Quiz 4 Flashcards
1
Q
How many Americans have HTN?
A
78M
2
Q
__ __ medical problem in adults in the industrialized world.
A
1 chronic
3
Q
___ ___ reason for visits to physicians.
A
Most frequent
4
Q
__ __ __ __ indications for prescription drug use.
A
One of the leading
5
Q
Increase of __/__ mmHg __ risk of CVD.
A
20/10 doubles
6
Q
Over age __, __ is more important risk of CVD than __.
A
over age 50
SBP more important than DBP
7
Q
Normotensive at age __ have __% lifetime risk of HTN.
A
age 55
90% risk
8
Q
Most will eventually require __ drugs to achieve BP goal.
A
>/=2
9
Q
Prevalence v. Control
why?
A
- black, white, Mexican
- white, black, Mexican
- access to care, cost, hesitance for treating asympomatic dz
10
Q
Natural course of HTN(4)
A
- Stroke - htn #1 RF
- hem and isc
- greatest effect on morbidity
- Coronary Heart Dz
- angina
- MI
- CHF
- Retinopathy - infarcts and hemorrhages
- Nephropathy - ESRD
11
Q
4 Primary sources of htn guidelines
A
- JNC - Joint National Commitee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure
- BHS - British Hypertension Society
- ESH/ESC - European Society of Hypertension/European Society of Cardiology
- WHO/International Hypertension Society - geared toward developing countries with limited access/range of meds
12
Q
JNC facts
A
- first pub 1977
- current JNC 8, 2014
- funded by National Heart Lung and Blood Institute NHLBI, a unit of NIH/DHHS
- written by National High Blood Pressure Education Program coordinating committee
13
Q
BHS facts
A
- first pub 1989
- current version 2011
- written by BHS working party
- funded by unrestricted grants from major pharm co’s
- no reps from drug co
- not advisory to committee
- 250 members
- htn researchers in UK and Ireland
- MD’s, Nurses, physiologists, other scientists
14
Q
ESH/ESC facts
A
- first pub 2003
- current version 2013
- written by joint task force from various EU countries
- Academic societies sim to ACC
- high presige, less questionable motivation
- funding sources not disclosed
15
Q
JNC 8 story
A
- in 2014, 14 yrs after JNC 7, nothing published
- NHLBI withdrew support and w/i months JNC 8 was released
- written by JNC 8 subgroup
- minority report published disagreeing with elements
- not sanctioned or endorsed by NHLBI
- major cardio and other societies came forward in disagreement
16
Q
AHA/ACC/ASH role.. did/will do
A
- will author new guidelines promised this year
- published interim bridge that only applies to CAD
17
Q
Blood Pressure Classification (JNC 7&8)
A
- normal <120/<80
- pre-htn 120-139/80-89
- stage 1 140-159/90-99
- stage 2 160/100+
18
Q
Lifestyle Modifications
A
- IBW
- DASH diet
- Reduce Na
- Exercise
- Avoid xs EtOH
- Stop smoking
19
Q
Being overweight increases risk for developing htn __ to __ x.
A
2-6x
20
Q
Factors defining “overweight”
A
- BMI >=30
- Waise >=34 women, 39 men
21
Q
BMI formula
A
kg/m2
22
Q
Wt loss…
A
- reduces SBP and DBP, 10lb loss significant
- augments activity of antihypertensives
- decreases CHD risks:
- hyperlipidemia
- DM
- CHD
23
Q
Dietary Na
A
- studies show assn Na intake and BP
- blacks and elderly more sens to changes in Na
- reduce to <2.3g/day in
- dec BP 6.3/2.2 in older pts
- inc resp to meds
- 75% Na is from processed foods
24
Q
EtOH
A
- Excess in
- inc BP, somewhat
- resistance to drug therapy, moreso
- Limit to… (half for women and light wt ppl)
- 1 oz/day
- 2 oz 100 proof
- 10 oz wine
- 24 oz beer
25
Physical Activity
* improve bp, healht, wt(rf)
* sedentary = 20-50% inc risk htn
* Guideline: 30-45 min/day aerobic, most days of week
26
Potassium
* with K wasting diuretic
27
Calcium
* RDA 800-1200mg/day
* inverse relationship between Ca and BP, low Ca inc BP
28
Magnesium
* No convincing data for supplementation
* used in hypo K, not BP per se
29
Dietary fats
* Omega-3 FA's may dec BP
* no longterm studies m/m
* common GI sfx
* prescribed for hypertrig
30
Caffeine
* may inc BP short term, but tolerance is rapid
* intermittant high bp ok, like in exercise
* no need to restrict
31
Garlic/onion
* no effect in controlled trials
32
SBP decreases with lifestyle modification
* wt loss 5-20mmHg (20lb)
* DASH 8-14mmHg
* Na reduction 2-8mmHg
* Exercise 4-9mmHg
* EtOH moderation 2-4mmHg
33
Thiazide Diuretic chars
* bad diuretics, diuretic action not sustained
* best for idiopathic htn
* JNC 7 drug of choice for essential htn
* diuretics generally not for htn, but thiazide yes
* combo for non-idio
34
Loop Diuretic use in htn when...
* when it results from volume overload (CDK)
35
K sparing diuretic chars
* weak diuretics
* weak antihypertensive effects
* used primarily to prevent K wasting from other diuretics
* side effects offset each other
36
ALD antagonist efficacy
* little long-term data on m/m (indep htn data)
37
Thiazide diuretic agents
* HCTZ
* chlorthalidone (EU)
* metolazone
38
Thiazide MOA
* Initial BP reduction through diuresis
* Chronically dec peripheral vascular resistance
* move Na and H2O from w/i arteriolar walls
* effect enhanced by Na restriction
39
Thiazide dosing and usage
* combo rx
* offsets compensatory Na retention of other rx
* qd dose in am dec noct diuresis (dim over time)
* 50mg qd opt/max - 25mg d/t AE's
40
Thiazide ADR's
* mild sfx
* hypo K, Mg
* hyper lip, gly\*
* ED
* 25mg not sig less effective than 50, but sfx sig less
41
RAAS pathway
* angiotensinoGEN --renin--\> ang I
* ang I --ACE--\> ang II
* ang II fx:
* activate SNS
* vasoconstriction
* ALD release
* Na + H2O retention
42
ACEI agents
-pril's
43
ACEI MOA
* blocks ang I to II conversion
* ang II -
* potent vasoconstrictor
* ALD secr - retain fluid
* stim SNS, norepi
* blocks degradation of bradykinin (vasodilator)
* inc natural vasodilator, may make it better than ARB
* use in HF and CKD - added benefit
44
ACEI specific advantages in? (2)
* HF
* CKD
45
ACEI warnings
* may inc rate of HF and stroke compared to thiazides
* maybe, ALLHAT
46
ACEI ADR's
* hyper K, moreso in HF
* AKF \<1%, stop or dec dose if 35% inc in Cr over baseline
* early benefit, may worsen CKD eventually
* this is not a reason not to use, monitor RF
* overall preserves RFx until it doesn't
* angioedema - rare but more in blacks and smokers
* persistant dry cough in 20%
* orthostatic hypotension, esp in vol depleted, elderly, or on other vasodilator drugs - uncommon in htn w/o these
* contraindicated in pregnancy - placental blood flow, teratogen
47
ACEI dosing
* start low and titrate up to desired effect, not specific dose
* half normal starting dose where risk for hypotension
* volume depleted
* HF exacerbation
* very elderly
* concurrent vasodilators or diuretics
* half normal starting dose where risk for severe renal dysfx
* elderly
* current CKD
48
ARB agents
-sartan
49
ARB MOA and effects
* ang II R agonist
* RAA system sources
* tissue sources
* no effect on bradykinins = no cough
* otherwise similar to ACEi's
* ADR's
* not in preg
* orthostasis
* angioedema (less than ACEi's)
50
Direct Renin Inhibitor
agent, moa, effects
* aliskiren (Tekturna)
* blocks angiotensinogen conversion to ang I by renin
* otherwise similar to ACEi's
* ADR's
* not in preg
* orthostasis
* angioedema (less than ACEi's)
* no advantage over ACEi/ARB's, still available
51
BB's
3 types and their agents
1. Cardioselective - no ISA (bisop, nebi, ate, beta, met)
* atenolol, betaxolol, bisoprolol, metoprolol, nebivolol
2. Non-selective - no ISA (tim, prop, **carv**, nad, labe)
* carvedilol, labetalol, nadolol, propanolol, timolol
3. Intrinsic Sympathomimetic Activity - not cardiac selective
* acebutolol, penbutolol, pindolol (acebut, penbut, pind)
52
BB moa
* many physiological effects documented but uncertain what causes BP lowering effect
53
BB: CS v. ISA
* CS: **greater affinity for B1R** (heart+kidney) than B2R (lungs, liver, panc, arteriolar sm. m.), preferred for htn (non-CS equally B1B2)
* preffered for htn, narrow range of R's, less sfx
* ISA: **partial BR agonists** = reversible blockade - high conc overcomes blockade and inc HR (CS irreversible)
* adv in exercise (for recommended wt loss)
* bad for anx, HF, angina (inc cardio o2 demand)
* really bad if demand inc _during MI_
* _not as effective_ in red CV events as other BB's
54
BB ADR's
brady, BBB, broncon, rayanaud, rebound
* brady (lowers d/t loss of adrenergic tone, could BB to brady)
* dizzy/drowsy - CNS dep in those that cross BBB
* bronchoconstriction in COPD/asthma - CS only at low dose
* don't use either, as dosage increases over time
* worsens Raynaud's - vasospasms
* **abrupt** d/c may cause **rebound** htn/hr - taper 1-2wks
* body producing NE to inc HR, blocked, make more
* also R upregulation and inc R sens - blocked
* remove BB - a lot of agonist and oversensitive R's...
55
CCB's
2 types and their agents
* dihydropyridine
* amlodipine, felodipine, isradipine, nicardipine, nifedipine, nisoldipine
* non-dihydropyridine
* diltiazem, verapamil
56
CCB moa
* block Ca influx across cell memb = coronary and peripheral vasodilation - potent vasodilators
* both equally effective in chronic htn
* all have some neg inotropic effect
* not first line tx, not as protective as thiazides
57
CCB utility
* 2nd c thz
* dhp/non = effective
* neg inotropes
* no CV event reduction
* ISH (+thz, esp elderly)
58
dihydro use, sfx, adr
ish, tach, orth, diz, flush, ha, p.ed thz
* very effective for ISH (esp in older pt), often added to thiazide
* poss reflex tach, have precipitated angina, d/t dropping BP (vasodilatioin)
* typically w/ **short-acting nifedipine** - other dihydro's are SR or have longer duration of action (less "peak effect")
* used to squirt or chew nif gel caps, frequent rebound tach
* inc card o2 demand - MI (htn tx caused MI)
* orth, diz, flush, h/a, peripheral edema (25mg HCTZ/wk for edema)
59
non-dihydro sfx, adr
* poss cardiac **conduction** abnormalities
* caution in **brady** + AV **block**
* no verapamil in **HF**, brady dec **CO**
* mostly at higher **doses** or in pt's with **pre-existing** conduction abnormalities
* **anorexia, nausea, peripheral edema (less than dhp), const (automatically** give sl sft)
60
non-dihydro chronotherapeutics
* =time released
* "timing of dosage form may be important in effacacy of drug"
* Covera HS and Verelan PM (both verapamil)
* dose at night = peak conc in early am hours
* theory: blunting early am bp surge = greater reduction in CV events - no evidence
61
Alpha Blocker agents
* prazosin, terazosin, doxazosin
62
Alpha Blocker moa
* selective a1 R antagonists in peripheral vasculature
* a1 R stim = vasoconstriction
* vasodilation and bp lowering
* note direct vasodilators not good antihypertensives, bp fluxuation, dizzy, ortho -- not same level evidence in red m/m (**end goal**)... so ablockers 2nd line added to other agent
* trial that showed acei caused hf/stroke showed same inc w/ ablockers
63
Alpha Blocker role in htn
* should only be used in combo w/ other anti-htn agents
64
Alpha Blocker adr's
* in one major trial inc risk of stroke, HF and CV events
* first dose effect - massive vasodilation - dizziness, faintness, syncope 1-3h p 1st dose
* take first few doses HS
* also occurs w/ dosage change or non-adherence
* sustained orthostatic hypotension - esp elderly, more prone to orth changes and inc danger in falls, hips, etc
* CNS effects - lassitude, vivid dreams, dep
* priapism
\*lassitude = a state of physical or mental weariness; lack of energy
65
Central Alpha Agonists
agents, moa, adr
* agents: clonidine, methyldopa
* moa: (effective...)
* reduces sympathetic outflow from the vasomotor center in the brain, decreasing hr, co and bp
* ablockers=**periph**
* these are **central** ags - mimic feedback effect of NE
* NE released to inc bp/hr, returns to brain to stop further release
* adrs: (...but at a cost)
* na/h2o retention, often used with diuretic
* dep
* orthostatic hypotension (caution in elderly)
* anticholinergic effects - sedation, dry mouth, urinary ret
* profound rebound htn from abrupt cessation
66
DASH diet
* fruit, veg, grain
* lo/no fat dairy, fish, poultry, beans, nuts, and vegetable oils
* lo sat fat (meats, dairy, tropical oils)
* lo suc
67
4 questions answered by guidelines
1. Who do you treat?
2. When do you treat?
3. **With what do you treat?**
4. **To what goal do you treat?**
68
JNC 7 principle
* Compelling Indications = reason to choose a class of htn drug because it also treats/prevents.... HF, post-MI, CAD risk, DM, CKD, stroke recurrence ...with added benefit of treating BP
69
1st intervention, common to majority of sources..
lifestyle mods, then drugs but continue these mods
70
changes from JNC 6 to 7
* fewer categories of htn
* compelling indications added
71
JNC 7 in a nutshell
* normal, pre, s1, s2 and \<130/80 in dm/ckd
* ci?treat ci
* :s1 thiazide (or poss ACEi, ARB, BB, CCB, or combo)
* :s2 thiazide +1
72
JNC 6 strategy not carried forward...
* other guidelines also, treat those at highest risk for comorbidities most aggressively
* **Risk Stratification** - A, B, C (notes not specific about ABC criteria)
* A - lifestyle mods 12 months into s1, or at s2, start 1st rx
* B - lifestyle mods 6 months into s1, or at s2, start 1st rx
* C - lifestyle mods, but start 1st rx at high normal (130/85)
* HF, RF, DM
* notes \*\* mult rf's, consider rx initially as in C
73
ALLHAT design and results
* Anti-htn and Lipid-Lowering tx to prevent HA Trial
* largest htn trial to date
* chlorthalidone (thz), lisinopril, amlodipine (CCB), doxazosin (aB)
* div ppl into these 4 groups - who dies less?
1. thz more effective wrt bp reduction and htn complications/sfx than other 3
2. inc risk of hf and stroke with ACEi
74
ALLHAT critique
primary outcomes, poor combos, naivety, dm/thz, aust bp study
* no diff in primary outcomes, i.e. r/t primary hypothesis study was designed to test, only in secondary outcomes
* not invalidate but low confidence
* if original drug not effective, add rx in combo
* better rx combo for thz
* suboptimal rx combo for ACEi and CCB
...legit conclusion would compare one combo to another, not thz to acei/ccb generalization
* subjects not naive to htn rx and were high risk
* authors discounted sig increase in incidence of dm in thz group
* results contradicted by Australian National BP Study
75
JNC 7 concerns
* 4 ALLHAT authors on JNC 7 executive committee
* inc advocacy, authors believe in study, or...
* JNC 7 concerned with selection of 1st rx at dx htn - naive
* many in ALLHAT had been on long term rx, s2 htn - not naive
* JNC 7 applied ALLHAT results to disparate pop
76
BHS thresholds
* Risk stratification (like JNC 6) major determinant
* age, smoker, sbp, total chol:HDL ratio... 10 yr risk for CVD
* (may be in new US guidelines)
1. Really high bp straight to tx
2. Really low reassessed in a few yrs
3. In the middle 140-159/90-99 (rx by JNC 7/8)
* target organ damage, CV complication, dm, or 20% 10yr risk --- Rx
* none of these --- reassess, no Rx
77
BHS choice of agent for new dx htn
* choose drug based on pathology
* \<55y ACEi/ARB (A)
* younger white pts htn tends to be d/t elevated RAAS
* next step - add C or D
* \>55 y or black CCB or Thz Diuretic (C or D)
* ACEi monotherapy less likely effective - we've known for 20 yrs, but not reflected in guidelines
* next step - block RAAS
78
ESH/ESC 2013
* not so focussed on first drug and inc doses
* quick to move to combos
* additive bp effects, not sfx
* smaller doses of more rx, combo that makes sense, not so focused on first rx like U.S.
79
JNC 8 goal
* #1 controversy in htn
* JNC 7 \<140/90 goal for most, \<130/80 for dm/rf
* JNC 8 \<140/90 inc dm/rf
* except \>60y s dm/rf -- \<150/90
* no data to support lower goals
* In a large cardiology practice pts not considered to have htn by these goals
* 14.6% hx stroke/TIA
* 65% had CAD
* AHA recommends clinicians reject JNC 8, use JNC 7 guideline
80
JNC 8 first drug
* black - D, C or combo
* white - D, A, C or combo (JNC likes thz even though won't benefit as much)
* CKD - A
81
ACC target
* \<140/90
* lower for older, black, hf, dm, ckd
82
ACC rx recommendations
compelling indications
* CAD, MI - BB, ACEi
* Stroke/TIA - thz, ACEi
* CKD, HF, DM - ACEi first..
83
New guideline for CAD only
AHA/ACC/ASH
* \<130/80 CAD
* \<140/90 everyone else
84
SPRINT
* Sys BP Intervention Trial
* 9,000 pts \>50y
1. Intensive tx \<120
2. Standard tx \<140
* Excluded stroke, dm, hf, ckd
* Outcomes observed - MI, ACS, Stroke, HF, CV death
* Intensive tx group significant reduction in primary outcomes
* suggests 120 goal for older
* problems - ortho changes, falls, RF - balancing risk...
* what about success at reaching 140 goal? now 120?
