Vasopressors/inotropes Flashcards
CO=
HRxSV
Positive chronotropy
Increased heart rate
Negative chronotropy
Decreased heart rate
Dromotropy
Related to velocity of conduction (degree of delay in AV node)
Positive-increased speed of conduction
Negative-decreased speed of conduction
Inotropy
Strength of contraction
Preload
LV End diastolic volume just prior to contraction
Factors that impact preload
Changes in SVR
Intravascular volume
Sympathetic outflow
Skeletal muscle contraction- enhances venous return
Lusitropy
Rate of myocardial relaxation- impacts diastolic filling of LV
After load
Force opposing LV contraction
-tension or stress of LV wall during systole- not synonymous with SVR
Law of Laplace
-after load directly related to intraventricular pressure/size
-after load inversely related to wall thickness
-Thus, after load will vary continuously during systole
Variables impacting afterload
SVR
LV hypertrophy
LVEDP
Sympathomimetic
Drugs that mimic or modify actions of sympathetic nervous system via stimulation of alpha or beta adrenergic receptors.
Catecholamines
Subset of sympathomimetics with -OH substitutions on benzene ring
Epi
Norepi
Isoproterenol
Dopamine
Dobutamine
Sympathomimetics that are not catecholamines
Ephedrine and phenylephrine
Common action of increased inotropy
Enhancement of Ca interaction with actin and myosin in cardiac myocytes
Beta-1 agonist mechanism
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
Phosphodiesterase Type III inhibitor
Milrinone
Inhibition of PDE III causes intra-cytosol cAMP increase
Levosimendan
Calcium sensitizer- does NOT increase cytosol Ca
Binds cardiac troponin C and stabilizes Ca bound form of the protein- prolonging contraction
Factor influencing duration of action vasopressors/inotropes
elimination instead of redistribution!
Catecholamine metabolism
MAO & COMT
Sequential metabolism to VMA- vanillylmandelic acid
Phenylephrine metabolism
MAO
Ephedrine and milrinone metabolism
Eliminated largely unchanged via kidneys
Vasopressin elimination
2/3 unchanged
1/3 vasopressinases metabolize in liver and kidneys
Levosimendan metabolism
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
Digoxin elimination
Unchanged via kidneys
Half-life is 32-40 hours
Drug interactions with catecholamines(2)
MAO inhibitors
TCAs
Unintended consequence of Epi induced B2 stimulation
Transient hyperkalemia
-potassium follows glucose out of hepatic cells, eventually leads to hypokalemia
Why don’t we see an increase in heart rate with B1 activity in norepi?
Increase in SVR induces reflex vagal activity… baroreceptor?
Consequences of low dose Vaso infusion and 1 adverse effect!
Potent vaso constrictor, however it selectively dilates renal afferent, pulmonary and cerebral arterioles
Increases blood pressure, urine output and creatinine clearance.
Gastrointestinal ischemia
Why is ephedrine longer acting than epinephrine?
Lack of catechol structure- resistant to metabolism by MAO
Why does ephedrine stop working?
Tachyphylaxis may develop with subsequent dosing because catecholamine stores become depleted
Conducted responses (definition)
Vascular smooth muscle induced at one level of circulation can be electrically propagated to others via conducted responses-modulated by gap junctions
Comparison of VSM to cardiac muscle
VSM is more dependent on extracellular Ca, contracts more slowly, develops greater force, and can function over a wider range of length
Modulation of VSM tone
Influx of Ca
Release of Ca from SR
Ca-CaM activation of myosin light chain kinase
Phosphorylation causes linking of actin/myosin
What is not required in the contraction of VSM?
Depolarization
-simply requires entry of Ca into the cytoplasm
Mechanisms of Vasodilation
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
