Pharm - Prog2 - Other Anti-Htn's

Front 1

How do sympathoplegics work?

Back 1

They decrease sympathetic outflow from vasopressors, still sensitive to baroreceptor control (no postural changes)

Front 2

What is the MOA of Methyldopa?

Back 2

Analog of L-dopa, false analog of DA, NE -- Stimulates CNS alpha2 receptors: dec PVR, dec HR/CO, dec renal vascular resistance

Front 3

What are the kinetics of methyldopa?

Back 3

Delayed effect bc must go through gut to brain by aromatic aa transporters, Long lasting-- metabolites stored in nerve endings

Front 4

What are the 3 toxicities of methyldopa? How long should it be used?

Back 4

1) CNS - sedation! depression, nightmares, vertigo 2) Lactation- inc prolactin 3) POSITIVE Coombs (>12 mo's): hemolytic anemia, hepatitis, drug fever. Change drug after pregnancy

MOTHER-dopa

Front 5

When is methyldopa used?

Back 5

Tx HTN in pregnancy

Front 6

What is clonidine's MOA?

Back 6

Partial agonist at alpha2 receptors in medulla: dec PVR, dec HR.
Dec BP while maintaining RBF (unlike methyldopa)
May cause some vasoconstriction
Dec circulating levels of catecholamines

Also dec renin secretion by affecting sympathetic activity

Front 7

How is clonidine given?

Back 7

Oral or PATCH/transdermal form

Front 8

What are the toxicities of clonidine?

Back 8

Rash at patch, CNS, REBOUND HTN: tachycardia -- need to wean off or tx with alpha/beta blockers

Front 9

When is clonidine CI? What is its use?

Back 9

Severe HTN bc partial agonist. Use for HTN.

Front 10

What is the MOA of peripheral adrenergic neuronal blockers? What are the 2 drugs?

Back 10

Lower BP by preventing release of NE from postsynaptic symp neurons.
Guanethidine, Reserpine

Front 11

What is the MOA of guanethidine?

Back 11

Enters nerve ending, concentrates in vesicles and displaces NE to dec release of NE from endings (dec CO and PVR) -- Severe reflex RAAS.

guaNEthedine

Front 12

What drugs interfere with guanethedine?

Back 12

Cocaine, Amphetamine, Tricyclic antidepressants, phenothiazines, phenoxybenzamine -- inhibit catecholamine reuptake pump (similar action)

Front 13

What are the toxicities of guanethidine?

Back 13

Sympathectomy: orthostatic hypotension, delayed ejaculation (sexual dysfunction)

Front 14

Where is guanethidine CI? What is its use?

Back 14

Pheochromocytoma and drug interactions: Sympathomimetics, leads to HTN. Used for severe HTN a long time ago (powerful!)

Front 15

What is the MOA of reserpine?

Back 15

Decreases uptake of amines into vesicles, deplete stores. NE, DA, 5HT. Lead to hypotensive effects (dec CO and PVR) with possible sedation, Parkinsonism

Front 16

What are the toxicities of reserpine?

Back 16

Minimal postural HTN, mental effects, diarrhea..

Front 17

Where are beta blockers used?

Back 17

HTN
Cardiac: Ischemic heart dz and angina, CHF, Arrythmias
Kidneys (dec RBF): chronic kidney dz, diabetic nephropathy

Front 18

What are the toxicities of beta blockers?

Back 18

Excess beta block: dec CO, heart block, bradycardia, bronchospasm, hypoglycemia, hyperkalemia during exercise, CNS depression, lipids, sexual dysfunction, postural hypotension

Front 19

When do you use beta blockers?

Back 19

Combine with vasodilators to block reflex tachycardia
LVH
Reduce mortality after MI

Front 20

Where are beta blockers CI?

Back 20

Caution with asthma, diabetes, COPD, PVD, depression, sinus bradycardia

Front 21

What are possible properties of beta blockers that you should take into account?

Back 21

Selective versus nonselective
Partial agonism
Lipid solubility: CNS penetration

Front 22

What are some properties and uses of propanolol?

Back 22

Nonselective beta blocker, dec renin production
Use in HTN, ischemic heart dz

Front 23

What are some properties and uses of metoprolol?

Back 23

Selective beta blocker, cardioselective
Use in asthmatics if worried with propanolol

Front 24

What are the uses of nadolol and atenolol?

Back 24

Nadolol-non, Atenolol-selective
Not use much due to renal failure, dose change bc excreted in urine

Front 25

What are the uses of betaxolol and bisoprolol?

Back 25

Selective, long half-life
Use in pts with renal failure (metab in liver)

Front 26

What are the uses of pindolol, acebutolol and penbutolol?

Back 26

Partial agonism: dec vascular resistance (partial beta2 agonism), doesn't reduce CO as much
Uses: HTN with CHF

Front 27

What are the uses of labetalol and carvedilol?

Back 27

Comb beta and alpha1 blocker: dec vascular resistance w/o change in CO or HR bc agonist effects.
Labetalol: HTN emergency (IV), also PREGNANCY
Carvedilol: Heart failure

Front 28

What is the use of esmolol?

Back 28

Selective, rapid IV.
Use: intra/post-operative HTN, HTN crisis (tachycardia)

Front 29

What are the 3 selective alpha blockers for HTN?

Back 29

Prazosin, Terazosin, Doxazosin

Front 30

What is the MOA of selective alpha blockers?

Back 30

Selective alpha1 blocker, dilates vessels, improve lipids.

Front 31

What are the toxicities of alpha-blockers?

Back 31

INC risk of HF when monotx, BAD.
Postural hypotension
RAAS (must use with diuretic)
First dose phenomenon (rapid fall in BP) -- start with low dose at bedtime
Dizziness, palpitations, HA, lassitude
Avoid reflex tachycardia with beta blockers

Front 32

What are the 2 nonselective alpha blockers?

Back 32

phen = phentolamine, phenoxybenzamine

Phentolamine dx pheochromocytoma (short), phenoxybenzamine tx

Front 33

What are the effects of vasodilators and why are they not ideal?

Back 33

Directly dilate arterioles, reflex tachycardia (beta blockers stop), RAAS (diuretics stop)

Front 34

What are the 2 oral vasodilators? The 3 IV vasodilators?

Back 34

Hydralazine, Minoxidil
Nitroprusside, Diazoxide, Fenoldopam

Front 35

What is the MOA and kinetics of hydralazine?

Back 35

Dilates arterioles only, metab first pass by liver
Metab by acetylation: rapid/slow

Front 36

What toxicities do hydralazine cause?

Back 36

LUPUS like syndrome: check ANA levels- rash, myalgia, arthralgia, fever
DOSE-dep and REVERSIBLE
Also, HA, nausea, anorexia, palpitations, edema, angina from reflex tachycardia

hydrALAzine - check ANA levels

Front 37

When can hydralazine be used?

Back 37

Pregnancy!

Front 38

What is the MOA of minoxidil? What are its uses?

Back 38

Prodrug, opens K channels in SM, hyperpolarizes and relaxes vascular SM (only arterioles)
Severe HTN (use with loop diuretics, beta blockers to avoid reflex responses)

Front 39

What toxicities does minoxidil cause?

Back 39

Compensatory tachycardia, angina, RAAS with possible pericardial effusion
Hirsuitism
Postural hypotension

MANoxidil is a vasodilator

Front 40

What is the MOA of sodium nitroprusside?

Back 40

Release of NO stimulates guanylyl cyclase and increases cGMP, relax SM, dilate BOTH arterioles and venules (CO same)

Front 41

What is the toxicity of sodium nitroprusside?

Back 41

Renal failure: drug goes into RBC, release of CN, metabolized to THIOCYANATE -- cleared by kidney but accumulates. Weak, disoriented, psychosis, spasms, convulsions

Front 42

When is sodium nitroprusside used?

Back 42

HTN emergencies (IV) and severe HF -strong drug! Start on oral meds at same time so Nitroprusside minimized

Front 43

What is the MOA and usage of diazoxide?

Back 43

Open K channels, hyperpolarize and relax SM in arterioles
IV, not used long term or often bc profound hypotension and RAAS

Front 44

What is the MOA of fenoldopam?

Back 44

D1 (dopa) agonist, causes dilation of peripheral arteries and natriuresis

fenolDOPAm

Front 45

What are the CI of fenoldopam? Toxicities? Uses?

Back 45

Glaucoma (increases IOP!)
Also, reflex tachycardia, HA, flushing

Use for HTN emergencies, postop HTN

Front 46

What is the MOA of Ca channel blockers?

Back 46

Slow influx of Ca in smooth muscles: L-Type channel for CARDIAC and VASCULAR effects
Slow AV conduction, dec inotropy, slow SAN
Relax/dilate vasculature

Front 47

What kind of effects do the dihydropyridines have mostly?

Back 47

Vascular effects, more effective if high BP from SM contraction

Nefidipine, amlodipine, felodipine, isradipine, nicardipine, nisoldipine

Front 48

Which dihydropyridine causes reflex tachycardia and gum hypertrophy? Which dihydropyridine is best?

Back 48

Nifedipine-bad choice. Use Amlodipine!

Front 49

What is verapamil's main effect? What AE does it cause?

Back 49

Phenylalkylamine Ca channel blocker-- primarily cardiac. Use for arrhythmias and slow heart

Causes constipation

Front 50

What is diltiazem's main effect?

Back 50

Benzothiazepine Ca channel blocker -- intermediate effects on cardiac and vascular.
Use for ischemia, HTN, angina

Front 51

What are the toxicities of Ca channel blockers?

Back 51

Inapprop cardiac effects (cardiac arrest, heart block, CHF) and inapprop vasodilation (HA, flushing, edema, postural hypotension)

Front 52

What drug interactions do the Ca channel blockers diltiazem and verapamil have?

Back 52

Beta-blockers worsen cardiac effects
Digitalis (slows heart) levels increase with use

Front 53

When are Ca channel blockers used? What advantages do these drugs have?

Back 53

Monotx for NEW HTN
Combined with ACE inhibitors and diuretic to block RAAS and vasodilation

Advantages: reverses LVH, lipid neutral, help vascular dz, preserve cerebral flow and GFR

Front 54

What two systems does Angiotensin-converting enzyme act on?

Back 54

1) RAAS: Angiotensinogen (renin) -> Angiotensin I (ACE) -> Angiotensin II

2) Kinin: Kininogen (kallikrein) -> Bradykinin (ACE) -> inactive metabolites

Front 55

What are the effects of Angiotensin II? Bradykinin?

Back 55

Stimulates autonomic ganglia to release Epi, NE (vasoconstriction)
Stimulates aldosterone (salt/water retention)
Renal vasoconstriction
Stimulates thirst and inc secretion of ADH, ACTH
Mitogenic for vascular/cardiac muscle (LVH)

Inc PG synthesis, vasodilation

Front 56

What pathologies and tx's lead to high renin states? What is the DOC?

Back 56

Renal artery stenosis, intrinsic renal dz, malignant HTN
Certain HTN tx's: diuretics, vasodilators
DOC: beta blockers can lower renin, Angiotensin inhibitors lower BP

Front 57

What are the 5 ACE Inhibitors?

Back 57

Captopril, Lisinopril, Enalapril, Benazepril, Enalaprilat (IV)

Front 58

What is the MOA of ACE inhibitors?

Back 58

Block ACE: dec SVR, NO inc HR, promotes natriuresis

inc vasodilation by inhibiting degrad of bradykinin (may cause cough and angioedema)

Front 59

Which 2 ACE inhibitors are active without conversion in the liver (not prodrugs)?

Back 59

Captopril, Lisinopril

Front 60

Where are ACE inhibitors used?

Back 60

HTN
Dec morbidity/.mortality in heart failure and LV dysfunction after MI
Delay diabetic nephropathy

Front 61

What are the side effects of ACE inhibitors?

Back 61

Hypotension, renal failure, Hyperkalemia (aldosterone -> Na/K/H antiporter), cough and angioedema (bc bradykinin)

Front 62

What are the toxicities of ACE inhibitors?

Back 62

Allergy to sulfhydral group - rash and fever
Dysgeusia (taste)

Front 63

Where are ACE inhibitors CI?

Back 63

Pregnancy (instead use methyldopa, labetolol, hydralazine)
Chronic renal failure, SLE - marrow suppression

Front 64

What are the 3 angiotensin receptor blockers?

Back 64

Losartan, Valsartan, Candesartan

Front 65

What is the MOA of angiotensin receptor blockers and how is it different from ACE inhibitors?

Back 65

Competitive antagonist or AT1 receptor, blocks AT II effects better without bradykinin dilation

Front 66

What are the side effects of angiotensin receptor blockers?

Back 66

Same as ACE inhibitors minus cough/angioedema

Hypotension, renal failure, Hyperkalemia (aldosterone -> Na/K/H antiporter)

Front 67

Where are ARBs CI?

Back 67

Pregnancy

Front 68

What drug reduces plasma renin activity?

Back 68

Aliskiren (reduce entire RAAS)