Ch 20 - Antihypertensive drugs - DONE Flashcards
(93 cards)
1
Q
Define hypertention:
A
persistent diastolic pressure greater than 90 mm Hg and systolic pressure greater than 140 mm Hg
2
Q
What is the most common presenting sign of hypertention?
A
There is none! When patients are first diagnosed they are usually asymptomatic
3
Q
What are some of the potential complications of hypertention?
A
- Coronary artery diesease
- cardiac and renal failure
- stroke
4
Q
What is the hydraulic equation for blood pressure?
A
BP = Cardiac output (CO) x total peripheral vascular resistance (PVR)
5
Q
What conclusion can be drawn from the hydraulic equation for blood pressure?
A
drugs that reduce either CO or total PVR will produce a reduction in BP
6
Q
What are the major classes of drugs that are used to treat hypertention?
A
- Sympatholytic agents
- Diuretics
- Vaodilators
- Angiotensin-converting enzyme (ACE) inhibitor
7
Q
Give examples of sympatholytic agents:
A
- methyldopa
- clonidine
- guanfacine
- α- and β-blockers
8
Q
Give examples of vasodilators:
A
- hydralazine
- minoxidil
- sodium nitroprusside
- diazoxide
- calcium channel blockers
9
Q
Give examples of angiotensin-converting enzyme (ACE) inhibitors, and angiotensin II receptor antagonis:
A
- captopril
- enalapril
- lisinopril
- losartan
10
Q
What does the sympatholytic agents do?
A
all of them reduce PVR or CO
11
Q
What does the vasodilators do?
A
reduce PVR
12
Q
What does the angiotensin-converting enzyme (ACE) do?
A
- PVR
- reduce blood volume by reducing the secretion of aldosterone
13
Q
Which antihypertensive drugs have their site of action at the vasomotor center?
A
- Methyldopa
- Clonidine
14
Q
Which antihypertensive drugs have their site of action at the sympathetic nerve terminals?
A
- Guanethidine
- Reserpine
15
Q
Which antihypertensive drugs have their site of action at the β-receptors of the heart?
A
- Propanolol and other β-blockers
16
Q
Which antihypertensive drugs have their site of action at the sympathetic ganglia?
A
- Trimethapan
17
Q
Which antihypertensive drugs have their site of action at angiotensin receptors of vessels?
A
Losartan
18
Q
Which antihypertensive drugs have their site of action at α-receptors of vessels?
A
- Prazosin and other α1- blockers
19
Q
Which antihypertensive drugs have their site of action at vascular smooth muscle?
A
- Hydralazine
- Minoxidil
- Nitroprusside
- Diazoxide
- Verapamil and other calcium channel blockers
20
Q
Which antihypertensive drugs have their site of action at the kidney tubules?
A
- Thiazide etc.
21
Q
Which antihypertensive drugs have their site of action at β-receptors of Juxtaglomerular cells that release Renin?
A
- Propanolol and other β-blockers
22
Q
Which antihypertensive drugs have their site of action on the Angiotensin-converting enzyme (ACE)?
A
- Captopril and other ACE inhibitors
23
Q
What are sympatholytic agents?
A
centrally acting hypertensives
24
Q
Methyldopa mechanism of action:
A
stimulates central presynaptic α2- adrenergic receptors and inhibits the release of norepinephrine
25
What is the primary effect of Methyldopa?
- the decreased sympathetic outflow results in decreased PVR
| - it also creates some reduction in CO
26
What is the route of administration of Methyldopa?
- oral
| - IV
27
What is the clinical indication for Methyldopa?
- moderate hypertention
- often given to patients with renal insufficiency since it does not decrease blood flow to the kidney
- can be used safely in pregnancy
28
What are the potential toxicities of Methyldopa?
- A drug induced positive Coombs test that is sometimes associated with hemolytic anemia
- Lactation associated with increased prolactin release
- Edema
- Sedation
- Impotence
- Dry mouth
- Hepatitis
29
Clonidine mechanism of action:
- Like Methyldopa, Clonidine stimulates central presynaptic α2- adrenergic receptors wich results in diminished central adrenergic outflow.
- Decrease PVR
- Decreases also heart rate and CO
30
When is Clonidine used clinically?
- for mild-to-moderate hypertention
| - usually a second line agent
31
What is the route for administration of Clonidine?
- Oral
- IV
- Transdermal (for extended use)
32
Clonidine AE:
- Sedation
- Dizziness
- Dry mouth
- Rebound hypertention after sudden withdrawal from high doses
- Bradycardia especially in patients with AV nodal disease
33
What do you use to treat Rebound hypertention after sudden withdrawal from high doses of Clonidine?
- Labetalol
| - Nitroprusside
34
What drug interactions should the physician be concerned about before giving Clonidine?
Clonidine should not be given with tricyclic dugs. This combination may inhibit the actions of Clonidine.
35
What is Guanfacine?
a centrally acting antihypertensive with a mechanism of action and side-effect profile very similar to those of Clonidine.
36
Give some examples of α1-adrenergic blockers:
- Prazosin
- Terazosin
- Doxazosin
37
How does the α-blockers work?
They block the α1-adrenergic receptors
38
What are the antihypertensive effect of α-blockers?
- decrease PVR
| - exert minimal effects on CO
39
Describe the clinical use of α-adrenergic blockers:
- moderate hypertention
| - benign prostatic hypertrophy (relaxes the smooth muscles in the bladder neck)
40
AE of Prazosin and its synthetic analogues:
- Dizziness
- Orthostatic hypotention - especially after the first dose (first-dose effect)
- Headache
41
Give some examples of β-blockers:
- Propanolol
- Metoprolol
- Atenolol
- Labetalol (both α-blocker and β-blocker)
- Carvedilol
42
Name a drug that is both a α-blocker and β-blocker:
Labetalol
43
β-blockers mechanism of action:
Blockade of β1- and β2- adrenergic receptors
44
What is the clinical use of β-blockers?
- Often one of the first-line agents chosen to treat patients with mild-to-moderate hypertention and a concominant disease such as angina and chronic heart failure.
- These drugs may be of particular use in high renin states because they reduce renin release
45
When should the β-blockers be avoided?
- peripheral vascular disease
- asthma
- acute heart failure
46
β-blockers SE:
- Sedation
- Fatigue
- Bronchoconstriction
- Impotence
- May decrease HDL and increase plasma triacyglycerol
47
Give two examples of ganglionic blockers:
- trimethaphan
| - hexamethonium
48
What is the clinical use of ganglionic blockers?
- no longer in use because of severe SE
49
Ganglionic blockers AE:
- parasympathetic blockade (urinary retention, blurred vision, and so forth)
- sympathetic blockade (sexual dysfunction and orthostatic hypotention)
50
Give two examples of Postganglionic adrenergic neuronal blockers:
- Reserpine
| - Guanethidine
51
What is the mechanism of action of Postganglionic adrenergic neuronal blockers?
block the release of stored norepinephrine
52
What is the clinical use of Postganglionic adrenergic neuronal blockers?
- rarely used to treat hypertention because of low efficacy and significant AE
53
Name the most effective Diuretics:
- loop diuretics
| - Thiazide diuretics
54
How are the Diuretics used therapeutically?
- first-line agent
| - mild-to-moderate hypertention
55
Diuretics SE:
- Potassium depletion (most common effect)
- Possible impairment of glucose tolerance
- Possible increase in plasma lipid concentration
56
Hydralazine mechanism of action:
- vasodilator of ARTERIOLAR smooth muscle => decreased PVR
* this reduction in resistance is usually followed by a reflex tachycardia and fluid retention
- β-blockers are often coadministered to minimize the sympathetic effect
57
How is Hydralazine clinically used?
For moderate hypertention and CHF (chronic heart failure)
58
Hydralazine AE:
- Lupus-like syndrome
- Cadriovascular effects:
* hypotention
* reflex tachycardia
* palpitations
* angina
- Headache
- Nausea
- Diarrhea
59
Minoxidil mechanism of action:
ARTERIAL vasodilator that works by opening potassium channels, which results in hyperpolarization and relaxation of smooth muscle cells
60
How is Minoxidil clinically used?
- For severe hypertention refractory to other drugs
- For hair replacement (Rogaine)
- Often administered with β-blockers and diuretics
61
Minoxidil AE:
- Edema due to sodium and water retention
- Reflex tachycardia
- Flushing
- Headache
- Hypertrichosis (increased hair growth)
62
Sodium Nitroprusside mechanism of action:
Sodium Nitroprusside release Nitric oxide (NO), which stimulates the enzyme guanylyl cyclase and increases the intracellular production of cGMP concenctrations.
-> This results in decrease of intracellular calcium ions and consequent relaxation of vascular smooth muscle (BOTH ARTERIAL AND VENOUS)
63
How is Sodium Nitroprusside clinically used?
for hypertensive emergenises and CHF
64
What is the route of administration of Sodium Nitroprusside?
IV
65
Sodium Nitroprusside AE:
- Hypotention
- Metabolic acidosis
- Cyanide toxicities (cyanide is produced during the metabolim of Sodium Nitroprusside)
- Thiocyanate toxicitiy
66
Diazoxide mechanism of action:
prevents arterial smooth muscle contraction by opening potassium channels and stabilizing membrane potentials
67
What other action does Diazoxide have?
it prevents insulin release from the pancreas
68
The rout of administration of Diazoxide
IV
69
How is Diazoxide clinically used?
for hypertensive emergensies
70
Diazoxide AE:
- hypotention
- reflex tachycardia
- hyperglycemia
71
Give three examples of Calcium channel blockers:
- nifedipine
- verapamil
- diltiazem
72
Calcium channel blockers mechanism of action:
Inhibition of calcium influx into smooth muscle cells.
| Nifedipine is the most selective for the peripheral vasculature
73
Calcium channel blockers AE:
- constipation
- headache
- dizziness
74
What are ACE inhibitors?
ACE inhibitors are angiotensin-converting enzyme inhibitors
75
Against which physiological system are ACE inhibitors effective?
the renin-angiotensin-aldosterone system
76
EXPLAIN THIS SYSTEM
PAGE 167... LONG
77
Give examples of ACE inhibitors:
- captopril
- lisinopril
- enalapril
- benazepril
78
ACE inhibitors mechanism of action:
- block the conversion of angiotensin I to angiotensin II and also increase levels of bradykinin, which is a potent vasodilator.
- these drugs do not have much of an effect on CO and heart rate
79
For what condition does a physician prescribe ACE inhibitors?
- mild-to-moderate hypertention
- CHF (vasodilatory effect)
- Diabetic nephropathy.
80
Describe the absorption of captopril:
it is well absorbed orally, but does not enter the CNS
81
How is captorpil eliminated?
elimination occurs primarily through the urine
82
ACE inhibitors AE:
- dizziness
- cough
- angioedema
- hyperkalemia
- sudden drop in blood pressure after an initial dose
- renal failure in patients who have bilateral renal artery stenosis
- proteinuria
- neutropenia
83
Should ACE inhibitors be administered in pregnant women?
No! in the second and third trimester there is a risk of fetal hypotention, anuria, and malformation.
84
What drug interactions should physician monitor while administrating ACE inhibitors?
Nonsteroidal anti-inflammatory drugs (NSAIDs) may reduce the vasodilatory effects of ACE inhibitors, because NSAIDs block the actions of bradykinin.
85
Name four Angiotensin II receptor antagonists:
- losartan
- valsartan
- candesartan
- irbesartan
86
Angiotensin II receptor antagonists mechanism of action:
- They block angiotensin II at its receptor site, thus inhibiting both the vasoconstriction and aldosterone-secreting effects of angiotensin II.
- They DO NOT affect the bradykinin system
87
What is the route of administration of Angiotensin II receptor antagonists?
oral
88
How are the Angiotensin II receptor antagonists used clinically?
for mild-to-moderate hypertention
89
Angiotensin II receptor antagonists AE:
- headache
- hyperkalemia: especially in patients taking potassium-sparing diuretics
- hypotention
* they DO NOT cause the cough seen in ACE inhibitors
90
Angiotensin II receptor antagonists CI:
Like ACE inhibitors, losartan and valsartan are CI in pregnancy becase they may cause fetal malformations, anuria, and hypotention.
91
What is malignant hypertention?
hypertention associated with target-organ vascular damage (i.e., hypertensive encephalopathy, retinal hemorrhage, angina)
92
How is malignant hypertention treated?
in the initial stages antihypertensive drugs such as diazoxide, labetalol and sodium nitroprusside are used. The goal is not normalization of blood pressure but rather a 25% reduction, because sudden hypoperfusion may result in brain injury. Excess fluid may be removed with loop diuretics or, if necessary, dialysis
93
Dialysis def (google):
the separation of particles in a liquid on the basis of differences in their ability to pass through a membrane.
