Vasodilators PPT part 1 through clonidine Flashcards
Systemic HTN is defined as
Stage 1: 150-159/90-99 mmHg
or > = to
Stage 2: 160/100 mmHg
The most common type of HTN is
“essential” or “primary”
-for which there is no clear unifying pathophysiology despite DECADES of research.
HTN is a major risk factor for: (5)
- atherosclerosis
- cardiovascular disease
- HF
- Renal disease
- Stroke
“Secondary” htn is much less common and can be d/t (5)
a variety of causes:
- Aortic coarctation
- Endocrine Disease
- Medications
- OSA
- Renal Disease
Name associated disorders of RENAL Disease in Systemic HTN (tbl 20.1) (2)
- Renal parenchymal disease
- Renal artery stenosis
Name associated disorders of ENDOCRINE Disease in Systemic HTN (tbl 20.1)
- Cushings’s disease
- Hyperparathyroidism
- Hyper-and hypothyroidism
- Pheochromocytoma
- Primary aldosteronism
Name specific MEDICATIONS associated with Systemic HTN (tbl 20.1) (4)
- Alcohol
- Antidepressants
- Chronic NSAID use
- Oral Contraceptives
Calcium Ch Blockade offers direct:
vasodilator effects
Calcium Ch Blockade offers direct vasodilator effects without the requirement of:
salt restriction
Are calcium ch blockers associated with side effects?
relatively few
ACE inhibitors or ARB target the:
renin-angiotensin system
*a major contributor to BP control
This system is a major contributor to BP control
renin-angiotensin system
Decreased renal perfusion and increased sympathetic nervous system activity cause the release of
Renin
Renin acts on:
“renin substrate” or angiotensin I
Renin acts on “renin substrate”/angiotensin I at variousu sites in the body to release
angiotensin II
Angiotensin II is a potent
Vasoconstrictor
Promotes Na and water retention
What type of medication inhibits Angiotensin II production?
ACE Inhibitor
Inhibition of angiotensin II production or blockade of receptor causes what:
a reliable and potent antihypertensive effect
What class of medication blocks the angiotensin II receptor?
ARB
In most types of cardiac patients, what drugs have a well known survival benefit?
ACE inhibitors
Another agent that may be associated with inferior stroke protection in pts >60yrs are:
Beta adrenergic blockers
Beta blockers may be associated with stroke protection however, they have a greater potential for
systemic side effects
Metoprolol
(moa/dose/onset/duration) Table 20.2
Beta 1 blocker
1-5mg
1-5min
1-4h
Labetalol
(moa/dose/onset/duration) Table 20.2
Alpha 1, Beta 1 and 2 blocker
5-20mg or 0.5-2mg/min
1-5min
1-4h
*Esmolol
(moa/dose/onset/duration) Table 20.2
beta 1 blocker
50-300 mcg/kg/min
1-2 min
Half life: 9 min (no clinical duration given)
Nicardipine
(moa/dose/onset/duration) Table 20.2
Dihydropyridine Ca Blocker
100 mcg or 5-15mg/h
2-10 min
2-4h
*Hydralazine
(moa/dose/onset/duration) Table 20.2
Arteriolar dilator
5-20mg
5-20 min
1-8h
Fenoldopam
(moa/dose/onset/duration) Table 20.2
dopamine type 1 agonist
0.05-1.6 mcg/kg/min
5-10 min
30-60 min
Nitroprusside
(moa/dose/onset/duration) Table 20.2
No donor
0.25-4 mcg/kg/min
1-2 min
1-10 min
Nitroglycerin
(moa/dose/onset/duration) Table 20.2
No Donor
5-300 mcg/kg/min
1-2 min
5-10 min
Beta blockers are less commonly used as ______ agents in HTN
first line agents
*as other agents may have a better safety profile for this indication in those > 60 yrs
Beta- adrenergic blockers are:
sympatholytics
What are the potential SE’s of Beta Blockers that limit their use in many patients?
Depression
Fatigue
Impotence
Why is impotence a SE that is important to know about?
compliance
Beta blockers are indicated for Long term tx of patients with:
CAD
HF
(and for their antihypertensive action in these pts)
Beta Blockers can be classed according to whether they exhibit /or possess (3 things):
- Beta 1 selective [versus]
- nonselective properties
- possess intrinsic sympathomimetic activity
Beta blockers with selective properties bind primarily to
Beta 1 (cardiac) Receptors
nonselective beta blocker properties bind to which receptors?
equal affinity for B1 and B2 receptors
vascular, bronchial SM, and metabolic
B Blockers with intrinsic sympathomimetic activity tend produce less
bradycardia
—-> thus, less likely to unmask left ventricular dysfunction
The antihypertensive effect of Beta Blockers and other vasodilators may be attenuated by
NSAIDS
NSAIDs may attenuate what?
The antihypertensive effect of Beta Blockers and other vasodilators
What type of B Blocker is likely to exacerbate symptoms of peripheral vascular disease?
B blockers w/ intrinsic sympathomimetic activity
*less likely to produce vasospasm / thus to exacerbate s/s of pvd
Name some cardioselective B1 blockers
acebutolol
atenolol
bisoprolol
metoprolol
Compared to Propranolol (NS B blocker), Cardioselective B1 blockers in low-moderate doses are unlikely to produce:
bronchospasm
mask hypoglycemia
decrease peripheral blood flow
Cardioselective B1 Blockers are the preferred drugs for patients with
pulmonary disease
Insulin-dept DM
or
Symptomatic PVD
This drug has been shown to improve survival in pts with systolic HF
Carvedilol (NS Beta; which has Alph 1 blocking action as well)
*metoprolol and bisoprolol also provide a survival benefit in this population; not as great as Carvedilol
Labetalol is a
nonselective B blocker
also has significant Alpha 1 blocking action
The presence of alpha-adrenergic blocking properties in NS BB’s results in
less bradycardia
negative inotropic effects
*compared to “pure”BB’s
The Alpha properties in some BB’s may lead to
orthostatic hypotension
*labetalol
Dose labetalol have an incidence of bronchospasm?
yes
similar to that seen w/atenolol or metoprolol
IV Labetalol is used in
- HTN emergencies
- managing pts w/Type B aortic dissections
- facilitating conversion from IV to oral medications
The risks associated with treat HTN with BB’s
- Bradycardia
- Heart Block
- HF
- Bronchospasm
- claudication
- masked hypoglycemia
- sedation
- impotence
- angia pectoris or even MI–> precipitated if abruptly d/c’d
what patient type generally cannot tolerate more than moderate doses of BB’s?
any degree of HF
Despite the low tolerance of BB’s in pts with CHF, what is clear about dosage and use?
- that when dosage is slowly increased
- given chronically
- the anti-adrenergic effect provides a significant benefit in chronic SYSTOLIC HF
B Blockers should be avoided in patients with:
symptomatic Asthma
B Blockers potentially increase the R/O serious
hypoglycemia in diabetics
Why do B B’s increase r/o hypoglycemia in pts w/DM?
they blunt autonomic Nervous System responses that would warn of hypoglycemia
Nevertheless, the incidence of hypoglycemia has not been shown to be ______ in diabetic pts being tx w/ B-adrenergic antagonists to control HTN
increased
Name the Alpha-1 receptor blockers:
- Doxazocin
- Prazosin
- Terazosin
Selective postsynaptic Alpha 1-adrenergic receptor antagonist result in:
vasodilating effects on both arterial and venous vasculature
Alpha-1 receptor blockers have vasodilating effects on arterial, venous, or both arterial/venous vasculatures?
Both - arterial and venous vasculature
The absence of [THIS] leaves intact the normal inhibitory effect on Norepi release from nerve endings
Presynaptic Alpha 2 receptor antagonism
These drugs are unlikely to elicit reflex increases in cardiac output and renin release:
Alpha 1 Receptor blockers
Oral phenoxybenzamine and IV phentolamine are
NonSelective Alpha Blockers that also block Alpha 2 receptors
What durgs are NonSelective Alpha Blockers that also block Alpha 2 receptors?
Oral phenoxybenzamine
IV phentolamine
Name two drugs used almost exclusively in the mgmt of pheochromocytoma
Oral phenoxybenzamine ([pre-op) and IV phentolamine (periop)
catecholamine-secreting tumor formed by chromaffin cells inside the adrenal medulla is known as
pheochromocytoma
Another pre-op drug for pheochromocytoma is
Prazosin
This drug may be of value for decreasing afterload in pts with CHF, as well as treating essential HTN
Prazosin
alpha 1 receptor blocker
This drug has been used to relieve the vasospasm of Raynaud’s phenomenon:
Prazosin
Prazosin is used for treatment of:
- essential HTN
- pheocromocytoma
- decreasing afterload in CHF
- raynaud’s
- shrinking the prostate gland (BPH)
A useful indication for Prazosin in addition to tx of essential HTN in the presence of BPH
this drug decreases the size of the gland
SE’s of Prazosin
- fluid retention
- orthostatic hypotension
- vertigo
What drugs may interfere with the antihypertensive effect of Prazosin?
NSAIDS
Prazosin is nearly completely metabolized after PO administration. This and the bioavailabilty <60% suggest
-substantial first pass hepatic metabolism
Because Prazosin is metabolized in the ____ permits its use in pts with ____ w/o altering the dose.
metabolized: LIVER
pts with: RF
The elimination half-time of Prazosin is about 3hrs.
It’s prolonged by ___, but not by ____.
Prolonged by HF
but not renal dysfunction
These symptoms may accompany tx with Prazosin (not SE’s):
- Dry mouth
- Lethargy
- Nasal congestion
- nightmares
- Sexual dysfunction
- Urinary frequency
In the presence of Prazosin, what may be exaggerated?
Why?
hypotension during epidural anesthesia
-reflecting drug-induced Alpha 1 blockade that prevents compensatory vasoconstriction in the unblocked portions of the body.
In epidural anesthesia and prazosin, what may occur?
hypotension
-reflecting drug-induced Alpha 1 blockade that prevents compensatory vasoconstriction in the unblocked portions of the body.
In epidural hypotension in the presence of prazosin, what medication should be administered? What would the pt likely be unresponsive to?
May not be responsive to phenylephrine
—-> d/t the resulting decrease of SVR results in hypotension.
Epi may be necessary to increase SVR and SBP.
The combination of prazosin and B Blocker could result in:
refractory hypotension during regional anesthesia.
Why does particularly refractory hypotension result in the combination of prazosin and a BB during regional anesthesia?
D/T potentially blunted responses to B1 and A1 agonists
Clonidine is a centrally acting
selective partial Alpha 2 - agonist
Clonidine acts as an antihypertensive drug by virtue of its ability to decrease:
sympathetic output from the CNS
Clonidine adult dose:
0.2-0.3 mg/daily
Clonidine is particularly effective in the tx of:
patients with:
- severe HTN
- renin-dependent disease
Clonidine MOA
Alpha 2 agonists
-binds to A2 receptor (3 subtypes)
Name the Alpha2 receptor subtypes:
Alpha-2A
Alpha -2B
Alpha-2C
- they’re distributed ubiquitously
- each may be uniquely responsible for some of the actions of Alpha 2 agonists
Alpha 2 receptors mediate:
- analgesia
- sedation
- sympatholysis
Alpha 2B receptors mediate:
-vasoconstriction
and possibly
-anti-shivering effects
Clonidine stimulates Alpha 2 adrenergic inhibitory neurons in the
medullary vasomotor center
Stimulation from the medullary vasomotor center results in a:
decease in SNS outflow from the CNS to peripheral tissues
Decreased sympathetic nervous system activity is manifested as
peripheral vasodilation and decreases
- Systemic BP
- HR
- CO
α2 receptors on blood vessels mediate
vasoconstriction
Alpha receptors on peripheral sympathetic nervous system nerve endings inhibit release of
norepinephrine
The ability of clonidine to do [this] may be the mechanism for profound decreases in anesthetic requirements
The ability of clonidine to modify the function of potassium channels in the CNS
*cell membranes become HYPERpolarized
Neuraxial placement of clonidine inhibits
spinal substance P release
and nociceptive neuron firing produced by noxious stimulation.
Clonidine is rapidly absorbed (PO) and reaches peak plasma concentrations with
60-90mins
Elimination half-time of clonidine is
b/w 9-12hrs
Clonidine is metabolized in
- 50% in the liver
- the rest is unchanged in urine
Clonidine duration (of hypotensive effect) after a singe PO dose is
about 8 hrs
How long does the TD route of Clonidine need to produce a steady-state, therapeutic plasma concentration?
48hrs
The decrease in systolic blood pressure produced by clonidine is more prominent than the decrease
in diastolic blood pressure.
patients treated chronically with Clonidine, SVR is little affected, how does CO change with chronic treatment
returns toward pre-drug levels
With clonidine homeostatic cardiovascular reflexes are maintained. This means
pts avoid orthostatic hypotension or hypotension during exercise
The most common SE of clonidine:
- sedation
- xerostomia (dry mouth)
Clonidine’s agonist effect on postsynaptic A2 receptors in the CNS do what for GA?
nearly 50% reduction :
- in MAC/anesthetic requirements for inhaled anesthetics
- injected, preanesthetic drugs
Pt’s pretreated with clonidine often manifest less ____ in response to surgical stimulation.
catecholamines
*occasionally require tx of bradycardia
Why is a combination of clonidine w/a diuretic often necessary?
retention of sodium and water
Additional SE’s of clonidine:
- skin rashes are frequent
- impotence occurs occas.
- orthostatic hypotension is rare
What drug prevents opioid-induced skeletal muscle rigidity and produces skeletal muscle flaccidity?
clonidine
Do A2 agonists have an effect on the responses evoked by NMBDs?
No
rebound htn from abrupt d/c of clonidine can result how many hours after the last dose?
8hrs and as late as 36hrs
Clonidine rebound htn is most likely to occur in daily dosages greater than
1.2mg /daily
what s/s typically precede the actual increase in SBP with clonidine rebound htn?
- abd pain
- diaphoresis
- H/A
- Nervousness
- tachycardia
β-Adrenergic blockade may exaggerate the magnitude of (clonidine) rebound hypertension by blocking the
- β2 vasodilating effects of catecholamines and
- leaving their Alpha vasoconstricting actions unopposed
TX of clonidine induced rebound htn:
- re-instituting clonidine
- administering vasodilators such as hydralazine or nitroprusside
What (other) drug may be useful in the management of patients experiencing rebound hypertension (from clonidine)
labetalol with α and β antagonist effects
How long can TD clonidine provide sustained, therapeutic levels should PO therapy need to be interrupted for surgery?
as long as 7 days
how should planned withdrawl of clonidine be done?
clonidine dosage should be gradually decreased over 7 days or longer
clinical evidence of excessive SNS activity has been associated with abrupt d/c of :
Beta Blocker therapy
Antihypertensive drugs that act independently on central and peripheral SNS mechanisms do not seem to be associated with:
rebound htn after sudden d/c of therapy
*these are Direct vasodilators, ACE inhibitors
Hydralazine administration in OR (supplied, dose)
supplied: 20mg/ml
Dose: 5-10mg – start low
