Med Chem - Shock Flashcards by Raeqa Mahmud

shock is defined as

an inadequate organ and peripheral tissue perfusion

How well did you know this?

Not at all

Perfectly

what are the categories of shock

hypovolemic
neurogenic
cardiogenic shock
restrictive - vasodilatory/distributive - septic
anaphylactic

How well did you know this?

Not at all

Perfectly

what kind of shock involves blood loss due to hemorrhage or fluid loss due to uncontrolled diarrhea/dehydration or losing plasma after serious burns

hypovolemic

How well did you know this?

Not at all

Perfectly

hypovolemic shock ____ cardiac output

decreases

How well did you know this?

Not at all

Perfectly

spinal cord injury leads to

neurogenic shock

How well did you know this?

Not at all

Perfectly

what kind of shock is characterized by sudden loss of sympathetic nerve activity

neurogenic shock

How well did you know this?

Not at all

Perfectly

during neurogenic shock the equilibrium shifts towards parasympathetic tone leading to the relaxation of blood vessels, hypotension, bradycardia, hypoxia leading to

multiple organ failure

How well did you know this?

Not at all

Perfectly

what kind of shock is caused by severe impairment of myocardial performance that results in reduced cardiac output, hypotension and end organ hypoperfusion

cardiogenic shock

How well did you know this?

Not at all

Perfectly

cardiogenic shock ___ inotropy and ____ chronotropy

decreases, decreases

How well did you know this?

Not at all

Perfectly

inotropy is

the force of heart muscle contraction

How well did you know this?

Not at all

Perfectly

chronotropy is

heart rate

How well did you know this?

Not at all

Perfectly

septic shock is cause by

infection

How well did you know this?

Not at all

Perfectly

what kind of shock involves massive vasodilation - hypotension and inadequate peripheral perfusion

septic

How well did you know this?

Not at all

Perfectly

a severe allergic response with decreased blood flow to the brain leading to fainting is known as

anaphylactic shock

How well did you know this?

Not at all

Perfectly

the treatment of shock patients involves the administration of

endogenous catecholamines
vasopressor agents
exogenous catecholamines

How well did you know this?

Not at all

Perfectly

what are the endogenous catecholamines

EPI and NE and DA

How well did you know this?

Not at all

Perfectly

vasopressin is a ___ agent

vasopressor

How well did you know this?

Not at all

Perfectly

what are the exogenous catecholamines

dobutamine and phenylephrine

How well did you know this?

Not at all

Perfectly

vasopressors ___ BP

increase

How well did you know this?

Not at all

Perfectly

inotropes ___ cardiac output

increase

How well did you know this?

Not at all

Perfectly

what are the inotropes

dopamine, dobutamine, milrinone

How well did you know this?

Not at all

Perfectly

what are the vasopressors that are adrenergic agonists

EPI NE DA

How well did you know this?

Not at all

Perfectly

what are the vasopressors that are GPCR agonists

vasopressin V1 V2

How well did you know this?

Not at all

Perfectly

what activates AT1 receptor and is an agonist

Angiotensin II

How well did you know this?

Not at all

Perfectly

AT1 receptor agonist acts by

vasoconstriction and increased BP

NE is a

endogenous NT in the sympathetic nervous system

adrenergic agonists are structurally related to

how do epi and ne differ

R group is H in NE and CH3 in EPI

catecholamines are ___ molecules with good solubility in body fluids

polar

___ is a circulatory hormone

epi

where is epi released from

the chromaffin cells in the adrenal medulla

what is the rate limiting step of epi and norepi synthesis

tyrosine hydroxylase

T or F Tyrosine hydroxylase is controlled by feedback inhibition by NE and EPI

EPI that is formed is stored in

granules until released

what primarily terminates the activity of NE and EPI

primarily by the reuptake into the presynaptic terminal followed by metabolism

other than reuptake, NE and EPI are terminated by metabolism by

COMT and MAO

what does COMT stand for

catechol o methyl transferase

what does MAO stand for

monoamine oxidase

where does MAO occur

mitochondria

COMT regioselectively methylates the ___ of catecholamines

meta OH

MAO acts on the primary amines of catecholamines by

oxidative deamination

T or F compounds that are resistant to even just one of the metabolic enzymes of EPI and NE have a longer duration of action and greater oral availability

what is the end metabolite of NE

vanillylmandelic acid VMA 4 hydroxy 3 methoxy mandelic acid

which catecholamine is most potent at alpha adenoceptors

NE EPI ISO

which catecholamines are most potent at beta adrenoceptors

ISO EPI NE

what are the three mechanisms of actions of adrenergic agonists

direct acting indirect acting mixed acting

direct acting adrenergic agonists have the

same affinity and intrinsic activity as the endogenous agonists NE and EPI

the indirect acting adrenergic agonists work by

stimulate release of NE from presynaptic terminals inhibit reuptake of released NE into presynaptic terminals inhibits the metabolic degradation of NE by MAO

the amino N of catecholamines must be

primary or secondary and separated by 2C from a substituted phenyl ring

if the amino N on catecholamines are ter or quaternary amines then they are

inactive

if R1 of catecholamines are H or CH3 then they

maintain affinity for both alpha and beta receptors, nonselective

if R1 of catcholamines are CHCH32 - isopropyl then

potent selectivty for beta receptors

if R1 of catecholamines is CCH33 - arylalkyl then confer

optimal beta affinity with some beta 2 selectivity but NO ALPHA RECEPTOR ACTIVITY

when are catecholamines sensitive to MAO mediated metabolism and why

when R2 has two alpha hydrogens because MAO requires an absolute 2 hydrogens on the alpha carbon

R3 of catecholamines must be in ___ configuration to effectively H bond with Asn293

what must R3 be in catecholamines and why

OH with catechol to yield direct adrenergic action at both alpha and beta receptors

the R4 and R5 side groups of catecholamines are attached to

catechol

if only one group of R4/5 is present with OH then it is preferred to be ___ to retain ___

R5 at 4, beta 2 activity

if in a catecholamine the phenyl group has no OH substituent then it may be

acting directly or indirectly

epinephrine is susceptable to ____ which is the removable of -ch3

n dealkylation

T or F epinephrine can penetrate the BBB

F, too polar to penetrate BBB, no CNS activity

NE is more or less polar than EPI

more -CH3 of EPI makes it more lipophillic

NE is a less potent ____ than EPI

inotrope

___ is a pure vasoconstrictor

when is NE preferred and why

settings in which heart rate stimulation is undesirable , minimal chronotropic effects

which pathway is generally desirable to treat shock patients mostly

alpha 1 stimulation

alpha 1 receptor stimulation leads to

vasoconstriction - contraction of vascular smooth muscle

beta 2 receptor stimulation leads to

vasodilation - relaxation of smooth muscle

_____ is a key regulator of cardiac contractility

phospholamban

alpha 1 signaling is ___ linked

Gq linked

alpha 2 signaling is ___ linked

Gi linked (inhibition)

alpha 2 signaling results in

reduction of camp

alpha 1 signaling results in

release of calcium and activation of calcium dependent pk

beta 2 signaling is linked to

Gs linked

beta 2 signaling leads to

increase in camp

epinephrine is CI in patients with

narrow angle glaucoma precaution in pregnancy

phenylephrine is a powerful vasoconstrictor due to

its lack of affinity for beta adrenergic receptors Ar-OF on 5 position instead of preferred 4

phenylephrine is more or less polar than EPI NE

less polar

because phenylephrine is less polar than EPI and NE it has a ___ half life

longer half life , duration of action

vasopressin is released from

posterior lobe of the pituitary fland

vasopressin is a ____ hormone

nonapeptide - 9 aa

there is ____ intramolecular disulfide bond between Cys1/6 in vasopressin

one

the effects of vasopressin are that it

regulates water reabsorption in the renal tubule

vasopressin is also known as

ADH antidiuretic hormone

what is the mechanism of action of vasopressin

V1 - gq and V2- gs receptor agonists

what are the primary actions of vasopressin

vasoconstriction and increased blood volume due to fluid reabsorption in the kidneys overall increased arerial pressure

dobutamine stimulates beta ___ receptor

dobutamine does not cause the release of

endogenous NE

dobutamine stimulates beta 1 receptors of the heart to

increase myocardial contractility and stroke volume resulting in increased cardiac output

milrinone is a

dihydrobipyridine

which drug is a PDEIII inhibitor

milrinone

what is the mechanism of action of milrinone

inhbits camp breakdown increases PKA inhibits MLCK which causes myosin light chains to contract leadign to no contract but relaxation

PDE III inhibition of milrinone prevents ___ which leads to vasodilation

cAMP hydrolysis

milrinone is a ___ inotrope and vasodilator

positive

milrinone acts by inhibiting PDE III which mimicks beta ___ activation

beta 1

when is milrinone active

R2 - CH3 R3 = H R5 = CN NH or BR all retain activity

milrinone is inactive when

R2 = H RH = CH3 and R5 is just H

for milrinone to be active the torsion angle must be

greater than 0 degrees

the renin angiotensin aldosterone system is ___ in septic shock which leads to impaired angiotensin II

altered

angiotensin II is a ____ peptide

octapeptide

what is the therapeutic use of angiotensin II

it is used to increase blood pressure in patients with hypotension

how is angiotensin II metabolized

by ACE 2 and aminopeptidase into heptapeptide

what is the half life of AG II in the circulation vs the tissues

about 30 seconds in circulation abot 15-30 minutes in tisses

AG II is used to increase

aldosterone and ADH secretion