Autonomic Hypertension Flashcards
Review of ANS
ANS divided into:
- Sympathetic
- Parasympathetic
Sympathetic divided into:
- Adrenergic agonist (fight)
- Adrenergic antagonist (rest)
Parasympathetic divided into:
- cholinergic agonist
- anticholinergics
What are the neurotransmitters of parasympathetic?
What are the neurotransmitters of sympathetic?
- ACh
- Epinephrine and Norepinephrine
Where does parasympathetic come from in the spinal cord?
Where does sympathetic come from?
- Brain and Lower vertebrae
- Lumbar and Thoracic
What is sympathomimetic?
What drugs are involved with this?
- Promoting the stimulation of sympathetic nerves
- Adrenergic agonists
What is sympatholytic?
What drugs are involved with this?
- Inhibiting the transmission of sympathetic nerve impulses
- Adrenergic antagonists
What are adrenergic drugs used to treat?
- Cardiovascular conditions
- Respiratory conditions
- Common cold
How do most adrenergic drugs exert their effect?
Binding to postsynaptic receptor
What are the subtypes of adrenergic drugs?
What are each of their actions?
Alpha:
1- mainly vascular smooth muscle (vasoconstriction or dilation)
2- presynaptic junctions to influence NE release
Beta:
1- heart, kidney
2- lungs
3-adipose tissue
Is there a clinical use of B3?
No
What are the three catecholamines?
Catecholamines:
- Epinephrine
- Norepinephrine
- Dopamine
What are catecholamines?
- Hormones produced by adrenal glands.
- Usually released in response to physical or emotional stress.
- Released by sympathetic nervous system.
- Sympathomimetic
Catecholamines: Cardiac effects? Vascular effects? CNS effects? Nonvascular Smooth Muscle effects? Metabolic effects?
Cardiac effects: CO=SV*HR
- Positive inotropic effect (↑SV)
- Positive chronotropic effect (↑HR)
Vascular Effects:
- Epinephrine reduced peripheral vascular resistance at low dose, opposite at high dose
- NE elevates BP
CNS Effects:
-large doses can produce anxiety, tremors, HA
Nonvascular smooth muscle effects:
- relax smooth muscle of GI tract
- urinary retention
- dilation of bronchiole smooth muscle
Metabolic effects:
- increases blood glucose and fatty acid levels
- inhibits insulin secretion
- enhance glycogenolysis and gluconeogenesis
Does epinephrine effect all alpha and beta receptors?
Yes
What effect does it have on each receptor?
What is the net effect of all of this?
- B1- increases strength/ rate of cardiac contraction
- B2- relaxes bronchiole smooth muscle, activates glycogenolysis
- B3- activate lipolysis in fat cells
- A1- constricts vascular smooth muscle
- A2- (presynaptically)
Net effect= potent vasoconstrictor and cardiac stimulant
What can epinephrine be used for?
- Anaphylactic shock (epipen)
- Cardiogenic shock (cardiac arrest)
What receptors does norepinephrine act on?
- Acts on A1 receptors to a greater extent than A2 and B1.
- It has little effect on B2
What does norepinephrine mainly do?
Increase BP
What is norepinephrine used to treat?
- Severe hypotension
- Septic shock
What is septic shock?
When an organ is injured or damaged in response to an infection, leading to dangerously low BP
What is the precursor to norepinephrine?
What receptors does it activate?
- Dopamine
- Activates A1 and B1 receptors
What is dopamine used to treat?
- Shock in renal failure
- Cardiac decompensation
What are vasopressor drugs?
Cause vasoconstriction leading to increased BP and MAP
What are some examples of vasopressors?
- Norepinephrine
- Epinephrine
- Dopamine
- Vasopressin
Difference between Direct and Indirect Acting Adrenergic Drugs?
- Direct- directly stimulate alpha or beta receptors
- Indirect- Enhance effects of NE or Epi by inhibiting their reuptake or inhibiting their degredation, or increasing release of NE
What are some examples of direct acting adrenergic drugs?
- Pseudophedrine
- Phenylephrine
Are indirect acting adrenergic drugs sympatholytic or sympathomimetic?
Sympathomimetic- they mimic the SNS
-Release stored NE, inhibit reuptake, and block degradation
What are some examples of indirect acting adrenergic drugs?
- Cocaine
- Amphetamine
- Ephedrine
What is the effect of these adrenergic drugs such as Amphetamine?
Amphetamine
- Taken up by NE transporters (blocks path) which leaves more NE available to have effect
- inrease alertness, decrease fatigue= used for ADHD, narcolepsy
- AE related to increased BP and HR, and decreased apetite
- Enters CNS, stimulating dopamine receptors= euphoria= abuse potential
What are the effects of cocaine, another indirect adrenergic drug?
- Also inhibits the reuptake of NE
- Significant vasoconstriction= hypertensive crisis, MI, stroke
S24-27
S24-27
What are mixed adrenergic agonists?
Work on both direct and indirect pathways
What are the rehab concerns with sympathomimetics?
- May induce: HTN, cardiac arrhythmias, angina
- Ephedra (weight loss products): cerebral hemorrhage, seizures, and death
Hypertension affects 1 in every _ adults worldwide and is the leading cause of cardiovascular morbitity and mortality. It can be “______”
- 6
- silent
What is the difference between primary hypertension and secondary hypertension?
Primary HTN
-multifactorial, accounts for 90% of cases
Secondary HTN
-produced by underlying disease process
What is the Frank-Sterling Law? What does this mean?
- Says that stroke volume increases as left ventricular volume increases
- Means that preload can be adversely affected by heart disease
What is MAP?
What is Ohm’s law?
- Cardiac output*peripheral resistance
- V=IR
- V= vascular pressure
- I= blood flow
- R= resistance
- If peripheral resistance is increased, so is BP
Drugs can affect variables in these equations to alter BP in what ways?
- Reduced HR→ decreased CO and arterial pressure
- Decrease contractility→ decrease SV→ decrease BP
- Increase vasodilation→ lower peripheral vascular resistance→ decrease BP
- Reduce plasma volume→ decrease SV→ decrease BP
What are factors producing HTN?
- Genetics
- Kidney function
- Potassium and calcium affects vasodilation
- Changes in myocardial tissue and vessels
- Relationship between HTN and hyperinsulinism/ insulin resistance
Renin-angiotensin system + sympathetic nervous system = _____________
potent vasoconstriction
What is renin?
Renal enzyme that promotes the production of angiotensin
What does renin lead to?
- Gets secreted when 1) decreased renal profusion or 2) decreased Na+
- Angiotensinogen→ angiotensin I + ACE → angiotensin II
- Angiotensin II is a VERY powerful vasoconstrictor
Go through the order in depth.
- Low fluid flow or Na+ is sensed
- Renin is secreted
- Kidney releases renin into blood, and liver releases angiotensinogen into blood
- This renin acts on the angiotensinogen to form Angiotensin I
- Angiotensin-converting enzyme (ACE) in pulmonary blood converts Angiotensin I into Angiotensin II
- This then stimulates widespread vasoconstriction
What do PGE2 and PGl2 counteract?
counteract vasoconstriction effect on kidneys
What does taking NSAIDs do to prostoglandin synthesis?
What can this cause?
- Inhibits prostoglandin synthesis
- Can cause renal failure and exacerbate HTN with individuals who have cirrhosis, heart failure, nephrotic syndrome, or HTN
What are 2 other things that control BP?
Baroreceptors:
-mechanoreceptors located in carotid sinus and aortic arch
Chemoreceptors:
-located in carotid body and aortic bodies
Baroreceptors help to do what?
Help blood vessels constrict and dilate as needed
What is the recommended initial therapy for HTN?
Diuretics
How do diuretics work?
Act directly on the nephron to limit water and sodium reabsorption, thus increasing excretion of Na+ and water by kidneys
- Increases amount of urine formed
- Decreases blood volume
- Inexpensive
What are the three major classifications of diuretics and what are they based on?
They are based on location
Loop Diuretics
- moderate antihypertensive/ strong diuretic
- descending loop on Henle
Thiazide diuretics
- powerful antihypertensive, moderate diuretics
- distal (early) tubules
Potassium-sparing diuretics
-distal (late) tubules
What is the MOA of loop diuretics?
Acts on ascending Loop of Henle and inhibits reabsorption of Na+/K+/2Cl- which prevents reabsorption of water follows these electrolytes
What is the most common side effect of loop diuretics?
-Dehydration
Other side effects include:
- hypokalemia (low potassium)
- hyponatremia (low sodium)
- hypocalcemia (low calcium)
- ototoxicity
- hyperglycemia
- increased LDLs
K+ supplements or K+ sparing diuretics may be given to reduce risk of what?
hypokalemia
Where do thiazide diuretics act?
What is their MOA?
- Acts on the early part of the distal convoluted tubes
- Inhibits mechanisms that favor Na+ reabsorption. Results in Na+ and K+ excretion and reabsorption of Ca+.
Thiazide diuretics _____ __________ __ more than any other classes of antihypertensive drugs.
Thiazide diuretics are the most ___________ diuretics.
- lower systolic BP
- frequently used
- prime choice for HTN
- may be given along with loop diuretics in cases of CHF and severe edema
- better choice for individuals prone to renal calculi
- favored for older adults to reduce to reduce Ca+ loss and maintain bone mass
What is the overall importance of thiazide diuretics?
Same function as loop diuretics but helps keep calcium in the body. This is important in the elderly who have issues with bone density or kidney stones
What are the AE of thiazide diuretics?
Similar to loop diuretics except possibly causing hypercalcemia and significant K+ loss (hypokalemia)
Where do potassium sparing diuretics act?
What is their MOA?
- Acts on the late distal convoluted tubules,
- Inhibits the sodium-potassium exchange mechanism, limiting the reabsorption of Na+ and excretion of K+
Potassium-sparing diuretics are less effective at producing _______ but are _______ _______.
- diuresis
- potassium-sparing
What are the AE of potassium sparing diuretics?
- hyperkalemia
- nausea
- lethargy
- mental confusion
_________ blocks aldosterone receptor, which produces gynocomastia in males and menstrual irregularities in females
-spiranolactone
What are the therapeutic concerns with diuretics?
- Be alert for signs of hypokalemia or hyperkalemia
- Hypokalemia- abonrmal ECG (flattened T waves)
- Hyperkalemia- abnormal ECG (elevated T waves)
- Both can trigger arrhythmias
- Syncope (fainting) may also be present
- Cardiac arrest can occur
- Frequently monitor K+ levels
What are the therapeutic concerns with diuretics?
- Risk for hyperglycemia and abnormal lipid levels
- Of concern for individuals with diabetes and high cholesterol/triglyceride levels
- Reduced plasma volume has issues with hyperglycemia because we are reducing the plasma volume which in return increases concentration
What are the therapeutic concerns with diuretics?
- Fluid depletion
- Dehydration may increase BP, which is counter productive
What is a normal blood glucose level?
70-130 mg/dL
What are the main concerns with diuretics?
- Be aware of sings of hypo and hyperkalcemia
- Fluid depletion
- Risk for hyperglycemia and abnormal lipid levels
Do NSAIDs make diuretics more or less effective?
Less, NSAIDs cause Na+ retention and decrease in renal profusion
Direct vasodilators MOA?
Act to directly vasodilate the peripheral vasculature by inhibiting smooth muscle contraction in the arterioles
Vasodilators: Calcium Channel Blockers MOA?
Blok Ca2+ entrance into vascular smooth muscle, reducing smooth muscle tone allowing for vasodilation
-This reduced Ca2+ influx results in decreased contractility and CO, and decreased cardiac function and energy demands on the heart
What was the original purpose of vasodilator: calcium channel blockers?
Originally developed for treating cardia disease
- HTN
- angina
- arrhythmia
When are calcium channel blockers useful?
When betablockers are contraindicated (asthma, DM, PVD)
What are the AE of calcium channel blockers?
- HA
- dizziness
- hypotension
- bradycardia
- reflex tachycardia
- sweating
- tremor
- flushing
- constipation
What are the three classes of Ca+ channel blockers and the drugs in these classes?
(Just know that these medications are Ca+ channel blockers)
Dihydropyridines: reduce arteriolar tone
- nifedipine
- nicardipine
- amlodipine
Phenylalkylamines: affect the heart
-verapamil
Benzothiazepines: affect heart and vasculature
-diltiazem
What are B-adrenoceptor blockers (beta blockers) and what are they used to treat?
They are adrenoreceptor antagonists used to treat cardiovascular dysfunction
- HTN
- angina
- arrhythmia
- post-MI survival
Beta blockers act as a _________ _________ of B-adrenoceptors.
competitive antagonist
results in:
- negative inotropic effects (reduced contractility)
- negative chronotropic effects (reduced HR)
- inhibitory effect on sympathetic nervous system (reduced peripheral vascular resistance)
Difference between betablockers that are nonselective or selective for B-adrenoreceptors?
- nonselective- blocks B1 and B2 adrenoreceptors
- selective- blocks B1 receptors only, but this selectivity is lost at high doses
What is beta blockers MOA?
- Normal sympathetic function is for NE to bind to B1 and B2 receptors causing an increase in HR, contractility, and conduction
- Beta blockers reduce the sympathetic influence by competing for the site causing decreased HR, contractility, and conduction
Primary location of beta receptors
B1- heart
B2- lungs (bronchiole smooth muscle
What is the response when these receptors are stimulated?
B1= increase in HR and contractility B2= smooth muscle relaxation resulting in bronchodilation
These beta blockers act to reduce the ________ of the heart
workload
HTN and angina are conditions where a decrease in the workload of the heart is very beneficial
What leads to the reduced workload on the heart?
- negative chronotropic (decreased HR)
- negative inotropic (decreased SV)
What do beta blockers typically end in?
-lol
What are the adverse effects of inhibiting the SNS via beta blockers?
- may contribute to peripheral vasoconstriction
- bronchoconstriction
- bradycardia
- reduced HR
What are cardioselective beta blockers?
Selectively block B1 receptors without causing bronchoconstriction
What are the AE of cardioselective beta blockers?
Same as nonselective minus pulmonary effects
What are the therapeutic concerns with beta blockers?
- Depressed HR and CO during exercise
- May contribute to orthostatic hypotension
- Watch for signs of CHF
- Masks symptoms of hypoglycemia in individuals with diabetes
Can we use HR as an indicator of patient response to exercise while they are on beta blockers?
NO
What is destention?
sticks out from backload of fluid
Where do A1 blocker medications work?
Post synaptic
What do A1 adrenoreceptor blockers end in?
What is their MOA?
- End in -azosin
- reduce sympathetic tone of blood vessels→ vasodilation→ decreased peripheral vascular resistance
How do A1 receptor blockers lower BP?
Are they typically used as a first drug option?
- Decreasing PVR (peripheral vascular resistance)
- No, they are generally used as an “add-on” drug to reduce BP
A1 receptor blockers have also been shown to lower ______ and ______
-LDL and triglyceride levels
What are the AE of these A1 adrenoreceptor blockers?
- orthostatic hypotension
- nasal stuffiness
- reflex tachycardia
- arrhythmia
What are the therapeutic concerns with A1 adrenoreceptor blockers?
- first-dose syncope
- take BP and watch for signs of OH
- FALLS precaution
- angina
- increased incidence of CHF with this class of drugs
When are dual alpha and beta blockers useful?
Beneficial for individuals who have increased PVR with pure beta blockers
Central-acting alpha 2 agonists for HTN MOA?
A2 receptor are primarily on presynaptic neurons→ stimulate in CNS→ decrease NE production→ decrease sympathetic outlflow→ decreased peripheral resistance, HR, and BP
Common AE of central acting alpha 2 agonists?
- Dizziness (15%)
- Drowsiness (38%)
- Fatigue (15%)
- HA (up to 30% chonidine, 10% methyldopa)
__ agonist and __ antagonist treat HTN
- A2
- A1
What drug is reserved for resistant HTN?
What type of drug is this?
What is it also used for?
- Clonidine
- Central-Acting A2 agonist
- Also used for ADHD
What is the 1st line for HTN in pregnancy?
Methyldopa
What are some concerns with central acting A2 agonists for HTN?
- Orthostatic hypotension
- Rebound hypertension
- Critical to not abruptly stop!
S77
S77
What does an ACEi drug end with?
What is its MOA?
- ends with -pril
- blocks the conversion of angiotensin I to angiotensin II→ increase blood vessel dilation, increase bradykinin which increases vasodilation
What patients would be on an ACEi drug for a long amount of time?
stroke patients
Common AE of ACEi drugs?
- Dry cough
- Hypotension
- Hyperkalemia
What are the rare, serious side effects of ACEi drugs?
- Acute renal failure
- Angioedema (face swelling)
Angioedema is more common with ____ than any other RAAS drugs.
ACEi
What is ARB (angiotensin II receptor blockers) MOA?
When should these be used?
What do ARBs end in?
- blocks binding of angiotensin II resulting in decreased blood vessel vasoconstriction
- Use when ACEi intolerant
- “-sartan”
When should you switch from an ACEi to an ARB?
Switch if cough is present while on ACEi
What is the best tolerated anti HTN?
What are the AE of ARBs?
- ARBs
- Same as ACEi except no dry cough
What are the therapeutic concerns for ACEi?
- Cough
- NSAIDs
What is the triple whammy?
ACEi, Diuretic, and NSAID
Direct renin inhibitor use?
MOA?
- HTN (but very uncommon)
- blocks conversion of angiotensinogen to angiotensin I
What are the AE of a direct renin inhibitor?
Similar to ACEi/ARB
Should you use RAAS inhibitors in combination?
No, due to increase in AE
Hypertension Guidelines
S85
1st line treatments for Hypertension
- Thiazide diuretic or CCB (or ACEi/ARB if not African American)
- If CKD- ACEi or ARB first
What are other agents to treat hypertension?
- loop diuretics
- K+ sparing diuretic
- beta blockers
- aldosterone antagonists
- A1 blocker
- centrally acting A2 agents
- direct vasodilator
What is the last line to treatment of hypertension?
centrally acting A2 agents due to effect on CNS
Additional therapeutic concerns about hypertensive agents.
- Orthostatic hypotension→ low Bp→ syncope→ FALLS
- Dehydration
- Caution with heat modalities
HTN Drugs Review
S89
