Antihypertensive drugs Flashcards
1
Q
Define hypertension
A
abnormally high blood pressure (increased systolic/diastolic/pulse pressure)
2
Q
How is a blood pressure measurement given?
A
systolic over diastolic e.g. ‘120 over 80’
3
Q
What’s systolic pressure?
A
pressure when the heart is contracting (max. pressure)
4
Q
what’s diastolic pressure?
A
pressure when the heart is filling (min. pressure)
5
Q
what’s pulse pressure?
A
the difference between systolic and diastolic BP
6
Q
what’s hypotension?
A
abnormally low BP
7
Q
What diastolic BP measurement would be severe hypertension?
A
> 120 mm Hg
8
Q
what diastolic BP measurement would be moderate hypertension?
A
105- 120 mm Hg
9
Q
what diastolic BP measurement would be mild hypertension?
A
90- 105 mm Hg
10
Q
what’s normal/ optimal diastolic BP?
A
around 80 mm Hg
11
Q
what are the 2 types of hypertension?
A
primary and secondary
12
Q
what’s primary hypertension?
A
where the cause is unknown
13
Q
what are 2 other names for primary hypertension?
A
essential or idiopathic hypertension
14
Q
what’s secondary hypertension?
A
where the cause has been identified (due to another disorder/drugs) e.g. renal artery stenosis
15
Q
what are the 2 important trials for Hypertensive drugs?
A
ASCOT and ALLHAT
16
Q
what does ASCOT stand for?
A
Anglo-Scandinavian Cardiac Outcomes Trial
17
Q
what was ASCOT testing?
A
compared Amlodipine (Calcium channel antagonist) and Perindropil (ACE inhibitor) with Atenolol (B-blocker) and Bedroflumethiazid (diuretic)
18
Q
what were the findings of ASCOT?
A
both groups had reduced BP and reduced incidence of CVD (better with Amlodipine group)
19
Q
what did ASCOT conclude?
A
that calcium agonists and ACE inhibitors should replace ‘older’ treatments (B- blockers and diuretics)
20
Q
What does ALLHAT stand for?
A
Antihypertensive and Lipid Lowering treatment to prevent Heart Attack Trial
21
Q
where was ALLHAT done?
A
USA
22
Q
which had a wider ethnic range, ALLHAT or ASCOT?
A
ALLHAT (as it was done in the USA instead of UK/Scandinavia)
23
Q
what was ALLHAT testing?
A
Compared Chlorthalidone ( thiazide-like diuretic) with Amlodipine (calcium channel antagonist) or Lisinopril (ACE inhibitor)
24
Q
what were the findings of ALLHAT?
A
- BP was controlled in all 3 groups, but Chlorthalidone was superior
- risk of HA was similar for all 3
- risk of some other CVDs was lower with chlorthalidone
25
what did ALLHAT conclude?
that thiazide diuretics are superior to calcium channel blockers and ACE inhibitors
26
What's the NICE care pathway for hypertension?
https://www.google.com/search?safe=active&rlz=1C1CHBF_en-gbGB767GB767&biw=1280&bih=610&tbm=isch&sa=1&ei=ye3CXOn8CemBjLsP7u2gyAU&q=NICE+carepathway+hypertension+stage+1+and+stage+2&oq=NICE+carepathway+hypertension+stage+1+and+stage+2&gs_l=img.3...14350.18046..18160...0.0..0.87.1188.20......1....1..gws-wiz-img.g4LiWCP5BMw#imgrc=-Jhi0wDHD7aUOM:
27
what's Peripheral resistance?
the resistance the heart has to push against
28
what is peripheral resistance controlled by?
resistance arteriole which can contract and dilate under the control of the ANS
29
what's the chain of events which causes contraction of the resistance arteriole?
SNS releases Noradrenaline --> binds to the a1 adrenoreceptor --> activates Phospholipase C activation --> activates Inositol Triphosphate (INP3) release --> activates calcium store --> influx of calcium ions increases intracellular concentration --> causes calcium sensitive ion channels to open --> Cl- efflux --> causes membrane depolarisation --> causes opening of L-type calcium channels --> Ca2+ influx --> increases intracellular Calcium concentration --> causes contraction of arteriole, therefore increased resistance and BP
30
which part of the flow chart to calcium channel blockers act on?
causes opening of L-type calcium channels --> Ca2+ influx
31
what are the 3 main classes of calcium channel blockers?
- Verapamil ( a phenylalkylamine)
- Diltazen (a benzothiazepine)
- Amlodipine (a dihydropyridine)
32
Give a summary of how Calcium Channel blockers work
```
Reduce L-type calcium channel opening
targets vasculature (BVs) and heart
inhibits Ca2+ entry in vessels and reduces contractility and AV conduction in the heart
```
33
what are 2 side effects of calcium channel blockers?
- Headaches
| - Hypotension (in early stages of treatment/ at high dosage) caused by a change in posture e.g. standing up from sitting
34
What's Diuresis?
increased urine output
35
what's the short-term effect of diuresis?
intravascular salt and water depletion
36
In what case can intravascular salt and water depletion be useful?
renal failure
37
what effect does diuresis have in the long term?
Arterial dilation
38
how does arterial dilation affect BP?
it reduces it
39
As well as hypertension, what else can diuretics treat?
Oedema (removes excess fluid)
40
Generally, what do diuretics do?
increase excretion of Na+, Cl- and water
41
what are the 3 main classes of diuretics?
Thiazide, Loop and Potassium sparing
42
what part of the renal system do loop diuretics act on?
Loop of Henle
43
give 2 examples of loop diuretics
Frusemide and Bumetanide
44
What do loop diuretics do?
inhibit Na+/K+/2Cl- cotransport in the ascending limb
45
How does the loop of Henle work?
the descending limb has no active transport but is water permeable. The loss of water for the descending limb is driven by the movement of NaCl from the ascending limb. The ascending limp actively transports Na+ and passively transports Cl- and is water impermeable
46
what are 4 clinical uses for loop diuretics?
Heart failure, Hypertension, Renal failure, Pulmonary Oedema
47
which are the most powerful type of diuretics?
loop (up to 10 litres of urine produced a day)
48
what do thiazide diuretics do?
inhibit Na+/Cl- cotransport in the distal convoluted tubule.
By inhibiting NaCl cotransport out of the convoluted tubule, more NaCl is passed onto distal segments. This means less difference in osmality between urine and plasma, reducing ability to reabsorb water in more distal portions
49
what are the 2 main examples of Thiazide Diuretics
Bendroflumethiazide and Chlorthalidone
50
what are 2 clinical uses of Thiazide diuretics?
Hypertension and Oedema due to heart failure
51
how strong are thiazide diuretics?
mild
52
what do potassium sparing diuretics do?
decrease trans-principal cell Na+ movement and decrease negative lumen potential
53
what are the 2 main examples of Potassium sparing diuretics?
Spironolactone and Amiloride
54
what does Spironolactone do?
it's an aldosterone antagonist. It increases the expression of Na/K ATPase (genomic effect). This makes sodium channels in the membrane work better (non- genomic effect)
55
what does Amiloride do?
Blocks sodium channels in lumenal membrane- conserves Potassium
56
How strong are Potassium sparing diuretics?
weak (usually used in combination)
57
what aspect of BP is Renin involved in?
slow 'compensatory' control of BP
58
describe the overall flow cart in the renin-angiotensin system to increase blood pressure
Renin --> Angiotensin--> forms aldosterone and causes vasocontriction--> Aldosterone causes salt and water retention --> both vasoconstriction and salt and water retention increase BP
59
describe the formation of angiotensin hormones
Angiotensinogen is cleaved by renin to form Angiotensin I (inactive decamer)
Angiotensin I is cleaved by Angiotensin Converting Enzyme (ACE) to produce the active octamer Angiotensin II.
This can be cleaved to make either Angiotensin III (heptamer active) or Angiotensin IV (active hexamer)
Angiotensin II and III bind to AT1R to increase Aldosterone secretion and cause vasocontriction
(if we can prevent active forms of Angiotensin, we can reduce BP- ACE inhibitors)
60
What is Captopril?
an ACE inhibitor
61
how was captopril discovered?
viper venom
62
what do the names of all ACE inhibitors end with?
-pril
63
name the 4 main ACE inhibitors
captopril, lisinopril, ramipril, anapril
64
what are 2 common side- effects of ACE inhibitors?
Initial Hypotension and cough
65
What do Angiotensin II receptor antagonists do?
the angiotensin II receptor type I
66
give 2 examples of Angiotensin II receptor antagonists
Iosartan and Candesartan
67
what's a common side effect of Angiotensin II receptor antagonist?
Hypotension
68
what's a benefit of Angiotensin II receptor antagonists over ACE inhibitors?
no cough as a side effect
69
How does alpha 1 adrenoreceptor activation affect BP?
it increases it as it causes vasocontriction
70
name 2 competitive a1-adrenoreceptor antagonists
Phentolamine and chloropromazine
71
name a non-competitive a1-adrenoreceptor agonist
Phenoxybenzamine
72
what does Doxazosin do?
it's an a1- adrenoreceptor antagonist that blocks the receptor
73
when is Doxazosin used?
when other therapy has proved ineffective
74
give 3 side-effects of Doxazosin
- initial hypotension
- urinary incontinence
- retrograde ejaculation
75
Give the 3 main adrenoreceptor Beta-blockers
- Propranalol
- Atenolol
- Bisopropolol
76
describe Propranalol
competitive antagonist, non-selective B- adrenoreceptor antagonist, relatively lipid soluble (good penetration of the CNS)
77
describe atenolol and Bisopropolol
Competitive antagonists, B-selectivity, relatively water soluble (poor penetration of the CNS)
78
what physiological effects do Beta adrenoreceptor antagonists have to reduce BP?
reduced cardiac output
reduced renin release
reduced sympathetic tone
79
give 3 side-effects of beta-blockers
- Bronchoconstriction (can't be given to asthmatics)
- precipitation of cardiac failure (heart block)
- hyperglycaemia (can't be given to diabetics)
- reynauds
- Vivid dreams (propranalol)
80
What's the NICE guidelines for antihypertensive drugs?
https://www.google.com/search?q=NICE+recommendations+for+antihypertensive+drugs&safe=active&rlz=1C1CHBF_en-gbGB767GB767&source=lnms&tbm=isch&sa=X&ved=0ahUKEwiMo5r68-3hAhWDblAKHefXB5cQ_AUIDigB&biw=1280&bih=610#imgrc=2beLUpi82ZgSwM:
81
what type of drug is chlorthalidone?
Diuretic
82
what type of drug is verapamil?
calcium channel blocker
83
what type of drug is phenoxybenzamine?
adrenoreceptor blocker
84
what type of drug is doxazonsin?
adrenoreceptor blocker
85
what type of drug is amiloride?
diueretic
86
what;s the difference between pharmacodynamics and pharmacokinetics?
Pharmacodynamics focuses on what the drug does to the body whereas pharmacokinetics focuses on what the body does to the drug
87
does phenoxybenzamine bind reversibly or irreversibly to adrenoreceptors?
irreversibly
88
```
which of the following isn't a cause of secondary hypertension?
tumours of the adrenal medulla
polycystic kidney disease
myocardial infarction
renal artery stenosis
```
Myocardial infarction (hypertension can cause IT but IT doesn't cause hypertension)
