Antihypertensive Flashcards
Blood pressure calculation
(BP) = CO × SVR
CO = cardiac output
SVR = systemic vascular resistance
High-normal BP
Systolic blood pressure (SBP) of 130–139 mm Hg or diastolic blood pressure (DBP) of 85–89 mm Hg
Affects estimated 7.5 million Canadians
CNS
SVR
Centrally acting adrenergic
Local
SVR
Peripherally acting adrenergic
Hypertension Defined by Its Cause
- Essential hypertension
- Secondary hypertension
- Malignant hypertension, it is a
Essential hypertension (idiopathic, primary)
90 to 95% of cases
Secondary hypertension
**5 to 10% of cases
**Most commonly result of pheochromocytoma, pre-eclampsia, renal artery disease, sleep apnea, thyroid disease, or parathyroid disease
Malignant hypertension
BP above 180/120; a medical emergency
Goals of antihypertensive therapy
Achieve pressure less than?
Reduction of cardiovascular and renal morbidity
Achieve pressure less than 140/90 mmHg
Hypertension + diabetes: less than _______ mmHg
Hypertension + chronic kidney disease: less than _______ mmHg
GOAL BP
Hypertension + diabetes: < 130/80 mmHg
Hypertension + chronic kidney disease: < 140/90 mmHg
Less than 140/90 or 120/ 80 (as per Brenda)
Parasympathetic nervous system
stimulates? 3
function in BVs?
Stimulates smooth muscle, cardiac muscle, glands
relax BVs
Sympathetic nervous system
stimulates? 3
function in BVs?
Stimulates the heart, blood vessels, skeletal muscle
Contracts BVs
Antihypertensive Drugs
Medications used to treat hypertension
Antihypertensive Drugs Categories 7
Adrenergic drugs
Angiotensin-converting enzyme (ACE) inhibitors
Angiotensin II receptor blockers (ARBs)
Calcium channel blockers
Diuretics
Vasodilators
Direct renin inhibitors
Parasympathetic NS hormone
ACh
Sympathetic NS hormone
NE
Adrenergic Drugs: Five Subcategories
α2-Receptor agonists (central)- brain
Adrenergic neuron blockers (central and peripheral)
α1-Receptor blockers (peripheral)- heart and BVs
β-Receptor blockers (peripheral)-heart and BVs
Combination α1- and β-receptor blockers (peripheral)- heart and BVs
Centrally Acting Adrenergic DrugS
clonidine
OTHER:
methyldopa
Centrally Acting Adrenergic:
clonidine and methyldopa
Mechanism of action:
Stimulate α2-adrenergic receptors in the BRAIN (which normally inhibit NE release from adrenergic terminals)
Decrease sympathetic outflow from the CNS (results in DILATION due to decreased sympathetic response)
Decrease norepinephrine (sympathetic) production
Stimulate α2-adrenergic receptors, thus reducing renin activity in the kidneys
BVs dilate, renin decreases and it result in decreased BP
Peripherally Acting α1-Blockers MEDICATION
doxazosin
OTHER:
prazosiN
terazosin
Peripherally Acting α1-Blockers:
doxazosin, prazosin, and terazosin
Mechanism of action:
Block α1-adrenergic receptors (which normally contricts BVs and viceral organ sphincter)
When α1-adrenergic receptors are blocked, BP is decreased.
Dilate arteries and veins
α1-Blockers also increase urinary flow rates and decrease outflow obstruction by preventing smooth muscle contractions in the bladder neck and urethra.
Use: benign prostatic hyperplasia (BPH)
Beta-blockers 3 medications
propranolol, metoprolol, and atenolol
ß-Blockers
propranolol, metoprolol, and atenolol
2 effects
Long term use causes?
Reduction of the heart rate through β1-receptor blockade
Cause reduced secretion of renin
Long-term use causes reduced peripheral vascular resistance.
Dual-Action α1- and β-Receptor Blockers
labetalol mechanism of action?
Used for?
Dual antihypertensive effects of reduction in heart rate (β1-receptor blockade) and vasodilation (α1-receptor blockade)
used for pregnant women with HTN
Adrenergic Drugs: Indications
All used to treat hypertension
Treats glaucoma
BPH: doxazosin, prazosin, and terazosin
Management of severe heart failure (HF) when used with cardiac glycosides and diuretics
Adrenergic Drugs: Adverse Effects
High incidence of orthostatic hypotension, syncope
Most common:
Bradycardia with reflex tachycardia
Dry mouth
Drowsiness, sedation
Constipation
Depression
Edema
Sexual dysfunction
Other:
Headaches
Sleep disturbances
Nausea
Rash
Cardiac disturbances (palpitations), others
Slow position changes!!
α2-Adrenergic Receptor Stimulators (Agonists)
clonidine and methyldopa
- INDICATION
- AE
- Used in conjunction with?
Not typically prescribed as first-line antihypertensive drugs
Adjunct drugs to treat hypertension after other drugs have failed
High incidence of unwanted adverse effects: orthostatic hypotension, fatigue, and dizziness
Used in conjunction with other antihypertensives such as diuretics
α1-Blockers
doxazosin mesylate (Cardura®)
prazosin hydrochloride (Minipress®)
tamsulosin hydrochloride (Flomax®)*
terazosin hydrochloride (Hytrin®)
*Tamsulosin is not used to control BP but is indicated solely for symptomatic control of BPH.
α1-Blockers
doxazosin mesylate (Cardura®)
How does it reduces PVR and BP?
Commonly used α1-blocker
Reduces peripheral vascular resistance and BP by dilating both arterial and venous blood vessels
Β-Receptor Blockermedication
nebivolol hydrochloride (Bystolic®)
Β-Receptor Blocker
nebivolol hydrochloride (Bystolic®)
Mechanism of action
Uses: hypertension and HF
Action: blocks β1-receptors and produces vasodilatation, which results in a decrease in systemic vascular resistance (SVR)
Less sexual dysfunction
Do not stop abruptly; must be tapered over 1 to 2 weeks.
Angiotensin-Converting Enzyme (ACE) Inhibitors
Large group of?
Often use?
May be combined with a? or a?
Large group of safe and effective drugs
Often used as first-line drugs for HF and hypertension
May be combined with a thiazide diuretic or a calcium channel blocker.
TO KNOW medications: ACE Inhibitors
Ends in suffix?
“Pril”
captopril (Capoten®)
enalapril (Vasotec®)
perindopril (Coversyl®)
ramipril (Altace®)
Other ACE Inhibitors
benazepril (Lotensin®)
fosinopril sodium
lisinopril (Prinivil®)
cilazapril (Inhibace®)
quinapril (Accupril®)
trandolapril (Mavik®)
ACE Inhibitors:
Explain mechanism of Action
2 functions of angiotensin II
Inhibit ACE, which is responsible for converting angiotensin I (through the action of renin) to angiotensin II
Angiotensin II is a potent vasoconstrictor and causes aldosterone secretion from the adrenal glands.
Block ACE, thus preventing the formation of angiotensin II
Prevent the breakdown of the vasodilating substance bradykinin
Ability to decrease SVR (a measure of afterload) and preload
Can stop the progression of left ventricular hypertrophy
Lower BP
[inhibits ACE enzymes which leads to vasodilation; ACE usually leads to vasoconstriction]
ACE Inhibitors:Indications
Hypertension
HF (drug used either alone or in combination with diuretics or other drugs)
Slow progression of left ventricular hypertrophy after myocardial infarction (MI) (cardioprotective)
Renal protective effects in patients with diabetes
ACE Inhibitors: Captopril and Lisinopril
Are not prodrugs.
Prodrugs are inactive in their administered form and must be metabolized in the liver to an active form so as to be effective.
Captopril and lisinopril can be used if a patient has liver dysfunction, unlike other ACE inhibitors that are prodrugs.
Prodrugs
inactive in their administered form and must be metabolized in the liver to an active form so as to be effective.
ACE Inhibitors: Mechanism of Action
Inhibit ACE
ACE: converts angiotensin I (formed through the action of renin) to angiotensin II
Angiotensin II: potent vasoconstrictor that induces aldosterone secretion by the adrenal glands
Aldosterone: stimulates sodium and water resorption, which can raise BP
Renin–angiotensin–aldosterone system
ACE Inhibitors thus lower BP.
ACE Inhibitors: Primary Effects on BP
Cardiovascular and renal
BP: reduce BP by decreasing SVR
ACE Inhibitors: Primary Effects on HF
How does it help with HF?
Diuresis?
Decreases? (2)
Prevent sodium and water resorption by inhibiting aldosterone secretion
Diuresis: decreases blood volume and return to the heart
Decreases preload, or the left ventricular end-diastolic volume [Preload: amount the ventricles stretch at the end of diastole/ filling of blood phase] [balloon fillng with air; how much it stretches]
Decreases work required of the heart
ACE Inhibitors: Cardioprotective Effects
ACE inhibitors decrease SVR (a measure of afterload) and preload.
Used to prevent complications after MI
Ventricular remodeling: left ventricular hypertrophy, which is sometimes seen after MI
Have been shown to decrease morbidity and mortality in patients with HF
Drugs of choice for hypertensive patients with HF
ACE Inhibitors: Renal Protective Effects
Reduce glomerular filtration pressure
Cardiovascular drugs of choice for patients with diabetes
Reduce proteinuria
Standard therapy for diabetic patients to prevent the progression of diabetic nephropathy
ACE Inhibitors: Adverse Effects
Fatigue, dizziness, headache, impaired taste
Mood changes
First-dose hypotensive effect
Possible hyperkalemia
Dry, nonproductive cough, which reverses when therapy is stopped
Angioedema: rare but potentially fatal
Others
captopril (Capoten)
- Uses.
- Half-life
- Adminstered
Uses: prevention of ventricular remodeling after MI; reduces the risk of HF after MI
Shortest half-life
Must be administered 3 or 4 times throughout the day
enalapril (Vasotec)
- Routes
- what does not require cardiac monitoring?
- What is considered a Prodrug?
- Improves?
- Reduces?
Only ACE inhibitor available in both oral and parenteral preparations
enalapril at intravenous (IV) does not require cardiac monitoring
Oral enalapril sodium: prodrug
Improves patient’s chances of survival after an MI
Reduces the incidence of HF
Angiotensin II Receptor Blockers
- Also referred to as?
- Effects?
Also referred to as angiotensin II blockers
Well tolerated
Do not cause a dry cough
Angiotensin II Receptor Blockers
Medications
losartan (Cozaar®)
telmisartan (Micardis®)
Other:
eprosartan mesylate (Teveten®)
valsartan (Diovan®)
candesartan cilexetil (Atacand®)
olmesartan (Benicar®)
azilsartan medoxomil potassium (Edarbi®)
Angiotensin II Receptor Blockers: Mechanism of Action
Affect primarily vascular smooth muscle and the adrenal gland
Selectively block the binding of angiotensin II to the type 1 angiotensin II receptors in these tissues
Block vasoconstriction and the secretion of aldosterone
Comparison of ACE Inhibitors and Angiotensin II Receptor Blockers
ACE inhibitors and angiotensin II receptor blockers (ARBs) appear to be equally effective for the treatment of hypertension.
Both are well tolerated.
ARBs do not cause cough.
There is evidence that ARBs are better tolerated and are associated with lower mortality after MI than are ACE inhibitors.
It is not yet clear whether ARBs are as effective as ACE inhibitors in treating HF (cardioprotective effects) or in protecting the kidneys (as in diabetes).
Angiotensin II Receptor Blockers: Indications
Hypertension
Adjunctive drugs for
the treatment of HF
May be used alone or with other drugs such as diuretics
Angiotensin II Receptor Blockers: Adverse Effects
Upper respiratory infections and headaches most common
Dizziness, inability to sleep
Diarrhea
Dyspnea, heartburn
Nasal congestion
Back pain
Fatigue
Hyperkalemia is less likely to occur than with the ACE inhibitors.
losartan (Cozaar)
Beneficial for pts with?
Used in caution in pts?
Not taken by?
Beneficial in patients with hypertension and HF
Used with caution in patients with renal or hepatic dysfunction and in patients with renal artery stenosis
Not to be taken by breastfeeding women
Calcium Channel Blockers
- Indication
- Mechanism of action
Primary use: treatment of hypertension and angina
Hypertension: cause smooth muscle relaxation by blocking the binding of calcium to its receptors, thereby preventing contraction
Calcium Channel Blockers:Mechanism of Action results in?
Results in:
Decreased peripheral smooth muscle tone
Decreased SVR
Decreased BP
Calcium Channel Blockers: Indications
Angina
Hypertension: amlodipine (Norvasc®)
Antidysrhythmias
Migraine headaches
Raynaud’s disease
Cerebral artery spasms after subarachnoid hemorrhage (prevention): nimodipine
amlodipine (Norvasc®) indication
Hypertension: amlodipine (Norvasc®)
Diuretics Indication
First-line antihypertensives in the Canadian Hypertension Education Program guidelines for the treatment of hypertension
Diuretics mechanism of action
Decrease plasma and extracellular fluid volumes
Results
1. Decreased preload
2. Decreased cardiac output
3. Decreased total peripheral resistance
Overall effect
Decreased workload of the heart and decreased BP
What are the most commonly used diuretics for hypertension.
Thiazide diuretics (e.g. hydrochlorthiazide)
Vasodilators drugs
sodium nitroprusside (Nipride®)
Others:
diazoxide (Proglycem®)
hydralazine (Apresoline®)
minoxidil (Loniten®)
Vasodilators:Mechanism of Action
Directly relax arteriolar or venous smooth muscle (or both)
Used for their ability to cause peripheral vasodilation
Results in decreased SVR
Vasodilators: Indications
Treatment of hypertension
May be used in combination with other drugs
Sodium nitroprusside and IV diazoxide are reserved for the management of hypertensive emergencies.
Vasodilators: Adverse Effects [hydralazine]
dizziness, headache, anxiety, tachycardia, edema, dyspnea, nausea, vomiting, diarrhea, hepatitis, systemic lupus erythematosus, vitamin B6 deficiency, and rash
Vasodilators: Adverse Effects [minoxidil]
T-wave electrocardiographic changes, pericardial effusion or tamponade, angina, breast tenderness, rash, and thrombocytopenia
Vasodilators: Adverse Effects [sodium nitroprusside]
bradycardia, decreased platelet aggregation, rash, hypothyroidism, hypotension, methemoglobinemia, and (rarely) cyanide toxicity
Vasodilators: hydralazine (Apresoline®)
Routes and usage
Orally: routine cases of essential hypertension
Injectable: hypertensive emergencies
Vasodilators: sodium nitroprusside (Nitropress®)
- Indication
- Contraindication
Used in the critical care setting for severe hypertensive emergencies; titrated to effect by IV infusion
Contraindications: known hypersensitivity to the drug, severe HF, and known inadequate cerebral perfusion (especially during neurosurgical procedures)
Treatment of Hypertension
eplerenone (Inspra)
Class
Contraindication
New class: selective aldosterone blockers
Blocks action of aldosterone in kidney, heart, blood vessels, and brain
Contraindicated in patients with known drug allergy, elevated potassium (>5.5 mmol/L), or severe kidney impairment
Treatment of Pulmonary Hypertension
bosentan (Tracleer®)
Other drugs used to treat pulmonary hypertension:
epoprostenol
treprostinil
ambrisentan
sildenafil and tadalafil
bosentan (Tracleer®)
Treatment of Pulmonary Hypertension
Specifically indicated only for the treatment of pulmonary artery hypertension in patients with moderate to severe HF
Action: blocks receptors of the hormone endothelin
What to assess prior administration?
General rule?
Monitor BP and HR prior to administration of antihypertensives (client and patient).
Need specific parameters. General rule: If apical HR <60 or SBP < 90 contact their HCP; medication will be held if BP and/or HR parameters are lower than above
Monitor lab values
(K+, possibly other electrolytes such as Na+ and Cl-, blood glucose, kidney function, liver function)
Nursing Implications
Before beginning therapy, obtain a thorough health history and perform a head-to-toe physical examination.
Assess for contraindications to specific antihypertensive drugs.
Assess for conditions that require cautious use of these drugs.
Educate patients about the importance of not missing a dose and taking the medications exactly as prescribed.
Instruct patients to check with their health care provider for instructions on what to do if a dose is missed; patients should never double up on doses if a dose is missed.
Monitor BP during therapy; instruct patients to keep a journal of regular BP checks
Nursing Implications
Instruct patients that these drugs should not be stopped abruptly, because this may cause a rebound hypertensive crisis and perhaps lead to stroke.
Oral forms should be given with meals so that absorption is more gradual and effective.
Administer IV forms with extreme caution
Must use an IV pump.
Nursing Implications
Remind patients that medication is only part of therapy.
Encourage patients to watch their diet, stress level, weight, and alcohol intake.
Instruct patients to avoid smoking and to avoid eating foods high in sodium.
Encourage supervised exercise.
Teach patients to change positions slowly to avoid syncope from postural hypotension.
Nursing Implications
Male patients who take these drugs may not be aware that impotence is an expected effect, and this may influence compliance with drug therapy.
If patients are experiencing serious adverse effects or if they believe the dose or medication needs to be changed, they should contact their health care provider immediately.
Monitor for adverse effects (dizziness, orthostatic hypotension, fatigue) and for toxic effects.
Monitor for therapeutic effects
Nursing Implications
Hot tubs, showers, or baths; hot weather; prolonged sitting or standing; physical exercise; and alcohol ingestion may aggravate low BP, leading to fainting and injury. Patients should sit or lie down until symptoms subside.
Patients should not take any other medications, including over-the-counter drugs, without first getting the approval of their health care provider
Educate patients about lifestyle changes that may be needed.
-Weight loss
-Stress management
-Supervised exercise
-Dietary measures
ACE Inhibitors can cause? (2) and Laboratory Values to identify and monitor?
ACE inhibitors can cause renal impairment, which can be identified by serum creatinine.
ACE inhibitors can also cause hyperkalemia, so potassium levels need to be monitored.
Monitor serum sodium during therapy.
An adrenergic drug for hypertension, the nurse must assess for?
(for every single HTN medication)
Hypotension
Are not prodrugs don’t need to be activated in the liver so we can give them to those with live disease
or
drug to give to those with pancreatitis/ cirrhosis?
Captopril and lisinopril
HTM medications given for pregnant women
labetalol
Has protective effects on the kidneys for pts with diabetes
ACE Inhibitors
Ventricular hypertrophy
thickening of wall of ventricular walls-poor pumping
ARBs
Angiotensin II Receptor Blockers
1. Suffix
2. Do not cause
3. Common adverse effects?
Sartan
Cough
chest pain
Alpha acting HTN medications increases risk for?
Orthostatic hypotension and syncope
Drop in BP/ fluid volume stimulates?
Renin acts on
ACE is released by?
ACE acts on angiotensin I to from?
Angiotensin II effects (2)
release of renin from kidneys
Renin acts on angiotensinogen to form angiotensin I
Lungs
angiotensin II
acts directly on BVs stimulating vasoconstriction
acts on adrenal glands to stimulate the release of aldosterone> aldosterone acts on kidneys to stimulate the reabsorption of salt (NACL) and water.
Drug that causes less impotence?
nebivolol hydrochloride (Bystolic®)
Prodrugs
must be metabolized in the liver to an active form so as to be effective
ACE inhibitors suffix
examples
PRIL
captopril (Capoten®)
enalapril (Vasotec®)
Nitroprusside is classified as
Results
Vasodilator- peripheral vasodilation
Doxazocin
α1-Blockers
2 drugs that are not prodrugs?
Captopril and lisinopril are not prodrugs.
AE of antihypertensives to an adult pt
hypotension
type of antihypertensive the nirse fill consider when giving 1st dose at bedtime
alpha blockers (prasozin)
ACE Inhibitor AE
ACE Inhibitor caution
dry, non-productive cough
renal insufficiency
Interaction of ACE I
potassium
NSAIDS
alpha 1 blockers
drugs that primarily cause arterial and venous dilation on peripheral sympathetic neurons
Cardiac output
SVR (systemic vascular resistance) or afterload
amount of blood ejected from the L ventricle, L per min
is the resistance to blood flow that is determined by the diameter of the BVs and the vascular musculature, calculated by dividing BP to CO
centrally acting adrenergic drugs
function of alpha 2 receptors
drugs that modify function of sympathetic NS in the BRAIN by stimulating alpha 2 receptors
alpha 2 receptors are inhibitory and revrses sympathetic effect and decreases BP
HTN values
exceeds 140/90
prevalence of HTN is highest in Africa and in low and middle-income nations
Canadians who are Black, Indigenous, South Asian, and those with low socioeconomic status are at greater risk
Major risk factors for CAD, cardiovascular disease, and death. Important RF for Stroke and HF, kidney failure, and peripheral vascular disease (the higher the BP, the higher the chance)
for 40 to 70 YO, the risk of developing cardiovascular diseases doubles with each 20 mmHG increase in systolic BP or 10 mm Hg increase in diastolic BP
malignant HTN
extremely high BP, above 180/120
medical emergency- develops rapidly and results in organ damage
orthostatic hypotension
AE of adrenergic blocking drugs involving a sudden drop in BP when pts change position
prodrug
a drug that is inactive in its given form
must be metabolized by the liver to its active form to be effective
essential HTN
secondary HTN
unknown cause of HTN (90-95% of cases)
high bp caused by another disease or medication (5 to 10%). If cause of this is eliminated, BP can return to normal
BP
mean arterial pressure
Bp is determined by the product of CO [4-8 L/min] and systemic vascular resistance (SVR)
MAP is a product of CO and SVR
Calculated as 1/3 (SBP- DBP) + DBP
MAP is a better indicator of tissue perfusion as 2/3 of the cardiac cycle is spent in diastole
greater or equal to 60 is necessary to maintain adequate tissue perfusion
Cardiac factors:
HR
Contractility
B-blockers
Calcium channel blockers
Centrally acting adrenergics
Circulating volume:
Salt
Aldosterone
ACE I
Diuretics
Hormones
Vasodilators
Vasoconstrictors
Vasodilators
Prostaglandin
ACE I
Calcium channel blockers
ANGIOTENSIN II blockers
Peripheral sympathetic receptors
constrictors
dilators
a1 blockers and b blockers
CNS
Local
centrally acting adrenergic
peripherally acting adrenergic
Nurses key roles
primary prevention
detection
treatment of HTN
130-139 over 85 to 89 mm Hg = high risk of developing HTN
Antihypertensive goals
reduce cardiovascular and renal mortality and morbidity
individualized (sexual dysfunction caused by non-adherence from males), demographic, ethnocultural, cost and ease of medication administration needs to be considered as well.
GOAL:
BP less than 140/90 -non-automated office BP machine
BP less than 135/85 -automatic office BP machine
In PTS with HTN/ diabetes
The goal is BP less than 130/ 80 and 140/90 respectively
Vasodilators
act directly on vascular SM cells, not through a or b receptors
ACh
somatic NS- acts on skeletal muscles
parasympathetic- acts on the heart, intestines
NE
sympathetic- acts on the heart, adrenal gland
Receptors of sympathetic NS
adrenergic and noradrenergic R (alpha or beta receptors)
Receptors of parasympathetic NS
located between the postganglionic fibre and the effector cells are called MUSCARINIC and CHOLLINERGIC receptors
physiological activity in the muscarinic receptors are stimulated by?
inhibited by?
ACh and cholinergic agonist drugs
cholinergic antagonists (antichollinergic drugs)
physiological activity at the adrenergic R is stimulated by?
Epi, NE, and adrenergic agonists drugs (adrenergic/ beta blockers)
Nicotinic R are found on
postganglionic cell bodies in all autonomic ganglia and cause depolarization by opening both sodium and potassium channels
Diuretics
first line, monotherapy/ combination
therapeutic effects: decreased volume of plasma and ECF which results in decreased preload. Leads to decreased CO & total peripheral resistance, which decreases the workload of the heart
thiazide diurects- common in HTN treatment
1st line treatment of adults
health behaviour management
thiazide, Ace-I, ARB, long-acting CCB, beta-blockers, single-pill combination
B-blockers are not indicated as 1st line for ages 60 and above
long-acting diuretics are preferred over short-acting ones like hydrochlorothiazide
SPC- ACE-I & CCB, ARB & CCB, ACE-1 OR ARB WITH A DIURETIC
RAS- contraindicated in pregnancy and caution in childbearing years
adrenergic drugs
central action (brain)
Peripheral action (heart/ BVs)
5 types
adrenergic neuron blocker (central & peripheral)
alpha 2 receptor agonists (central)
alpha 1 receptor blockers (peripheral)
beta receptor blockers (peripheral)
combination alpha 1 and beta receptor blockers (peripheral)
centrally acting alpha 2 receptor agonists
function of SNS and result
clonidine & methyldopa- modify the function of SNS.
the function of SNS: leads to an increased heart rate and force of contraction, the constriction of BVs, and the release of renin from the kidneys- result is HTN
centrally acting adrenergic drugs
alpha 2 adrenergic receptors
renin
act by stimulating the alpha 2 adrenergic receptors in the brain
receptor stimulation reduces sympathetic outflow from the CNS. this reduction results in a lack of NE production which reduces BP. Also reduces the activity of renin; the hormone and enzyme that converts the protein precursor of angiotensinogen to the protein angiotensin I, the precursor of angiotensin II, a potent vasoconstrictor that raises BP
alpha 1 blockers location of action
in the periphery
doxazosin, prazosin, and terazosin- also modify the function of SNS
BY:
blocking the alpha 1 adrenergic receptors
when alpha 1 adrenergic receptors are stimulated by NE, they increase BP. When these receptors are blocked, BP is decreased.
Drug effects of alpha 1 blockers - dilate arteries and veins which reduces peripheral vascular resistance and decreases BP
reduces systemic and pulmonary venous pressures and increases CO.
they also increase urinary flow rates and decrease outflow obstruction by preventing smooth muscle contractions in the bladder and urethra. Beneficial in BPH
beta blockers
periphery
propanolol, metoprololand atenolol
for angina and conduction problems
effects: reduction of the HR through beta 1 receptor blockade. Also causes a reduction in the secretion of the hormone renin which reduces both angiotensin II-mediated vasoconstriction and aldosterone-mediated volume expansion
Long term use of beta blockers reduces peripheral vascular resitance
Dual action of alpha and beta receptor blocker
labetalol
periphery
dual antihypertensive effects- reduces HR (beta 1 receptor blockade) and vasodilation (alpha 1 receptor blockade)
Indications of adrenergic drugs
HTN
Glaucoma
Clonidine- menopausal flushing
prophylaxis of migraine
symptoms of withdrawal symptoms
alpha 1 blockers- prazosin: helps with symptoms of BPH. Used in severe HF when taken with cardiac glycosides and diuretics
Contraindications of adrenergic drugs
adrenergic antihypertensive drugs- known allergy
may HF, concurrent MAOIs, severe depression, peptic ulcers severe liver/ kidney disease
Asthma- nonselective beta-blockers
vasodilating drugs- contraindicated in HF
AEs of adrenergic drugs
bradycardia with reflex tachycardia
orthostatic hypotension
dry mouth, drowsiness, dizziness, depression, edema, constipation, sexual dysfunction
headache, sleep disturbances, nausea, rash, and palpitations
alpha blockers- orthostatic hypotension, syncope (move slowly)
abrupt discontinuation of centrally acting alpha 2 receptor agonists can result in
rebound HTN
(may be true for other antihypertensive as well)
nonselective blocking drugs: associated with bronchoconstriction and metabolic inhibition of glycogenolysis in the liver which can lead to hypoglycemia. Hyperglycemia can occur as adrenergic drugs can impair insulin release.
change in the dosing regimen should be undertaken gradually and with appropriate patient monitoring and follow-up.
Adrenergic drugs interactions
alcohol, benzodiazepines, and opioids- additive CNS depression
clonidine- MAOIs, appetite suppressants, amphetamines (decreased hypotensive effects)
diuretics, other hypertensive drugs (increased hypotensive effects)
B-blockers (potentiate bradycardia and increase rebound HTN)
doxazosin-
CNS depressants, alcohol (increase CNS depression
b-blockers, hypotensive drugs (increased hypotension)
Alpha 2 adrenergic receptor stimulators (agonists)
clonidine- commonly used
methyldopa- used in pregnancy mostly
high incidence of orthostatic hypotension, fatigue, and dizziness (not 1st line)
clonidine
alpha 2 adrenergic receptor agonists
centrally actinhg
decrease BP and opioid withdrawal
do not D/C abruptly as it can lead to severe rebound HTN
Alpha 1 blocker
doxazosin, prazosin, tamsulosin (for BPH)
not for pregnancy
doxazosin
alpha 1 blocker
peripherally acting
reduces peripheral vascular resistance and BP bu dilating arteries and veins
HTN and BPH
Dual action alpha 1 and beta receptor blockers drug
beta receptor blocker- nebivolol
nebivolol
beta 1 selective blocker
HTN
decreases SVR
reduces sexual dysfunction
do not stop abruptly, tapered over 1-2 weeks
ACE I
safe and efficacious- one of the 1st line for HTN and HF, diabetes for kidney protection
catopril
captopril
short half-life- dosed more frequently than other ACE I
ACE I that are not prodrug?
captopril and lisonopril
an advantage for people with liver dysfunction
Enalapril
ACE I available parenterally
ACE inhibitors may cause
significant fetal morbidity or mortality during 2nd and 3rd trimester (do not use in pregnancy)
ACE Inhibitor action and explain hormones involved
Kininase- an enzyme that normally breaks down bradykinin, a potent vasodilator
inhibit ACE enzymes which are responsible for converting angiotensin I (formed from the action of renin) to angiotensin II
angitensin II- potent vasocontrictor and induces aldoesterone secretion
Aldosterone stimulates NA and water resorption- which can raise BP
together they are referred to as the renin-angiotensin-aldosterone system > inhibiting this process BP is lowered
Primary effects of ACE I
cardiovascular and renal
cardio > ability to reduce BP by decreasing SVR. By preventing the breakdown of the vasodilating substance bradykinin and substance P (another potent vasodilator), thus preventing the formation of angiotensin II
this decreases the afterload- the resistance against which the left ventricle must pump to eject its volume of blood during contraction
Effective in the treatment of HF because they prevent sodium and water resorption by inhibiting aldosterone secretion. This causes diuresis, which decreases blood volume and return to the heart, This in turn decreases preload- the left ventricular end-diastolic volume and the work required of the heart
ACE I- indicator
Contraindications
AE
HTN, HF
decrease preload and afterload
stop the progression of left ventricular hypertrophy- MI (ventricular remodelling). The ability of ACE-I to stop this is called (cardioprotective effects)
protects kidney- decreases GF pressure- a choice for diabetes- reduces proteinuria and diabetic neuropathy
Contraindications
-allergy, angioedema,
-baseline potassium level of 5 mmol/L because this medication can cause HYPERKALEMIA
-kidney decline
-women who are lactating, children, bilateral renal artery stenosis
AEs
fatigue, mood changes, headache, dizziness
DRY NON-PRODUCTIVE COUGH- reversible with discontinuation of therapy (switched to an ARB
Hyperkalemia, hypotension
loss of state, rash, anemia, neutropenia, thrombocytosis, agrunocytosis
acute kidney failure
serum potassium levels must be monitored carefully
ACE I overdose symptoms
hypotension
treatment is symptomatic and supportive- give IV fluids to expand BV
hemodialysis is effective for the removal of captopril and lisonopril
ACE I interacttions
NSAIDS- reduces antihypertensive effect, may also predispose pts to acute kidney injury
lithium carbonate- lithium toxicity
potassium- hyperkalemia
captopril (ACE I)
minimize and prevent left ventricular dilation and dysfunction (ventricular remodelling) that can occur in the acute period after an MI
reduce the risk of HF
short half-life - given 3-4 times a day
enalapril sodium (ACE I)
oral and parenteral (only one)
IV-does not require cardia monitoring unlike beta blockers and CCBs do.
slightly longer half life- given BID
prodrug, pt must have a functioning liver for drug to be converted into an active form
improve chances of survival after MI to reduce HF
Angiotensin II receptor blockers (ARBs)
Medications
Action
Indication
similar to ACE I
losartan, valsartan, eprosartan, irbesartan, candesartan, telmisartan, azilsartan
block the binding of angiotensin II to type 1 angiotensin II receptors.
type 1 receptor- mediate effects of important effectors in controlling BP and volume in the cardiovascular system,
type 1 R are activated by angiotensin II with resulting effects that include vasoconstriction and aldosterone synthesis and secretion
ACE I such as enalapril- blocks the conversion of angiotensin I to angiotensin II, but angiotensin II may be formed by other enzymes that are not blocked by ACE I
*in contrast to ACE I- ARBs primarily affect vascular smooth muscle and the adrenal gland. By selectively blocking the binding of angiotensin II to the type 1 angiotensin II receptors in these tissues. ARBs block vasoconstriction and the secretion of aldosterone. Angiotensin II receptors have been found in other tissues throughout the body, but the effects of ARB blocking the R are unknown.
Aldosterone stimulates NA and water resorption- which can raise BP
ARBs do not cause cough!
lower mortality after an MI than ACE Is
Indication> potent vasodilating properties
HF, HTN
decrease SVR (a measure of afterload)
ARBs contraindications
Interaction
allergy, pregnancy, lactation
caution in OAs and pts with kidney dysfunction because of increased sensitivity to their effects and risk of AEs
Assess BP and apical impulse (like other drugs)
interaction- can promote hyperkalemia (esp. when taking with potassium drugs)
ARBs AEs
upper respiratory infections, and headache
dizziness, inability to sleep, diarrhea, dyspnea, heartburn, nasal congestion, back pain, and fatigue
Rarely, anxiety, muscle pain, sinusitis, cough, and insomnia
Hyperkalemia is less likely to occur with ARBs than with ACE I
ARBs toxicity and overdose
hypotension and tachycardia
bradycardia occurs less often
treatment is symptomatic and supportive -IV fluids to expand BV
losartan potassium
HTN, HF
used in caution in pts with kidney/ liver dysfunction, renal artery stenosis
not for breastfeeding women- AE on the infant
CCBs
HTN, angina (antihypertensive, antidysrhythmic)
treat HTN by their ability to cause smooth muscle relaxation by blocking the binding of calcium to its receptors
first line
amlodipine
nimodipine- prevents cerebral artery spasms that occur after a subarachnoid hemorrhage
used to treat Raynaud’s disease and migraine
Vasodilator
medication
action
indication
contraindication
AE
act directly on arterial and venous smooth muscle to cause relaxation. DO NOT WORK through adrenergic receptors
minoxidil, hydralazine, diazoxide, sodium nitroprusside
direct-acting vasodilators- ability to cause peripheral vasodilation. This reduces SVR.
Most nitable effets- hypotensive effect
MINOXIDIL- HAIR GROWTH
indication- HTN emergencies in which BP is severely elevated
contra- allergy, hypotension, CAD, HF secondary ti diastolic dysfunction
AE- dizziness, headache, anxiety, N & V, diarrhea, hepatitis, lupus
Minoxidil AE- T wave ECG changes, pericardial effusion, angina, breast tenderness, rash, thrombocytopenia
sodium nitroprusside AE: bradycardia, decreased platelet aggregation, rash, hypothyroidism, hypotension, methemoglobinemia, cyanide toxicity (byproduct of nitroprusside)
minoxidil, hydralazine, diazoxide (VASODILATOR)
work primarily through arteriolar vasodilation
sodium nitroprusside (VASODILATOR)
arteriolar and venous effects
given in intensive care, IV (for severe HTN emergencies)- overdose; d/c infusion
contains cyanide- released upon its metabolism- can cause cyanide toxicity
antidote-sodium nitrite and sodium thiosulfate for injection and amyl nitrite for inhalation
contra- allergy, severe HF, inadequate cerebral perfusion
Vasodilator toxicity or overdose
produces hypotension, tachycardia, skin flushing
treatment-supportive and symptomatic- administer IV fluids, digitalization if needed, and the administration of beta blockers for the control of tachycardia
epinephrine should not be used because of excessive cardia stimulation
Vasodilator contraindications
other antihypertensive drugs
hydralazine hcl
essential HTN
less common now
has an injection form
may not require cardiac monitoring
contra- drug allergy, CAD, mitral valve dysfunction
direct acting peripheral vasodilator
Direct renin inhibitors
most recent
treat primary HTN
sole drug- aliskiren
aliskiren
mild to moderate HTN
monotherapy/ combination
action- it binds directly to the renin enzyme and blocks the conversion of angiotensinogen to angiotensin I and angiotensin II. This action results in the reduction of plasma renin activity and angiotensin I, angiotensin II, and aldosterone.
AES: HEADACHE, DIZZINESS, FATIGUE
eplerenone
selective aldosterone blockers.
reduces BP by blocking actions of aldosterone at its R in kidneys, heart, BVs, and brain.
not for those with elevated serum potassium levels (higher than 5.5) or severe kidney impairment
HTN, postmyocardial infarction
bosentan monohydrate
hormone related?
works by blocking receptors of the hormone endothelin- which acts to stimulate the narrowing of BVs by binding endothelin Rs in the endothelial (innermost) lining of BVs and in vascular smooth muscle
pulmonary artery HTN
Ambrisentain is similar to bosentan
Pulmonary HTN- epoprostenol and treprostinil
trepostinil
pulmonary artery HTN
analogue of prostacyclin, a metabolite of arachidonic acid, a naturally occurring prostaglandin that lowers BP; by dilating pulmonary and systemic BVs and by inhibiting platelet aggregation
prehypertension
systolic- 120 to 129
diastolic- 80 to 89
lab test
serum sodium, potassium, chloride, magnesium, calcium
serum levels of troponin (elevated after an MI, a reliable indicator of a heart attack)
kidney function studies- including blood urea test, creatinine
liver function studies, ALT, AST
scans and imaging studies- noninvasive ophthalmoscopic exam of the eye structures
assess for conditions- CAD, Addison’s disease, culture, race, ethnicity, obesity, preeclampsia…
alpha-adrenergic agonists
assess BP, HR, weight
fluid retention and edema- assess heart and breath sounds, intake and output, dependent edema
associated with first dose syncope - encourage pt to lay supine on 1st dose/ give at hs
alpha adrenergic antagonists
dizziness and syncope
centrally acting alpha blockers
WBCs
serum potassium
sodium levels
protein in urine
nonselective b blockers
block both b1 and b2 receptors and will have both heart and respiratory effects
may cause exacerbation of respiratory diseases because of increased bronchoconstriction due to beta 2 blocking) or exacerbation of HF (negative inotropic effects- decreased contractility due to beta 1 blocking)
beta 1 blockers
cardiac system is affected (pulse and BP will decrease)
assess BP and apical pulse rate before each dose
If systolic BP is less than 90 mm HG or pulse is less than 60 betas/ min (notify DR)
if a pt needs b blocker but has rstrictive airway problems
beta 1 blocker to avoid bronchoconstriction
if no respiratory illness
non-selective beta-blockers may be effective
beta blockers have inotropic effect
on the heart (decrease contractility) may worsen HF
ACE Inhibitors (-pril)
BP, apical pulse rate, respiratory status (because of the adverse effect of a dry hacking cough)
report angioedema immediately- wean off to avoid rebound HTN
Monitor sodium and potassium levels
potassium increases as an adverse effect
loss of taste
may take weeks to see the full effects
potassium supplements are not needed
-pine
CCBs
cause smooth muscle relaxation by blocking the binding of calcium to its receptors
ARBs
caution in OAs and kidney dysfunction
tolerated with meals
reduce dosage if pt has hypovolemia/ liver dysfunction
report dyspnea, dizziness, excessive fatigue
Vasodilator
baseline neurological assessment, LOC, cognitive ability
hypotension, dizziness, syncope
never give drug without adequate monitoring
always dilute nitroprusside; never infuse at the max dose for more than 10 minutes; may cause cyanide and thiocyanate toxicity; when combined with sodium thiosulfate, toxicity is reduced
-dilute the drug
-avoid use of infusion that has turned blue, green, red
-use volume infusion pump, IV
-monitor BP
-beware of cyanide production
BP goals
120- 139 mm Hg - systolic
80- 89 mm Hg - diastolic
those with diabetes- less than 130/80
diuretics
dizziness and electrolyte imbalances
centrally acting alpha blockers
AEs are more pronounced; hypotension, sedation, bradycardia, edema
CCBs
negative inotropic (decreases cardiac contractility)
digoxin
increase heart contractility
decreased chronotropic effects
decreased dromotropic effects
decreased HR
decreased conduction
eye exam
HTN impacts vasculature of the eyes-reliable indicator of the long term effectiveness of treatment than BP readings
alpha adrenergic agonist
first dose syncope- avoid situations that exacerbate this
avoid activities that require mental alertness
report dizziness, palpitations, and orthostatic hypotension
assess sexual functioning
Beta blocker
change position slowly to avoid syncope, dizziness, and falls
report pulse rate of less than 60/ systolic less than 90 mm Hg
avoid heat, prolonged sitting, standing, exercise
ACE I
-pril
prevent vasoconstriction caused by angiotensin II
prevent aldosterone which stops sodium and water resorption
prevent breakdown of bradykinin (a potent vasodilator) by angiotensin II
ARBs
-sartan
work by blocking the binding of angiotensin at the receptors; which decreases BP
CCBs
-dipine (amlodipine)
may be used to treat angina, dysrhythmias, and HTN
help reduce BP by relaxing smooth muscles and dilating BVs.
if calcium is not present, the smooth muscle cannot contract
