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Therapeutics 2 - Fall 2017 > HTN - Hockerman > Flashcards

HTN - Hockerman Flashcards

1
Q

Vasoconstriction:

________ receptors are main cause

A

alpha (1) adrenergic

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2
Q

Vasoconstriction:

pathway from receptor to cell to potentiate constriction (@ alpha 1 receptor)

A

Gq –> PIP(3) –> Diacyglycerol and IP3 –> IP3 will cause increase in calcium…

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3
Q

How does Calcium lead to contraction?

A

Ca2+ + Calmodulin –> stimulates myosin light chain kinase which will phosphorylate myosin LC –> Myosin LC-PO(4) + actin - CAUSE CONTRACTION

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4
Q

2 main mechanisms for controlling smooth muscle tone

A

voltage gated Ca2+ channels
&
pharmaco mechanical coupling (Gq to IP3 to Ca2+ etc..)

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5
Q

what are the endogenous peptide vasoconstrictors?

A

angiotensin, vasopressin, endothelin, urotensin

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6
Q

which endogenous peptide vasocontstrictor is elevated in diabetes?

A

Urotensin

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7
Q

which endogenous peptide vasocontstrictor is elevated in PAH (pulmonary arterial hypertension)?

A

Endothelin

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8
Q

Urotensin (an endogenous vasoconstrictor) binds to ______ in ______ & _______

A

GPCRs; VSM (vascular smooth muscle); cardiac muscle

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9
Q

Urotensin is produced where?

A

heart, liver, kidney

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10
Q

Endothelin is produced where?

A

vascular endothelium…

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11
Q

Endothelin binds to ______ in _____ and contracts ______

A

GPCRs; VSM; VSM

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12
Q

3 main reasons we would want to modulate vascular smooth muscle?

A

resistance vessels; controlling blood flow, cerebral arteries

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13
Q

What are therapeutic uses of vasoconstrictors?

A

TREATING HYPOTENSION:

b/c shock, anesthesia, or chronic orthostatic hypotension

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14
Q

For treating hypotension - what receptor agonists are used?

A

alpha 1 adrenergic

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15
Q

what are examples of drugs that treat hypotension (aka what are some alpha 1 adrenergic drugs)

A

epinephrine, ephedrine, midodrine

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16
Q

what types of shock can be treated with vasoconstrictors

A

anaphylactic shock, brain trauma, hemorrhagic

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17
Q

Using Vasoconstrictors for controlling of blood flow: what are reasons to do this?

A
  • using with anesthetics b/c it will reduce blood flow to site of injection
  • Hemostasis during surgery
  • Nasal/Opthalmic Decongestants
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18
Q

what type of vasoconstrictor is used adjunctively with anesthetics

A

epinephrine

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19
Q

what type of vasoconstrictors are used for hemostasis during surgery

A

epinephrine, cocaine

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20
Q

What is a direct acting vasoconstrictor used as a decongestant

A

phenylephrine

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21
Q

What is a indirect acting vasoconstrictor used as a decongestant

A

pseudoepedrine, ephedrine, phenylpropanolamine

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22
Q

What is a partial acting vasoconstrictor agonist used as a decongestant

A

naphazoline, tetrahydrolozine, oxymetazoline

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23
Q

what are the 4 main groups of vasodilators talked about?

  • ________ modulators
  • _______ Agonists
  • _______ Antagonists
  • _______ Analogs
A
  • Cyclic GMP modulators
  • K+ Channel Agonists
  • Endothelin Antagonists
  • PGI2 Analogs
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24
Q

what are the 3 group/subsets of cyclic GMP modulators

A
  • organic nitrates/nitrites
  • PDE inhibitor
  • Natriuretic peptide
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25
Q

Nitric Oxide Synthase has __(#)___ of isoforms and there names are….

A

3!

nNOS; iNOS; eNOS

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26
Q

which isoform of NOS (nitric oxide synthase) is most important to us?

A

eNOS (endothelial)

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27
Q

NOS (nitric oxide synthase) is found in the _________

A

vascular endothelium

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28
Q

What is the pathway/process of Nitric Oxide Synthase?

A

L-Arginine –? L-Citruline + NO

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29
Q

eNOS is found in ________ and gets activated by ______

A

vascular endothelium/ Ca2+-CAM

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30
Q

where is Guanylate Cyclase found? (talking about Nitric Oxide-Cyclic GMP Pathway)

A

vascular smooth muscle

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31
Q

______ is an activator of guanlyl cyclase

A

NO

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32
Q

Why/How does Ach (acetylcholine) lead to Smooth Muscle Relaxation

A

Ach will increase Ca2+ in endothelium which will stimulate eNOS –> eNOS makes NO –> NO causes smooth muscle relaxation

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33
Q

NO stimulates Guanlyl cyclase –> what does guanlyl cyclase do?

A

it will take GTP and make it into cGMP

GTP –> cGMP

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34
Q

Nitric Oxide binds to ___________ in guanylate cyclase

A

heme iron prosthetic group

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35
Q

NO binds to Guanlyate cyclase and will stimulate production of ______ and will activate _______

A

cGMP; cGKI (aka PROTEIN KINASE G aka PKG)

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36
Q

how does cGMP lead to relaxation (talking about Nitric Oxide-Cyclic GMP Pathway)

A

cGMP will cleave the PO(4) group from Myosin-LC (this leads to relaxation)

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37
Q

Myosin-LC will cause ________
vs
Myosin-LC-PO(4) will cause ______

A

relaxation; contraction

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38
Q

how does PKG (cGKI) cause relaxation in smooth muscle (talking about Nitric Oxide-Cyclic GMP Pathway)

  • ________ of L-Type Ca2+ Channels
  • ________ of Ca2+-activated K+ channels
  • ________ MLC phosphorylation
  • ________ Ca2+ uptake in to ER
A

inhibit (Ca2+ channels)
Stimulate (Ca2+ activated K+ channels)
decrease (MLC phosphorylation)
enhance (Ca2+ into ER)

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39
Q

how does PKG (cGKI) cause relaxation in smooth muscle (talking about Nitric Oxide-Cyclic GMP Pathway)

A

inhibit (Ca2+ channels)
Stimulate (Ca2+ activated K+ channels)
decrease (MLC phosphorylation)
enhance (Ca2+ into ER)

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40
Q

PKG will _______ L-Type Ca2+ Channels - why does this cause relaxation of smooth muscle?

A

inhibit ;less Ca2+ influx = less contraction

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41
Q

PKG will _______ Ca2+ activated K+ Channels - why does this cause relaxation of smooth muscle?

A

STIMULATE (because it will cause repolarizaiton of the membrane potential)

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42
Q

PKG will _______ myosin phosphorylation -

why does this cause relaxation of smooth muscle?

A

decrease (because when there is NOT a PO4 group on myosin head dettaches from myosin and no contraction can happen aka relaxation…)

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43
Q

PKG will _______ Ca2+ uptake in to ER -

why does this cause relaxation of smooth muscle?

A

enhanced (b/c less Ca2+ available = less contraction)

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44
Q

what channel does PKG inhibit?

A

Ca(v1.2)

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45
Q

what channel does PKG stimulate

A

BK(Ca)

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46
Q

what is used by PKG to enhanceCa2+ uptake in the ER

A

phospholamban (it gets phosphorylated and then will increase the reuptake of Ca2+)

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47
Q

Organic Nitrates cause vaso________

A

dilation

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48
Q

Organic Nitrates are (selective or non-selective) vasodilators

A

NON-selective

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49
Q

Organic Nitrates (do or do not) require a functional endothelium

A

DO NOT

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50
Q

Organic nitrates can be used (acutely, chronically, or both)

A

BOTH!

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51
Q

Organic nitrates require ________ to get broken down to _____

A

bioactivation; Nitric Oxide

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52
Q

Organic Nitrates can be by what routes for prolonged prophylaxis

A

Transdermal/Orally

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53
Q

Organic Nitrates can be by what routes for acute attacks of angina

A

give sublingually

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54
Q

T or F: Organic Nitrates cannot develop tolerance

A

FALSE

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55
Q

Which of the following Organic Nitrates has the greatest oral bioavailability?
GTN, ISDN, 5-ISMN

A

5-ISMN (isosorbide mononitrate)

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56
Q

Which of the following Organic Nitrates has the lowest oral bioavailability?
GTN, ISDN, 5-ISMN

A

GTN ( super freaking low)

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57
Q

Which of the following Organic Nitrates has the longest half life?
GTN, ISDN, 5-ISMN

A

5-ISMN

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58
Q

which organic nitrate is commonly known to not be efficacious in the Asian Population

A

GTN (Glycerol Trinitrate)

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59
Q

what is the polymorphism known to decrease the efficacy of GTN

A

GLU 504 –> LYS 504 (in ALDH-2)

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60
Q

what enzyme is needed to activate GTN

A

ALDH-2

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61
Q

The ______ allele is the reason for decreased efficacy of GTN AND it can cause _____

A

LYS 504; Alcohol intolerance (aka “Asian Glow”)

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62
Q

what is the idea behind organic nitrate tolerance? (Example given in class is GTN bc it is the most understood)

A

GTN gets metabolized by ALDH-2 into a thionitrate intermediate. ALDH-2 needs to be regenerated and a reduced form of LIPOIC ACID is needed (can eventually deplete lipoic acid store!)

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63
Q

Explain the differences in GTN vs ISMN/ISDN activation

A

GTN - needs lipoic acid/needs ALDH-2!!

ISMN/ISDN = uses enzymes outside of mitochondria to be metabolized (P450 and others…)

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64
Q

which organic nitrate is used for acute management of HTN crisis/severe decompensated heart failure

A

Sodium Nitroprusside (SNP) (GIVEN IV)

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65
Q

SNP - Sodium Nitrodpursside will ______ veins and arterioles

A

Dilate

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66
Q

SNP - Sodium Nitrodpursside gets metabolized by _______

A

erythrocytes

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67
Q

SNP - Sodium Nitrodpursside is metabolized and made into what things?

A

NO (duh), 4 CN (obvs not good to have hella cyanide in your body), and Cyanmethemoglobin

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68
Q 
SNP - Sodium Nitrodpursside:
Its metabolite (CN-) can inhibit \_\_\_\_\_\_\_ metabolism/ \_\_\_\_\_\_\_ accumulation
A

oxidative; lactic acid

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69
Q

SNP - Sodium Nitrodpursside:

CN- gets converted to _______ by ______ (bc it is less toxic in this form) and then is excreted by ______

A

SCN (thiocyanate); rhodanase; kidney

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70
Q

what 2 things can be used for detoxification (of CN-) after using SNP - Sodium Nitrodpursside

A

Sodium thiosulfate OR hydroxocobalamin

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71
Q

what class of drug is Hydralazine apart of? (Organic nitrate? Natriuretic Peptide? PDE Inhibitor? K+ Channel Agonist?)

A

Organic Nitrate!

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72
Q

Hydralazaine causes vaso______

A

dilation (its a nitrate!) of ARTERIOLES

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73
Q

Predicted mechanism of Hydralazine

A

interferes w/ release of Ca2+ from the ER

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74
Q

Hydralazine can induce a _______ syndrome

A

lupus-like

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75
Q

Hydralazine dilates what?

A

ARTERIOLES! (not veins like other organic nitrates)

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76
Q

what is drug called that is a combo of ISDN and Hydralazine?

A

BiDil

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77
Q

why is hydralazine and ISDN in a combo pill together?

A

the antioxidant activity of Hydralazine will potentiate vasodilatory activity of ISDN

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78
Q

What is Natrecor (Nesiritide)?

A

a vasodilator;

a natriuretic peptide

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79
Q

Natrecor (Nesiritide) is given by what route?

A

IV

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80
Q

Natrecor (Nesiritide) is given IV for what?

A

acutely decompensated HF

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81
Q

how does Natrecor (Nesiritide) work?

A

it BINDS to and ACTIVATES membrane bound guanylate cyclase in vascular smooth muscle and endothelial cells
ALSO
causes you to lose fluid = less blood volume = less work load on the heart

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82
Q

Natrecor (Nesiritide) is synthesized and secreted from where?

A

heart muscle

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83
Q

Natrecor (Nesiritide) is released from the heart in response to what?

A

response to INCREASED blood volume

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84
Q

PDE Inhibitors cause vaso_______

A

dilation

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85
Q

What are the 2 groups of PDE inhibitors we learned about?

A

PDE3 inhibitor/ PDE5 inhibitor

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86
Q

PDE3 inhibitors prevent the breakdown of c____ and PDE5 inhibitors prevent the breakdown c____

A

AMP; GMP

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87
Q

How do PDE3 inhibitors work?

A

NORMALLY PDE3 will breakdown cAMP into AMP; but if that is inhibited you have more cAMP –> more MLCK-PO(4) –> Relaxation

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88
Q

a part of what drug class is Amrinone?

A 
PDE3 inhibitor (cAMP modulator -
Vasodilator)
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89
Q

a part of what drug class is Milrinone?

A 
PDE3 inhibitor (cAMP modulator -
Vasodilator)
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90
Q

a part of what drug class is Dipyridamole?

A 
PDE5 inhibitor  (cGMP modulator -
Vasodilator)
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91
Q

a part of what drug class is sildenafil?

A

SELECTIVE PDE5 inhibitor (cGMP modulator -

Vasodilator)

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92
Q

a part of what drug class is Hydralazine?

A

Organic Nitrate (cGMP modulator - Vasodilator)

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93
Q

a part of what drug class is Tadalafil?

A

SELECTIVE PDE5 inhibitor (cGMP modulator -

Vasodilator)

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94
Q

a part of what drug class is Vardenafil?

A

SELECTIVE PDE5 inhibitor (cGMP modulator -

Vasodilator)

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95
Q

Amrinone/Milrinone (cAMP PDE3 inhbitors)

Are given by _____ route

A

IV

96
Q

Amrinone/Milrinone (cAMP PDE3 inhbitors)

have a direct ________ effect on the ______

A

positive inotropic; Myocardium

97
Q

Amrinone/Milrinone (cAMP PDE3 inhbitors):

has (minimal or maximal) chronotropic effect

A

MINIMAL

98
Q

Amrinone/Milrinone (cAMP PDE3 inhbitors) has a direct vasodilatory effect on _________

A

vascular smooth muscle

99
Q

Amrinone/Milrinone (cAMP PDE3 inhbitors)

is used mainly in _____ (acute treatment)

A

CHF

100
Q

PDE 5 is predominant in _______ (what area of the body)

A

corpus cavernosum (why ED meds work where they do)

101
Q

Sildenafils effect on the blood flow of the penis:

_______ artery dialtes + ______ smooth muscle –> increased _______ space

A

Helicine (artery); relaxaed; Sinusoidal

102
Q

Brand for Tadalafil

A

Cialis

103
Q

Brand for Vardenafil

A

Levitra

104
Q

Brand for Sildenafil

A

Viagra

105
Q

which ED med…
has a shorter time to onset than Viagra
AND
is more selective for PDE5 than viagra

A

Levitra (Vardenafi)

106
Q

which ED med…
is more selctive for PDE5 than viagra
AND
has a longer duration of action than the other drugs in its class

A

Cialis (Tadalfil)

107
Q

K+ channel agonists/openers cause vaso______

A

dilation

108
Q

why do K+channels cause vasodilation?

A

when the K+ channel is open - the membrane potential gets closer and closer to K+ equilibrium potential —–> makes it harder to depolarize the membrane enough to open the voltage gated Ca2+ channels (and Ca2+ channels normally cause vasoconstriction)

109
Q

what drug class is Minoxidil apart of ?

A

K+ channel agonists/openers (Vasodilator)

110
Q

what drug class is diazoxide apart of?

A

K+ channel agonists/openers (vasodilator)

111
Q

what are the K+ Channel agonists/openers we learned about

A

Minoxidil; Diazoxide

112
Q

Minoxidil: activated by ________

A

sulfonotransferase 1A1

113
Q

Minoxidil: used with what 2 medications

A

loop diuretics and beta blockers (why? idfk)

114
Q

Minoxidil: is a very potent vaso______

A

dilator!! (used for severe/drug resistant forms of HTN)

115
Q

Minoxidil: is given by what route?

A

orally

116
Q

Minoxidil: __________ may contribute to its efficacy

A

cAMP PDE inhibition

117
Q

Diazoxide: used by what route for acute HTN

A

IV

118
Q

Diazoxide: very potent vaso_______

A

dilator!! (used for severe/drug resistant forms of HTN)

119
Q

Diazoxide: inhibits the release of _________ from _______

A

insulin; pancreatic Beta-cells

120
Q

Diazoxide: used orally for ___________

A

hypoglycemia secondary to hyperinsulinemia

121
Q

Adenosine is a vaso______

A

dilator

122
Q

adenosine binds to __________

A

A1 receptor GPCR

123
Q

Adenosine increases conductance of a ________ which causes _____ polarization and relaxation of vascular smooth muscle

A

K+ channel; hyper

124
Q

A1 receptor causes hyperpolarization - via the ______ channel

A

GIRK

125
Q

Adenosine uses what type of GPCR/works how

A

G(beta/gamma) binds to GIRK to conduct K+ and causing membrane hyperpolarization

126
Q

What classes of drugs can be used for PAH (Pulmonary Arterial HTN)

A

Vasoconstrictor Antagonists; Prostacyclin Analogs

127
Q

what drug class is Bosentan in?

A

Vasoconstrictor antagonist for PAH (aka a vasodilator)

128
Q

what drug class is Macitentan?

A

Vasoconstrictor antagonist for PAH (aka a vasodilator)

129
Q

what drug class ambrisentan?

A

Vasoconstrictor antagonist for PAH (aka a vasodilator)

130
Q

how do vasoconstrictor antagonists work?

A

they are antagonists to endothelin receptors

131
Q

which vasoconstrictor antagonist(s) (-entans) block both ET(A) and ET(B)

A

Bosentan; Macitentan

132
Q

which vasoconstrictor antagonist(s) (-entans) block only ET(A)

A

Ambrisentan

133
Q

T or F: Vasoconstrictor antagonists can be used in pregnancy

A

FALSE!!

134
Q

Which (entan) drug can cause hepatotoxicity

A

bosentan

135
Q

Prostacyclin analogs can be used to cause vaso_____

A

dilation

136
Q

Prostacyclin analogs can be used to treat ___________

A

PAH (pulmonary arterial HTN)

137
Q

what are the possible prostacyclin analogs?

A

PGI2; Trepostinil; Iloprost; Selexipag

138
Q

What are the 4 different classes of drugs that can be used for PAH

A
  • Vasoconstrictor antagonists (endothelin antagonist)
  • Prostacyclin analogs (vasodilator)
  • Allosteric Activator of sGC
  • Selective PDE5 inhibitors (Cialis/Viagra)
139
Q

what is the drug used for PAH that is known as an allosteric activator of sGC

A

Riociguat (Adempas)

140
Q

how does the Riociguat (Adempas) work?

A

it is an allosteric activator of sGC; it potentiates the effect of NO; will increase cGMP concentration in VSM

141
Q

Riociguat (Adempas)

  • Not combined with _______ or ______
  • Contraindicated in _________
  • Risk of ________
A

Nitrates or PDE 5 inhibitors; Pregnancy; Hemorrhage

142
Q

What two things that determine the direction of flow of ions?

A

Concentration gradient and Electrical

143
Q

Ion Channels are ______ that form ______ in the plasma membrane

A

proteins; pores

144
Q

Ion Channels can be categorized by what 3 main things

A

Gating mechanism; Ion selectivity, Pharmacology (Passive-ness?)

145
Q

Membrane Potential:

Excitable cells have a ______ inward potential across the membrane due to the selective permeability of the resting membrane to ______

A

negative; K+

146
Q

K+ is ____ inside of the cell and ____ outside

A

HIGH INSIDE; LOW OUTSIDE

147
Q

Na+ is ____ inside of the cell and ____ outside

A

LOW INSIDE; HIGH OUTSIDE

148
Q

Ca2+ is ____ inside of the cell and ____ outside

A

HIGH OUTSIDE; VERRRRRY LOW OUTSIDE

149
Q

Ca2+/Na+/K+ - which one has the highest gradient (difference between outside and inside of the cell)

A

Ca2+!!

150
Q

Ca2+ channel - open slow or fast?

A

V slow

151
Q

Structure of Voltage Gated-Channels:

There is a _______ filter to allow the ion to come in and a _____ of ______ to block the ion

A

selectivity; bundle of helicies

152
Q

______ is a H+ gated K+ channel from bacteria

A

Kcsa

153
Q

______ is a Ca2+ gated K+ channel from bacteria

A

MthK

154
Q

what are the possible types of Calcium Channels

A

L-Type; P/Q type; N-type; R-type

155
Q

What Calcium channel do we care the most about for Ca2+ blockers for HTN

A

Cav1.2

156
Q

where is Cav1.2 calcium channels found

A

Cardiac & Smooth Muscle

Ca2+ entry triggers contraction

157
Q

The following are the responses that come from Calcium Channel Blockers:
Decrease in ________
Relief of _________
Anti________

A

Decrease in BLOOD PRESSURE;
Relief of ANGINA PECTORIS
AntiARRHYTHMIC

158
Q

Vasc. Smoot Muscle Contraction (related to Calcium)

(_ _ _ _) - a four letter acronym and what does it stand for

A

CICR; Ca2+ induced Ca2+ release

159
Q

[Vasc. Smoot Muscle Contraction - CICR]

How does it work?

A

Ca2+ comes into cell (influx) via Cav1.2 which induces Ca2+ from intracellular stores via RYR2 in the SR

160
Q

[Vasc. Smoot Muscle Contraction - CICR]
Ca2+ comes into cell (influx) via Cav1.2 which induces Ca2+ from _____cellular stores via ______ (_________) in the _____

A

INTRAcellular; via RYR2 (ryanodine receptor 2); in the SR

161
Q

Beta-adrenergic Modulation via Ca2+ Channels: (aka epinephrines effect on Ca2+/vasc. smooth muscle)
The adrenergic receptor will cause ___________ of _____ and increase Ca2+ influx

A

PKA phosphorylation; Cav1.2

162
Q

Beta-adrenergic Modulation via Ca2+ Channels: (aka epinephrines effect on Ca2+/vasc. smooth muscle)
This will cause the increase in what two things?

A

Increase in contractility/force of contraction

Increase AV nodal action potential conduction rate

163
Q

T or F: Extracellular calcium is NOT required for contraction of cardiac and vascular smooth muscle

A

FALSE! it is required

164
Q

Myosin LC-PO4 is needed to work with _____ to cause contraction

A

ACTIN

165
Q

T or F: Myosin LC-PO4 is INACTIVE and will not cause contraction

A

FALSE! Myosin LC has to be phosphorylated to work with actin and cause contraction

166
Q

T or F: Myosin LC kinase - PO4 is INACTIVE and will not cause contraction

A

True! if the KINASE is phosphorylated then no contraction…(opposite of just straight up myosin LC)

167
Q

[Cardiac Muscle Contraction]

the Ca2+ ion gets released from _________ and binds to _________

A

sarcoplasmic reticulum; Troponin C

168
Q

[Cardiac Muscle Contraction]

When Ca2+ binds to ________ it causes the displacement of _________

A

troponin C; Tropomyosin

169
Q

[Cardiac Muscle Contraction]

When Tropomyosin is displaced it allows ______ to bind to _____ which causes ________

A

myosin; actin; contraction! (duh)

170
Q

What calcium channel and receptor is used in skeletal muscle? (close to cardiac and smooth but different…)

A

Cav1.1 and RYR1

aka 1’s instead of 2’s

171
Q

T or F: Extracellular Ca2+ is NOT required for contraction in skeletal muscle

A

TRUE! (opposite of cardiac/smooth)

172
Q

CCBs (calcium channel blockers) work at which location(s)?
Cardiac
Skeletal
Smooth

A

Cardiac and Smooth! (NOT skeletal)

173
Q

what are the 3 main classes of CCBs

A

Dihydropyridines
Phenylalkylamines
Benzothiazepines

174
Q

What are the clinical applications of CCBs (per Hockerman)

A

Angina Pectoris
Arrhythmia
HTN

175
Q 
what class of CCB is the drug a part of?
Nifedipine
A

DHP

176
Q 
what class of CCB is the drug a part of?
Felodipine
A

DHP

177
Q 
what class of CCB is the drug a part of?
Isradipine
A

DHP

178
Q 
what class of CCB is the drug a part of?
Amlodipine
A

DHP

179
Q 
what class of CCB is the drug a part of?
Nisoldipine
A

DHP

180
Q

what class of CCB is the drug a part of?Nicardipine

A

DHP

181
Q 
what class of CCB is the drug a part of?
Nimodipine
A

DHP

182
Q 
what class of CCB is the drug a part of?
Clevidipine
A

DHP

183
Q 
what class of CCB is the drug a part of?
Dilitiazem
A

Benzothiazepine

184
Q 
what class of CCB is the drug a part of?
Verapamil
A

Phenylalkylamine

185
Q

List the Structural Qualities of DHPs

A

Dihydropyridine Ring….
Aryl group
Chrial Center!! (@ pos 4)
Ester linked side chains

186
Q

which CCB is formulated w/ lipids from soy and egg

A

Clevidipine

187
Q

which CCB is known as a short acting DHP & why is it short acting

A

Clevidipine; fast metabolism by esterases!

188
Q

DHP’s blocking mechanism: stems form clues seen from _________

A

enatiomers

189
Q

DHP’s Enantiomer:

a (+) enantiomer will _____ current

A

BLOCK

190
Q

DHP’s Enantiomer:

a (-) enantiomer will _____ current

A

POTENTIATE

191
Q

DHP’s Enantiomer:

Mechanism involves interference with _______

A

gating

192
Q

DHP’s Enantiomer:

(+) enantiomer will interfere with (opening or closing?

A

opening!

193
Q

DHP’s Enantiomer:

(-) enantiomer will interfere with (opening or closing?

A

closing!

194
Q

DHP Enantiomer:

(+) enantiomer - what is its effect on gating and current?

A

it BLOCKS current by OPENING the gate (opening a gate will stop voltage)

195
Q

DHP Enantiomer:

(-) enantiomer - what is its effect on gating and current?

A

it POTENTIATES current by CLOSING the gate

196
Q

T or F: DHPs are not selective for vasculature

A

FALSE! they are dope bc they are selective for vasculature –

197
Q

T or F: DHPs are NOT antiarrhythmics

A

True! - they do not compromise cardiac function

198
Q

How do DHP drugs work at their binding site/in what “state” must the channel be in for the drug to bind

A

channel must be CLOSED!

this is known as TONIC BLOCK/Voltage Dependence

199
Q

Explain Voltage Dependence (related to DHP block)

A

The affinity of the drug is dependent on the voltage. If the voltage is more positive - there is greater binding/blockage. this is because if it is MORE (+) of a voltage - channel more likely to be closed and DHPs need the channel to be closed to bind!

200
Q

which DHP exhibits selectivity for cerebral arteries

A

Nimodipine (aka good for brain bleeds)

201
Q

Do DHPs have reflex tachycardia/cause an increase in Heart rate?

A

Yes

202
Q

Which DHP has LESS vascular specificity

A

Nifedipine

203
Q

Why do DHPs have efficacy in angina?

A

the reduce oxygen demand in the heart

204
Q

DHPs reduce the _______ demand in the heart

A

Oxygen

205
Q

DHPs (except ________) do or do not depress cardiac function

A

Nifedipine; DO NOT

most DHPs do NOT depress cardiac function

206
Q

DHPs - what is their binding to serum proteins like? (low or high binding?)

A

HIGH protein binding

207
Q

DHPs - do they undergo 1st metabolism in the liver? yes or no?

A

yes they do - extensive 1st pass

208
Q

which DHP has a slow onset and long duration of action

A

amlodipine

209
Q 
DHPs have VASCULAR SELCTIVITY:
This means that they have 
- Marked decrease in \_\_\_\_\_\_\_\_\_\_
- Decreased \_\_\_\_\_\_\_\_\_
- Have little effect on \_\_\_\_\_\_\_\_\_
A

Decrease in Peripheral resistance;
Decreased afterload
Little effect on heart rate/force of contraction

210
Q

DHPs have VASCULAR SELCTIVITY:
This means that they dilate ______ but have little effect on ______
(fill the blanks with arterioles or venules)

A

dilate arterioles

little effect on venules

211
Q

which DHP had increased risk of subsequent of MI?

A

Nifedipine

The fast/prompt release formulations could increase risk of subsequent MI

212
Q

Why could Nifedipine cause a subsequent MI?

A

the prompt release formulations - can cause rapid decrease in BP may lead to reflex sympathetic response (Tachycardia)

213
Q

Phenylalkylamine - Verapamil:

Is it more or less potent at vasodilation compared to DHPs

A

LESS potent

214
Q

Phenylalkylamine - Verapamil:

Reduces HR/Force of Contraction via what mechanism?

A

it slows conduction through SA and AV nodes

215
Q

Phenylalkylamine - Verapamil:

Tachycardia reflex present ?

A

no! the tachycardia is blunted

216
Q

Phenylalkylamine - Verapamil:

Has an inhibitory effect on the heart - this is due to ________ block

A

frequency dependent

217
Q

Phenylalkylamine - Verapamil:

Binds to the channel when it is ______ aka _______ block

A

OPEN! (drug has to enter the pore); frequency dependent block

218
Q

Explain Frequency dependent block

A

the drug (Verapamil) has to bind to the channel when it is OPEN - therefore higher frequency of the channel opening = higher potency.

219
Q

DHP or Phenylalkylamine:

has NO effect on the heart

A

DHP (its not like 0 effect but it is much lower than Phenylakylamine)

220
Q

DHP or Phenylalkylamine:

will reduce HR and force of contraction via slowing conduction through SA/AV nodes

A

phenylalkylamine

221
Q

DHP or Phenylalkylamine:

which one has LESS vasodilation

A

Phenylalkylamine:

222
Q

DHP or Phenylalkylamine:

which one has greater vasodilation

A

DHP

223
Q

DHP or Phenylalkylamine:

which one has reflex tachycardia

A

DHP

224
Q

DHP or Phenylalkylamine:

Which one does NOT have reflex tachycardia

A

Phenylalkylamine:

225
Q

DHP or Phenylalkylamine:

which one uses frequency dependent block

A

Phenylalkylamine:

226
Q

DHP or Phenylalkylamine:

which one uses tonic block?

A

DHP (voltage dependence)

227
Q

which drug is apart of the benzothiazepine class?

A

diltiazem

228
Q

Benzothiaxepine - Diltiazem

Causes vasodilation but is less potent than ______

A

DHPs

229
Q

Benzothiaxepine - Diltiazem

will directly inhibit the heart but is less potent than ______ but more than _____

A

verapamil; DHPs

230
Q

which CCB causes constipation?

A

Verapamil

231
Q

which CCB causes ankle edema and why?

A

all of them do!! because they are dilating vessels

232
Q

which CCB causes facial flushing

A

DHPs

233
Q

which which CCB causes tachycardia

A

DHPs (not amlodipine)

234
Q

which CCB has a greater decrease in heart rate?

A

Verapamil (diltiazem also decrease HR but not as much as verapamil)

235
Q

which CCB has the greatest vasodilation effect

A

DHPs (all cause vasodilation tho)

236
Q

which CCB has the greastest effect/decrease in AV conduction and myocardial contraction?

A

Verapamil (Diltiazem does it too but not as much as Verapamil)

Therapeutics 2 - Fall 2017 (22 decks)

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