Anti-hypertensive drugs 2 - CCB's, Thiazides & related

Question 1

list the dihydropyridine CCB’s

Answer 1

1) Amlodipine
2) Felodipine
3) Lercanidipine
4) Nifedapine,
5) Nicardipine , lacidipine, nimodipine

Question 2

why should verapamil and diltiazem be avoided in heart failure?

Answer 2

They may further depress cardiac function and cause clinically significant deterioration

Question 3

What is the most common side effect of verapamil?

Answer 3

Constipation

↳ can cause bradycardia, heart block and cardiac failure

Question 4

what is verapamil mainly indicated for used in? (3)

Answer 4

1) supraventricular arrhythmias, including supraventricular tachycardia, atrial flutter and atrial fibrillation
2) Angina
3) Hypertension

Question 5

outline the mechanism of action of CCB’s

Answer 5

1) CCB’s decrease Ca2+ entry into vascular and cardiac cells reducing intracellular [Ca2+]. This causes relaxation and vasodialation in aterial smooth muscle, lowering arterial pressure.
2) in the heart, CCB’s reduce myocardial contrictility. they supress cardiac conduction across AV node, slowing ventricular rate. reduced cardiac rate, contractility and afterload reduce myocardial oxygen demand preventing angina.

Question 6

CCB’s can be divided into dihydropyridines and non-dihydropyridines, explain how the two differ from each other

Answer 6

1) Dihydropyridines are relatively selective for the vasculature (cause relaxation of peripheral blood vessels)
2) non-dihydropyridines are more selective for the heart.
↳Verapamil most cardioselective, whereas diltiazem also has some effects on blood vessels

Question 7

explain the difference between positively and negatively ionotiopic drugs

Answer 7

1) Negatively inotropic agents weaken the force of muscular contractions. (negative inotropic effects of anti-arrythmic drugs tend to be additive)
2) Positively inotropic agents increase the strength of muscular contraction

Question 8

compare the ionotropic effects of verapimil and diltiazem

Answer 8

1) verapimil is highly negatively ionotropic, it reduces cardiac output , heart rate, and impairs AV conducation
2) diltiazem has less negative inotropic effects then verapamil

Question 9

what conditions are nifedipine, amlodipine, felodipine and nicardipine manly indicated for?

Answer 9

angina or hypertension

Question 10

Unlike verapamil which can cause participate heart failure and exacerbate conduction disorders, why does nifedipine, amlodipine, felodipine and nicardipine not cause this problem?

Answer 10

1) Nifedipine relaxes vascular smooth muscle and dilates coronary and peripheral arteries. it has more influence on vessels and less on myocardium, it also has no anti-arrhythmic activity unlike verapamil.
2) Any negatively negative ionotropic effects are offset by a reduction in left ventricular work.
3) The other drugs are simillar, as they do not reduce myocardial contractility and thus do not produce deterioration in heart failure patients

Question 11

what are the common side effects associated with amlodipine, nifedipine?

Answer 11

1) Headache and flushing (gets better after a few days)
2) ankle swelling
3) Palpitations
↳ caused by vasodialation and compensatory tachycardia

Question 12

why should amlodipine and nefedipine be avoided in patients with unstable angina and severe aortic stenosis?

Answer 12

1) angina : because vasodialation causes a reflex increase in contractility and tachycardia, which increases myocardial oxygen demand
2) aortic stenosis: they can provoke collapse

Question 13

what two conditions is nifedipine and diltiazem are indicated for use in and how should they be prescribed?

Answer 13

1) used in angina and hypertension

2) M/R preparations need to be prescribed by brand (this is the same for diltiazem)

Question 14

what are the features of a CCB overdose?

Answer 14

1) nausea and vomiting
2) dizziness
3) agitation
4) confusion
5) coma in severe
6) severe hypotension (in dihydropyridine CCB’s)

Question 15

what are the common indications for thiazide and related diuretics?

Answer 15

1) Alternative first-line treatment for hypertension where a CCB would otherwise be used but is either unsuitable (e.g. due to odema) or there are features of heart failure
2) Add-on treatment for hypertension

Question 16

Identify the thiazide and the thiazide-like diuretics from the following:

1) Bendroflumethiazide
2) Indampamide
3) Chlortalidone
4) Hydrochlorothiazide

Answer 16

1) Thiazide: Bendroflumethiazide, hydrochlorothiazide
2) Thiazide-like indapamide, chlortalidone

↳ Both types differ chemically but have similar effects and clinical uses

Question 17

Outline the MOA of thiazide diuretics

Answer 17

1) Inhibit Na+/Cl- co-transporter in distal convoluted tubule of the nephron
2) This prevents reabsorption of sodium and osmotically associated water. Resultant diureses causes an initial fall in extracellular fluid volume.
↳ also mediated through vasodilation

Question 18

what conditions should thiazide diuretics be used in caution or avoided in?

Answer 18

►caution in:
1) Diabetes- increase plasma concentrations of glucose
2) Gout- reduced uric acid secretion may precipitate attack
3) Hyperaldosteronism
►Avoid in:
3) Avoid in hypokalaemia, hyponatraemia, hypercalcaemia, symptomatic hyperuricaemia, addisons disease

Question 19

what electrolyte disturbances can be caused by thiazide diuretics?

Answer 19

1) Hypokalaemia- this is due to increased delivery of Na+ to distal tubule where it is exchanged for K+
2) Hyponatraemia- but not usually problamatic

Question 20

Hypokalaemia can occur with the use of thiazide diuretics. Explain why this can be dangerous in patients with severe CV disease and those taking cardiac glycosides

Answer 20

1) high potassium levels can cause arrhythmias
2) Loop and thiazide diuretics can increase the risk of digoxin toxicity
↳ (also avoid with lithium- Na+ depletion inc risk of toxicity)

Question 21

How can hypokalaemia be avoided in those taking thiazide diuretics?

Answer 21

1) Potassium-sparing diuretics or potassum supplements
↳ although rarely necessary when used in treatment of hypertension
2) Avoid combining with other drugs that lower K+ concentration e.g loop diuretics

Question 22

what can hypokalaemia cause in patients with hepatic failure?

Answer 22

Encephalopathy esp in alcoholic cirrhosis

Question 23

how should thiazide diuretics be dosed in elderly patients?

Answer 23

1) Lower initial doses should be used as they are esp susceptible to SE
2) Dose should then be adjusted according to renal function

Question 24

list the common side effects of thiazide diuretics

Answer 24

1) constipation
2) electrolyte imbalance
3) headache
4) postural hypotension
5) impotence in men

Question 25

Are thiazides effective in renal impairment?

Answer 25

1) Ineffective if eGFR <30mL/min and should be avoided. (metolazone remains effective)
↳ electrolytes should be monitored in renal impairment

Question 26

Comment on the effectiveness of thiazide diuretics when taken with NSAIDS

Answer 26

effectiveness of thiazide may be reduced ( not a problem with low dose aspirin)

Question 27

what are the monitoring requirements for thiazide diuretics

Answer 27

measure serum electrolytes before starting, at 2-4w into therapy and after any change in therapy that might alter balance

Question 28

Why might it be beneficial to give thiazides in combination with ACEi or ARB’s?

Answer 28

1) Main adverse effect of ACEi and ARB’s is hyperkalaemia, while the main adverse effect of thiazides is hypokalaemia.
2) Synergistic BP lowering effect- Thiazides then to activate RAS while ACEi/ARB’s block it

Question 29

when should diuretics be administered during the day?

Answer 29

Best to take them in the morning so the diuretic effect is maximal during the day rather than at night and does not interfere with sleep