PHARM- Anti-hypertensives Flashcards
Clonidine
centrally acting selective partial.
-Alpha2- adrenergic receptor agonist
Clonidin ration for A-2 receptor
22:01 A-2 to A-1 selectivity
Clonidine Anesthesia effects
- inc the duration of analgesia and reduces dose req for narcotic pain meds
- inc duration of analgesia, sensory and motor blockage of local anesthetics and reduces the dose requirements for local anesthetics
Clonidine compared to Precedex
Precedex can do all the same things as clonidine
-slide 13
Clonidine can be used for what post-anesthetic (post-op) symptom
-post-anesthetic “shivering”
(75mcg I.V)
Clonidine peri-operative
reduces incidence of MI, infarction, and mortality following cardiovascular surgery
Most common use of clonidine
hypertension
Clonidine mechanism of aciton
-stimulated inhibitory Alpha-2 receptors in the vasomotor canter in the brainstem which results in decrease in SNS outflow from this region to peripheral tissues resulting in:
A decrease HR, decrease myocardial contractility which decrease CO,
- peripheral vasodilation (dec SVR) which dec BP
- dec renin activity and dec circulating plasma catecholamine levels
Clonidine distribution
- highly lipid soluble and readily crosses into the CNS and the placenta
- portent binding 20-40%
Clonidine metabolism/ excretion:
Metabolism: 50% hepatic
Excretion: 50% unchanged in urine
Clonidine adverse effect most common
- Dry mouth (xerostomia)
- Sedation and dry mouth
Clonidine adverse effect common when admin. epidurally
- Bradycardia
- Hypotension
Clonidine very low risk of
Ventilatory depression
Clonidine withdrawal syndrome symptoms
- _Rebound HYPERTENSION
- the higher the dose, the worse the withdrawal symptoms
Treatment of Clonidine induced rebound HTN depends on the urgency of reducing the arterial blood pressure:
- Restart clonidine if non-life treating situation
- Administering vasodilation such as hydralazine, so nitroprusside pr a combination of alpha and beta adrenergic blockade (Labetalol IV)
- beta blocking agents (esp. non-selective) SHOULD NOT be used alone is the setting, b/c they may accentuate the rebound HTN by allowing unopposed alpha-1 vasoconstriction caused by activation of the SNS and elevated circulating catecholamines
Renin
is an enzyme that is produced primarily by juxtaglomerular (JAG) cells of the kidney afferent arteriole
Renin converts ______ to _______
angiotensinogen to angiotensin I
-this is the rare limiting factor in angiotensin II production
Renin secretion increased by:
- hypotension, decrease renal perfusion (dehydration)
- decrease blood volume (hemorrhage)
- reductions of Na+ conc. in early distal tubule
- Inc SNS activity which activates beta-1 receptors on JAG calls from circulating catecholamines
Angiotensin Converting Enzyme (ACE)
is a dipeptidyl peptidase enzyme that converts Ang I to Ang II
ACE breaks down
bradykinin (a vasodilation substance)
Angiotensin II (Ang II)
a very POTENT vasoconstriction hormone
ACE inhibitors end in ____ except _____
“Pril”, Enalaprilat
Enalaprilat
- only Ace-inhibitor IV
- is the active moiety of the pro-drug enalapril
What increases as a result of ACE inhibition
Bradykinin levels
What PO ACE-inhibitor is a prodrug (only one Rick wants us to know )
Enalapril
Ace Inhibitors metabolism
ones that are prodrugs are all esterase’s in the liver by hepatic esterase’s to form their active moieties
ACE inhibitors dilate arteries and veins by
-blocking angiotensin II formation and inhibiting bradykinin metabolism
ACE inhibitors dilate arteries and veins by..
blocking angiotensin II formation and inhibiting bradykinin metabolism
ACE inhibitors dilate arteries and viens by
blocking angio II formation and inhibiting bradykinin metabolism
ACE’s do not cause what period
tachycardia and bradycardia
ACE inhibitors side effects main one
DRY COUGH (block the enzyme ACE so that it can no longer degrade bradykinin; thus bradykinin accumulates and can cause a dry cough
ACE inhibitors induced angioedema
Treatment option include the use of FFP and new drug Rick wants us to look up {Icatibant (Firazyr). A selective bradykinin B2 Receptor Antagonist. SubC only, 30mg first dose, repeat in 6hrs if symptoms do not improve or worsen.
The clinical features of ACE inhibitor angioedema are related to elevated levels of
Bradykinin
ACE inhibitor main contraindication
Bilateral renal artery stenosis
ACE inhibitor: Pre-op management
-Circulatory effect pt. -recommend these agents be held 12-24 hrs before anesthesia surgery. “its up to the provider”
-Concerns: hemodynamics instability and hypotension when ACE’s are given the morning of.
-If large blood loss or suspected fluid shift; it may be acceptable to hold dose
-Exaggerated hypotension cause by ACE-I therapy
has been responsive to crystalloid infusion or sympathomimetic (Ephedrine or Phenylephrine)
-Use Vasopressin if hypotension is unresponsive to Ephedrine or Phenylephrine.
Angiotensin II Receptor Blockers (ARB’s) all end in
“Sartan”
ARB’s mechanism of action
Angiotensin II receptor blockers are selective antagonists of angiotensin II at the AT-1 receptor
ARB’s DO NOT inhibit ____ or effect levels of _____
ACE ; bradykinin
ARB’s have less incidence of what compared to ACE’s
cough and angioedema
The antihypertensive offer of ARB’s may be attenuated by
NSAID’s
