EXAM #2: CV PHARM VI Flashcards
What is the mechanism of action of the ACE inhibitors?
Block of Angiotensin Converting Enzyme (ACE) to reduce the amount of circulating Angiotensin II
Note that this also inhibits the breaksdown Bradykinin, which leads to vasodilation
What is the role of ACE inhibitors in antihypertensive therapy?
- 1st line or add-on for uncomplicated HTN
- 1st line therapy for comorbidities
Effects are enhanced by combining with diuretic*
How are ACE inhibitors cleared? What are the clinical implications?
Cleared by the kidney; thus, reduce dose in patients with kidney failure
What is the effect of elevated plasma renin activity in ACEI therapy?
Can cause hyper-responsiveness b/c:
- Renin converts angiotensinogen to ANG I
- Individuals are accostomed to having high ANG I levels that are NOT going to be converted to ANG II
What patients will have a high plasma renin activity?
Patients in heart failure and those with Na+ depletion
When are ACEIs contraindicated?
1) Pregnancy
2) Bilateral renal artery stenosis
3) Angioedema
What are the situations with potentially favorable effects of ACEIs?
1) Patients with low-normal K+ b/c these drugs INCREASE plasma K+
2) Prediabetes
3) Albuminuria
What are the situations with potentially unfavorable effects of ACEIs?
1) High-normal K+
2) Hyperkalemia
3) Volume depletion
ACEIs will cause vasodilation in patients with volume depletion and lead to HYPOTENSION*
What are the adverse effects of ACEIs?
1) Hypotension
2) Cough
3) Angioedema
4) Increased plasma K+
5) Acute renal failure
6) Fetopathic potential
7) Skin rash
What causes coughing in ACEI therapy? What can you consider as an alternative therapy?
Bradykinin
—> ARBs
What patient is a “good responder” to ACEI?
Young/ middle aged Caucasians
What patient population is labled as “bad responders” to ACEIs?
Elderly African Americans
Remember from the ED, increased angioedema in African Americans*
List the ACEIs. List the ARBs. How do you tell the difference?
Lisinopril
Captopril
Fosinopril
Losartan
Valsartan
Candesartan
Remember:
- pril= ACEI
- artan= ARB
What is the mechanism of action of the Angiotensin Receptor 1 Blockers?
Antagonize Angiotensin II Receptors, Type-I, which block ANG II from binding to the adrenal gland
Note that ANG II concentrations will either stay the same or increase with these drugs
What is the role of Angiotensin Receptor I blockers in antihypertensive therapy?
Alternative for patients with intolerance to ACE inhibitors
Think of as an alternative for elderly African American patients
When should you consider ARBs as first-line therapy?
1) DM
2) CKD
3) CAD
4) LV-Dysfunction
But NOT CVA
When is ARB use contraindicated?
1) Pregnancy
2) Bilateral renal artery stenosis
What patient populations have favorable and unfavorable responses to ARBs?
Same as ACEIs.
Favorable:
- Low-normal K+
- Pre-DM
Unfavorable:
- Hyperkalemia
- Volume depletion
What is the mechanism of action of the DHP Ca++ blockers for HTN?
Recall that these are the Ca++ channel blockers with a 10:1 vasodilatory effect compared to the NDPH
Note that this vasodiatory effect will induce reflex tachycardia, especially in the first week of use
What is the role of DHP Ca++ blockers for HTN?
- First line or add-on therapy for uncomplicated HTN
- Add-on for DM and CAD
When should DHP Ca++ blockers be avoided?
Left ventricular dysfunction
List the DHP Ca++ blockers that are used as anti-hypertensive drugs.
Nifedipine
Amlodipine
Felodipine
What are the situations that are favorable for DHP Ca++ blockers?
1) Reynaud Syndrome
2) Elderly patients with isolated systolic HTN
3) Cyclosporine-induced HTN
What are the situations that are unfavorable for DHP Ca++ blockers?
1) Peripheral edema b/c one of the side effects is peripheral edema
2) High normal rate–>Tachycardia
What is the mechanism of action of the Non-DHP Ca++ blockers?
These are the Ca++ blockers that have a 1:1 vasodilatory to cardiac effect
What is the role of Non-DHP Ca++ blockers in anti-HTN therapy?
1) First-line or add-on for uncomplicated HTN
2) Add-on for DM
3) Alternative to B-blockers in CAD**
These drugs will decrease myocardial contractility and thus reduce myocardial oxygen consumption
When should Non-DHP Ca++ blockers be avoided?
1) 2nd or 3rd degree heart block
2) LV dysfunction b/c of decreased contracility
What are the situations with potentially favorable effects for NDPH Ca++ blockers?
1) Reynaud Syndrome
2) Migraine headache
3) Arrhythmias
4) Tachycardia/ high-normal rate
What are the situations with potentially unfavorable effects for NDPH Ca++ blockers?
- Peripheral edema
- Low-normal heart rate
- AV block
What is the mechanism of action of the Thiazide diuretics for HTN?
- Block the NaCl Cotransporter in the DCT
- Na+ in the lumen increases water excretion
What is the role of Thiazide diuretics in anti-HTN therapy?
1) First line or add on therapy for uncomplicated HTN
2) First line therapy for:
- LV-Dysfunction
- Prior ischemic stroke
When should the use of Thiazide diuretics be avoided?
1) Allergy to sulfa
2) Gout
3) Hyponatremia
4) Hypokalemia (drugs cause further loss of K+)
Note that patients with CHF will already have depleted Na+*
What are the favorable situations for Thiazide diuretic use?
HTN with
- Osteoporosis b/c drug will INCREASE Ca++ reuptake
- High- normal K+
What are the unfavorable situations for Thiazide diuretic use?
- Gout
- Pre-DM
- Low-normal K+
- Elevated fasting glucose
List the Beta-adrenergic receptor antagonists that are used for HTN. What are their receptor specificities?
1) Propanolol–non-selective
2) Metoprolol- cardio-selective
3) Pindolol–ISA
4) Labetalol–mixed alpha and beta
What is the role of Beta-antagonists in antihypertensive therapy?
1) 1st line for HTN w/
- CAD
- LV dysfunction
2) Add on therapy for DM
What are the favorable situations for Beta-blocker use?
- Migraine
- Tachycardia
- Hyperthyroidism
- Tremor
- Preoperative tremor
List the two aldosterone antagonists. What is their role in antihypertensive therapy?
Spironolactone
Eplerenone
Add on therapy for
- Resistant HTN
- CAD
- LV dysfunction
When is aldosterone antagonists use favorable for HTN?
- Low K+
- CKD
When is aldosterone antagonists use unfavorable for HTN?
High K+ e.g. late stage kidney disease/ rhabdomyolsis
What is the definition of the “other agents” for HTN?
These are agents that are:
- Effective in lowering BP
- Approved for treatment of HTN
- Have NOT been shown in clinical trials to reduce the risks of CV events
List the classes of “other” agents for use in HTN?
1) Alpha blockers
2) Arterial vasodilators
3) Central alpha 2 agonists
4) Direct rennin inhibitors
5) Rauwolfia alkaloids
List the alpha 1 adrenergic receptor blockers.
Prazosin
Doxazosin
Terazosin
What is the role of alpha 1 blockers in antihypertensive therapy?
- Enhanced efficacy when used in conjunction with a diuretic
- Lowers: LDL, TG, and total cholesterol
What are the adverse effects of alpha-1 blockers?
- Tolerance
- Reflex tachycardia
- Sexual dysfunction
List the central alpha-2 agonists.
Clonidine
Methyldopa
What limits the use of Clonidine?
Anticholinergic effects e.g.
- Constipation
- Dry mouth
- Drowsiness
**Note that a relatively high degree of rebound HTN is seen
What is the role of a-methyldopa in antihypertensive therapy?
Gestational HTN
Also used in patients with chronic HTN that get pregnant*
What are the adverse effects seen with alpha-methyldopa?
1) Hepatotoxicity
2) Positive direct coombs’ test
Note that methyldopa has fewer anticholinergic effects than Clonidine
What is the mechanism of action of Hydralazine?
Arterial vasodilator
- Decreases IP3 induced Ca++ release
- Opens K+ channels to hyperpolarize smooth muscle and cause vasodilation
What is the role of hydralazine in the management of HTN?
1) Add-on therapy for resistant HTN, esp w/ chronic kidney disease
2) Safe in pregnancy
What are the adverse effects of Hydralazine?
- Drug induced Lupus
- Tachycardia and Na+ retention
Thus, it should be combined with a diuretic and Beta-blocker
What is the mechanism of action of Minoxidil?
Open K+ channels to relax arteriolar vascular smooth muscle cells
What are the cardiac effect of Minoxidil?
- Decrease BP
- Increases blood flow to skin, muscles, GI tract, and CNS
- Increased CO
- Increased RBF
What is the role of Minoxidil as an antihypertensive?
Severe refractory HTN in conjunction with a beta blocker
What are the adverse effects of Minoxidil?
- Fluid and salt retention
- Reflex increase in contractility
What is the mechanism of action of Sodium Nitrporusside?
IV agent that is a potent arterial vasodilator
- Donates NO for cGMP mediated Ca++ sequestration
- Decreases both afterload and preload (cardiac workload)
What are the adverse effects of Sodium Nitroprusside?
- Methemoglobinemia
- Cyanide poisoning
- Cell death via inhibition of cellular respiration (CN)
What is the clinical indication for Sodium Nitroprusside?
Hypertensive emergency
What is the mechanism of action of Aliskiren?
Direct renin inhibitor
What is the clinical use of Aliskrein?
Monotherapy or combination therapy for HTN
What are the precautions associated with Aliskrein?
- Hyperkalemia
- NEVER use in pregnancy
What is the mechanism of action of Reserpine?
Blocks transport of NE into storage granules
What is the role of Reserpine in antihypertensive therapy?
Used for resistant HTN
What is the most effective use of reserpine?
In conjunction with a thiazide diuretic
What are the side effects of Reserpine?
Sympatholytic i.e. increases PNS activity
What is one of the major contributing factors to Resistant HTN? What are the implications?
Excessive dietary Na+
Thus, Na+ reduction should ALWAYS be integrated into the management of resistant HTN
What diuretic is preferred to treat resistant HTN?
Chlorthalidone
What should be added to Clorthalidone treatment for Resistant HTN?
Spironolactone
What is the surgical procedure that can be used for resistant HTN?
Renal sympathetic denervation
