Fcm Hypertension Pharm

Front 1

What are the basic classes of anti-hypertensive drugs?

Back 1

1. Sympatholytics
2. Angiotensin-Inhibitors
3. Diuretics
4. Vasodilators

Front 2

What is one of the main reasons for patient non-compliance with HTN meds? What can be done to resolve this problem?

Back 2

Patients dont usually have symptoms of HTN, so the drugs dont APPEAR to be doing anything... BUT the drugs often have SIDE EFFECTS, which make the pt feel WORSE...

**Resolution: use combination therapy, which allows lower doses of each drug, and thus lowers side effects

Front 3

What are the main benefits of low-dose, combination therapy for HTN treatment?

Back 3

1. Decrease side-effects --> increase compliance

2. Decrease long-term dysregulation of system components - e.g., long-term use of sympatholytics can upregulate adrenergic receptors

Front 4

Sympatholytics
- aka
- what is the main mechanism of action?
- what are the different types?
- what is the main cause of their side-effects

Back 4

- aka: sympathoplegics


- MOA: interrupt sympathetic communication to effector tissues

- Beta Blockers, Alpha Blockers, Ganglion Blockers

- Interfering with baroreceptor reflex causes main side-effects

Front 5

Beta Blockers
- MOA

Back 5

Block beta-receptors --> decrease sympathetic effects on myocardium --> decrease cardiac output --> decrease BP

Block renin release

**Decrease mortality in pts wiht HF!

Front 6

Beta Blockers
- Side Effects
- what causes them?
- Contraindications

Back 6

Side Effects cuased by blocking cardiac, vascular, bronchial beta-receptors

- sinus bradycardia
- induced bronchospasm
- decreased CO
- exercise intolerance
- asthmatic sx
- sleep disturbances
- decreased libido and ED in men

Contraindicated: asthma, AV block, uncompensated HF

Front 7

Beta Blockers - Cause of withdrawal sx

Back 7

While on beta-blockers, there is an increased sensitivity of beta-receptors --> causes withdrawal symptoms

Front 8

Beta Blockers - how is their effectiveness racially distributed?

Back 8

More effective in Caucasians than African Americans

Front 9

What are the beta-blockers used for HTN tx?

Back 9

Propanolol
Atenolol
Metoprolol
Carvedilol

Front 10

Propanolol
- What type of drug?
- Use?
- MOA
- Side effects?

Back 10

= Sympatholytic
- Tx for mild-moderate HTN
- MOA:
- non-selective B1/B2 antagonist
- blocks renin release
- Side Effects:
- ***crosses BBB: nigthmares, insomnia, depression, etc.
- increase TGs
- decrease HDL
- masks hypoglycemia and slow recovery from acute hypoglycemia (caution diabetics)

Front 11

Atenolol
- What type of drug?
- Use?
- MOA

Back 11

= Sympatholytic
- Tx for mild-moderate HTN
(also used in acute MI)
- MOA: Selective B1 antagonist

Front 12

Metroprolol
- What type of drug?
- Use?
- MOA

Back 12

= Sympatholytic
- Tx for mild-moderate HTN
(also used in acute MI)
- MOA: Selective B1 antagonist

Front 13

Carvedilol
- What type of drug?
- Use?
- MOA
- Side effects?

Back 13

= Sympatholytic
- Tx for mild-moderate HTN
(also used for post-MI and CHF)
- MOA: Selective B1 antagonist and Alpha antagonist

Front 14

Alpha Blockers
- MOA

Back 14

MOA: alpha antagonists on peripheral vasculature --> decrease BP

Front 15

What are the Alpha Blockers used to treat HTN?q

Back 15

Prozosin
Doxazosin

Front 16

Prazosin
- Type of Drug
- MOA
- Why preferred over certain others?

Back 16

= Sympatholytic
= Selective alpha-1 antagonist
- Preferred over non-selective alpha-antagonists (phentolamine; phenoxybenzamine) because less reflex tachycardia (not blocking a-2 as well)

Front 17

Alpha Blockers
- Side Effects

Back 17

- Mild reflex tachycardia
- 1st dose-hypotension --> syncope
- Orthostatic hypotension
- Headaches
- Palpitations
- Urinary incontinence
- Priapism ("wooden penis")

Front 18

Doxazosin
- Type of Drug
- MOA
- Other use

Back 18

= Sympatholytic
= alpha blocker
- also used for Benign Prostatic Hypertrophy (BPH)

Front 19

Central Acting Adrenergic Blockers
- MOA
- Side Effects

Back 19

MOA: stimulate brainstem to decrease sympathetic outflow
*Do not interfere with baroreceptor reflex
- Note: not widely used as anti-HTN therapy, but offer good options for difficult cases

Side Effects:
- ***Cross BBB - nightmares, insomnia, depression, etc.

Front 20

What are the Central Active Adrenergic Blockers used to tx HTN?
What are their specific mechanisms?

Back 20

Clonidine - alpha-antagonist that stimulates brainstem; partial alpha-agonist activity

Methyldopa - alpha-antagonist that stimulates brainstem; partial alpha-agonist activity; causes early rise in BP followed by prolonged decrease

Front 21

NE-Depleting Agents
- MOA
- Name of drugs

Back 21

MOA: taken up into adrenergic nerve terminals --> enter presynaptic vesicles --> displace NE --> sympathectomy-like toxicities (**Not widely used in clinical practice)

RESERPINE - no longer in clinical use; crosses BBB and uses up amine stores there too

Front 22

Renin-Angiotensin Blockers
- general MOA
- final common pathway?

Back 22

Block effects of Ang II - either at formation (ACE inhibitors) or at its receptor (ARBs)

Final common pathway: reduce sodium retention by kidney and reduce constriction of arteriol smooth muscle (thus, decreasing TPR)

Front 23

ACE
- What does ACE stand for?
- Function
- What type of enzyme group does ACE belong to?

Back 23

Angiotensin Converting Enzyme
- cleaves the 2 terminal AAs of Ang I to form Ang II

= sugroup of Kininase enzymes - incolved in breaking down Kinins

Front 24

ACE-Inhibitors
- MOA?

Back 24

= competitive antagonists of ACE

1. prevent changing Ang I into Ang II
- Ang II levels reduced --> reduced circulating Aldosterone
- Less Na+ retention and fluid retention --> lower BP

2. prevent degredation of Bradykinin, so it accumulates
- VASODILATION
*side-effect: dry cough

3. prevent superoxide anion formation from NADPH oxidase and subsequent cellular hypertrophy

Front 25

Bradykinin
- MOA

Back 25

= potent vasodilator
- increases NO and prostacyclin

*also contributes to DRY COUGH (main side-effect of ACE-inhibitors, which increase bradykinin)

Front 26

NADPH Oxidase
- location?
- how stimulated?
- function?

Back 26

- In vascular smooth muscle
- Stimulated by Angiotensin II Receptors...

- Generate superoxide anion (regulates cell growth) --> cellular hypertrophy of HTN

Front 27

ACE-Inhbitors
- contraindications?

Back 27

Pregnancy --> increased fetal mortality

*Use cautiously in patients with expected renal failure

Front 28

ACE-Inhibitors
- Racial distribution of effectivness?

Back 28

Less effective in African Americans

Front 29

ACE-Inhibitors
- Side Effects?

Back 29

#1 - Dry cough (due to increased Bradykinin)
- Angioedema (due to Bradykinin)
- Hyperkalemia (due to decreased aldosterone)
- Severe hypotension in hypovolemic patients
- Renal failure in patients wiht renal artery stenosis
- Inpaired renal function - proteinuria, increased BUN and creatinine

Front 30

What are the ACE-Inhibitors used to treat HTN?
- notes on each?

Back 30

Captopril - first one; for mild-severe HTN; *toxicity - loss of taste sensation

Enalopril - prodrug (converted by de-esterification to enaloprilat); good on tissue ACE

Lisinopril - prodrug similar to enalopril

Quinopril - long-acting ACE-inhibitor

Ramipril - long-acting Ace-inhibitor; good on tissue ACE

Front 31

What is "tissue ACE" and what is it's association with heart problems?

Back 31

RAAS systems present in cardiovascular cells, including ventricular myocytes and ventricular smooth muscle cells
- responsibly for tissue plasticity seen in pathologic states of the heart

Front 32

Angiotensin Receptor Blockers (ARBs)
- MOA
- Effectiveness compared to ACE-Inhibitors?
- Side Effects?

Back 32

Competitive antagonists of AT1 receptors

Just as effective as ACE-Inhibitors at reducing both systolic and diastolic BP

Side Effects:
*since do not inhibit ACE, no alteration of kinin metabolism (no NO or prostacyclin stimulation) --> no dry cough or angioedema

Front 33

What are the Ang II Receptor Class subtypes?

Back 33

AT1, AT2, AT3, AT4
(physiologic roles of 2-4 unknown)
*ARBs target AT1

Front 34

ARBs
- Contraindications?

Back 34

Pregnancy

Front 35

ARBs
- Racial distribution of effectiveness?

Back 35

Less effective in African Americans

Front 36

What are the ARBs used for HTN tx?

Back 36

Losartan
Candesartan
Valsartan

Front 37

Diuretics
- MOA

Back 37

Work on kidneys
- Increase urinary output in excess of normal --> reduce total body water
**Interstitial fluid, intercellular fluid, blood volume -- all in equilibrium
- Thus, DIURESIS causes DEHYDRATION and BLOOD VOLUME CONSTRICTION
- Reduced blood volume causes reduced CO and BP

... after several days, CO and blood volume return to normal, but BP stays reduced!!

Front 38

What is the name of the process of loss of interstitial fluid as urine?

Back 38

Diuresis

Front 39

Diuretics
- contraindications?

Back 39

Pregnancy
Renal Failure
(preg and renal failure bc diuretics can cause circulatory collapse)

NSAIDs - decrease PGs, which diuretics need to function

Front 40

Types of diuretics

Back 40

Thiazide Diuretics
Loop Diuretics
Potassium-Sparing Diuretics

Front 41

Thiazide Diuretics
- MOA
- Uses

Back 41

Inhibite Na/Cl co-transportar in luminal membrane of Distal Convoluted Tubule
--> less reabsorption; more loss of Na and Cl into tubular fluid
--> increases urinary output by osmotic drag

- Use for HF
- **First line tx for HTN

Front 42

Thiazide Diuretics
- Side Effects
- Possible solution to side effects??

Back 42

Main problem is depletion of potassium
--> Use in conjunction with potassium-sparing diuretics to ofset some K loss

Front 43

Thiazide Diuretics - what can be done when target BP is not achieved?

Back 43

Use in combination with other antihypertensives: ACE-Is, ARBs, BB, CCBs, K-sparing diuretics

Front 44

What are the Thiazide Diuretics used to treat HTN?

Back 44

- Hydrochlorothiazide (also used to relieve bloating in PMS)
- Chlorothiazide

Front 45

Loop Diuretics
- MOA
- Uses

Back 45

Inhibit Na/K/Cl co-transporter in luminal membrane of Thick Ascending Loop of Henle
--> not reabsorbed
--> more lost into tubular fluid --> increases urine output by osmotic drag

**Not often used for HTN bc such strong K loss... tertiary option
- Main Use: relieve edema

Front 46

What Loop Diuretics are used for HTN tx?
- toxicity?

Back 46

Furosemide
- toxicity: dose-related, reversible hearing impairment

Front 47

Potassium-Sparing Diuretics
- benefit
- side effects

Back 47

Induce diuresis without depleting K
- MOA different than thiazide and loop diuretics, so can be given in combination to improve diuresis without too much K loss!

Main Side Effects: HYPERKALEMIA - can be life-threatening in pts with renal disease, or pts on ACE-Is or ARBs

Front 48

Spironolactone
- type of drug?
- MOAs

Back 48

= Potassium-sparing diuretic
= aldosterone receptor antagonist

- Aldosterone normally binds to promoter of gene for Na/K ATPase on epith cells of basolateral membrane of the colecting duct --> makes pumps

- Spironolactone decreases density of Na/K ATPase enzyme (pump) on luminal membrane of collecting duct --> DEcreases Na REABSORPTION and K SECRETION (Na out; K in) --> increases urine output by osmotic drag

Front 49

Amiloride and Triamterine
- type of drugs
- MOAs

Back 49

= Potassium-sparing diuretic
= Na Channel Blockers

Blocks Na Channel on Collecting Duct, which prevents inward movelment of Na (coupled to K efflux)
--> Na stuck in tubular lumen --> increases urine output by osmotic drag

***Not recommended monotherapy, but used in combo with thiazide diuretics to offset K loss

Front 50

Vasodilators
- MOA
- main Side Effect?
- categories of vasodilators?

Back 50

Stimulate reduction in peripheral vascular resistance by actions on vascular SMCs --> decrease in BP

Main Side Effect: Reflex Tachycardia

Types:
- Calcium Channel Blockers (CCBs)
- "Direct" Vasodilators
- Combination Therapy

Front 51

Calcium Channel Blockers (CCBs)
- MOA
- types of CCBs
- important goal of these drugs

Back 51

MOA: Block L-type Ca Channels in cardiac and vascular myocytes --> reduce Ca influx --> decrease cytoplasmic Ca levels --> reduces contractile strength

DHPs = Dihydropyridines (e.g., amlodipine)
non-DHPs

Want vascular selectivity >> cardiac
**DHPs have better selectivity over non-DHPs

Front 52

CCBs
- contraindications

Back 52

All contraindicated in patients with CHF except Amlodipine

Front 53

CCBs
- Side Effects

Back 53

- Depress SA Node (HR) and contractility --> depress CO and BP --> can lead to serious HYPOTENSION

Note: Short-acting CCBs linked to increased mortality, but controversial!

Front 54

CCBs
- Drug Interactions

Back 54

CCBs are metabolized by cytochrome P450
- Cimetidine inhibits CYP450 --> elevates levels of CCBs and leads to toxic side effects

Front 55

What are the CCBs used to treat HTN? Describe...

Back 55

Amlodipine
- long-acting DHP
- vascular selectivity
- **only CCB shown to reduce atherogenisis
- **does NOT increase mortality in patients with CHF

Nifedipine - short-acting DHP; extended-release

Diltiazem - short-acting DHP; extended-release

Verapamil - short-acting DHP; extended-release
- can cause severe constipation

Front 56

"Direct" Vasodilators
- MOA

Back 56

MOA: non-CCB drugs that decrease systemic peripheral resistance by relaxing effects on peripheral arteriolar smooth muscle

Front 57

"Direct" Vasodilators
- names
- administration
- uses

Back 57

Hydralizine - ORAL; arteriolar dilator
**tachyphylaxis if used alone -- must be used in combo with other HTN drugs
- often for outpatient tx

Nitroprusside - IV; vasodilator of both arterioles and veins
*thus, reduces both PRELOAD and AFTERLOAD
- releases lots of NO in blood --> stimulates cGMP in VSM --> vasorelaxation
***Good for hypertensive crisis!

Nitroglycerine - similar MOA to nitroprusside
**For angina (most common) - sublingual and transdermal patch
**For hypertensive crisis - IV

*****Note: male patients on Nitrovasodilators should be cautious when using PDE-5 inhibitors for ED

Front 58

Poly Pills
- what are they?
- most popular?

Back 58

Multiple drugs combined into one pill

Caduet = amlodipine + atorvastatin
- 1/day - better compliance
- efficacy, side effects, contraindications = same as the 2 drugs given alone

Front 59

What is the order of treatment choice for HTN?

What is the best treatment for MILD HTN?

What is the best treatment for SEVERE HTN?

Back 59

HTN:
Renin-Ang Inhibitors > CCBs > beta-bockers or diuretics > vasodilators

Mild HTN:
monotherapy = ACE-Inhibs or ARBs

Severe HTN:
combo: renin-ang inhib + beta-blocker OR + CCB OR + Diuretic

Front 60

CCBs
- Non-DHP Contraindications
- Non-DHP Side Effects

Back 60

Contraindicated in:
- CHF!
- bradycardia
- sick sinus syndrome
- AV block
- give with severe care for aortic stenosis

Side Effects:
- headaches
- flushing
- cardiac conduction disturbances

Front 61

CCBs
- DHP Contraindications
- DHP Side Effects

Back 61

Contraindicated in CHF (except amlodipine)

Side Effects:
- ischemic cardiac pain (at initiation of tx, esp with high starting dose)
- tachycardia palpitations
- leg edema

Front 62

Which drug classes are indicated for HEART FAILURE?

Back 62

Beta-Blockers
ACE-Inhibitors
ARBs
Diuretics

Front 63

Which drug classes are indicated for POST-MI TREATMENT?

Back 63

Beta-Blockers
Ace-Inhibitors
Statins

Front 64

What is the DASH diet?
Results?

Back 64

Dietary Approaches to Stop Hypertension (DASH):

= increased fruits, vegetables, low-fat dairy

--> overall reduced cholesterol and total/saturated fat
--> reduced LDL

**Produced significant decrease in SBP and DBP (= to monotherapy!!)

- Results greater in African Americans than whites
- Results greater in pts with HTN than non-hypertensive pts

Front 65

CCBs:
-MOA
-selectivity heart vs. vascular

Back 65

MOA: block L-type Ca channels in cardiac and vascular myocytes---> reduces Ca inflow----> reduces contractile strength

-vascular selectivity over cardiac effects is important

Front 66

Which CCBs have the best selectivity for vascular effects? What are some examples?

Back 66

dihydropyridines

Ex: amlodipine, felodipine, isradipine

Front 67

contraindications of CCBs

Back 67

- pts with CHF (with the exception of amlodipine)

Front 68

-toxicities of CCBs
- drug interactions of CCBs

Back 68

depress HR, contractility and thus CO and BP--->hypotensive crisis

-cimetidine---> slows metabolism (inhibits CYP), elevates blood concentrations on effects of CCBs.

Front 69

-Amlodipine

Back 69

long acting DHP, good selectivity for vascular effects.

*** ONLY CCB shown to reduce atherogenic activity

- DOES NOT increase mortality in CHF (other CCBs do)

Front 70

-Nifedipine
-Diltiazem
-Verapamil

Back 70

-short acting, extended release
-short acting, extended release
-short acting, extended release---> SEVERE CONSTIPATION

Front 71

what are "direct vasodilators"?

Back 71

non CCBs that decrease systemic peripheral resistance by their relaxing effects on peripheral arteriolar smooth muscle.

Front 72

what are the "direct vasodilators"?

Back 72

hydralizine
nitroprusside
nitroglycerine

Front 73

which "direct vasodilator" is commonly given PO? IV?

Back 73

-hydralizine (PO)
-nitroprusside (IV)

Front 74

Hydralizine:
-MOA
-side effect

Back 74

-ateriolar dilator

-tachyphylaxis develops rapidly when used alone

*** is used only in combination particularly in severe hypertension

Front 75

Nitroprusside-
-MOA:
-use?

Back 75

MOA: arteriolar and venous dilator, reduces both BP and venous return (afterload and preload). Releases large quantities of NO (stimulates cGMP formation--->vasorelaxation)

-used in hypertensive crisis (ex: malignant hypertension)

Front 76

Nitroglycerine
-MOA
-uses?

Back 76

-relaxes both arterioles and veins via release of NO

-most commonly used to control angina, also used for hypertensive crisises

Front 77

what are "poly pills"?

Back 77

multiple drugs combined in one pill... growing in popularity, emerging as new paradigm in pharm. tx.

Front 78

Caduet
-MOA

Back 78

MOA: poly pill, 2 drugs for 2 different diseases (amlodipine and atorvastatin)

Front 79

Tx of mild hypertensives

Back 79

monotherapy may be effective (ACEi and ARBs)

Front 80

Tx of more severe hypertensives

Back 80

combo therapy (R-A inhibitor + something else)

Front 81

important key to achieving BP control

Back 81

using therapies with the least side effects

Front 82

Beta-Blockers
- Adverse rxns?
-contraindications?

Back 82

ARxns: many due to blocking cardiac, vascular and bronchial beta receptors.

-bradycardia, decreased CO, cold extremities, bronchospasms, sleep disturbances, may aggrevate CHF and affect glucose tolerance

CI: asthmatics, pts with AV block or uncompensated HF

Front 83

Alpha Blockers
-Adverse rxns?

Back 83

-first dose hypotension leading to syncope, orthostatic hypotension, headaches, palpatations, urinary incontinence, priaprism

Front 84

ACE inhibitors
adverse rxns?
contraindication?

Back 84

-MOST COMMON IS COUGH
-angioedema (much less frequent)
-first dose hypotension
-hyperkalemia (due to supression of aldosterone secretion)

CI: pregnancy, severe renovascular disease

Front 85

Thiazide diuretics
-adverse rxns
-CI

Back 85

AR: electrolyte disturbances
-hyperuricemia
dyslipidemia
-sudden cardiac death (high doses)
*** adverse rxns are dose dependent, occur at high doses


CI- gout, renal failure, pregnancy

Front 86

CCBs
-adverse rxns?
-CI?

Back 86

AR:
-(Non-DHP) headache, flushing, use with caution in Aortic stenosis.
- can induce cardiac conduction disturbances.
-(DHP)
-ischemic cardiac pain on initiation of therapy.
-tachycardia
-edema

CI:
(Non-DHP)
pts with bradycardia
sick sinus syndrome
AV Block

*** ALL CCBs (except amlodipine) contraindicated in CHF