Pharmacology - Antihypertensives and Inotropes Flashcards
Class: Clonidine
alpha-2 agonist
Anti-hypertensive
Class: Methyldopa
alpha-2 agonist
Anti-hypertensive
What is the effect of alpha-2 stimulation, as caused by drugs like clonidine and methyldopa?
Decrease in sympathetic outflow;
Decrease in TPR and HR (because lowers NE, therefore indirect effects to lower alpha 1 and beta 1 effects)
Use:
Clonidine
Methyldopa
Mild to moderate HTN
*use methyldopa for HTN in pregnancy
Unique application: Clonidine
Opiate withdrawal
Side effects:
Clonidine
Methyldopa
Rebound HTN is stopped abruptly;
edema
CNS depression
Class: Reserpine
Ganglion-blocking agent
Anti-hypertensive
MOA: Reserpine
Destroys vesicles for NE, dopamine, serotinin
Use: Reserpine
Not used anymore bc of SE (suicide);
Decreases CO and systemic vascular resistance
What is a common side effect of antihypertensives and why?
Edema
Bc lower BP –> activate renin-angiotensin system
Class: Doxazosin (Prazosin and Terazosin also…)
alpha-1 blockers
Use: Doxazosin (Prazosin and Terazosin also…)
Decreases arteriolar and venous resistance –> causes reflex tachycardia;
BPH (decrease tone or urinary sphincter);
Second-tier medication for HTN, use when other conditions exits
What re the only class of anti-hypertensives associated with reflex tachycardia?
Alpha-1 blockers (causes worsening of angina)
Side effects: Doxazosin (Prazosin and Terazosin also…)
Orthostatic hypotension (bc venous resistance down), “first-dose syncope”;
edema;
worsening angina due to reflex tachycardia
Class: Esmolol
Beta-1 selective blocker
Use: Esmolol
AV nodal blockade in unstable pts
Esmolol is know for having what characteristic?
Beta-1 selective blocker;
Short half-life
Class: Hydralazine
Direct-acting vasodilator
Anti-hypertensive
Class: Minoxidil
Direct-acting vasodilator
Anti-hypertensive
MOA:
Hydralazine
Minoxidil
Decreases TPR via arteriolar dilation
Hydralazine - acts through NO
Minozidil - opens K channels
Use: Hydralazine
Moderate to severe HTN;
patients with both advanced CHF and hypertension
What is a unique side effect of hydralazine?
Can cause drug-induced SLE
Use: Minoxidil
Hair loss;
Refractory HTN
Side Effects: Hydralazine
Reflex tachycardia;
Edema;
Drug-induced SLE (high protein binding)
Can hydralazine be used in pregnancy to treat HTN?
Yes
Class: Verapimil and Diltiazem
Anti-arrhythmics AND
Anti-hypertensives
MOA: Verapimil and Diltiazem
Block L-type Ca channels
**good tropism for the heart
Use: Verapimil and Diltiazem
HTN;
Anti-anginal effect (decrease myocardial O2 demand);
SVT (because class IV anti-arrhythmic)
Side effects: Verapimil and Diltiazem
Edema in legs; Bradycardia; AV nodal blockade (bc reduced chronotropy); Hypotention; Worsening HF; Constipation (Ca channels in gut)
In what conditions are Verapimil and Diltiazem contraindicated?
Decompensated HF;
Bradycardia;
SA dysfunction;
High-degree AV block
**Same contraindications for amlodipine, nifedipine
How are verapimil, diltiazem and amlodipine/nifedipine similar?
They are all Ca channel blockers. They exist on a spectrum based on their tropism. Verapimil has the most cardioselectivity (non-dihydropyridine) –> Diltiazem –> Amlodipine and Nifedipine (dihydropyridine). The latter two have tropism for blood vessels
Class: amlodipine, nifedipine
Ca channel blockers
Anti-hypertensives (dihydropyridine)
Use: amlodipine, nifedipine
Hypertension;
Raynaud’s;
3rd choice drug for angina (bc they work better in the vasculature than the heart)
Side effects: amlodipine, nifedipine
leg edema, HF AV nodal blockade, ***reflex tachycardia; constipation; gingival hyperplasia (like phenytoin)
What is the role of renin (kidney)?
Catalyzes angiotensinogen –> angiotensin I
What is the role of ACE (plasma)?
Catalyzes angiotensin I –> angiotensin II
What is the effect of angiotensin II on the adrenal cortex?
Increased aldosterone secretion
What is the effect of angiotensin II in the blood vessels?
Vasoconstriction
Class: Aliskiren
Renin inhibitor (not very effectve as an antihypertensive)
Class: Losartan (and Valsartan, Irbesartan)
Angiotensin II receptor blockers “ARBs”
MOA: Losartan (and Valsartan, Irbesartan)
ARBs
Competitive inhibition of angiotensin II in vascular endothelium
Use: Losartan (and Valsartan, Irbesartan)
Drop in peripheral resistance w/o change in HR, CO
Use in CHF, LV hypertrophy, post-MI
Side effects: Losartan (and Valsartan, Irbesartan)
Angioedema
Decreased renal fx;
Hypotension
In what conditions are Losartan (and Valsartan, Irbesartan) contraindicated?
Pregnancy;
Renal artery stenosis;
Hyperkalemia;
Prior angioedema
SAME contraindications as ACE inhibitors ie lisinopril, captopril
Class: Captopril
ACE-I inhibitor
short-acting
MOA: Captopril
Lisinopril (Benzapril, Quinapril, Ramipril)
blocks formation of angiotensin II
lowers aldosterone levels
vasodilates
prevents bradykinin degradation
Use: Captopril;
Lisinopril (Benzapril, Quinapril, Ramipril)
CHF;
LV hypertrophy;
post-MI
**prevents remodeling of LV
Side effects: Captopril;
Lisinopril (Benzapril, Quinapril, Ramipril)
dry cough;
***angioedema;
decreased renal fx;
hypotension
Class: Lisinopril (Benzapril, Quinapril, Ramipril)
ACE-I inhibitor
long-acting
What is the antihypertensive of choice in a patient with HTN and angina?
Beta blockers (ie metoprolol); Calcium channel blockers (ie diltiazem, amlodipine)
What is the antihypertensive of choice in a patient with HTN and diabetes?
ACEIs (ie lisinopril)
ARBs (ie losartan)
What is the antihypertensive of choice in a patient with HTN and HF?
ACEIs (ie lisinopril);
ARBs (ie losartan);
Beta blockers (ie metoprolol);
What is the antihypertensive of choice in a patient with HTN and is post-MI?
Beta blockers (ie metoprolol);
What is the antihypertensive of choice in a patient with HTN and BPH?
Alpha blockers (ie terazosin, doxazosin)
What is the antihypertensive of choice in a patient with HTN and dyslipidemias?
Alpha blockers (ie terazosin, doxazosin);
Calcium channel blockers (ie diltiazem, amlodipine);
ACEIs (ie lisinopril);
ARBs (ie losartan)
DO NOT USE beta blockers
Captopril is an ACE inhibitor that is first-line therapy for:
CHF
**inhibits LV remodeling
All ACE inhibitors: Captopril, Enalapril, Lisinopril, Ramipril, Quinapril, Fosinopril
are 1st line for CHF tx.
Class: Dobutamine
beta 1 agonist
inotrope/chronotrope
**use in acutely decompensated patients only
Why is dobutamine indicated for short-term use only?
The effect of a beta-1 agonist such as dobutamine is beta-1 receptor insensitivity over time. Need a longer-term solution for CHF patients.
Digoxin is an anti-arrhythmic that is effective therapy for:
CHF; good for SVTs
increases vagal activity (indirect effect) to the heart;
inhibits Na/K ATPase;
reduces SA firing rate and conduction through AV node;
increases contractility
improves LV fx
Why does digoxin have a long half life?
High protein binding
Large volume of distribution
How is digoxin cleared?
Renally
An arrhythmia of the conduction accessory pathways defines what syndrome?
Wolff-Parkinson-White Syndrome
SA node –> direct to ventricles (AV node might not be depolarized yet)
Treat either with surgery–lasar ablation or drugs (class IA such as quinidine or class III)
In the management of Wolff-Parkinson-White Syndrome, NEVER do what?
In the management of Wolff-Parkinson-White Syndrome, NEVER:
Slow AV conduction;
Give digoxin, beta-blockers, Ca channel blockers, or adenosine
When are diuretics indicated in the treatment of CHF?
Add-ons for Class III and IV CHF
Class: Sprinonolactone (and Epleranone)
Aldosterone antagonist AND K+ sparing diuretic
Sprinonolactone (and Epleranone) are diuretics also indicated for what?
Add-ons for Class III and IV CHF
Beta blockers, such as:
Bisoprolol, Carvedilol, Metoprolol, are indicated for CHF and dramatically reduce mortality. What is a pearl to remember about their administration?
Do not stop beta-blocker use suddenly.
Titrate slowly, start with a very low dose
Patients with HF have increased levels of:
NE; Endothelin; Cytokines; Angiotensin II; Aldosterone; Vasopression --all due to lower perfusion of the periphery --> all adversely affect the heart further
What is the first-line pharmacological choice for treating HF patients
ACE-I ie lisinopril benazepril quinapril ramipril captopril (shorter acting) enalapril
can increase CO without increases in HR or contractility;
benefits seen in patients with mild, moderate and severe HF
What is responsible for the side effects of cough in ACE inhibitors?
The prevention of breakdown of bradykinin;
NOT seen in ARBs
What is a significant shared effect of ACE inhibitors and ARBs on the heart?
Both inhibit cardiac and vascular remodeling (ie LV)
When should you consider an ARB in a HF patient?
If cough or other side effects of ACE inhibitors are an issue
When is it ok to add an ARB to an ACE-I?
If the patient has healthy kidneys and is maxed out on other anti-hypertensives
Losartan Irbesartan Valsartan Candesartan Olmesartan Telmisartan --all belong to what drug family?
ARBs!!
Anti-hypertensives use in HF
Same uses as ACE-I
Once you have had angioedema as a side effect of taking an ACE-I, what drug class must you also avoid?
ARBs
There is some cross-over with this SE, not well understood
When using diuretics to reduce volume in CHF patients, what is a dangerous side effect if the diuresis is unmonitored?
Hypovolemia –> ventricular fibrillation
Spironolactone carries what unsightly side effect for men?
Gynecomastia
Also, peptic ulcer disease is an issue…but not unsightly
What are the only beta blockers indicated for HF?
Carvedilol
Bisoprolol
Sustained-release metoprolol
must start very low and titrate up and down
What are the two drugs of choice (IV) indicated for patients who present to the hospital in decompensated HF?
Dobutamine;
Milrinone
MOA: Dobutamine
Beta-1 agonist in myocardium; increases contractility; increases HR; --> increases CO **arrhythmia threshold**
Would you use dobutamine in a patient who presents with acute MI and is chronically ischemic?
No, bc it’s a positive inotrope, and the dobutamine would only increase the demands on the heart.
Class: Milrinone
Phosphodiesterase IIIa inhibitor;
positive inotrope
Why are thiazides better than loop diuretics for HTN?
Longer half life;
Less intense depletion of volume
When GFR
Loop diuretics ie furosemide
Hypokalemia carries what major risk?
Cardiac arrythmia
What diuretics RAISE K+?
Spironolactone
Amilioride
Triamterene
T/F: Thiazide diuretics may promote insulin resistance.
True (so can beta blockers in raising serum glucose)
Also promotes gout (uric acid up)
To prevent kidney stones, what kind of diuretic would be recommended?
Thiazides
reduce Ca excreted
What is hypoglycemic unawareness?
Beta blocker use in diabetics can blunt the catecholamine response, when patients “sense” their blood sugar is low - cause for caution when using beta blockers in diabetics
Lower extremity edema is a major side effect of what drugs?
CCBs
ie verapamil
diltiazem
nifedipine
amlodipine
felodipine
isradipine
Name the NON-dihydropyridine CCBs.
Verapmil;
Diltiazem
Different from other CCBs because they lower HR
Are alpha-blockers indicated for patients with CAD?
NO NO NO
Alpha blockers worsen CAD and increase mortality.
What is the effect of bradykinin in the body?
It is a vasodilator. ACE inhibitors, by preserving extra bradykinin, are thought to have added value as antihypertensives, in addition to their inhibition of angiotensin I conversion to angiotensin II.