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CV Module > Anti Hypertensives II > Flashcards

Anti Hypertensives II Flashcards

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1
Q

On which receptor does Angiotensin II act?

A

The AT-I receptor

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2
Q

What is the basis of the hypotensive effects of ACEi?

A
  1. Inhibit the vasconstrictive effect of ATII

2. Stimulating action on the Kallikerin-kinin system

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3
Q

How do ACEi affect Aldosterone?

A

Secretion of Aldosterone is reduced but not seriously impaired

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4
Q

How do ACEi affect renin and Angiotensin-I?

A

Production of Renin and Angiotensin-I is increased

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5
Q

What happens to the Ang-I in presence of ACEi?

A

Directed down an alternative pathway resulting in increased production of vasodilator peptides like Ang 1-7 which is believed to be protective

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6
Q

How do ACEi affect renal perfusion?

A

ACEi increase renal blood flow via vasodilation of the afferent and efferent arterioles

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7
Q

Where does ATII act in the kidney and what are its actions?

A

In the proximal tubule and it causes the retention of Na+ and H20!

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8
Q

What is PK-C?

A

A transcription factor for the genes responsible for neo-intima thickening

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9
Q

What is the effect of ACEi on PK-C?

A

Binding of Ang-II to the AT-I receptor results in theincrease of PK-C which further results in intima thickening this is inhibited by ACEi

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10
Q

How do ACEi affect Baroreceptor mechanisms?

A

Baroreceptor mechanisms are not affected, postural hypotension is not seen!!!

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11
Q

What condition would predispose a patient to have a na even greater decrease in BP while taking an ACEi?

A

Subjects with NA+ retention or high Renin

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12
Q

What is the additional benefit of Captopril?

A

Captopril increases the synthesis of prostaglandins in vascular renal endothelium and delays and even prevents the progression of renal disease in type I diabetics

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13
Q

Which ACEi is renoprotective?

A

Captopril

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14
Q

Whick of the ACEi are prodrugs?

A

Enalapril, and Ramipril

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15
Q

When is Enalaprilat mostly used?

A

IV in hypertensive emergencies

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16
Q

Besides Captopril what is the other renoprotective ACEi?

A

Lisinopril

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17
Q

Ramipril, what are its advantages?

A

It has a long half-life so it can be given once a day

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18
Q

What are the contraindication of ACEi?

A
  1. Patients ho take potassium or an potassium sparring diuretics, may cause hyperkalemia
  2. Contraindicated in pregnancy 2nd and 3rd trimesters
  3. In patients with renal artery stenosis
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19
Q

What are the side effects of the ACE inhibitors

A
  1. Dry Cough
  2. Possible Angioedema which could be fatal
  3. Hypotension in hypovolemic and or Na+ depleted patients
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20
Q

How to ARB work?

A

Selectively block AT II type receptors which are responsible for all of the vascular, renal and central effects of AngII

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21
Q

What are the beneficial actions of ARBs?

A

1.Cause vasodilation and Na+ and water excretion thus reducing TPR, plasma volume, CO, and BP

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22
Q

What is the effect of ARB on ACEi?

A

No effect on Bradykinin so they don’t produce the cough of ACEi

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23
Q

What is another protective side effect of ARBs?

A

They do not block the action of AII on AT2 receptors which is thought to be protective

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24
Q

What is the most Potent metabolite of of the PRODRUG LOSARTAN?

A

EXP 3174

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25
What are the two added actions of Losartan?
1. Increases Uric Acid urinary excretion (Uricosuric) | 2. Is a Thromboxane A2 receptor competitive antagonist that attenuates platelet aggregation
26
How does Losartan affect CYP?
Lorsartan is a CYP inhibitor,
27
What are the differences between Irbesartan, Varlsartan, Telmisartan and Losartan?
Irbesartan, Varlsartan, and Telmisartan do not inhibit CYP enzymes or affect uric acid excretion
28
What is the ARB used in patients with HTN and GOUT?
Losartan
29
Which of the ARBs are Prodrugs?
Losartan and Valsartan
30
Which of the ARBs is not cleared by the Kidney?
Telmisartan
31
Which ARB has that shotest half life and which has the longest?
Losartan has the shortest and Telmisartan the longest
32
What are the 2 ARBs known to cause Hepatic dysfunction?
Losartan and Valsartan
33
What are the side effects of the ARBs?
1. Fetotoxicity-Not used in pregnancy 2. Hyperkalemia 3. Hypotension
34
What is Aliskiren?
A renin inhibitor
35
What are the clinical effects of Aliskiren?
1Produces significant dose dependent decrease in BP
36
How is Aliskiren mostly used?
In combination therapy with other hypertensive agents such as ACEi ARBs and diuretics
37
Which of the Calcium channel blockers have selectivity for the heart?
Verapamil, and Dltiazem
38
How do Calcium channel Blockers (CCB) work?
The agents block the L-type calcium channel which greatly restricts the influx of calcium and lowering intracellular calcium which restricts vascular tone in arterioles and for verapamil and Diltiazem lowering contractility in the heart
39
What are the benefits of using CCBs?
Do not cause large baroreceptor-mediated sympathetic discharge and changes in HR are usually mild
40
Which vessels do CCBs work on?
Arteriolar smooth muscles
41
Which of the CCBs are more likely to be used as anti-anginal agents?
Verapamil, and Diltiazem
42
In which subsets of patients are CCBs most used/effective?
Patients with Low renin hypertension such as the elderly and AA
43
Which CCB is notorious for causing reflex Tachycardia?
Nifedipine (much less with SR Nifedipine
44
How do CCBs affect the G.I?
May cause constipation
45
What is Hydralazine?
A selective arteriolar smooth muscle relaxer
46
What are the effects of Hydralazine administration?
1. Reflexively increases HR and Contractility 2. Causes Venoconstriction 3. Causes Sodium and water retention
47
How does Hydralazine have its negative effects?
It reflexively activates the SNS and causes NA+ retention
48
What drugs are used in combination with Hyralazine to mitigate some of its negative effects and increase the effectiveness of therapy?
1. Beta Blockers | 2. Diuretics
49
What are the side effects of Hydralazine administration?
1. Palpitations 2. Pronounced Tachycardi 3. Lupus like syndrome dependent on HLA phenotype 4. Autoimmune reactions; hemolytic anemia
50
How does Minoxidil work?
Relaxes arteriolar smooth muscle by opening K-ATP potassium channels in smooth muscles
51
What vessels dos Minoxidil specifically have its actions in?
Arterioles but not veins
52
What are side effects of Minoxidil administration?
1. Reflex Tachycardia 2. Powerful activation of renin release 3. HIRSUTISM
53
How is Diazoxide administered?
IV
54
How does Diazoxide work?
Prevents vascular smooth muscle contraction by opening K+ channels which statbilizes the resting membrane potential
55
What are the side effects of Diazoxide?
1. Causes sympatho-excitation and reflex tachycardia 2. Retention of Sodium and water due to increased renin and CO 3. Hyperglycemia because it inhibits insulin release
56
What drug should be given in combination with Diazoxide?
Beta-Blocker
57
What is another use of Diazoxide?
Used in insulinomas
58
What is Fenoldopam?
A dopamine-1 receptor activator that causes prompt, marked arteriolar vasodilation
59
What are the added benefits of Fenoldopam?
1. Short half life 10 mins | 2. Increases renal perfusion
60
What is the contraindication for Fenoldopam?
In patients with Glaucoma
61
What is Nitroprusside?
A prodrug that forms Nitric Oxide which stimulates muscle Guanylate Cyclase, increasing levels of cGMP in vascular smooth muscle and causing relaxation
62
What are the pharmacological effect of Nitroprusside?
1. Dilates both arteries and veins 2. Reduces TPR and induces venous pooling 3. May increase CO in patients with left ventricular failure because TPR is reduced
63
In what circumstance is Nitroprusside most recommended?
HT patients with ventricular failure
64
What are the side effects of Nitroprusside?
1. Excessive Hypotension 2. Pronounced Tachycardia, palpitations 3. Metabolized to cyanide 4. cyanate or thiocyanate toxicity
65
How do the Alpha-2A agonist work?
By stimulating the Alpha-2A receptors they inhibit the sympathetic nervous system
66
Where are the postsynaptic Aplpha-2A adrenoreceptors?
In the Rostral ventrolateral medulla RVLM
67
What are the pharmacological actions of the Alpha-2A agonist?
1. Sympathetic impulses from RVLM to heart and blood vessels are decreased 2. Decrease in peripheral resistance and Heart rate
68
What is an added effect of Clonidine?
1. Releases endogenous Opiates and is used as an analgesic in neuropathis pain 2. Also approved for treatment of ADHD
69
What is an addittional benefit of Guanabenz?
Lowers Cholesterol in plasma
70
What are the side effects of the Alpha-2A agonist?
1. Sedation 2. Contact Dermatitis with Patch formation 3. Clonidine withdrawal causes Hypertension so it should be withdrawn slowly
71
Which of the Alpha-2A Agonist would cause Lactation due to prolactin secretion?
Alpha-methyl dopa
72
What is Bosentan?
An endothelin-1 and Endothelin-2 receptor antagonist
73
What does endothelin do?
Endothelin is a potent vasoconstrictor
74
What is the primary indication for Bosetan?
Treatment of pulmonary artery hypertension
75
What are the side effects of Bosetan
Serious and severe Liver toxicity and potential Fetotoxicity
76
What is the cause of pulmonary artery hypertension?
Right ventricular failure
77
What should be the initial therapy in patients with HTN and CHF?
ACE inhibitors
78
Which Drugs are not recommended in HTN patients prone to HF?
Alpha-1 blockers
79
What drug should be considered in HTN with diabetes?
ACEi

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