Drug Therapy + Management of Common Comorbidities Flashcards
Non-pharmacologic treatments to help reduce BP include:
Think simple
Physical activity, weight reduction, improved diet/alcohol use, relaxation therapy, smoking cessation
Common classes of drugs that reduce BP are:
Thiazide diuretics, ACEI/ARB, CCB’s, B-Blockers
Majority of antihypertensive drugs usually lower BP by this much…
-10/-5
The time to maximal effect for most antihypertensives is…
Around a month
Therefore do not change doses quickly!
50% of an antihypertensive maximal dose achieves this % of its effect…
80% of effect achieved with 50% of max dose
What is preferred: Adding therapy, or switching drugs?
Additional therapy (BP drugs are weak) - target different HTN pathway
Lifestlye modification can help ALOT
What is the AB-CD rule?
Combining antihypertensives drugs based on mechanism; renin-based (ACEI/ARB, BB) with non-renin (TZD, DHP-CCB)
A non-DHP CCB and a BB should be cautioned because:
Their pharmacology is similar and increases risk of adverse effects
These two drugs should be avoided in combination:
ACEI and ARB
VERY similar mechanism
A notable evidence-based combination is:
A - C
ACEI + DHP-CCB
ACEI’s or ARB’s will be chosen to be added over a BB unless…
Patient has a specific condition that requires a BB
HF, Cirrhosis, AFib
The biggest difference between ACEI’s and ARB’s are…
Frequency of cough with ACEI
ACEI’s + ARB’s should be avoided in these three scenarios…
Pregnancy, Bilateral renal artery stenosis, Hyperkalemia
If therapy is added on and still not uncontrolled, these factors need to be considered:
Nonadherence
Secondary HTN
Interfering drugs or lifestyle
White coat effect
Triple/Quadruple therapy should contain…
A diuretic
Volume control
Single pill combinations should be used as often as possible, to…
Increase compliance
The best addition for treatment resistance with the most success is…
Spironolactone (or MRA)
Other additions besides an MRA for treatment resistance include:
Alpha-2 agonists (clonidine/methyldopa) or Non-DHP CCB + Beta-blocker
The three drugs that have shown benefit in isolated systolic hypertension are:
Thiazide diuretic, ARB, Long-acting DHP-CCB
Caution should be taken if DBP drops to… in ISH treatment
Below 60 mmHg
Analyze and modify drug therapy accordingly
Efficacy of thiazide diuretics state for HTN state:
Excellent effectiveness with added benefit of decreasing edema/fluid overload
Thiazide diuretics may have reduced effectiveness when…
CrCl drops below 30 mL/min
Switch to loop diuretics
The MOA of a thiazide diuretic is as follows:
Blocks sodium reabsorption in the distal tubule of the nephron, thereby blocking water reabsorption as well
The most common electrolytes that may be affected by a thiazide diuretic are:
Decreases in potassium and sodium
Other electrolytes (rather than sodium and potassium) may be affected by thiazide diuretics:
Decreases in magnesium and chloride, increases in calcium
Other adverse effects of thiazide diuretics are:
Slight increase in BG
May increase uric acid
Increase urinary frequency
Drug interactions with thiazide diuretics include:
Other BP drugs (enhance effect)
Electrolyte interactions with K+ and Na+
Diuretics will impact urine production by:
Increasing urine production - excretion of more fluid
The major driver of fluid retention is…
Reabsorption of sodium
Wherever sodium goes, water follows
And 99% of filtered fluid is reabsorbed
Mechanism of commonly used diuretics will impact sodium reabsorption by…
Inhibiting sodium reabsorption
More sodium in urine = more fluid excreted
High BP often involves high blood volumes so can help lower BP
The MOA of loop diuretics is:
Inhibiting sodium reabsorption in the ascending loop of henle
Loop diuretics can have adverse effects such as:
Electrolytes and… (gout)
Loss of calcium and magnesium
Increased potassium loss
Uric acid retention
Most common loop diuretic used is…
Furosemide
Loop diuretics are NOT good for BP control because…
2 reasons
Short half-life
Stimulator of RAAS
Loop diuretics could be used for BP control in a specific group of patients…
Poor kidney function
Prolongation of half-life
Compared to loop diuretics, thiazide diuretics are usually better for BP control because…
Longer half-life + more gentle action
Weaker due to location of action
Loop diuretics are best for fluid excretion
Thresholds for hypokalemia treatment are usually:
Consider treating 3.5-4.0, usually treat 3.0-3.5, always treat <3.0
Ways to help treat hypokalemia include:
3: natural, diuretic itself, other drugs
Dietary measures
Lowering diuretic dose or d/c if very low
Add K+ sparing drugs or supplement
Hyperkalemia is dangerous because…
Affect conduction - delays, Ventricular arrythmia
Drugs that increase potassium include:
RAAS drugs, NSAID’s, vitamins
K+ sparing diuretics, TMP/SMX
Also consider baseline potassium AND kidney function
RAAS is a system that…
Increases blood pressure
The major hormone products of RAAS include the two fololowing hormones:
Alodsterone + Angiotensin 2
Angiotensin 2 is derived from…
Angiotensinogen
In 2 steps
Angiotensinogen is converted to Angiotensin 1 via…
Renin activation
Angiotensin 1 is converted to angiotensin 2 via…
Angiotensin converting enzyme (ACE)
The three major actions of angiotensin 2 include:
Rapid pressor response
Slow pressor response
Cardiac hypertrophy/remodelling
Rapid = vasoconstriction. Slow = Kidney
RAAS is related to kidneys, as low blood pressure in the afferent blood vessel means that…
Low blood volume (fluid depletion) is suspected - low blood pressure in the kidney (afferent arteriole)
Consequences of low pressure to the kidney includes:
Decreased filtration, excretion of substances, collapse of tubules
Low pressure in the glomerulus will trigger…
Release of renin into the blood
Renin release is triggered by 3 pathways:
Low renal pressure
Low sodium in the loop
SNS activation
After conversion to angiotensin 2, the hormone will cause ____ in the kidney.
Preferential vasoconstriction of the EFFERENT arteriole
Exit blood vessel
Will also cause vasoconstriction in several tissues (receptors all over the body)
Vasoconstriction of the efferent arteriole will cause…
Increased pressure on the glomerulus - increase in BP without increasing blood volume, more fluid will be filtered (GFR increased)
Angiotensin 2 will also cause the release of _____.
Another hormone
Aldosterone
Slow pressor response, stimulation of angiotensin-type 1 receptor
Aldosterone will cause reabsorption of ____ and excretion of ____
Reabsorption of sodium and excretion of potassium
…water follows sodium
Increased activity and synthesis of sodium channels
Aldosterone is considered a ____ hormone.
Mineralocorticoid
Secreted from the adrenal gland
The three drugs that directly inhibit RAAS activity are…
ACE inhibitor (ACEI)
Angiotensin receptor blocker (ARB)
Direct renin inhibitors (DRI)
MOA of an ACE inhibitor is to…
Inhibit Angiotensin converting enzyme, preventing conversion to ANG2
Also inhibits kininase 2
Occurs on endothelial cells throughout circulation
ACE inhibitors can be identified by the suffix…
-pril
ACEI/ARB helps with HTN by:
Vasodilation + lowered aldosterone secretion
ACEI/ARB helps with CKD by…
Decreasing glomerular pressure by decreasing vasoconstriction on efferent arteriole
CAUTION! May decrease renal perfusion to dangerous levels
ACEI/ARB can help with heart failure and ischemic heart disease by…
Decreasing adverse effects of ANG2 and aldosterone on heart tissue + blood vessels
Dry cough may occur in ACEI usage due to…
Bradykinin accumulation
Inhibition of kininase 2
This electrolyte may be increased with ACEI/ARB usage due to…
Potassium (hyperkalemia), due to aldosterone inhibition
ALL Drugs that inhibit RAAS will increase potassium
Remember that aldosterone reabsorbs sodium and excretes potassium.
Reduced BP with ACEI/ARB may be a nuisance because…
Drug can be used for other conditions than just HTN
ARB MOA is…
Inhibiting the AT-1 receptor, blocking actions of ANG2
VERY similar effect as ACEI
ARB adverse effects are similar to ACEI, except for…
Lower incidence of cough
Likely due to bradykinin able to be degraded
ARB suffix is…
-sartan
DRI MOA is…
Binding active site of renin, blocking conversion of angiotensinogen to ANG1
Not widely used, minimal use
Common mineralocorticoid-receptor antagonists (MRA) are these two:
Spironolactone
Eplerenone
MOA of MRA is…
Inhibiting aldosterone receptor
Usage of MRA is usually reserved for
In relation to CV
Resistant HTN due to aldosterone excess
Heart failure
Primary adverse effects of MRA include:
Increased potassium
Hormonal effects (stimulation of progesterone + androgen receptors)
Gynecomastia, impotence, menstrual irregularities
If a patient presents with HTN and Diabetes together, it is important to identify…
Proteins in urine are???
Nephropathy
Urinalysis: urinary albumin to creatinine ratio, or CKD present
Diabetes with nephropathy or renal disease indicates the following drugs…
ACEI or ARB
Add-on therapy of HTN with diabetes + nephropathy recommends this drug rather than…
DHP-CCB
Add-on TZD
HTN treatment with diabetes WITHOUT nephropathy recommends these drugs…
1st line drugs - ACEI, ARB, DHP-CCB, or TZD
Combination if appropriate (ACEI + CCB preferred)
First-line therapy for HTN and CKD includes:
ACEI/ARB for proteinuria
Diuretics as add-on
Beneficial effects proven of lowering glomerular pressure proven
Long-standing HTN and diabetes can increase risk for CKD because…
Increased pressure can damage glomerulus (and glucose harms vessels)
Proteinuria, as protein escapes
Renal harm is possible from ACEI/ARB usage, because…
Decreased pressure may lower filtration and GFR too much - nephron collapse, urine production halted, toxin accumulation
Acute renal failure - reversible if caught early
NO direct damage to tubules, just lowered pressure
The following should be monitored when starting an ACEI/ARB, and in 1-2 weeks after starting:
Kidney !
SCr, BUN, fluid balance, and electrolytes (sodium and potassium)
Pre-eclampsia is related to HTN because…
In pregnancy - high BP with proteinuria, after 20 weeks
Associated with poor outcomes + can progress to seizures (eclampsia)
Gestational HTN is…
In pregnancy - high BP without proteinuria after 20 weeks
Chronic HTN is…
Pregnancy !
HTN was present before pregnancy began
The following drugs should be avoided for HTN during pregnancy:
ACEI’s + ARB’s
First line options for HTN during pregnancy include…
3!
Labetalol, methyldopa, long-acting oral nifedipine
Other beta-blockers could also be used
Same options for lactation, plus enalapril or captopril
2nd line options for HTN during pregnancy include…
Clonidine, hydralazine, and thiazide diuretics
Two things that could help lower risk of pre-eclampsia are…
Calcium 1-2g/day
Low-dose ASA starting late in 1st trimester
The SNS impacts tissues via:
Alpha and beta receptors
Activation of beta-receptors in HEART MUSCLE will result in…
Increased cardiac contractility and rate of contractions
BETA1 RECEPTORS
Increased cyclic AMP, increased intracellular calcium
Activation of beta-receptors in ARTERIAL WALLS will result in…
Relaxation - vasodilation
BETA2 RECEPTORS
Increased cyclic AMP, decreased intracellular calcium
Beta-1 receptor stimulation causes…
Incresaed heart rate + contractility
Renin release from pancreas
Beta-2 receptor stimulation causes
Vasodilation
Alpha-1 receptor stimulation causes
Vasoconstriction
Beta-receptor antagonists work by…
Beta-blockers
Blocking the effects of beta-receptors
Beta-blockers can be differentiated by…
Selectivity for Beta1 and Beta2
Blockade of alpha receptors
Intrinsic sympathomimetic activity
Beta-1 selective blockers would impact the body by…
Inhibiting beta-1 receptor activity; lower heart rate and contractility, and renin release
Most common uses for beta-1 selective blockers include:
HTN, High Heartrate
Cardiac workload/demand (angina)
Cardiac damage (HF, heart attack)
Shield from negative effects of norepinephrine
Beta-1 selective blockers may be helpful for HTN due to:
Decrease in cardiac output, and renin production
Exact mechanism is unclear
Beta-1 selective blockers may be helpful for an increased cardiac workload and damage
Block negative effects of norepinephrine - prevent further damage, and decrease demand for blood to heart muscle
Non-selective beta-blockers include…
Nadolol, pindolol, propranolol, timolol
Addition of beta-2 receptor blockade include:
Smooth muscle - Constriction of blood vessels
Lung - Inhibition of beta2 receptors in airways
Possible interaction between non-selective beta-blockers and beta2 agon
Non-selective beta blockers are not used much for CV conditions anymore because…
Not much benefit over selective, and tolerability issues
Beta1 selectivity is not absolute, especially when…
Using increased doses of beta-1 selective beta-blocker
Non-selective beta + alpha blockers include these two…
Carvedilol + Labetalol
Compared to selective beta-blockers, non-selective beta + alpha blockers are expected to…
…related to BP
Cause a greater fall in BP expected to other beta-blockers
Primary dx: heart failure
Notable adverse effects from beta-blocker usage includes…
Decreased BP
Decreased cardiac output
Bradycardia
FATIGUE
AV block can occur from beta-blocker usage because…
AKA heart block
Beta-blocker can slow AV conduction further (too much)
Beta-blockers could increase potassium levels because…
Related to kidney
There are beta-receptors in the glomerulus - blockage of RAAS (aldosterone) means less potassium excretion
Circulation problems may arise with beta-blocker usage because…
Beta-2 receptors are responsible for vasodilation in smooth muscle
Beta-blockers have a theoretical impact with respiratory medications because…
Beta-2 receptors are also present in lungs
Beta-2 agonists used in asthma
A patient taking a non selective beta-blocker and a beta2 agonist should…
Watch for signs of decreased response
Typically not problematic
A primary issue that needs to be addressed when using beta-blockers in people with diabetes…
Reduced recognition of hypoglycemia - SNS trigger
Slight increase in BG is secondary and minor.
Alpha-1 receptor antagonists MOA is to…
Inhibit vasoconstriction induced by the SNS
But is usually involved with baroreceptor activation
Baroreceptor activation = increased heart rate, CO, and RAAS
Alpha-1 receptor antagonists are not used often for BP control anymore because…
Little protection from CV disease
Just because a drug lowers BP does not mean it is CV protective
CAN be used for add-on therapy.
Instead of being used for BP, alpha-1 receptor antagonists are often used for…
Benign prostatic hyperplasia
Urinary issues
Alpha-2 agonists MOA works by…
Stimulating alpha-2 receptors - decrease SNS nerve transmission and circulating norepinephrine
Alpha-2 agonist usage results in:
Lowered BP, HR, and cardiac output
Alpha-2 agonists are most commonly used for…
Pregnancy + treatment resistance
Frequent adverse effects from alpha-2 agonists include…
Sedation
Anticholinergic effects (dry mouth)
Alpha-2 agonists commonly used include these two…
Clonidine
Methyldopa
DHP-CCB’s MOA works by…
Inhibiting L-type calcium channels, less intracellular calcium in vascular smooth muscle means less contraction
DHP-CCB MOA impacts blood vessels by…
Also which blood vessel is it specific for??
Promoting vasodilation in arteries
A major advantage of DHP-CCB’s over other vasodilators is…
Lack of impact on heart rate
NO reflex tachycardia
In general, arterial vasodilators increase heart rate via…
EXCEPT DHP-CCB’s !
SNS stimulation - reflex tachycardia mediated by baroreceptors
How do baroreceptors work?
Stretch receptors linked to nerve endings signalling CNS.
Increased stretch = vagal outflow (decreased HR). Decreased stretch = SNS outflow (increased HR)
Most vasodilators prevent baroreceptors from being stretched
The three most common DHP-CCB’s are:
Amlodipine, felodipine, nifedipine
Hydralazine and minoxidil are classified as… and work by…
Direct acting vasodilators - directly relax arteriolar smooth muscle
The reason why hydralazine + minoxidil are never used as first line agents for HTN is because…
Reflex tachycardia (baroreceptors) and fluid retention (RAAS stimulation via vasodilation of kidney)
Typically used for resistance, in combination with drugs that prevent tachycardia + fluid retention (beta-blockers + diuretics)
The two drugs classified as Non-DHP CCB’s are…
Diltiazem and verapamil
Non-DHP CCB’s differ from DHP CCB’s due to…
Primary effect on cardiac smooth muscle vs vascular smooth muscle
Usage of non-DHP CCB’s will result in…
Lowered heart rate + contractility - will lower BP but not commonly used for uncomplicated HTN
Useful where heart rate + myocardial demand is high - comorbid conditions
The following should be monitored for ALL BP drugs in terms of adverse effects:
BP - dizziness, headache, hypotension
Orthostatic hypotension
Erectile dysfunction
Orthostatic hypotension = reduction of 20/10 upon standing
ED is usually caused by arterial dysfunction, not drugs
A key adverse effect with DHP-CCB’s includes:
…Swelling
Edema
Beta-blockers aren’t considered 1st line for uncomplicated HTN since…
The other 1st line drugs have shown better evidence of clinical outcomes.
Alternative for patients <60
NOTE that BB’s are extremely protective in certain complicated cases (Afib, HF)
ACEI/ARB’s may even be used if BP is normal for high-risk CV patients because…
ACEI and ARB reduce CV injury beyond BP
The following should be monitored when starting an ACEI/ARB for CKD patients:
SCr and K+ before starting, and within 1-2 weeks of starting drug/increasing dose
SCR expected to increase, but should be less than 20-25%
BP + Edema should get better, NOT worse
Presence of orthostatic hypotension is a signal for us to…
Start with lower doses and titrate with caution
