathetic response (cardiac output + peripheral resistance) instead of modifying heart activity

Question 23

armamentarium of Heart failure

Answer 23

1. Symptomatic treatment of congestion:
   Diuretics (usually loop)
2. Disease influencing therapy – neurohumoral blockade
   Inhibition of renin-angiotensin-aldosterone system Inhibition of the sympathetic nervous system

a. First line:
1st ACE inhibitors and
2nd Dual therapy: beta blocker therapy both sides of heart performance systems - RENIN & SNA

Low dose and slow uptitration

b. Aldosterone antagonists - Spironlactone - can cause gynecomastia

c. ACE-I intolerant: Angiotensin receptor blocker

d. ACE-I and ARB intolerant: Hydralazine/nitrate combination

e. Consider digoxin or ivabradine

Question 23

Types of CAD

Answer 23

Coronary Artery Disease

1. Chronic stable angina
   Anginal chest pain
   Predictable
   Exertional
   Infrequent
   Stable
   ****
2. Unstable angina / acute coronary syndrome (NSTEMI)
   Unpredictable
   May be at rest
   Frequent
   Unstable
   ****
3. ST elevation Myocardial Infarction (STEMI)
   Unpredictable
   Rest pain
   Persistent
   Unstable