Pharmacology Unit 3 Exam Study Guide

hypertension

what is the most common cardiovascular disease?

- essential (primary) - idiopathic

- secondary - d/t a comorbidity

what are the 2 different types of hypertension?

"cardiac preload" - cardiac output

"cardiac afterload" - systemic vascular resistance

what terms are also known as cardiac preload and cardiac afterload?

1) baroreflexes (ANS) for short-term regulation; rapid regulation

2) renin-angiotensin-aldosterone system for long-term regulation

BP is controlled by 2 main mechanisms. what are they?

- epinephrine

- norepinephrine

stimulation of the SNS results in increased release of what neurotransmitters?

renin

what do the kidneys release in response to low blood pressure?

1) diuretics (loop, thiazide, K+ sparing)

2) CCBs (dihydropyridine, nondihydropyridine)

3) beta-blockers (cardioselective vs non cardioselective)

4) alpha-blockers

5) RAAS inhibitors (ACE inhibitors, ARBs, renin inhibitors)

with what types of drugs is HTN treated?

adherence

what is the most common failure of HTN tx?

- lisinopril

- enalapril

- benazepril

ACE inhibitor drugs?

- inhibit ACE (enzyme that turns AT1 to AT2)

- inc bradykinin levels

- dec BP by dec PVR

how do ACE inhibitors work?

ACE inhibitors

* slows progression of diabetic nephropathy

what drug is nephroprotective?

- dry cough (d/t inc bradykinin levels)

- angioedema

- hyperkalemia

- teratogenic

what are the main AEs of ACE inhibitors?

- valsartan

- losartan

ARB drugs?

- block AT1 receptors (where angiotensin II binds)

how do ARBs work?

ARBs do not have an AE of dry cough bc they do not inc bradykinin levels

what is the main difference between ACEs and ARBs?

aliskiren

renin inhibitor drugs?

false

* never use ANY of them together

true or false:

- we always use ACE inhibitors with an ARB or a renin inhibitor

MoA: dec BP by dec CO

how do beta blockers work?

- metoprolol

- atenolol

- bisoprolol

what beta blockers are cardioselective (b1 selective)?

no

are beta blockers 1st line for HTN?

propranolol

what beta blocker is extensively metabolized by the liver d/t the 1st pass effect?

bradycardia and hypotension

what is the main AE of beta blockers?

non-cardioselective

what type of beta blocker has the potential to alter cholesterol negatively?

1) asthma/COPD

2) unstable HF

3) peripheral vascular disease

4) AV block

5) withdrawal

to what type of patient should we NOT prescribe a beta blocker?

- block inward movement of Ca2+ by binding to L-type Ca2+ channels

- relaxes smooth muscle

- also has an intrinsic natriuretic effect (so don't have to prescribe a diuretic with it)

how do calcium channel blockers work?

yes

are calcium channel blockers used 1st line for HTN?

non-dihydropyridine (verapamil, diltiazem): affects AV conduction by causing (-) inotropy

dihydropyridine (amlodipine): more useful for HTN; long t 1/2, so 1x/day dosing

distinguish between non-dihydropyridine and dihydropyridine CCBs.

constipation (with verapamil)

* do not give verapamil to pts with HF or AV block d/t its (-) inotropy or (-) dromotropy

what are the main AEs we would expect from CCBs? what does this tell us about the population we can and cannot prescribe these to?

- syncope (esp w/ first dose)

- reflex tachycardia

- tolerance to anti-HTN effects

what AEs should we be concerned with in regards to alpha-blockers?

used for HF

* carvedilol

* labetalol

when do we use a-b-blocking agents? what are some examples?

- clonidine - a2-agonist

- methyldopa - a2-agonist

central acting agent drugs? what class does each belong to?

central acting agents (a2-agonists)

* clonidine

* methyldopa

what medications are safe to prescribe to individuals with HTN and renal impairment but may cause drowsiness and sedation?

hydralazine

vasodilator drugs?

combine vasodilator with diuretic (to ensure fluid is not retained since vasodilators may increase plasma renin concentration) and a beta blocker (to prevent reflex tachycardia)

what medication is often given with a diuretic and beta blocker? why combine it with these two things?

HTN emergency: BP > 180/120 with end organ damage

HTN urgency: BP > 180/120 without end organ damage

what is the difference between hypertensive emergency and hypertensive urgency?

1) Na+ nitroprusside (AE: cyanide ion production)

2) Labetalol (a-b-blocker)

3) Nicardipine (CCB)

4) Fenoldopam (dopamine-1 receptor agonist)

what drugs do we use to treat HTN emergency?

Na+ nitroprusside; tx of HTN emergency

what drug may produce the AE of cyanide ion production? what is this drug used to treat?

fenoldopam; tx of HTN emergency

what drug is a dopamine-1 receptor agonist? what is this drug used to treat?

resistant HTN

terminology:

- BP that remains above goal despite admin of optimal 3-drug regimen that includes a diuretic

1) poor adherence

2) excessive ethanol intake

3) concomitant conditions

4) concomitant medications

5) insufficient dose/drugs with similar MoA

what are the primary reasons for resistant HTN?

coronary artery disease d/t atherosclerosis of arteries feeding the heart

what is the main cause of angina?

1) stable (most common) - during exercise only d/t coronary atherosclerosis

2) unstable - during exercise and rest

3) prinzmetal / variant - uncommon pattern of episodic angina at rest d/t coronary spasm

what are the 3 different types of angina?

a fixed obstruction

mixed forms of angina suggest....?

acute coronary syndrome

terminology:

- emergency resulting from a rupture of an atherosclerotic plaque or partial or complete thrombosis of a coronary artery

1) organic nitrates

2) beta blockers

3) CCBs

4) Na+ channel blockers

how do we treat angina?

organic nitrates

what drug do we have to take a drug free holiday from d/t the ease of acclimatization to the drug?

headaches

what is the most common side effect of nitrates?

blood vessels become desensitized to vasodilation

what is the pathology behind tolerance to nitrates?

nitrates

in the tx of angina, beta blockers are often combined with what drug to improve exercise duration and tolerance?

those with intrinsic sympathomimetic activity

what type of beta blockers should we avoid in patients with angina?

CCBs d/t (-) inotropic effects

what drug may worsen heart failure? how?

variant

in what type of angina are CCBs most useful?

Na+ channel blocker (ranolazine)

* used for chronic angina

what type of drug inhibits the late phase of Na+ current, improving the O2 supply and demand equation? when do we use this drug?

L HF: pulmonary congestion

R HF: peripheral edema

what main conditions are involved in left heart failure? right heart failure?

1) myocardial ischemia d/t CAD

2) HTN

what are the top 2 most common causes of heart failure?

true

true or false:

- compensatory mechanisms of heart failure are eventually associated with cardiac remodeling of tissue, loss of myocytes, hypertrophy, and fibrosis and eventually lead to death

1. SNS activation

2. RAAS activation

3. natriuretic peptide activation

4. myocardial hypertrophy

5. increased inflammation and oxidative stress

6. resistance to natriuretic peptide

what are the major compensatory responses of the body to heart failure?

B1 receptor activation - inc HR, (+) inotropy

A1 receptor activation - vasoconstriction

*overall effect: inc workload of the heart

as a compensatory mechanism to HF, how does the body increase SNS activity?

what is the overall effect of this?

- HF pts have dec CO, so dec blood to kidneys

- kidneys sense this and release renin --> releases angiotensin II and aldosterone

how is RAAS activated as a compensatory mechanism in HF patients?

BNP (b-type natriuretic peptide)

what type of natriuretic peptide has the largest effect on cardiac function?

- improve cardiac function

- improve HF sx

how do natriuretic peptides affect cardiac functioning?

HFrEF (heart failure with reduced ejection fraction)

terminology:

- initial stretching leads to a stronger contraction, but excessive elongation of fibers

- weaker contractions and a diminished EF

- dec ejection ability = systolic failure

hypertrophy

the ability of the ventricles to relax and fill with blood is impaired by ___________________.

HFpEF (heart failure with preserved ejection fraction)

terminology:

- thickening of ventricular wall

- dec in ventricular volume and filling ability = diastolic dysfunction

HFrEF: mitochondrial dysfunction (issue with metabolism)

HFpEF: comorbidities trigger cardiac dysfunction

how does each type of HF increase inflammation and oxidative stress on the heart?

true

true or false:

- together, HFrEF and HFpEF impair...

1) calcium regulation

2) cardiac hypertrophy

3) cardiac myocyte death

4) fibrosis

1) hypertrophy

2) fibrosis

3) inflammation

4) vasoconstriction

5) reduced renal blood flow

what results d/t resistance to natriuretic peptide?

compensated: compensatory mechanisms are working to give adequate CO

decompensated: compensatory mechanisms are not providing adequate CO

distinguish between compensated versus decompensated heart failure.

HFrEF: improve sx AND improve survival

HFpEF: improve sx

distinguish between HFrEF and HFpEF in terms of sx alleviation and survival elongation.

1) NSAIDs

2) alcohol

3) CCBs

4) some antiarrhythmics

what medications may worsen HF?

1) diuretics

2) RAAS inhibitors

3) inotropic agents

4) beta blockers

what medications help HF?

cardiac remodeling

high levels of angiotensin II and aldosterone favor _______________.

- improve sx

- improve survival

how do ACE inhibitors affect sx alleviation and survival elongation?

spironolactone (a K+ sparing diuretic and aldosterone antagonist)

what drugs are direct antagonists of aldosterone? be specific.

gynecomastia (endocrine issue)

what is the most notable AE of spironolactone?

true

true or false:

- eplerenone (an aldosterone antagonist) reduces mortality in 1) L ventricular systolic dysfunction and 2) HF after acute MI

- inhibition of RAAS activation, but no further potentiation of bradykinin

- minimizes risk of angioedema

when do we combine an ARB with a neprilysin inhibitor?

sacubitril and valsartan (entresto)

terminology:

- a prescription med used to reduce the risk of death and hospitalization in people with certain types of chronic HF

ACE inhibitors

* stop ACEIs ≥ 36 hours before starting entresto

what type of drugs should we discontinue prior to initiating therapy with sacubitril/valsartan (entresto)?

1) improved systolic functioning and prevention of remodeling

2) reversal of remodeling

what are the benefits of beta blockers in heart failure?

1) bisoprolol (b1 selective)

2) carvedilol (a-b-blocker)

3) metoprolol tartrate (2x/d) and metoprolol succinate (1x/d) (b1 selective)

what beta blockers are FDA approved for heart failure?

- improve sx

- improve survival

how do beta blockers affect sx alleviation and survival elongation?

- improve sx (PND, orthopnea, pulmonary congestion, peripheral edema)

- NO IMPROVEMENT OF SURVIVAL

how do diuretics affect sx alleviation and survival elongation?

1) thiazides (hydrochlorothiazide) - don't work in ppl w/ kidney issues

2) loops (furosemide) - good in ppl w/ kidney issues; best at diuresis

3) K+ sparing / aldosterone antagonist (spironolactone)

what are the 3 types of diuretics? give examples.

true

true or false:

- ivabradine aids in sx improvement but may increase the risk of a fib and enhanced brightness

- hydralazine (vasodilator)

- isosorbide dinitrate (venodilator)

if a patient needs 2 dilators, what would you give them?

SGLT2 inhibitors

* dapagliflozin

* empagliflozin

what type of drugs inhibit SGLT2 in the proximal tubule to reduce reabsorption of glucose and Na+?

SGLT2 inhibitors

* dapagliflozin

* empagliflozin

what medication is especially helpful for patients with both diabetes AND HTN?

soluble guanylate cyclase stimulators (vericiguat)

what medication do we avoid using with nitrates or phosphodiesterase inhibitors d/t risk of excessive hypotension?

REDUCE SURVIVAL

how do inotropic drugs affect sx alleviation and survival elongation?

digoxin

terminology:

- MoA: regulation of cytosolic calcium concentration

- narrow therapeutic index; long t 1/2

hypokalemia

digoxin toxicity is enhanced by ______________.

people with renal dysfunction

is what population is digoxin toxicity most frequent?

true

true or false:

- dobutamine and dopamine are B-agonists that are given IV for short-term tx of acute decompensated HF in the hospital

nesiritide

* MoA: binds to guanylate cyclase receptor, increasing cGMP (relaxes smooth m)

what drug is an example of a recombinant B-type natriuretic peptide? what is its MoA?

milrinone

phosphodiesterase inhibitor drug?

- digoxin (inotropic drug)

- phosphodiesterase inhibitor (milrinone)

what drugs to treat HF may increase mortality?

class IA (Na+ channel blockers) - quinidine, procainamide

class IB (Na+ channel blockers) - lidocaine, phenytoin

class IC (Na+ channel blockers) - flecainide, propafenone

class II (beta blockers) - propranolol, metoprolol

class III (K+ channel blockers) - amiodarone, sotalol

class IV (CCBs - nondihydropyridines) - verapamil, diltiazem

what are the different classes of antiarrhythmics and their drugs?

abnormal automaticity

terminology:

- pacemaker activity originating outside of the SA node

abnormal conduction

terminology:

- conduction of impulse does not follow the defined path, often resulting in reentry into tissues through which the impulse has already passed