Antihypertensive drugs Flashcards
1
Q
Angiotensin II
A
- Peptide hormone that acts as a AT1
- Activated by a Gq coupled receptor
- Vasoconstriction activation
- Stimulates the thirst
2
Q
ACE inhibitor
A
- Zinc containing dipeptidyl carboxypeptidase
- Produced in the lung
3
Q
Arterial and venous vasodilation
A
- Decrease arterial and venous pressure
- Decrease in ventricular preload
- Decrease blood vol
- Downregulation of sympathetic activity
- Suppression of hypertrophy
3
Q
What is the ending of ACE inhibitor
A
- Ending of -pril lowering blood pressure reduce vasoconstriction decrease peripheral resistance
4
Q
Pharmacokinetics of ACE inhibitor
A
- 40-60% bioavailable depending on drug
- Bind to tissue
- Metabolism in the liver
- Eliminated through the kidney
5
Q
Captopril
A
- Absorbed and eliminated quickly
6
Q
Enalapril
A
- Later ACE inhibitor inactive pro-drug that requires hydrolysis
during or active absorption
7
Q
Lisinopril
A
- Itself active
- Lisinopril is not metabolized and is
excreted as an unchanged drug - Completely eliminated in the urine
8
Q
Mechanism of ACE
A
- Bradykinin is a potent vasodilator and this is stimulated by specific endothelial B2 receptor
- Dilates arterioles releasing prostacyclin and nitric oxide
- ACE converts bradykinin to inactive peptide
9
Q
Common Adverse effect of ACE inhibitor
A
- Dry irritated cough due to bradykinin accumulation
10
Q
Function Of ACE inhibitor
A
- Block breakdown of bradykinin therefore there is an increase in levels
- Effects sensory nerves adapting stretch receptors and C-fiber receptors that release neurokinin
- Cause contraction of smooth muscle causes bronchoconstriction and dry cough
11
Q
Rare adverse effects
A
- Hyperkalemia - increase potassium cause depolarization can be lethal - aldosterone mediated
- Taste disturbance - contain zinc bitterness in the mouth
- Hypotension - rapid decease bp become low
- Renal impairment (stenosis in kidney)
- Increase in bradykinin cause angioedema rash and large lip
12
Q
Clinical considerations
A
- Cough is not dose dependent it is a class effect
- Hypotension - combine with low dose diuretics
Dehydration - vom and diarrhea temp suspend
13
Q
Renal risk assessment
A
- Beneficial for patients with chronic renal failure and hypertension
- Assess renal function
- Monitor serum creatinine
14
Q
When to avoid ACE inhibitor
A
- Patient 55 and above years
- Caribbean black or African origin
- Pregnant and breastfeeding women
- Diabetic patients
15
Q
Angiotensin receptor blocker
A
- Receptor antagonist that block type 1 angiotensin II
- AT1 receptors are coupled with Gq-proteins and IP3 signal transduction for muscle contraction
- Ending with sartan
16
Q
Advantages of using ARB instead ACEi
A
- Avoids Bradykinin level rising no dry cough
17
Q
ADME of ARB
A
- Readily absorbed 20-66%
- Binds to plasma protein >90%
- Metabolized in liver eliminated in kidney
18
Q
Adverse effects of ARB
A
- Hyperkalaemia due to potassium retention
- Renal impairment - Challenging nephron
- Headache, fainting, nausea, back pain, liver fail, low white blood cells
19
Q
Clinical considerations for ARB
A
- Patients with bilateral renal artery stenosis ARB
- Damage both sides of the artery
- Monitor glomerulus filtrate rate and creatinine levels
20
Q
Renin inhibition
Aliskiren
A
- Inhibit the proteolytic enzyme causing vasodilation
- Non-peptide renin inhibitor with antihypertensive activity bind to S3 sub pocket
21
Q
Calcium channel blocker
A
- Blocks the calcium channel (L-type in vascular smooth muscle)
- Regulates Calcium influx stimulating contraction
22
Q
‘dipine’ drugs (CCB)
A
- Vascular effect - smooth muscle relaxation (Amlodipine) (Dihydropyridines)
- Cardiac effect - decrease myocardial force generation and decreased heart rate and conduction velocity (Verapamil) (non-dihydropyridine)
23
Q
Dihydropyridines
A
- Highly vascular selective reduce systemic vascular resistance
- Flushing, headache, excessive hypotension and ankle oedema
- Reflex tachycardia
24
Q
Nondihydropyridines side effects
A
- Bradycardia
- AV node block
- Contractility
25
Q
Verapamil
A
Selective for the myocardium and is less effective as a systemic
vasodilator drug
26
Q
Diltiazem
A
- Intermediate between verapamil and dihydropyridines in its selectivity for vascular
calcium channels
27
Q
Thiazides and Thiazide-like diuretics
A
- Moderately powerful diuretics
- Block Na+ / Cl- symporter of early Inhibit active Na+ reabsorption and accompanying Cl-
transport - Suffix ‘-ide’ and ‘-one’
- Bendroflumethiazide
- Indapamide
28
Q
Side effects of Thiazides and Thiazide-like diuretics
A
- Hypokalemia increased sodium delivery to distil tube
- Metabolic alkalosis (increased hydrogen ion loss in the urine)
- Dehydration (hypovolemia),
- Hypotension
29
Q
Major clinical problems with CCB
A
- Negative membrane potential
- Cardiac arrhythmias
- Reduced activity of K+/Na+ pump
30
Q
Clinical considerations
A
- Potassium supplements
- Potassium-sparing diuretics
31
Q
Potassium-sparing diuretics
(Aldosterone receptor antagonists)
A
- Antagonize aldosterone
- Example spironolactone & eplerenone
32
Q
Potassium-sparing diuretics
(Na+ channel blockers)
A
- Block apical ENaC in late DCT and CD
- Na+ no longer retained at expense of K+
33
Q
Beta-adrenergic receptor antagonist
A
- Increase heart rate and cardiac muscle contraction
- Block beta-receptors and ending -lol
34
Q
Beta-blocker cardiac effects
A
- Decrease contractility
- Decrease relaxation rate
- Decrease heart rate
- Decrease conduction velocity
35
Q
Beta-blockers vascular effects
A
- Smooth muscle contraction
36
Q
Reason why aged and ethnic background is not suitable
A
- Reduced renal function with age less nephron
- ACE inhibitor less functioning as African less dependent on RAAS mechanism
37
Q
Furosemide
A
- Inhibits sodium reabsorption in the loop of henle as a diuretic
38
Q
Alpha-adrenoreceptors antagonist
A
- Smooth muscle and lead to vasodilation like doxazosin
- Acting as a arterial dilator
39
Q
Minoxidil
A
- Potassium channel openers the ATP sensitive potassium channel in vascular smooth muscle
