Pt I Exam 3

Front 1

CNS MOA for Methlydopa

Back 1

Agonist for presynaptic CNS α2-adrenergic receptors b/c converted to a-methylnorepinephrine.

Front 2

Methyldopa MOA

Back 2

Competitive inhibitor for DOPA decarboxylase . Dopamine is a precursor to NE.

Front 3

Normal BP

Back 3

<120/<80

Front 4

Prehypertension

Back 4

120-139 or 80-89

Front 5

Stage 1 HTN

Back 5

140-159 or 90-99

Front 6

Stage 2 HTN

Back 6

>=160 or >=100

Front 7

Types of hypertension

Back 7

Chronic HTN, hypertensive urgency, hypertensive emergency

Front 8

Chronic HTN

Back 8

Slow, damage accumulates over years

Front 9

Hypertensive urgency

Back 9

Need to lower the BP over a few days or longer

Front 10

HTN emergency

Back 10

Diastolic >120. The differentiation is target organ damage. Rare, requires immediate treatment to prevent more organ damage.

Front 11

Visually inspectable HTN

Back 11

See target organ damage immediately in the eyes fundoscopic exam, look at the vessels inside the eye. These are really the only vessels that you can see.

Front 12

Non-pharm treatments for HTN

Back 12

Weight, sodium, alcohol (1 wine 3x week is good!), aerobic, behavior

Front 13

Behavioral modification for HTN

Back 13

very hard to do, especially if they have a Type A personality. They don’t know how to relax and be cool.

Front 14

Trials of HTN drugs head to head

Back 14

Which ones are better is hard to tell because drug companies don’t like to test drugs head to head. The studies that do head to head comparisons are funded by the NIH.

Front 15

Thiazide examples

Back 15

Chlorthiazide (Diuril); chlorthalidone, HCTZ (Microzide, HydroDIURIL), others

Front 16

Most powerful duretics

Back 16

Loop

Front 17

Effective anti-HTN diuretics

Back 17

Thiazides

Front 18

Loop diuretics

Back 18

Bumetanide, furosemide, torsemide

Front 19

Potassium sparing diuretics

Back 19

Amiloride, triamterene

Front 20

Aldosterone receptor blockers

Back 20

Epleroenone, spironolactons

Front 21

Suffix for beta blocker

Back 21

“-olol”

Front 22

Timolol for the eye

Back 22

Timoptic

Front 23

Timolol for HTN

Back 23

Blocadren

Front 24

Beta Blockers with ISA

Back 24

Acetutolol, penbutolol, pindolol

Front 25

Combined alpha and beta-blockers

Back 25

Carvedilol; labetalol

Front 26

Suffix for ACE inhibitors

Back 26

"pril"

Front 27

Suffix for Angiotensin II antagonists

Back 27

"sartan"

Front 28

CCB non dihydropyridines

Back 28

Diltiazem, verapamil

Front 29

CCB - dihydropyridines

Back 29

Amlodipine, felodipine, nifedipine

Front 30

Suffix for CCB- dihydropyridines

Back 30

"ipine"

Front 31

Suffix for HTN alpha-1-blockers

Back 31

"azosin"

Front 32

Examples of central alpha-2 agonists and other centrally acting drugs

Back 32

Clonidine, methyldopa, reserpine, guanfacine

Front 33

Examples of vasodilators

Back 33

Hydralazine, minoxidil

Front 34

Adverse remodeling

Back 34

Not useful changes in the muscular structure of the heart

Front 35

Impact of RAAS

Back 35

Important BP control mechanism; embryogenesis (if disturbed get teratology);

Front 36

Contraindicated in pregnancy

Back 36

ACEI, ARB, maybe in lactation too

Front 37

How do you make a dog permanently hypertensive

Back 37

Restrict blood to one kidney but not fully occlude one renal artery. It will secrete renin.

Front 38

Renovascular HTN

Back 38

One renal artery occluded, maybe atherosclerosis, uneven flow creates HTN

Front 39

3 control systems for renin release

Back 39

1.)Macula densa reabsorbs some sodium and senses conc; 2. pressure at afferent arteriole; 3. degree of symp outflow at juxtaglomerular cell

Front 40

Too much Na in DCT?

Back 40

Macula densa senses this and causes sodium loss

Front 41

Furosemide and the macula densa

Back 41

Furosemide causes sodium loss, there will be lower sodium concentrations in the urine, so the macula densa will sense this and release more renin in order to retain sodium, and vice versa

Front 42

Impact of Blood pressure changes at the kidney

Back 42

If BP goes up that decreases renin, which decreases ALD, which causes Na+ loss

Front 43

Macula densa innervation

Back 43

SNS mediated by beta receptors. Beta blockers work here to decrease beta influence and affect blood pressure.

Front 44

Increase in sympathetic tone at macula densa

Back 44

Increase renin and retains sodium

Front 45

Angiotension production

Back 45

Continuous in the liver

Front 46

One of most potent vasoconstrictors

Back 46

Angiotensin II

Front 47

How is one way beta blockers raise BP?

Back 47

Suddenly stop stimulation at kidney beta receptors, will get large renin release so BP increase and arrhythmias

Front 48

Fast limb of RAAS

Back 48

Angiotensin II can increase BP in just a couple of heartbeats

Front 49

Slow limb of RAAS

Back 49

Aldosterone takes a while to adjust, a slow buffered response at the DCT

Front 50

Tekturna acts on

Back 50

Rate limiting step of RAAS, which is conversion from angiotensinogen to angiotensin I

Front 51

Angiotensin produced by

Back 51

Liver

Front 52

Angiotensin synthesis can be stimulated by

Back 52

Incrase in glucocorticoids, increase in thyroid hormone

Front 53

Oral contraceptive and BP

Back 53

Increase antiotensinogen and cause HTN in some people

Front 54

Ideopathic HTN

Back 54

Old term before we knew about renin mech

Front 55

Homeostasis set wrong in HTN

Back 55

Long term HTN, body thinks that is what is normal. Body will fight you when you try to bring it down to normal

Front 56

Where is ACE

Back 56

Moslty bound to the lumenal wall of the vascular endothelium. Very little circulating

Front 57

Genetic defect of ACE

Back 57

Homozygous intron deletion in the ACE gene get highe than normal circulating levels of ACE. Increase risk of IHD, SCED, LV hypertrophy, diabetic nephropathy, early death

Front 58

Activitiy of angiotensin I

Back 58

Little to none, but converts rapidly to angiotensin II

Front 59

Angiotensin III

Back 59

May exist. Possibly made in adrenal cortex leading to aldosterone release

Front 60

Local control of BP

Back 60

Complete Renin/angiotensin systems in brain, heart, kidney, blood vessels

Front 61

Angiotensin receptors

Back 61

AT1 & AT2

Front 62

AT1

Back 62

GPCR; IP3 coupled, increase Ca++, increase cascular contractility

Front 63

AT2

Back 63

Unknown function

Front 64

Major effect of Angiotensin II

Back 64

Peripheral resistance, renal thing, cardiovascular structure, embryonics

Front 65

Peripheral resistance effect of Angiotensin II

Back 65

a.) direct vasoconstriction; b.)stimulation of adrenergic neuron endings (increased NE release and decreased NE reuptake); c.) incre sympathetic tone and increased release of NE from adrenal medulla

Front 66

Angiotensin effect on renal function

Back 66

Aldosterone thing, direct eff on PCT to increase NA+ reabsorption

Front 67

Angiotensin II on CV structure

Back 67

Hypertrophy, decr renal blood flow from CHF; growth factors, proto-oncogenes, collagen deposition, Constrict? Relax?

Front 68

Benazepril prodrug? Elim?

Back 68

Yes, kidney

Front 69

Captopril prodrug? Elim?

Back 69

No, kidney

Front 70

Enalapril prodrug? Elim?

Back 70

Yes, kidney

Front 71

Enalaprilat prodrug? Elim?

Back 71

No, kidney

Front 72

Fosinopril prodrug? Elim?

Back 72

Yes, kidney & liver

Front 73

Lisinopril prodrug? Elim?

Back 73

No, kidney

Front 74

Meoxipril prodrug? Elim?

Back 74

Yes, kidney

Front 75

Perindopril prodrug? Elim?

Back 75

Yes, liver

Front 76

Quinapril prodrug? Elim?

Back 76

Yes, kidney

Front 77

Ramiprilprodrug? Elim?

Back 77

Yes, kidney

Front 78

Spirapril prodrug? Elim?

Back 78

Yes, kidney and liver

Front 79

Trandolapril prodrug? Elim?

Back 79

Yes, Liver

Front 80

Byetta from

Back 80

Gila monster

Front 81

Hirudin from

Back 81

leeches

Front 82

Uses for ACEIs

Back 82

May become first line for HTN, esp valuable for diabbetics, MVO2 reduction (CHF, AMI), prevent adverse remodeling and maybe some reversal

Front 83

Reversing adverse remodeling, not ACEI

Back 83

Aldosterone inhibition

Front 84

Captopril diabetic benefit

Back 84

Decrease rate of diabetic nephropathy

Front 85

ACEI Cough

Back 85

20%, prolonged duration of kinins

Front 86

Metabolizes kinins

Back 86

ACE

Front 87

Help with ACEI cough

Back 87

Cromalin and/or theophylline

Front 88

Adverse effects of ACE

Back 88

Hyperkaliemia, esp with K sparing diuretics/supplements, beta blockers or NSAIDS; Renal failure when GFR<30ml/min

Front 89

ACEI in pregnancy

Back 89

Fetotoxic, Category D

Front 90

Pregnancy category A

Back 90

Well studies and has not shown increased risk of fetal abnormalities

Front 91

Pregnancy Category B

Back 91

Animal studies only, no evidence of fetal harm OR animal studies show harm but human studies have failed to show risk

Front 92

Pregnancy C

Back 92

Animal studies show harm + no adequate human studies; PR no animal studies and no adequate /well controlled studies in women

Front 93

HTN leads to

Back 93

Stroke (hemorrhagic & ischemic), CHD, Retinopathy, Nephropathy (ESRD). These are all really bad.

Front 94

Benefits of lowering BP

Back 94

Stroke incidence by 35-40%, MI by 20-25%, Heart failure by 50%. These are huge, by just lowering BP to goal

Front 95

Why are we treating BP?

Back 95

To prevent morbidity and mortality associated with high BP.

Front 96

SBP reduction for weight reduction

Back 96

5-20 mmHg/10kg loss

Front 97

SBP reduction for DASH diet

Back 97

8-14 mmHg

Front 98

SBP reduction for sodium reduction

Back 98

2-8 mmHg

Front 99

SBC reduction for physical activity

Back 99

4-9 mmHg

Front 100

SBP reduction of moderation of alcohol consumption

Back 100

2-4 mmHg

Front 101

We're still not at our BP goal after we've done lifestyle

Back 101

Who, when, with what do we treat? Multiple guidelines

Front 102

"safest" guideline for BP to quote

Back 102

Can probably never go wrong quoting that, but Karboski doesn't think it's the best.

Front 103

Drugs for BP in 1977

Back 103

All the 1977 step 2 drugs have substantial side effects. Recall that BP has not symptoms and we're asking them to take meds with SE.

Front 104

Why isn't BP "fun" to treat?

Back 104

Asymptomatic. Don't feel better like with Zyrtec. The BP meds cost $75/month and their daily life is a little worse (but might be saving their life.

Front 105

JNC5

Back 105

Step care was out. Algorithms are in. Put all drugs in one block (diuretics or BB preferred). Really there was no change from 4. Algorithm instead of steps.

Front 106

JNC6

Back 106

Algorithms were supposed to make things easier. This added compelling indications which used a drug the treated BP and that indication. 2 birds; 1 stone.

Front 107

A big part of JNC7(I think he meant 6)

Back 107

is what is the first drug.

Front 108

Risk stratification in BP

Back 108

This is from JNC6. Risk stratification group the risk levels in urgency of needing to get it under control. If you just have stage 1, not bad. If you have other risks then it's a problem.

Front 109

High normal BP in JNC6 risk stratification

Back 109

Drug therapy if in Risk Group C

Front 110

Risk stratification

Back 110

takes a look at the BP in context of everything else that is going on.

Front 111

Trial the seemed to influence JNC7 heavily

Back 111

ALLHAT - antihypertensive and lipid lowering treatment to prevent heart attack trial

Front 112

What drugs did ALLHAT study

Back 112

Chlorthalidone, lisinopril, amlodipine, and doxazosin

Front 113

Chlorthalidone is

Back 113

a thiazide like diuretic.

Front 114

Conclusions of ALLHAT

Back 114

Thiazide diuretics are more effective with regard to BP reduction, prevention o fHTN-related complications and SE; Increased risk of heart failure with ACEI <--WHOA!

Front 115

Impact of ALLHAT on prescribing

Back 115

ACEI use went down. Thiazide use when up.

Front 116

Conspiracy theory?

Back 116

4 of 9 on the JNC7 executive committee wrote ALLHAT. Too much influence at JNC from the ALLHAT investigators.

Front 117

Studies, in general are designed to study

Back 117

Primary outcomes

Front 118

All the differences in the ALLHAT trial came from

Back 118

Secondary outcome differences only: that's not strong methodology.

Front 119

Concern about initial therapy in ALLHAT

Back 119

Those studies had had HTN for a long time and guidelines are for initial drug. Not naïve and were high risk, multi drug therapy

Front 120

Not naïve ALLHAT

Back 120

Versus naïve newly diagnosed HTN: very different patient populations.

Front 121

For the study purposes, ALLHAT didn't consider

Back 121

multiple drugs. What if you had a bad result to one drug, just wait ten years? Nope, added more drugs but thiazide is the only one measured. (or maybe another category - only 4 of them)

Front 122

ACEI / CCB complaints about ALLHAT

Back 122

If it didn't work, the next supporting drugs weren't very effective. They were disadvantaged by the combinations that were used to support them.

Front 123

What would be a helpful but unethical way of designing BP med trial

Back 123

Line up people and give them one drug. See you in 10 years.

Front 124

ALLHAT didn't report something

Back 124

Authors identified a higher rate of increase in new onset diabetes for thiazide group. That's the last thing you want with HTN.

Front 125

Parallels between Diabetes and HTN complications

Back 125

They're exactly the same: Stroke, heart disease, retinal disease and renal disease. Overlapping, additive complications.

Front 126

Australian study and ALLHAT

Back 126

- found very different results for new onset first time diagnosed HTN. Was disregarded by JNC7

Front 127

JNC7 summary

Back 127

Start w/thiazide, think about compelling indications, not a lot of risk stratification

Front 128

BHS

Back 128

British Hypertension society

Front 129

TOD:

Back 129

target organ damage

Front 130

BHS first concern

Back 130

Look for complications or TOD

Front 131

BHS added complications over JNC7

Back 131

Fundal hemorrhages, proteinuria, PVD, CABG, more

Front 132

BHS when first decide to treat

Back 132

Split in groups: under 55/55+ or black

Front 133

Older patients and black patients both have

Back 133

salt sensitivities.

Front 134

BHS says likely cause of elderly, black HTN

Back 134

"high renin"? HTN

Front 135

If have revved up RAAS, what will help

Back 135

ACEI will help. If you don't, those won't work . It inhibits angiotensin

Front 136

If you don't have a RAAS (BHS)

Back 136

ACEI probably won't work, so use CCB or thiazide diuretic

Front 137

BHS is trying to find

Back 137

the likely cause of HTN and treat that. JNC used ALLHAT to determine drug.

Front 138

If you use an ACEI and don't get to goal, what does that say about the patient's cause of HTN? is it solely a revved up RAAS?

Back 138

No. So add CCB or thiazide. Keep the ACEI because it's working (probably) but not to goal. If nothing happened then drop it.

Front 139

Risk of straying from JNC7

Back 139

Preceptors might not know this. This may have been reasonable until JNC7 got too old.

Front 140

Which guidelines to use with MTM?

Back 140

You decide. BHS, JNC7, EAS.

Front 141

EAS multidrug Theory

Back 141

Use 2 or 3 drugs in small doses, the good things will add up without a lot of side effects.

Front 142

EAS first drug theory

Back 142

Who cares what the first drug is, most will end up with a combo. Get to the combo more quickly. Pick a drug. Whatever

Front 143

Target BP goal in JNC7

Back 143

140/90, but lower if have comorbidities. Target is 130/80 if have diabetes of renal disease. Good luck getting to 130/80. And, it makes good sense but no good evidence it works.

Front 144

BHS BP target goal

Back 144

Wishy washy. "acceptable, optimal" doesn't help much

Front 145

1st BP drug for JNC7

Back 145

Thiazides best for long term outcomes

Front 146

1st BP drug for BHS 4

Back 146

Focus on risk stratification and make logical coice of combination therapy

Front 147

1st BP drugs for ESH/ESC 2007

Back 147

Focus on risk stratification and move quickly to combination therapy

Front 148

SBP and race

Back 148

is independent of race.

Front 149

For elderly beginning BP treatment

Back 149

Starting dose should be 1/2 that of younger patients. It's usually an acute problem, so don't try to treat too fast.

Front 150

<<JNC Says alt to thizide

Back 150

Beta blockers and dihydropyridine CCB.

Front 151

BP Drug Cautions in elderly

Back 151

Alpha blockers, adrenergic blockers (beta), high dose diuretics can cause postural BP changes, clonidine can cause cognitive dysfunction

Front 152

Stepwise strategy to lower BP in seniors

Back 152

More likely to have atherosclerotic changes, may need more pressure to shove blood to head. So use caution -dropping pressure to much can hypoperfuse their brain. If over 180 get to 160. If over160 get down 20. Ultimate goal 140

Front 153

Blacks and epidemiology of HTN

Back 153

Earlier onset, higher prevalence, greater severity than whites, TOD earlier

Front 154

High prevalence in Black population w/r/t HTN

Back 154

Salt sensitivity, obesity, smoking

Front 155

What kind of HTN can you expect in blacks and what works/doesn’t

Back 155

They say BB and ACEI don't work in blacks. Those work in revved up RAAS. So more likely to have low renin HTN - so use thiazide diuretics quickly.

Front 156

Don't let people talk you out of using ________ with black population for HTN and why

Back 156

BB and ACEI; these can help if have renal probs.

Front 157

For blacks prescribing in BP

Back 157

BB and ACEI do work but not in monotherapy.

Front 158

One study shows BP lowering benefits?

Back 158

No, many

Front 159

Lowering BP helps which races/gender?

Back 159

all

Front 160

Current version of JNC

Back 160

2003

Front 161

Current version of BHS

Back 161

2004, updated 2010

Front 162

Key to success:

Back 162

Guideline adherance

Front 163

Significance of BP treatment for blacks and elderly

Back 163

More sensitive, so choose treatment accordingly

Front 164

Dietary fats and BP (omega 3's)

Back 164

Might lower BP, but no longterm studies, more important with lipid disorders. We have better ways to manage BP. Massive doses needed so GI probs, expensive

Front 165

Caffeine and BP

Back 165

Acute increase, which isn't a problem. You adjust to that and tolerance develops.

Front 166

Garlic/onion and BP

Back 166

No trials tell us this is effective

Front 167

JNC-4

Back 167

Stepwise: nonpharm, one drug, then more or second drug, etc

Front 168

JNC7 first split

Back 168

Do they have a compelling indication?

Front 169

JNC7 second split

Back 169

Stage 1 vs Stage 2; thiazide diuretics drug of choice for stage 1. That plus ACEI-ARB-BB-or-CCB for Stage 2

Front 170

JNC7 loves

Back 170

Thiazide diuretics

Front 171

List JNC7 compelling indications

Back 171

Heart Failure; post MI, High Coronary Disease Risk; Diabetes, Chronic Kidney Disease; Recurrent Stroke Prevention

Front 172

BHS risk charts

Back 172

Tries to identify higher risks, includes almost everybody in the 60+ group

Front 173

Different BHS risk charts groups

Back 173

Men/women; Diabetic/non;

Front 174

Easy treatment decisions with BHS

Back 174

Really high or low BP

Front 175

BHS doesn't treat 150/95 when

Back 175

No TOD; no CV complications, no diabetes, and 10 year CVS risk <20%. They have high BP but low risk.

Front 176

BHS does treat 140/90 with med when

Back 176

TOD or CV complications or diabetes or 10 year CVD risk>= 20%.

Front 177

BHS vs ALLHAT

Back 177

Treat based on overall risk rather than BP

Front 178

EAS decides when to use drugs based on

Back 178

BP (norm, high norm, 1,2,3), # of risk factors, Diabetes, CV/renal disease

Front 179

EAS advocateswhat for BP drugs

Back 179

Go quickly to multi drug.

Front 180

EHS/ESC target BP

Back 180

Goes lower for more groups than BHS

Front 181

BP epidemiolgy

Back 181

A lot of people have it, a lot of people getting old

Front 182

Diuretics reduce volume?

Back 182

No, kinda no. That effect goes away within a couple of weeks.

Front 183

Treat edema

Back 183

Loop diuretic, so can we agree lasix is stronger than thiazide?

Front 184

Why thiazides good at lower BP

Back 184

We don't really know, many theories, but whatever it does it's not due to its diuretic properties.

Front 185

When use loop for BP

Back 185

Obviously volume overload

Front 186

____ and lipids

Back 186

DIURETICS. Increase total cholesterol, VLDL, TG, LDL, decrease HDL. Can still use

Front 187

Higher doses of diuretics

Back 187

Not BP lower and more metabolic Ses

Front 188

Concern with hyperglycemia and diuretics

Back 188

New diabetics due to treatment with diuretics, remember ALLHAT.

Front 189

x

Back 189

Preserve CV response to exercise

Front 190

x

Back 190

Exacerbates LVH, an indication that we see physical changes to the heart. Directly correlated to ____, a really bad thing

Front 191

ISA

Back 191

Property of some beta blockers - think of it as being a reversible blockade. This is the non-pharmacological answer. With enough stimulation the HR can go up. Implies non-ISA beta blockers are irreversible (rate can't go up)

Front 192

Non-ISA

Back 192

Can't get effect of exercise. Will fatigue quickly, reduced exercise tolerance.

Front 193

Beta blockers with ISA

Back 193

Pindolol, acebutolol, carteolol, penbutolol

Front 194

Angina, treatment

Back 194

Ischemic chest pain, non-ISA beta blocker, because you don't want the HR to go up because that's what causing the chest pain.

Back 195

Don't offer cardio protection

Front 196

Women treatment for BP

Back 196

No evidence that treatment needs to be different, but we haven't studied much

Front 197

BP and oral contraceptives

Back 197

Small bump in SBP & DBP, but not

Front 198

When OC use in BP

Back 198

2-3x more commin in women taking OC for >5 yrs

Front 199

Diabetes/HTN bad to have together

Front 200

HTN+Diabetes drug

Back 200

ACEI + ?

Front 201

Secretes angiotensinogen

Back 201

Liver

Front 202

Secretes renin

Back 202

Kidney

Front 203

AA's in angiotensin I

Back 203

10

Front 204

AA's in angiotensin II

Back 204

8

Front 205

Secretes aldosterone

Back 205

Adrenal Cortex

Front 206

Rate limiting factor in angiotensin II formation

Back 206

Plasma concentration of renin

Front 207

Class of Angtiotensin II

Back 207

Peptide hormone

Front 208

What does aldosterone impact

Back 208

Sodium reabsorption. Water follows sodium, so BP increases

Front 209

Which of the RAAS leads to vasoconstriction?

Back 209

Angiotensin II

Front 210

Saralasin

Back 210

Angiotensin II partial agonist and some antagonist activity. Phe to Ala at C-term.

Front 211

Ki

Back 211

Dissociation constant for an inhibitor. Low Ki means high affinity for the receptor

Front 212

IC50

Back 212

[I] that gives 50% inhibition of antagonism

Front 213

ED50

Back 213

Dose of agonist required for 50% maximal effect

Front 214

LD50

Back 214

Lethal dose of a drug to get rid of 50% of the population

Front 215

Significance of Takeda discovery

Back 215

Non-peptide antagonist of angiotensin II receptor. Peptides don't make good drugs

Front 216

Improvement of Takeda lead compound

Back 216

Electron withdrawing groups on phenyl ring, reduced IC50 (need less to have same effect) (more potent)

Front 217

Procainamide

Back 217

Also undergoes N-acetylation

Front 218

Epidemiology of CHF

Back 218

400k new case/yr; 5mil current, most common hosp discharge diagnosi in >65YO; 30-40% die w/in one year.

Front 219

Etiology of heart failure

Back 219

#1 ischemic heart disease (50-70%); #2 HTN (pressure overload); #3cardiomyopathy: alcoholic, viral, idiopathic