drug treatments for cardiovascular disease (lectures 1-4) Flashcards
(61 cards)
1
Q
what is hypertension?
A
persistently higher than normal blood pressure
2
Q
when do you treat hypertension?
A
when mean BP is >150/95 mmHg
3
Q
how do you treat hypertension?
A
appropriate pharmacological treatment required a knowledge of the physiological regulation of BP and knowledge of how drugs work
4
Q
what is the equation of blood pressure?
A
BP = CO x TPR
5
Q
what is the equation of cardiac output?
A
cardiac output = stroke volume x heart rate
6
Q
what regulates stroke volume?
A
the ventricles
7
Q
what regulates heart rate?
A
SA node
8
Q
what is the total peripheral resistance a measure of?
A
the degree of constriction of the arterioles
9
Q
how does extrinsic regulation work?
A
- autonomic nervous system
- sympathetic system increased frequency and force of contraction via beta 1 receptors —> increased cAMP
- –> increased calcium —> increased rate and force of contraction
- parasympathetic system decreases frequency by decreasing cAMP via M2 receptors
10
Q
how does the sympathetic nervous system regulate TPR?
A
- SNS –> NA –> alpha 1 receptor –> IP3 –> Ca2+ –> constriction
- SNA –> A –> beta 2 receptor –> cAMP –> relaxation
11
Q
how do you generally regulate TPR?
A
- increase in Ang II —> increase IP3 —> increase intracellular [Ca2+]
- causes constriction of arterioles and an increase in total peripheral resistance and increases in BP
12
Q
how do you regulate preload by RAAS?
A
- constriction of venules via AT1-R
- RAAS also facilitates Na+ and H2O retention
- aldosterone activates cytoplasmic receptors which bind to the nucleus to increase expression of Na+ channels and so aid Na+ and water retention
13
Q
what factors affect the choice of drug treatment?
A
- age: <55 years old ACE inhibitor/angiotensin receptor blocker (ARB); >55 year old or all-black African/American calcium channel blocker
- race: ACE inhibitors/beta blockers may be less efficacious in black African/Americans
- co-existing diseases
14
Q
what are the different classes of anti-hypertensives?
A
- ACE inhibitors and angiotensin receptor blockers
- calcium channel antagonists
- diuretics
- beta-blockers
- vasodilators
15
Q
what are the side effects and contraindications of ACE inhibitors?
A
- dry cough
- 1st dose hypotension
- renal impairment
- contraindicated in bilateral renal artery stenosis
- may cause hyperkalaemia
- no adverse effect on serum glucose or lipids
16
Q
what is hyperkalaemia?
A
high potassium levels
17
Q
what do angiotensin receptor antagonists do?
A
block the actions of Ang II on AT1-R
18
Q
what is an example of an aldosterone antagonist?
A
spironolactone
19
Q
when do you use spironolactone?
A
used as an add on for resistant hypertension but FRONTLINE for hypertension in patients with primary aldosteronism
20
Q
what are the different types of calcium channel antagonists and how do they work?
A
- main type = dihydropyridines
- target L-type calcium channels on smooth muscle of arterioles
- phenylalkylamines and benzothiazepines target L-type channels in the heart and decrease the frequency and force of contraction
21
Q
what are the side effects of calcium channel antagonists?
A
- peripheral oedema
- flushing and headaches
22
Q
how does peripheral oedema occur?
A
preferential dilation of pre-capillary arteriole and impairment of the function of the pre-capillary sphincter increases hydrostatic pressure across the capillary and reducing fluid reabsorption
23
Q
what enhances the action of calcium antagonists?
A
grapefruit juice
24
Q
how do thiazide and thiazide-like diuretics work?
A
some diuretic action but also acts via activation of Katp in smooth muscle of blood vessel to dilate arteriole and decrease blood pressure
25
how does indapamide work?
it hyperpolarises smooth muscle cells causing relaxation/dilation of the arteriole and decrease in total peripheral resistance
26
what are the side effects and contraindication of hiazide and thiazide-like diuretics?
- hypokalaemia
- increase in urate
- increase in glucose
- increase in blood lipids
27
what are the side effects and contraindications of beta blockers?
fatigue
28
how do beta blockers cause vaso/bronchoconstriction?
smooth muscle cell in the airways of peripheral arterioles perfusing skeletal muscle
29
what does low blood glucose activate?
the release of adrenaline, mobilises glucose release from liver leading to tremor, palpitations and sweats
30
what blocks the action of low blood glucose?
beta blockers
31
what combination of 2 drugs is contraindicated in diabetics?
beta blockers and thiazides
32
what are the different types of beta blockers?
- non selective (beta 1 and beta 2)
| - selective beta 1 anatgonists
33
what type of drug are vasodilators?
alpha 1 antagonists
34
how do vasodilators work?
NA --> alpha 1 --> IP3 --> calcium ion --> constriciton
35
when are vasodilators used to treat hypertension?
when the patient have benign prostatic hypertrophy
36
what do vasodilators such as minoxidil do?
open potassium channels
37
what increases myocardial oxygen supply?
- work rate (heart rate, force)
| - work load (TPR)
38
what decreases myocardial oxygen supply?
- thrombus
- atheroma
- vasoconstriction
39
what helps with the regulation of coronary blood flow?
endothelium derived relaxing factor (nitric oxide)
40
how do you regulate cardiac workload?
- end diastolic volume (preload) regulated by smypathetic system, RAAS
- heart rate (sympathetic system/Ca2+)
- contractility (sympathetic system/Ca2+)
- total peripheral resistance (sympathetic system RAAS)
41
what is the definition of stable angina?
a predictable pattern of pain during exercise that is relieved by rest
42
what is the treatment for angina?
drug treatment designed to decrease work done by the heart and/or increase blood supply and treat risk factors
43
what are the side effects of drug treatment for angina?
- postural hypotension
- headache
- dizziness
- reflex tachycardia
44
why does reflex tachycardia occur and how do we stop it?
- it is due to activation of the sympathetic nervous system
| - we look to block effects of the sympathetic nervous system with beta blockers
45
what do beta blockers do?
inhibit release from the kidney and inhibit RAAS
46
what are the side effects of beta blockers?
- bronchoconstriction
- fatigue
- contraindicated in patients with peripheral vascular disease
47
what are calcium channel antagonists used for?
in asthmatics or other groups where beta blockers are contradicted the cardiac selective calcium channel blockers can be used
48
what happens when you use a mixture of cardiac selective calcium eds and beta blockers?
can cause severe bradycardia and even heart block
49
what do calcium channel blockers do?
can reduce heart beat by blocking L-type channels in the SA and AV nodes which slows the rate of depolarisation and therefore reduces the rate of action potential generation
- they also decrease the force of contraction of the ventricles by reducing calcium entry through L-type channels
50
what does ivabradine do?
- blocks the pacemaker current (Ih/f) in the nodal tissue of the heart
- it reduces the Na+ entry through If channels and slows the rate of depolarisation of the SA node cells and reduce firing frequency and therefore heart rate
- it will not directly alter the force of contraction of the heart
51
what are the side effects of ivabradine?
- luminous phenomena (ih) in retina
- blurred vision
- dizziness
52
what are the alternatives to ivabradine?
- long acting nitrates (isosorbide mononitrate)
- decreased preload
- nicorandil
- ranolazine
53
how do you treat to reduce hypercholesterolaemia 2 degrees prevention?
- cholesterol from 2 main sources
- drugs designed to either inhibit uptake from GI tract or reduce production in liver
- frontline treatment are the statins
54
how do statins prevent cholesterol synthesis?
- statins decrease the production of cholesterol in the liver by inhibiting the HMG CoA enzyme
- this stimulates the liver cells to express LDL receptors and allows the liver cells to scavenge LDL cholesterol from the plasma
- this reduces plasma LDL cholesterol levels
55
what are the secondary prevention methods cholesterol synthesis?
- aspirin: antiplatelet agents
| - ACE inhibitors: decrease the workload on the heart
56
how do you treat acute coronary syndromes?
- same as for stable angina and antiplatelet
| - aspirin and clopidogrel
57
what is the mechanism of action for some key antiplatelet agents?
- platelet activation occurs when the endothelial cells become damaged
- this releases ADP which on P2Y12 receptors to stimulate the platelet to express GPIIb/IIIa receptors
- fibrinogen binds to these receptors to cross link different platelets
- activation of COX also helps platelet activation through the production of Thromboxane A2
- aspirin inhibits COX irreversibly
- clopidogrel and prasugrel are ADP antagonists and block P2Y12 receptors
58
how do you diagnose chronic coronary syndromes?
- pain
| - sweating, tachycardia, cold clammy skin
59
how do you treat chronic coronary syndromes?
- pain relief: diamorphine to decrease pain, anxiety, sympathetic drive and vasodilators
- oxygen
- aspirin/GTN
- clot busting drugs: tenecteplase
- beta blockers: decrease cardiac workload, prevents arrhythmias
- ACE inhibitors: decrease cardiac workload, prevents remodelling development of heart failure
- anticoagulants: in case of long term best rest, prevents thrombus formation
60
how does digoxin work to treat heart failure?
- digoxin binds to the Na+/K+ ATPase and inhibits its action
- this will increase levels of Na+ ions inside the heart muscle cells
- this increase will in turn inhibit the Na+/Ca2+ exchanger which will lead to a build up of Ca2+ inside the muscle cell and a stronger contraction
61
how does amiodarone treat dysrhythmias?
- K+ channel blockers that increase the refractory period of ventricular myocytes and can terminate arrhythmias
