Vasopressors/inotropes

Question 1

CO=

Answer 1

HRxSV

Question 2

Positive chronotropy

Answer 2

Increased heart rate

Question 3

Negative chronotropy

Answer 3

Decreased heart rate

Question 4

Dromotropy

Answer 4

Related to velocity of conduction (degree of delay in AV node)

Positive-increased speed of conduction
Negative-decreased speed of conduction

Question 5

Inotropy

Answer 5

Strength of contraction

Question 6

Preload

Answer 6

LV End diastolic volume just prior to contraction

Question 7

Factors that impact preload

Answer 7

Changes in SVR
Intravascular volume
Sympathetic outflow
Skeletal muscle contraction- enhances venous return

Question 8

Lusitropy

Answer 8

Rate of myocardial relaxation- impacts diastolic filling of LV

Question 9

After load

Answer 9

Force opposing LV contraction

-tension or stress of LV wall during systole- not synonymous with SVR

Question 10

Law of Laplace

Answer 10

-after load directly related to intraventricular pressure/size
-after load inversely related to wall thickness
-Thus, after load will vary continuously during systole

Question 11

Variables impacting afterload

Answer 11

SVR

LV hypertrophy

LVEDP

Question 12

Sympathomimetic

Answer 12

Drugs that mimic or modify actions of sympathetic nervous system via stimulation of alpha or beta adrenergic receptors.

Question 13

Catecholamines

Answer 13

Subset of sympathomimetics with -OH substitutions on benzene ring

Epi
Norepi
Isoproterenol
Dopamine
Dobutamine

Question 14

Sympathomimetics that are not catecholamines

Answer 14

Ephedrine and phenylephrine

Question 15

Common action of increased inotropy

Answer 15

Enhancement of Ca interaction with actin and myosin in cardiac myocytes

Question 16

Beta-1 agonist mechanism

Answer 16

Elevated cAMP followed by activation of protein kinase A

Opening of Ca channels

Ca influx and improved inotropy

Improved lusitropy due to PKA mediated activation of ATPase leading to increased calcium uptake in diastole

Question 17

Phosphodiesterase Type III inhibitor

Answer 17

Milrinone

Inhibition of PDE III causes intra-cytosol cAMP increase

Question 18

Levosimendan

Answer 18

Calcium sensitizer- does NOT increase cytosol Ca

Binds cardiac troponin C and stabilizes Ca bound form of the protein- prolonging contraction

Question 19

Factor influencing duration of action vasopressors/inotropes

Answer 19

elimination instead of redistribution!

Question 20

Catecholamine metabolism

Answer 20

MAO & COMT

Sequential metabolism to VMA- vanillylmandelic acid

Question 21

Phenylephrine metabolism

Answer 21

MAO

Question 22

Ephedrine and milrinone metabolism

Answer 22

Eliminated largely unchanged via kidneys

Question 23

Vasopressin elimination

Answer 23

2/3 unchanged

1/3 vasopressinases metabolize in liver and kidneys

Question 24

Levosimendan metabolism

Answer 24

Duration of action could be up to a week after a 24hr infusion

Metabolites form slowly

Actual drug levels fall rapidly after stopping the infusion

Question 25

Digoxin elimination

Answer 25

Unchanged via kidneys Half-life is 32-40 hours

Question 26

Drug interactions with catecholamines(2)

Answer 26

MAO inhibitors TCAs

Question 27

Unintended consequence of Epi induced B2 stimulation

Answer 27

Transient hyperkalemia -potassium follows glucose out of hepatic cells, eventually leads to hypokalemia

Question 28

Why don’t we see an increase in heart rate with B1 activity in norepi?

Answer 28

Increase in SVR induces reflex vagal activity… baroreceptor?

Question 29

Consequences of low dose Vaso infusion and 1 adverse effect!

Answer 29

Potent vaso constrictor, however it selectively dilates renal afferent, pulmonary and cerebral arterioles Increases blood pressure, urine output and creatinine clearance. Gastrointestinal ischemia

Question 30

Why is ephedrine longer acting than epinephrine?

Answer 30

Lack of catechol structure- resistant to metabolism by MAO

Question 31

Why does ephedrine stop working?

Answer 31

Tachyphylaxis may develop with subsequent dosing because catecholamine stores become depleted

Question 32

Conducted responses (definition)

Answer 32

Vascular smooth muscle induced at one level of circulation can be electrically propagated to others via conducted responses-modulated by gap junctions

Question 33

Comparison of VSM to cardiac muscle

Answer 33

VSM is more dependent on extracellular Ca, contracts more slowly, develops greater force, and can function over a wider range of length

Question 34

Modulation of VSM tone

Answer 34

Influx of Ca Release of Ca from SR Ca-CaM activation of myosin light chain kinase Phosphorylation causes linking of actin/myosin

Question 35

What is not required in the contraction of VSM?

Answer 35

Depolarization -simply requires entry of Ca into the cytoplasm

Question 36

Mechanisms of Vasodilation

Answer 36

Decreased entry of Ca Outward conductance of K Decreased release of Ca from SR Enhanced uptake of Ca into SR Decreased myofilament sensitivity to Ca