PHARM- Anti-hypertensives

Question 1

Clonidine

Answer 1

centrally acting selective partial.

-Alpha2- adrenergic receptor agonist

Question 2

Clonidin ration for A-2 receptor

Answer 2

22:01 A-2 to A-1 selectivity

Question 3

Clonidine Anesthesia effects

Answer 3

• 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

Question 4

Clonidine compared to Precedex

Answer 4

Precedex can do all the same things as clonidine

-slide 13

Question 5

Clonidine can be used for what post-anesthetic (post-op) symptom

Answer 5

-post-anesthetic “shivering”

(75mcg I.V)

Question 6

Clonidine peri-operative

Answer 6

reduces incidence of MI, infarction, and mortality following cardiovascular surgery

Question 7

Most common use of clonidine

Answer 7

hypertension

Question 8

Clonidine mechanism of aciton

Answer 8

-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

Question 9

Clonidine distribution

Answer 9

• highly lipid soluble and readily crosses into the CNS and the placenta
• portent binding 20-40%

Question 10

Clonidine metabolism/ excretion:

Answer 10

Metabolism: 50% hepatic
Excretion: 50% unchanged in urine

Question 11

Clonidine adverse effect most common

Answer 11

• Dry mouth (xerostomia)

- Sedation and dry mouth

Question 12

Clonidine adverse effect common when admin. epidurally

Answer 12

• Bradycardia

- Hypotension

Question 13

Clonidine very low risk of

Answer 13

Ventilatory depression

Question 14

Clonidine withdrawal syndrome symptoms

Answer 14

• _Rebound HYPERTENSION

- the higher the dose, the worse the withdrawal symptoms

Question 15

Treatment of Clonidine induced rebound HTN depends on the urgency of reducing the arterial blood pressure:

Answer 15

1. Restart clonidine if non-life treating situation
2. Administering vasodilation such as hydralazine, so nitroprusside pr a combination of alpha and beta adrenergic blockade (Labetalol IV)
3. 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

Question 16

Renin

Answer 16

is an enzyme that is produced primarily by juxtaglomerular (JAG) cells of the kidney afferent arteriole

Question 17

Renin converts ______ to _______

Answer 17

angiotensinogen to angiotensin I

-this is the rare limiting factor in angiotensin II production

Question 18

Renin secretion increased by:

Answer 18

• 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

Question 19

Angiotensin Converting Enzyme (ACE)

Answer 19

is a dipeptidyl peptidase enzyme that converts Ang I to Ang II

Question 20

ACE breaks down

Answer 20

bradykinin (a vasodilation substance)

Question 21

Angiotensin II (Ang II)

Answer 21

a very POTENT vasoconstriction hormone

Question 22

ACE inhibitors end in ____ except _____

Answer 22

“Pril”, Enalaprilat

Question 23

Enalaprilat

Answer 23

• only Ace-inhibitor IV

- is the active moiety of the pro-drug enalapril

Question 24

What increases as a result of ACE inhibition

Answer 24

Bradykinin levels

Question 25

What PO ACE-inhibitor is a prodrug (only one Rick wants us to know )

Answer 25

Enalapril

Question 26

Ace Inhibitors metabolism

Answer 26

ones that are prodrugs are all esterase’s in the liver by hepatic esterase’s to form their active moieties

Question 27

ACE inhibitors dilate arteries and veins by

Answer 27

-blocking angiotensin II formation and inhibiting bradykinin metabolism

Question 28

ACE inhibitors dilate arteries and veins by..

Answer 28

blocking angiotensin II formation and inhibiting bradykinin metabolism

Question 29

ACE inhibitors dilate arteries and viens by

Answer 29

blocking angio II formation and inhibiting bradykinin metabolism

Question 30

ACE’s do not cause what period

Answer 30

tachycardia and bradycardia

Question 31

ACE inhibitors side effects main one

Answer 31

DRY COUGH
(block the enzyme ACE so that it can no longer degrade bradykinin; thus bradykinin accumulates and can cause a dry cough

Question 32

ACE inhibitors induced angioedema

Answer 32

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.

Question 33

The clinical features of ACE inhibitor angioedema are related to elevated levels of

Answer 33

Bradykinin

Question 34

ACE inhibitor main contraindication

Answer 34

Bilateral renal artery stenosis

Question 35

ACE inhibitor: Pre-op management

Answer 35

-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.

Question 36

Angiotensin II Receptor Blockers (ARB’s) all end in

Answer 36

“Sartan”

Question 37

ARB’s mechanism of action

Answer 37

Angiotensin II receptor blockers are selective antagonists of angiotensin II at the AT-1 receptor

Question 38

ARB’s DO NOT inhibit ____ or effect levels of _____

Answer 38

ACE ; bradykinin

Question 39

ARB’s have less incidence of what compared to ACE’s

Answer 39

cough and angioedema

Question 40

The antihypertensive offer of ARB’s may be attenuated by

Answer 40

NSAID’s