Hypertension Flashcards
Average Heart Rate
70 beats per minute
What/how controls the heart beat? Where is it located?
SA Node
- Depolarizes about every second or 70 times a minute
- Located in right atrium
“Sick Sinus” Define. What population is it common in? What is the tx?
Sick sinus” syndrome is a fairly common problem among elderly. (SA NODE not firing at same cycle; so, Granny needs a pacemaker)
You will frequently come across people with “pacemakers”. –> Electrical signal that’s sets the pace; rather than the SA Node
What is the job of the AV Node?
Gateway for electrical impulse into ventricles (delays ventricular contraction*)
Only way for an impulse to trigger ventricles in a healthy heart
Describe the process of AV Node conduction? What drugs are used to decrease contraction?
The AV NODE DELAYS ventricular contraction
LUB –> After LUB, impulse goes to AV NODE
–> Allows one impulse in at one time, delays LUB-DUB to allow the ventricle to fill with blood
BETA-Blockers and NHCCB (non-hydromonium Calcium Channel Blcokers) –> Slow the conduction slower
What is AV block? What drugs are C.I.?
AV Block –> Conduction delayed for too long
Do not use NHPCCB and Beta-blockers
prior to conduction, what is the voltage of cardiac myoctes? This is ____ compared to outside of the cell?
Heart muscle cells are ‘polarized’
80-90mV negative compared to outside the cell
The resting membrane potential in cardiac myocytes is maintained by…..
Ion pumps work to maintain this resting membrane potential (RMP)
Describe a polarized cardiac myocyte? What ion is responsible for the membrane potential?
Pump out all Na+ ions –> little Na+ inside the cell
Too little positive ions or too many negative ions in there –> Mix of both
The Na+ ion is on the cell membrane and dying to get inside. The cell has created a force (magnetic force)
Are polarized cardiac myocytes leak proof? If not, what phase in cardiac cycle is leakage occuring? Why does it occur?
No –> There is some leakage through maintenance channels
- Phase 4
K+ loss diminishes negative charge.
Eventually, an abrupt increase in Na permeability will occur when a certain ‘threshold potential’ is reached
In cardiac myocytes the gates are ______ dependent
Voltage Dependent
- they will open up at a certain level of polarization
In phase 0 of the cardiac cycle, what occurs? What voltage does calcium need?
Increase in permeability to sodium influx (i..e, into cell)
Calcium channels open at around – 60 mV –> Ca2+ causes contraction
In phase 1 of the cardiac cycle, what occurs?
Brief re-polarization from K escaping cell
In phase 2 of the cardiac cycle, what occurs?
Calcium continues to enter cell (started in phase 0)
Calcium enters through “L type” calcium channels
Calcium movement initiates muscle contraction
How can an arrhythmia develop?
If a neighboring is depolarizing, it will depolarize its neighboring cell
If a cell is stimulated before further recovered can lead to an arrythymia
Can cardiac muscles contract in phase 2?
A cardiac muscle cannot contract during phase 2
Further impulse from neighbouring cell will not cause it to contract (if cell is phase 2)
Want cells to be in refractory period when stimulated
What occurs in phase 3 of the cardiac cycle?
Membrane remains permeable.
Na and K ejected to ‘repolarize’ the cell
What occurs in phase 4 of the cardiac cycle?
Na+ is cleared from the cell and K+ loss slows
Eventually, an abrupt increase in Na permeability will occur when a certain ‘threshold potential’ is reached
List the phases of the cardiac cycle in order?
Phase 4, 0,1,2,3
Depolarization means…
Muscle Contraction
What ion causes muscle contraction?
Calcium
More calcium entering a cell is indicative of…..
stronger contraction (inotropy/contractility)
Faster calcium entry into a cell is indicative of…
faster contraction (chronotropy/heart rate)
A cardiac muscle cannot contract again until….
Muscle cannot contract again until repolarization occurs
What is an ECG?
Graph of electrical activity in heart
An ECG is detected by…..
by electrodes (i.e., “leads”) attached to the patient
Why are leads placed in different locations?
The location of the “leads” allows different angles of the heart to be examined.
How many leads are often used?
6 or 12 leads are often used
On a 12 lead ECG, where are the leads placed?
6 “limb leads”
6 “precordial leads”
ECG’s are the test of choice for _____ Why?
Most sensitive and effective test to determine if having heart attack or not
The P-Wave of an ECG detects?
Depolarization of atria
Normal duration = 0.12 seconds
The QRS complex measures….
Depolarization of ventricles
Normal duration < 0.12 seconds
In a normal ECG, what is the width of the QRS complex?
Narrow
A wide QRS indicates what?
Tell tale sign that ventricular impulse did not originate AV node
The QT interval indicates…..
Represents the time it takes from ventricular contraction until repolarization –> Full cycle
What is QT prolongation? Why does it occur? What is it a risk factor for?
If have drugs that can prolong the QT interval, takes longer for repolarization. If have one cell that was not ready for depolarization, will be ready when others are in repolarization
Some people with long Q-T –> Risk factor arrhythmia –> Risk when one cell affects the neighbours so when AV conduction comes down a lot of cells are in the refractory period
The T-Wave is responsible for….
REPOLARIZATION of ventricles
Why is basic knowledge of the ECG important for pharmacists?
Assessing patients with ischemic conditions (ST elevation, Non-ST elevation, ST depression)
Evaluating the risk for arrythmia with drugs (QT prolongation)
Evaluating patients with arrythmia (narrow QRS, wide QRS, tacychardia, bradycardia, normal sinus rhythm - NSR)
Evaluating contraindications of drugs (QT prolongation, heart block (p-r delays))
What are the four approaches to asses blood pressure?
- Automated Office Blood Pressure (unattended)
- Office Blood Pressure Monitoring (attended)
- Ambulatory Blood Pressure Monitoring
- Home Blood Pressure Monitoring
AOBP Blood Pressure is considered high when….
Displayed mean SBP ≥ 135 mmHg or DBP ≥ 85 mmHg is high
OBPM blood pressure is considered high-normal and high when…..
Mean SBP 130-139 mmHg or mean DBP 85-89 mmHg is high-normal
Mean SBP ≥ 140 mm Hg or DBP ≥ 90 mmHg is high
ABPM is considered high when…..
Mean awake SBP ≥ 135 mmHg or DBP ≥ 85 mmHg or mean 24-hour SBP ≥ 130 mmHg or DBP ≥ 80 mmHg are high
HBPM is considered high when…..
Mean SBP ≥ 135 mmHg or DBP ≥ 85mm Hg are high and associated with an increased overall mortality risk
Should pharmacy blood pressure machines be used? What should they be used for?
Pharmacy BP machines have not been evaluated for their association with clinical outcomes
It is highly unlikely they can be relied upon for determining risk or deciding about treatment
These machines should serve as screening tools only
Home Blood pressure Monitors Benefits
Considered highly accurate
AND
Highly correlated with usual resting BP levels
What is the correlation between OBP, ABPM, and Home BP?
The correlation between target organ damage, such as left ventricular hypertrophy (LVH), and albumin excretion ratio was weaker with office BP (OBP) and stronger with ambulatory BP measurement (ABPM).
Moreover, the correlation with self (home) BP was higher than with OBP, but less than with ABPM, for both systolic and diastolic BP.
For home blood pressure monitoring, the home values reference is….
< 135/85
What advice should pharmacist give to pt’s about physician visits?
Take it with you to the physicians office
What are guidelines for blood pressure monitoring as set out by the Candian Hypertension Guidelines?
- Sitting position
- Back Supported
- Arm bare and supported
- Use an appropriate sized cuff
- Middle of cuff at heart level
- Lower edge of cuff 3 cm above elbow crease
- Do not talk or move
- Legs uncrossed
- feet flat on floor
- Traditionally recommended to avoid exercise, caffeine, or a full bladder prior to taking BP (30min).
Home Blood Pressure monitoring conditons….
Resting, –> stimulation/stimulants/irritants
Duplicate measures
Timing for patient of Home Blood Pressure Monitoring
Before doses of medication (troughs)
Morning and night (estimate 24 hr control)
Duration of Home Blood Pressure
One week blocks during times of interest
Do not have to measure every day for extended periods if stable.
What body part is blood pressure monitoring is preferred? Exception?
- Arm BP are preferred
- Validated wrist devices may be used for BP estimation ONLY in patients with large arm circumference when standard arm methods cannot be used (Grade D recommendation from Canadian hypertension guidelines)
High Blood Pressure during activity is (useful/bad) because….
↑ blood flow = ↑oxygen and
glucose delivered to muscle.
Very useful –>Run faster, hit harder, yell louder, etc…
Regular activity (with rests!) will trigger cellular changes (e.g., ↑protein, ↑ mitochondria)
High blood pressure during rest is (useful/bad) because….
↑ afterload = ↑ energy to pump blood
Wastes energy
Fatigues tissues/cells –> adverse changes over long term
Damages specific tissues/cells
High blood pressure is defined as…..
Continuous high blood pressure readings at rest
Damage as a result of hypertension is usually as a result of….
↑ afterload
Arterial damage
Hypertension risk increase with:
a) Diabetes
b) Age
c) Arthritis
d) Cancer
AGE
Hypertension is a ____ -factorial problem and can result due to….
MULTI
Fluid and electrolyte balance
RAAS
Natriuretic hormone
Electrolyte imbalance (e.g. Na*)
Renal dysfunction / poor renal perfusion
Sympathetic nervous system / baroreceptor function
Increased SNS activity
Metabolic syndrome
Hyperinsulinemia/insulin resistance, abdominal obesity, low HDL, high BP, high Tg
Vascular endothelial function
Prostacyclin, Nitric Oxide production
Since Hypertension is multifactorial, drug tx often involves…
Multiple agents
Chronically ’d BP results from multiple factors, no single factor predominates
Thus, single antihypertensive drug regimens often have limited success in control (-10/-5 average)
Single Anti-hypertensives on average, lower blood pressure by….
10/-5 average
Hypertension is often commonly associated with…..
Metabolic Syndrome
Secondary hypertension definition
is high blood pressure that’s caused by another medical condition
Is Hypertension often due to significant damage of a single system?
Rarely, HTN is caused by significant dysfunction of a single system
In secondary hypertension, hypertension is commonly not recognized until?
Often not recognized initially until patients show resistance to conventional treatment
Treatment resistant hypertension definition
“Treatment resistance” in hypertension is usually defined as lack of BP control despite a combination of 3 antihypertensive medications, one of which being a diuretic.
Risk factors for hypertension are often… and therefore….. is important
SILENT, SCREENING
In which stage of life would the identification of HTN have the biggest impact to lifespan?
Earlier stages of life
Is hypertension a disease?
Hypertension is a risk factor for disease; but it is not a disease itself
Modifiable risks for developing hypertension….
Obesity
Poor dietary habits
High sodium intake
Sedentary lifestyle
High alcohol consumption
High-normal blood pressure
Diabetes or metabolic syndrome (“pre-diabetes”)
The main goal of tx for blood pressure
Preventing life-threatening cardiac consequences
3 goals of tx for hypertension (specific)
- Reduce/prevent myocardial cell dysfunction
- Reduce/stabilize artherosclerosis burden and endothelial cell dysfunction
- Reduce/prevent weakened vessel walls
Overall, managing risk factors is important because…
Managing risk factors such as hypertension is meant to improve the health of blood vessels and myocytes (i.e., heart cells).
Preventing damage to these cells is meant to Prevent life-threatening events and slow deterioration of major organs over the lifespan.
Are guidelines perfect?
NO
Recognized guidelines have…..
Clear description of the committee and the potential conflicts of interest
Evidence of a “systematic search” of the literature (for all relevant information)
Clear description of strength of evidence supporting every recommendation
Clear description of the strength/certainty about every recommendation
Canadian Guidelines for Optimal Blood Pressure
less than 120/80
Normal Blood Pressure Values
less than 130 (systolic) and/or 85(diastloic)
High-Normal Blood Pressure
130-139 –> Systolic
and/or
85-89 diastolic
Grade 1 (mild hypertension) guideline values
140-159 and/or 90-99
Grade 2 (moderate hypertension) guideline values
160-179 and/or 100-109
Grade 3 (severe) hypertension values
Greater than or equal to 180 and/or greater than or equal to 110
Isolated systolic hypertension is defined as….
Greater than or eqaul to 140 and/or less than 90
For diagnosis of hypertension….
Must be high at rest
Unrelenting/ consistent
Can hypertension be diagnosed in a pharmacy?
CANNOT be diagnosed in a pharmacy
Hypertension diagnosis requires…..
Requires the physician to find if blood pressure is consistent and/or unrelenting
Hypertension can be directly diagnosed from blood pressure readings when….
Mean office BP ≥ 180/110 mmHg or hypertensive emergency
No need for additional BP assessment to make the hypertension diagnosis
Diagnose with hypertension and initiate treatment
What is normotensive?
No hypertension at office/clinic/hlthcare setting and no hypertension at home/nonhlthcare/ABPM Setting
Sustained hypertension is…
Hypertension at office/clinic/hlthcare setting and hypertension at home/nonhlthcare/ABPM Setting
Masked hypertension is….
No hypertension at office/clinic/hlthcare setting and hypertension at home/nonhlthcare/ABPM Setting
White coat hypertension is…
Hypertension at office/clinic/hlthcare setting and no hypertension at home/nonhlthcare/ABPM Setting
Think of white coat hypertension when….
- Young age
- Lean/healthy body weight
- No other risk factors or target organ damage
- No family history
- Blood pressure is high in clinic examinations
- Someone you wouldn’t expect to have htn
One should think about masked HTN when….
Older age
Overweight / sedentary lifestyle
Has other conditions (e.g., diabetes, kidney dysfunction) or other target organ damage
Possibly positive family history
Blood pressure is NORMAL in clinic examinations.
Someone you WOULD expect to have HTN
Metabolic syndrome consists of….
“Metabolic syndrome” (at least 3 of)
Insulin resistance / incr’d blood sugar
Low HDL
Abdominal obesity
High triglycerides
High blood pressure
Before starting tx of hypertension, a ___ assesment should be done beacuse….
Blood pressure may be treated differently depending on the patients short-term risk of a life-threatening event
It is essential that a risk assessment be undertaken before treatment is determined
CV Non-modifiable risk factors of hypertension
Age ≥55 years
Male
Family history of premature
cardiovascular disease
(age <55 in men and
<65 in women doubles FRS)
CV Modifiable risk factors include…
Sedentary lifestyle
Poor dietary habits
Abdominal obesity
Dysglycemia (or diabetes)
Smoking (even 2nd hand)
Dyslipidemia
Stress
Hypertension
People at the highest risk for CV events will demonstrate….
Target organ damage
Target Organ Damage Includes
Cerebrovascular disease
Hypertensive retinopathy (would only know if you got an eye exam)
Left ventricular dysfunction (more about function)
Left ventricular hypertrophy (enlarged left ventricle; but, nothing about function – slow change over time )
Coronary artery disease
CKD
Peripheral Artery Disease
Target organ damage is a sign that damage….
Has already occured
When detrming someone’s risk factors for CV disseas ethey should be considered
Together
What is the framingham risk calculator?
A widely used tool to assess overall CV risk in Canada
A simple algorithm estimates an individual’s 10-year risk of experiencing a major CV event (MI, stroke, etc) or death.
What are limitations of the framingham risk score?
Just an estimate (not a crystal ball)
Poor performance in extremes of age (young, old)
10-year risk may not always correlate to lifetime risk
Study absolute risk, relative risk and number to treat
Look at notes
What is a relative risk reduction?
Relative risk reductions are commonly used to convey risk/benefits in health care
What is the absolute risk?
This magnitude of benefit represents approximately 100% of the available risk assuming age and sex cannot be modified
Are high blood pressure readings an emergency? What should we do?
No
Check technique and re-take BP
Ask patient if they are experiencing symptoms
If no signs/symptoms of danger, ask patient to make an appointment within a day or two. Might have to go to walk-in clinic
What are some symptoms of concern in regards to a high blood presusre reading?
1) Neurologic
2) Cardio-repsiratory
3) Any symptoms suggestive of major CV event
Neuroligic sx may include:
Severe headache, numbness, weakness, slurred speech,
Vision problems
Cardio-respiratory sx:
Chest pain, difficulty breathing
A hypertensive urgent situation is when….
Situations where BP should be reduced within hours
BP ≥180 / ≥130 AND
papilledema or other target organ changes
A hypertensive emergency is when….
Situations that require immediate BP reduction
E.g. hypertensive encephalopathy, intracranial bleed, unstable angina/MI, acute heart failure
At the physicians office, a clinical assessment will include
Physical Assesment
Labratory testing/Imaging
Jugular Venous pressure (JVP) indicates
Indirect assessment of right atrial pressure
Edema will indicate
May represent ‘volume’ or tissue-specific fluid
Pulse indiactes
Heart rate
Pressure/circulation (feet) –> pedal Pulses
heart sounds indicates
Normal: S1 = systole (lub); S2= diastole (dub)
Not normal: murmur, S3 or S4 (may indicate disease)
Point of Maximal Impulse indicates
Normal = 4-5 ICS, 5th intercostal of mid clavicular line
Assessment of LVH
Bruit indicates
an audible vascular sound associated with turbulent blood flow
- Carotid and renal
Is edema detrimental to cardiac function?
Not necessarily
What conditions can increase volume?
HF, Kidney Disease and hypertension (to a lesser degree)
JVP is a test used to asses….
assessed to gauge volume/preload
Is JVP a good estimate? When is it used?
JVP is a rough assessment but conducted routinely –esp in HF patients
JVP normal values….
Normal is < 2cm above sternal angle
pressure can be crudely examined by looking at it
peripheral Pulses can be used for….
arms and legs (if diminished – may mean reduced stroke volume or PAD)
The ankle-brachial indecx means….
– if less than 0.9 means PAD (peripheral arterial disease –> atherosclerosis in peripheral blood vessels)
What does pressure in ABI indicate?
Weak pedal (feet) pulses –>Unhealthy finding
Strong pedal findings –> Blood pressure in top is same as bottom part of body –> Probably healthy arteries that are npt obstructed
If blocked artery, weak pedal pulse
Ideally –> Ankle and arm should be the same
ABI is calculated by….
ankle pressure divided by arm pressure
What are the 2 heart sounds?
S1 (Lub)
S2 (Dub)
S1 indicates….
First heart sound – start of ventricular contraction
S1 is due to….
Due to closure of the mitral and tricuspid valves
S2 indicates…. and is due to….
2nd heart sound – closure of aortic and pulmonic valves during to ventricular relaxation
What are the abnormal heart sounds? What do they indicate?
S3 and S4 are not normal heart sounds and may indicate presence of problem. (abnormal heart sounds)
Heart murmurs result from….
Result from ‘turbulent flow’ within the heart
A mild sytolic murmur may indicate….
pulmonic stenosis, aortic stenosis, hypertrophic obstructive cardiomyopathy (see other examples)
When a murmur is detected, diagnosis of the problem can be done with…..
echo, angio or other testing procedures
What is a bruit? How can it be detected?
Bruits also represent turbulent flow
Stethoscope can pick up bruits in some arteries such as carotid or renal artery
In a healthy veseel, flow should be….
Flow through a healthy (unobstructed) vessel should be silent
What are the baseline laboratory tests done for people with hypertension?
Urinanlysis
Electrolytes
Cretinine
Glucose
Cholesterol
Urinary Albumin Excretion
Urinanalysis includes….
Several tests performed on a sample of urine
Protein, glucose, RBC, WBC, bacteria, etc
What electrolytes are we monitoring in hypertension?
K and Na
Creatinine is used to determine
Renal function
Glucose is used to…
screen for diabetes
Cholesterol is used to screen for….
dyslipidemia
urine Albumin Excretion is used to….
Urine protein is a possible sign of kidney dysfx
When analyzing a pt’s hypertension, a pharmacist should look for what cause of the HTN? Examples?
- Drug induced BP elevations
NSAIDS
Corticosteroids (glucocorticosteroids and anabolic steroids)
Oral contraceptives and sex hormones
Decongestants (stimulants)
Certain antidepressants (MAOI’s, SNRI’s, SSRIs)
Stimulants (e.g., methylphenidate, dextroamphetamine)
Excessive alcohol
How do NSAIDS raise BP?
Inhibition of renal Pg production
Lowers renal perfusion
How do steroids raise bp?
Mineralocorticoid effect (i.e., acts like aldosterone)
How do hormonal contraceptive raise bp?
Triggers angiotensinogen production from liver
How do decongestant, certain anti-depressants and stimulants raise bp?
SNS activity (vasoconstriction +/- ↑CO)
How does alcohol raise bp?
In excess only. Impairs ADH + other mechanisms likely important
According to the Canadian Hypertension Guidelines, a high risk patient is…..
Individuals over 50 and with sbp 130-180 mmHg and with one of the following:
a) Clinical or sub-clinical CV disease
b) CKD (Proteinuria <1g/d, or EGFR 20-50)
c) Estimated 10-year global risk >15%
d) Age> 75 years
High Risk Patient Blood Pressure for Intitiation of Tx
> 130 mmHg
Diabetes Mellitus High Risk BP to initiate tx
> 130/80 mmHG
Moderate-to-high risk BP to initiate tx
> 140/90
Low-risk to initiate tx
> 160/100 mmHg
High risk target BP
<120
Diabetes BP Target
<130/80
Moderate-High BP target
<140/90 mmHg
Low risk BP target
<140/90 mmHg
First Line tx of Hypertension (adults)
1) Thiazide and thiazide-like diuretic
2) ACE-i
3) ARB
4) Long-acting CCB
5) B-blockers
6) Single Pill combo
Which diuretics are preferred? Why?
Long acting diuretics like indapamide and chlorthalidone are preferred over shorter acting diuretics like hydrochlorothiazide
Are ebta-blcokers first line? Age?
B-blcokers are not indicated as first line for age 60 and above
Should shor acting nifedipine be used?
NO
The recommended single pill options are:
a) ACE-i combined with CCB
b) ARB with CCB
c) ACE-I or ARB combined with a diuretic
What are some non-pharm tx?
- Being more physically active
- Weight reduction
- Moderation in alcohol intake
- Eating Behaviour
- relaxation Techniques
- Smoking cessation
Hydrochlorothiazide 25 mg OD time to effect….
- Maximal effect greater than 1 month
When should combo tx be started?
BP drugs are WIMPY (sometimes do not get 10/5 drop)
Combinations often required in 2/3 patients
Adding therapy usually preferred over switching
Lifestyle modification might be a big help
What mechanism should be used for combo?
AB-CD rule
AB –> (Renin-active) –> Beta-adrenergic blocker, ACE, ARB
CD –> THiazide diuretic, long-acting calcium channel blocker
Should an ACE and ARB be used together?
NO –> May be dangerous
Caution should be taken when combining a…. Why?
DHP-CCb and a beta-blocker
Both can decrease heart rate
What is the most notable evidence based combo?
DHP-CCB and ACE Inhibitor
What is the major difference between Ace’s and ARB’s?
Biggest difference is frequency of cough with ACEI (higher than ARB)
When should
ARBS suffix
Sartan’s
ACE-inhibitor suffix
Pril’s
When should ACE’s and ARB’s be avoided?
Pregnancy
Bilaterial renal artery stenosis (predispose people (narrow renal arteries on both sides) can be harmed by ACE’s and ARB’s)
Hyperkalemia (All RAAS drugs increase K+)
What is the ladder for adding on therapy?
If partial response to monotx –> Add on tx –> Triple or Quadruple TX
If blood pressure is not controlled, consider non-drug issues such as….
Non-adherence
Secondary HTN
Interfering drugs/lifestyle
White coat effect
Triple tx should always include….
a diuretic
Treatment resistance is defined as a poor blood pressure response despite:
3 antihypertensive drugs used in combination
One of the drugs is a diuretic
Non-adherence is ruled out
Tx-Resitant HTN TX. What is causing tx resistance? Which one achieves the greatest effect? WHy?
Spironolactone (or MRA) –>Most success achieved here –> Very weak bp reducing effects in uncomplicated hypertension. Reasoning: Tx resistance is due to aldosterone excess
Clonidine / methyldopa (alpha-2 agonists)
Hydralazine/minoxidil + beta-blocker
What are some causes of tx resistance?
Hyperaldosterism
Pheochromocytoma (unregulated SNS activity)
CKD
Renovascular Disease
Obstructive Sleep Apnea
Hyper/Hypo-thyroidism
Hyperaldosterism tx
MRA’s or K+ sparing diuretics
Pheochromocytoma Tx
Alpha-blockers +/- Beta-blockers (surgery is required)
CKD TX
manage as recommended
In renovascular disease, which drugs should be avoided?
Caution with ACE and ARB’s
In obstructive sleep apnea and hyper/hypo-thyroidism, tx involves….
Correcting underlying problem
ISH is common in what population….
Elderly
ISH is due to…
Stiff arteries do not accommodate systolic pressure
Creates a high “pulse-pressure” (SBP – DBP)
The target of ISH
<140 mmHg systolic BP
What meds are used in ISH?
- Thiazide Diuretic
- ARB
- LOng acting CCB
Then Dual Tx
Then triple or Quadruple Tx
In ISH, caution should be taken when DBP drops below….
Caution if DBP drops < 60mmHg (esp in patients with coronary atherosclerosis)
What is the added benefit of thiazide diuretics?
Decreased edema and fluid overload
When do thiazides become ineffective? What should be done?
Reduced effectiveness if CrCl <30m/min (switch to loop)
What electrolytes should be cautioned in TZD diuretics?
↓ K and ↓Na the most common electrolyte disturbance
↓ Mg and ↓ Cl also possible
May ↑ calcium (differs from loop diuretics which ↓ Ca)
Thiazides and Blood Sugar
May ↑ blood sugar slightly (but does NOT cause risk)
Thiazide and Uric Acid
May ↑ uric acid (caution in people with hx of gout)
TZD and urination
May ↑ urinary frequency (likely minimal with TZD)
D.I. of thiazide diuretics
caution with other BP reducing drugs
Electrolyte interactions (K, Na)
Convienience of TZD. When should they be dosed?
Once daily dosing – dose in AM to reduce nighttime urination
C.I. of TZD
Consider other options in people with low K or low Na
“Sulfa” allergy – Antibiotic sulfa allergies usually do not cross react. Avoid if reaction was severe (steven’s johnsons, etc)
Caution if hypercalcemia is present
Cost of TZD
- One of the cheapest avilable
Do diuretics differ in lowering blood pressure?
YES
- Some better handle blood pressure and some eliminate more fluid
What are the classses of diuretcis and their role in tx?
Thiazides –> best for BP reduction –> Less impact on RAAS, 24 hours of action
Loop –> best for fluid excretion
K sparing –> K+ supplement –> late late distal tubule –> Not good at lowering bp
What is a common consequence of diuretic tx?
Hypokalemia
What are the TZD drugs? GFR effects?
Ineffective if GFR<30:
Chlorothialidone
Hydrochlorthiazide
More effective in reduce renal function:
Indapmaide
Metolazone
What are some other causes of hypokalmeia?
Inadequate K intake (elderly)
High dietary Na+ intake –> High RAAS itself causing K+ loss
Hypomagnesemia
Prolonged diarrhea (laxatives)/vomiting
Hyperaldosteronism (i.e., secondary HTN)
Heart failure (HF)
Catecholamines
Insulin
Low K+ Thresolds for TX (IMPORTANT)
<3.0 mmol/L –> Always undesirable
3.0-3.5 –> Usually treated
3.5-4.0 –> Action may be taken
Persistent Hypokalemia has been associated with….
has been associated with a higher risk for death in many patient groups (esp HF and CKD).
What can be done if K+ is low due to a diuretic?
General measures
- Reduce sodium intake
- Increase K intake (dietary)
Lower diuretic dose
Discontinue diuretic if K seriously low
Add K sparing drugs
- BB, ACEI/ARB, K-diuretics –> All interrupt RAAS
Add K supplement
Is Hyperkalmeia serious?
YES
↑ K is also a potential cause of serious harm
Caution must be taken in replacing K AND using drugs that increase K levels.
How much of daily intake of K+ do the kidneys excrete?
Normal functioning kidneys excrete 90% of daily K intake
Hyperkalemia effects on ECG
- Widening of P-R interaval (conduction delay)
- Loss of p-wave
- Conduction delay through ventricles (widening of QRS)
What is the most feared complication of hyperkalmeia?
Ventricular arrhythymia
What drugs increase K+?
RAAS drugs,
NSAIDs,
vitamins/supplements,
K sparing diuretics,
Trimethoprim and sulfamethoxazole
What are some pt factors that may cause hyperkalmeia?
CrCl <60ml/min
Baseline K >4.5mmol/L
What defecit often accompanies hypo-K?
Magnesium
In Hypokalmeia, is dietary repletion sucessful?
Often not successful to correct hypoK (ok for prevent’n
In Hypokalemia tx and prevention, what doses of K+ should be used?
20mmol/day for prevention; 40-100mmol/d for tx
In Hypokalmeia tx, it is important to monitor…..
K levels!!! (muscle fatigue/cramping, GI effects)
Timing depends on baseline levels
Indications implicating complicated HTN include….
Diabetes with nephropathy
Diabetes w/t nephropathy
Non-diabetic Kidney disease
Coronary Heart Disease
Heart Failure
Left ventricular hypertrophy (LVH)
Stroke or transient ischemic attack (TIS)
Diabetes Threshold and Target BP
Threshold equal or over 130/80 mmHg and target below 130/80
Diabetes with (blank conditions) should be treated with….
Microalbuminuria, renal Disease, CVD, or additional CVD risk factors
- ACE or ARB
- Addition of DHP-CCB preferred over diuretic as add on
Diabetes w/t comorbities tx…
ACE, ARB, DhP-CCB, or TZD
If using a combo, DHP CCb is preferred over a TZD
In CKD, what drugs are first line?
ARB and ACE
How can hypertension cause kidney disease?
Long-standing hypertension + diabetes increases risk for chronic kidney disease (↑ pressure can damage glomerulus)
Filtering function is damaged (E.g., protein escapes!)
Kidney damage progresses (slow/fast) as a result of HTN and can cause….
↓rate of glomerular filtration
↑ serum creatinine (easily excreted in healthy state)
Difficulties excreting fluid and toxins
Leakage of protein, large molecules
nephropathy refers to….
Protein (albumin) escapes from glomerulus
RAAS Summary
Angiotensinogen converted to angiotensin I by Renin. ACE converts Angiotensin I to ANgiotensin II
Renin secretion occurs due to…
Reduced renal artery blood flow/pressure
Increased sympathetic stimulation
Angiotensin II is responsible for…
- Increased contraction
Vasoconstriction (especially efferent artery) - Aldosterone secretion
How do ACE and ARB’s protect the kidney?
- Decrease efferent constriction, decrease pressure at glomeruls
What are the 3 types of HTN seen in preganancy?
- Pre-eclampsia
- gestanional HTN
- Chronic HTN
Pre-eclampsia is….
High BP with proteinuria
pre-eclampsia onset
Onset after 20 weeks of pregnancy
pre-eclampsia and mother and baby health? Can progress to?
ASsociated with poor outcomes for baby and mother
Can progress to seizures (eclampsia)
gestational HTN is….
High BP without proteinuria after 20 weeks
Chronic HTN is…
HTN was present before pregnancy began
First-line Tx in pregancy
Labetalol
Methyldopa and long acting oral nifedine
Other B-blockers (lol’s)
2nd Line Tx in pregancy
Clonidine, Hydrazlaine, and thiazide diuretics
Should ACE and ARB’s be used in pregancy?
NO
Lactation First Line and 2nd Line TX
Labetalol, methyldopa, long-acting nifedipime, enalapril or catopril
2nd line –> combo
Monitor baby for adverse effects
Other preveantative tx of pre-eclampsia include…
Calcium 1-2g/day ↓ risk of pre-eclampsia
Low-dose ASA starting late in the first trimester may ↓ risk of pre-eclampsia in women at risk (BMI, diabetes, chronic conditions pre conception)
centrally ACting Agents include…
Alpha-2 Adrenergic Agonists
Clonidine & Methyldopa
Centrally Acting Agents MOA and results
Stimulate alpha-2 rec’s in the brain
Lowers sympathetic outflow
Increases vagal tone (cholinergic effects)
Results in
Lower HR / Cardiac output (CO)
Lower BP
Where is that alpha-2 receptor located?
pre-synaptic terminal
When stimulated, a-2 receptors…. a-2 agonists…..
When stimulated, shuts down further release of messengers into the SNS nerve fibre
Decrease sympathetic discharge from CNS
↓ circulating NE, and ↓ SNS nerve transmission
Lowers blood pressure and heart rate
S/e of alpha-2 agonists…
Sedation – cause should be obvious
Dry mouth anti-cholinergic drugs
Monitoring S/e of all BP medications
BP (if feeling s/e, take it in 4 wks)
Outcomes (kidney, heart, arteries)
Dizziness / headache / hypotension
Orthostatic Hypotension (OH)
Reduction >20 / > 10 upon standing
Erectile dysfunction
Arterial dysfunction very common cause
ACE’s and ARB’s should be monitored for…
K+ levels
ACE’s should be monitored for….
Cough
Diuretics should be monitored for…
gout, electrolytes, SCr, urination
DHP CCB’s should be monitored for….
edema
BB and Non-DHp CCB should be monitored for….
heart Rate
Alpha-2 agonists should be monitored for….
Fatigue
Vasodilators should be monitored for….
Tachycardia
Beta-1 Selective Blocker Examples
Most commonly used agents in this sub-type:
Atenolol (Tenormin)
Bisoprolol (Monocor)
Metoprol (Lopressor)
Others:
Acebutolol (also has ISA – discussed later)
Esmolol
Non-selective Beta-Blockers
Nadolol
Pindolol
Propranolol
Timolol
No Nasty Penn Please Tony
What is different about carvediol? Indication?
- Non slective BB that also blocks alpha-1
- Indicated for heart failure with LVSD
Beta-Blockers effectivenss in uncomplicated HTN
Minimal role in UNCOMPLICATED patients even if <60
When would a beta-blocker be considered?
Might consider if individual presents with high heart rate (after excluding conditions associated with tachycardias)
BB are extremely protective in certain ‘complicated’ cases (i.e., people with HF, afib, ACVD, etc)
Vasodilator Classes
Alpha blockers (sympathetic NS)
DHP Calcium Channel Blockers
Smooth muscle relaxants –> Need diuretic and beta-blocker to revent reflex tachcardyia
B-2 receptors When stimulated lead to….
Vasodilation
Alpha-1 receptors when stimulated lead to….
Vasoconstriction
Alpha-1 Antagnosits MOA
Stimulation causes smooth muscle around vessel to contract
Actions blocked by alpha-1 antagonists –> prevent constriction
May play an important role in circulation
Calcium Channels role in muscle cells
Smooth muscle contraction can be stopped by blocking Ca entry into myocytes
Alpha-1 blocker Examples
Doxazosin, prazosin, terazosin
“osins”
Are Alpha-1 blockers first line?
Not recommended for first line b/c shown less effective than others (ALLHAT)
Can be used for add-on therapy
What condition are alpha-1 blockers useful for?
Used frequently for Benign prostatic hyperplasia (BPH)
Which vasodilators are indicated as first-line?
- DHP-CCB
When are other vasodialtors used?
Other agents are avoided EXCEPT as add-on therapy for people with treatment resistance – ALWAYS in combination with beta-blockers to prevent reflex tachycardia
Can an ACE be used in someone who has normal BP?
You will see ACEI recommended in most patients at “high-risk” for CV events
EVEN if their BP is normal.
Which is more effective:
ACE + TZD
ACE+ DHP CCB (when is this used)
ACE + TZD according to ACCOMPLISH
High Risk Pt’s
What lab value should be used for determining if nephropathy is occuring?
Urinalysis is not very sensitive for protein in the urine
i.e., will only detect protein if the amount is large
Albumin-creatinine ratio is more sensitive and should be reviewed before deciding if nephropathy is present.
ACE/ARB in CKD Benficial?
Benefit to kidneys increases in people with more severe disease
In lower risk people (i.e., lower SCr/higher GFR) other drugs appear to provide similar protection
Some BP-independent benefits on kidneys are likely in higher risk situations
is renal harm possible from ARBS and ACE’s?
YES
- Decrease Angiotensin II
- Decrease GFR
↓ GFR means lower ability to excrete fluid (i.e., edema, incr’d BP, etc)
if not resolved,
Acute renal failure can result (rarely)
Nephron ‘collapse’ due to lack of pressure
Urine production halted
Toxins and fluid accumulate over short term (acutely)
When starting an ARB, which tests should be orderd and how often?
Obtain SCr and K within 1 – 2 weeks of starting drug (or increasing dose)
SCr is EXPECTED to increase from baseline but must be less than 20-25%
BP and edema should get better – not worse after ACEI or ARBs
After starting and ACE or ARB, Scr should increase but should be less than….
20-25%
