Chapter 4 Cardiovascular and hematology drugs --- general + diuretics/presynpatic adrenergic inhibitors

Question 1

Heart failure

Answer 1

• the heart no longer pum enough blood to meet metabolic demands of body

common cause:
myocardial injury d/t
1) ischemia
2) inflammation
3) chronic inflammation

Question 2

Angina

Answer 2

• chest pain
• heart’s way of signalling that some of its cell are not getting enough o2 (too little blood flow)

Myocardial infarction happens when o2 started areas of the heart begin dying

Question 3

Diuretics

Answer 3

• reduce blood pressure and edema by inc urine output
• all diuretics inc water and na+ secretion (but effect of diuretics vary depending on mechanism of action

Question 4

thiazide diuretics

Answer 4

• inhibit na+ and cl- reabsorption in distal tubule (result in mild diuresis)
• POTASSIUM needed d/t k+ wasting effects

Question 5

Strategies for HTN

Answer 5

1) diuretics
2) clonidine (a2 receptor agonist, clonidine inihibits further release of sympathetic agonist, NE, and inhibits sympathetic outflow from the brain)
3) atenolol (b1 adrenergic antagonist — reduces HR and myocardial work)
4) prazosin (blocks a1 adrenergic receptors causing vasodilation)
5) nifdeipine (blocks ca++ entry into smooth muscle cells of arterial walls, preventing contraction)
6) hydralazine (relaxes arterioles)
7) captopril (reduce production of angiotensin II – causing vasodilation)

goals — reduce volume overload, reduce sympathetic outflow, block adrenergic receptors, dilate vessels

Question 6

Strategies for angina

Answer 6

Stable:
1) nitroglycerin – reduce preload by venodilation (markedly reduce venous pressure, venous return to the heart, and cardiac filling pressures
2) atenolol - decreases myocardial work (b1 antagonist)
3) ditilazem (dec BP via vasodilation, by blocking calcium entry + decrease HR => result in dec o2 demand and consumption

Unstable
1) beta blockers - reduce HR and myocardial work
2) aspirin - prevent platelet aggregation in myocardial arteries
3) heparin - inhibit clotting in myocardial arteries
4) nitroglycerin - reduce preload
5) eptifibatide or tirofiban — inhibit platelet aggregation

goals - reduce work of heart and improve cardiac circulation

Question 7

strategies for myocardial infarction

Answer 7

goal —- reperfuse ischemic tissue

1) streptokinase – converts plasminogen to plasmin (it can digest fibrin and fibrinogen, thus dissolving clots)
2) antianginal agents (nitroglycerin?… not nifedipine which is dangerous for MI)

Question 8

strategies for heart failure

Answer 8

goal – reduce workload + improve myocardial contractility

1) diuretics (decrease blood volume)
2) natrecor (nesiritide), a BNP analog causes naturesis (process of sodium excretion in the urine through the action of the kidneys), decrease preload and improve cardiac contractility
3) captopril (vasodilation)
4) atenolol (b blocker) — reduce HR and workload
5) nitroglycerin — reduce venous tone => dec preload (also dilates coronary arteries, enchancing blood delivery to heart)
6) hydralyzine and nitroprusside (relax arterioles)
7) diogxin (inc ca++ influx into myocardial cells)
8) amrinone (inhibits cAMP degradation — cAMP is a biochemical messenger that stimulates the heart
9) dobutamine (increase cAMP production by stimulating b1 adrenergic receptors

Question 9

strategies for arrhythmias

Answer 9

goal – restore synchronous myocardial contraction

table 4.7 A/B

Question 10

strategies for vascular occulsion

Answer 10

goals — prevent coagulation, prevent platelet aggregation, destory clots that already formed

1) warfarin, heparin
2) direct thrombin inhibitors (bivalirudin)
3) aspirin
4) thienopyridines (clopidogrel)
5) GP IIb/IIa inhibitors (abciximab)
6) tPA

Question 11

loop diuretics

Answer 11

• more powerful than thiazides and must be used cautiously to avoid dehydration
• may cause hypokalemia, follow this level closely

Question 12

potassium sparing diuretics

Answer 12

• enhance na+ and h2o excretion while retaining potassium

Question 13

osmotic diuretics

Answer 13

• draw water into the urine, w/o interfering with ion secretion or absroption in the kidney

Question 14

o

antiadrenergics

Answer 14

• inc BP by stimulating the heart (b1) and/or constricting peripheral blood vessels (a1 receptors)
• central — prevent sympathetic (adrenergic) outflow from brain by activating inhibitory a2 receptors [parasympathetic predominance]
• peripheral — prevent NE release from peripheral nerve terminals (e.g. such as ones that terminate on the heart); depleting NE stores in nerve terminals
• alpha and beta blockers — compete with endogenous agonists for adrenergic receptors // antagonist occupation of a1 receptors l/t vasoconstriction and occupation of b1 receptors prevents adrenergic stimulation of the heart

selective a1 or b1 blockers replacing nonspecific d/t fewer undesirable effects
* several b blockers have intrinsic sympathomimetic activity (act as weak agonists at some adrnergic receptor)
* these drugs stiulate b2 receptors, which reduces likelihood of rebound HTN (sympathetic reflex to fall in blood pressure) b/c b2 receptors dilate large central arteries which provide a reservoir for blood

Question 15

hydrochlorothiazide (oretic)

thiazide diuretic

Answer 15

• inhibit na+/cl- reabsorption in distal tube
• loss of K+, na+, and cl- l/t inc urine output
• sodium loss l/t decreased GFR

indication:
* ideal start pt for HTN, chronic edema, idiopathic hypercalcuria

effects
1) hypokalemia
2) hyponatremia
3) hyperglycemia (low potassium, secreted a lot ===> responsible for decreased insulin secretion and/or reduced insulin sensitivity)
4) hyperuricemia (elevated uric) [increase urate reabsorption in the proximal tubule]
5) hypercalcemia (increase renal tubular reabsorption of calcium)
5) oliguria (abnormally small amount of urine)
6) anuria (failure of kidney to produce urine)
7) weakness
8) decreased placental flow
9) sulfonamide allergy
10) GI distress

PO

contraindication
* pregnant women (unless have pathogenic edema)
* anuria

interaction
* inc toxicity of digitalis or lithium
* hypokalemia w/ corticosteroids or ACTH (seceret more K+)
* orthostatic hypotension w/ alcohol, barbiturates or w/ narcotics
* decreases effects of vasopressors

Question 16

Furosemide (lasix)

loop diuretic

Answer 16

• inhibits cl- reabsorption in thick ascending loop of henle
• high loss of K+ in urine

indication
* preferred diuretic for pt w/ low GFR
* HTN emergencies
* edema
* pulmonary edema
* mobilize large volumes of fluid
* reduce potassium levels (sometimes)

effects
* hyponatremia
* hypokalemia
* dehydration/hypotension
* hyperglycemia
* hyperuricemia (decreases release of uric acid)
* **hypocalcemia **
* ototoxicity
* sulfoamide allergy
* hypomagnesemia
* hypochloremic alkalosis (Hypochloremic alkalosis results from either low chloride intake or excessive chloride wasting)
* hypovolemia

contraindication
1) anuria
2) electrolyte depletion

interaction
* increase toxicity of ototoxic/nephrotoxic ddrugs + lithium
* probenecid (Uric acid reducer, It can treat gout and gouty arthritis.) and indomethacin (Nonsteroidal anti-inflammatory drug, osteoarthritis) inhibit diuretic effects of furosemide
* enhance antihypertensive drugs

signs of hypochloremic alkalosis – tetany, inc’d bicarb, inc’d HR + BUN, and inc’d hematocrit
* decreased BP, sodium, and skin turgor

Question 17

ethacrynic acid (ethcrynate)

loop diuretic

Answer 17

• inhibits cl- reabsorption in thick ascending loop of henle
• high loss of K+ in urine

indication:
orally – edema
IV — pulmonary edema

effects
1) MOST ototoxic
2) more GI distress
3) less likely to cause alkalosis
* hyponatremia
* hypokalemia
* dehydration/hypotension
* hyperglycemia
* hyperuricemia (decreases release of uric acid){
* **hypocalcemia **
* hypomagnesemia
* hypovolemia

contraindication
* anuria
* electrolye depletion

Question 18

bumetanide (bumex)

loop diuretic

Answer 18

most potent…

indication
1) orally – edema
2) IV — pulmonary edema

effects:
* hyponatremia
* hypokalemia
* dehydration/hypotension
* hyperglycemia
* hyperuricemia (decreases release of uric acid){
* **hypocalcemia **
* hypomagnesemia
* hypovolemia
* NO ototoxicity has been reported
* larges doses —- cause severe myalgia (pain in a muscle or group of muscles.)

PO/IV — 95% protein bound

contraindications:
anuria
electrolyte depletion

Question 19

amiloride (midamor)

potassium sparing diuretic

Answer 19

• directly inc. na+ excretion
• and decrease K+ secretion in distal convoluted tubule (2nd last part)

indication
* used w/ other diuretics b/c K+ sparing effects less hyypokalemic effects
* may correct metabolic alkalosis

effects
* hyperkalemia
* sodium or water depletion
* pts w/ DM may develop glucose intolerance (used w/ thiazide..?)

PO can be used with hepatic insufficiency

interactions
* potassium supplements
* other k-sparing diuretics

more rapid onset than spironolactone

Question 20

spironolactone (aldactone)
eplereone (inspra)

potassium sparing diuretic

Answer 20

• antagonist of aldosterone (since it retains Na+)
• actions similar to amiloride (dec K+ secretion in DCT)

indication
* used with thazides for edema (CHF)
* cirrhosis
* nephrotic syndrome (Nephrotic syndrome causes your kidneys to release too much protein in your urine. Causes include kidney diseases that affect the tiny filters inside your kidneys. Symptoms include swelling, high amounts of protein in your urine and low amounts of protein in your blood. )
* tx or diagnose hyperaldosteronism

effects
* hyperkalemia
* sodium or water depletion
* pts w/ DM may develop glucose intolerance (used w/ thiazide..?)
* endocrine imbalcnes (acne, oily skin, hirsutism [excess hair around mouth and skin], gynecomastia)
* FOR EPLERENONE (look @ left) — less gynecomastia

contraindications
* anuria
* substantial renal insufficiency
* hyperkalemia
* avoid in diabetics

interactions
* watch out K+ supplements or K+ sparing diuretics
* inc’d risk of digoxin toxicity
* decrease vasopressor action of norepinephrine

metabolite canrenone responsible for action

Question 21

triamterene (dyrenium)

potassium sparing diuretic

Answer 21

• directly inhibits Na+ reabsorption
• inhibits K+ and H+ secretion in collecting tubule

indication
* used w/ thiazide for edema (CHF, cirrhosis, nephrotic syndrome)
* NOT USED FOR HYPERALDOSTERONISM

effects
* blue urine
* decreased renal blood flow
* hyperK+
* Na+ or water depletion
* DM can develop with glucose tolerance

contraindications
* anuria
* substantial renal insufficiency
* hyperkalemia
* avoid in diabetics

interactions
* watch out K+ supplements or K+ sparing diuretics
* inc’d risk of digoxin toxicity
* decrease vasopressor action of norepinephrine

marketed in combination w/ thiazide drugs

Question 22

acetazolamide

carbonic anhydrase inhibitors

Answer 22

• block carbonic anhydrase
• Carbonic anhydrase is found in the proximal tubule of the nephron and red blood cells. It works to reabsorb sodium, bicarbonate, and chloride. Once acetazolamide inhibits carbonic anhydrase, sodium, bicarbonate, and chloride get excreted rather than reabsorbed; this also leads to the excretion of excess water.
• Carbon dioxide is produced as waste from breaking down sugars and fats and in respiration, so it has to be transported through the body to the lungs. Carbonic anhydrase converts CO2 to carbonic acid as it’s transported by blood cells, before being converted back to carbon dioxide. As many bodily functions are dependent on a certain pH, carbonic anhydrase adjusts the acidity of the chemical environment to prevent damage to the body.

indication
* CHF
* also used for open angle glaucoma — lowering aqueous humor production

effect
* acidosis
* rash
* hypersensitivity

PO/IV

contraindication
* acidosis
* closed angle glaucoma
* hypersensitivity

interactions
* cyclosporine (immunosuppressive agent used to treat organ rejection post-transplant. )
* salicylate (aspirin)

Question 23

mannitol

osmotic diuretic

Answer 23

• osmotically inhibits Na+ and water reabsorption
• initially inc plasma vol and BP

indication
* renal failure (acute)
* acute closed angle glaucoma
* brain edema
* remove OD of some deugs

effects
* headache
* nausea
* vomiting
* chills
* dizziness
* polydipsia
* lethargy/confusion
* chest pain

IV

contraindication
* HF, HTN, pulmonary edema dlt transient inc in BP

THE increase central venous pressure may induce HF in susceptible patients

Question 24

clonidine (catapres)

central anti-adrenergic

Answer 24

• acts in brain as postsynaptic a2-adrenergic agonist => reduce SNS activity (decreased HR, cardiac output, and blood pressure)

indication:
* mild to moderate HTN

effects
* rash
* drowsiness
* dry mouth
* constipation
* rebound HTN if withdrawn abruptly
* impaired ejaculation
* TO LIMIT toxicity ==> start low, then inc slowly

must decrease dose w/ renal insufficiency

contraindication
* hypersen to this drug

drug interaction
* tricyclic antidepressants (they reduce antiHTN effects)
* alcohol, barbiturates and sedatives inc. CNS depression
* if using beta blockers as well, sudden withdrawal of them while using this drug can inc REBOUND HTN

if BP drop too great then reflex renin production may cause Na+ and h2o retention ——> DIURETICS can counter this?

Question 25

methyldopa (aldomet) | central anti-adrenergic

Answer 25

* post-synaptic a2-adrenergic agonist (dec HR, cardiac output, blood pressure) * synthesized to **methylnorepinephrine** -- weak sympathomimetic false NT which dec sympathetic outflow from CNS indication * mild-moderate HTN * USED TO TX HTN IN pregnant women effects * dry mouth * sedation * slight orthostatic * impotence * psychic disturbances, nightmares * involuntary movements * hepatotoxicity CAN BE USED with pts w/ renal insufficiency contraindication * signs of HF (d/t fluid retention b/c of dec renal blood flow) occur, d/c drug * **contraindicated in those w/ liver dysfunction** drug interaction * tricyclic antidepressants (they reduce antiHTN effects) * alcohol, barbiturates and sedatives inc. CNS depression * if using beta blockers as well, sudden withdrawal of them while using this drug can inc REBOUND HTN **antibodies to methyldopa ==> hemolytic anemia [potentially severe] -- FOLLOW CBC**

Question 26

guanabenz (wytensin) guanfacine (tenex) | central anti-adrenergic

Answer 26

* acts in brain as postsynaptic a2-adrenergic agonist => reduce SNS activity (decreased HR, cardiac output, and blood pressure) * also depletes NE stores in peripheral adrenergic nerve terminals indication * mild-moderate HTN effects * dry mouth * sedation * REBOUND HTN is observed less... hehe decrease dose w/ renal or hepatic dysfunction interactions * **thiazide inc antihypertensive effects** * tricyclic antidepressants (they reduce antiHTN effects) * alcohol, barbiturates and sedatives inc. CNS depression * if using beta blockers as well, sudden withdrawal of them while using this drug can inc REBOUND HTN

Question 27

reserpine (serpasil) | peripheral anti-adrenergic

Answer 27

* partially depletes catecholamine stores in PNS + perhaps CNS * decreasees total peripheral resistance, heart rate, and cardiac output indication * seldom used -- mild-mod HTN * no longer recommended for psychiatric d/o effects: * parasympathetic predominance 1) bradycardia 2) diarrhea 3) bronchoconstriction 4) inc sec * decreased cardiac contractility and output * postural hypotension (d/t depleting of NE ----> inhibit vasoconstriction) * peptic ulcers * sedation + suicidal depression * impaired ejaculation * gynecomastic * **low risk of rebound HTN d/t long duration of action** PO contraindication * contraindicated in pt's w/ CHF, asthma, bronchitis, peptic ulcer disease * plus pt w/ HX of depression interaction * action of direct acting catecholamines SHARPLY INC * reduce effectiveness of mixed or indirect sympathomimetics * severe HTN w/ MAO inhibitors (serotonin, norepinephrine, and dopamine) * **severe bradycardia, heart block, or failure with digitalis, quinidine, or beta blockers** * potentitate action of antihypertensives or CNS depressants **DO NOT ADMINISTER MAOI's AND RESPERINE WITHIN 2 WEEKS OF EACH OTHER**

Question 28

guanethidine | peripheral anti-adrenergic

Answer 28

* go to adrernic nerve endings * initially release NE (inc BP and HR) * then deplete NE from terminal and interfere w/ release * **reflex tachycardia impossible b/c of depleted NE** indication * severe HTN when other agents fail * RARELY used effects * resting and orthostatic HTN * bradycardia * orthostatic hypotension * dec cardiac outpuet * dyspnea in COPD patients * severe nasal congestion * no depression (d/t poor CNS penetration) **very long half life 5 days --- maximal actions may not develop for 2 weeks** contraindications * patients with pheochromocytoma will experience severe HTN Usually, a pheochromocytoma develops in only one adrenal gland. But tumors can develop in both. If you have a pheochromocytoma, the tumor releases hormones that may cause high blood pressure, headache, sweating and symptoms of a panic attack. If a pheochromocytoma isn't treated, severe or life-threatening damage to other body systems can result. Surgery to remove a pheochromocytoma usually returns blood pressure to normal. /////////////////////////////////////////////////// interactions * tricyclic antidepressants inhibit uptake of DRUG into neuron decreasing antihypertensive effects * action of direct acting catecholamines SHARPLY INC * reduce effectiveness of mixed or indirect sympathomimetics * severe HTN w/ MAO inhibitors (serotonin, norepinephrine, and dopamine) * **severe bradycardia, heart block, or failure with digitalis, quinidine, or beta blockers** * potentitate action of antihypertensives or CNS depressants **d/t long half life effects may persist up to two weeks after d/c**

Question 29

guanadrel (hylorel) | peripheral anti-adrenergics

Answer 29

* faster than guanethidine, releases (NE) initially causing transient inc in BP and has little CNS effects * eventually deplete NE from terminal and interfere w/ release indication * mild-moderate HTN effect **less severe than guanethidine** * resting and orthostatic HTN * bradycardia * orthostatic hypotension * dec cardiac outpuet * dyspnea in COPD patients * severe nasal congestion * no depression (d/t poor CNS penetration) shorter half life than guanethidine contraindications * patients with pheochromocytoma will experience severe HTN Usually, a pheochromocytoma develops in only one adrenal gland. But tumors can develop in both. If you have a pheochromocytoma, the tumor releases hormones that may cause high blood pressure, headache, sweating and symptoms of a panic attack. If a pheochromocytoma isn't treated, severe or life-threatening damage to other body systems can result. Surgery to remove a pheochromocytoma usually returns blood pressure to normal. /////////////////////////////////////////////////// interactions * tricyclic antidepressants inhibit uptake of DRUG into neuron decreasing antihypertensive effects * action of direct acting catecholamines SHARPLY INC * reduce effectiveness of mixed or indirect sympathomimetics * severe HTN w/ MAO inhibitors (serotonin, norepinephrine, and dopamine) * **severe bradycardia, heart block, or failure with digitalis, quinidine, or beta blockers** * potentitate action of antihypertensives or CNS depressants