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Cardio Week 1 > ICL 1.6: Autonomic Nervous System Pharmacology II > Flashcards

ICL 1.6: Autonomic Nervous System Pharmacology II Flashcards

1
Q

what is the main way that catecholamine effects are terminated?

A

reuptake into the presynaptic cells via transport

catecholamines = epinephrine, norepinephrine

cholinergic is mainly degradation via AChE

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2
Q

what are the targets for direct-acting drugs?

A

receptors

ex. adrenergic receptors aka α, β and DA

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3
Q

how might you increase NE signaling?

A
  1. agonist at adrenergic receptors**
  2. block reuptake transport**
  3. inhibit enzymatic degradation
  4. auto/heteroreceptors that control negative feedback
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4
Q

how do presynaptic auto receptors and heteroreceptors work?

A

they are negative feedback mechanisms

if you get enough norepinephrine in the synapse it binds to the autoreceptors on the presynaptic neuron and turns down NE signaling

heteroreceptors are when other NT bind and turns down NE signaling

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5
Q

how might you decrease NE signaling?

A
  1. adrenergic receptor antagonists**
  2. up regulate transporters or degradative enzymes
  3. block neurotransmission in general
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6
Q

what is the mechanism of adrenergic receptors?

A

they’re all GPCRs!

α1 = Gq
α2 = Gi
β1-3 = Gs
DA = Gs

Gq = IP3 pathway, increases Ca+2, contraction

Gi = decreases cAMP, contraction

Gs = increases cAMP

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7
Q

what are the key effects of α1 adrenergic receptors?

A
  1. vascular smooth muscle constriction in skin and splanchnic**
  2. radial muscle contraction = mydriasis
  3. bladder sphincter and prostate contraction
  4. increases heart force
  5. ejaculation
  6. constrict GI sphincters
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8
Q

what are the key effects of α2 adrenergic receptors?

A
  1. inhibits NE release presynaptically** (basically autoreceptors)
  2. decreases SNS outflow from the brain**
  3. constriction of blood vessels
  4. decreases eye fluid production
  5. decrease tone, motility and secretions in the GI
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9
Q

what are the key effects of β1 adrenergic receptors?

A
  1. increase heart rate and force**

2. increases renin release in the kidney

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10
Q

what are the key effects of β2 adrenergic receptors?

A
  1. bronchodilator of airway smooth muscles**
  2. vascular smooth muscle dilation in skeletal muscles**
  3. increase eye fluid production
  4. relaxation of the detrusor in the bladder to keep bladder in
  5. uterus relaxation to keep baby in
  6. increase glycogenolysis and gluconeogenesis
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11
Q

what are the key effects of β3 adrenergic receptors?

A

increase lipolysis

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12
Q

what’s the bioavailability of catecholamines?

A

catecholamines are rapidly and extensively metabolized by COMT and MAO in periphery

short t½

poor PO bioavailability

poor CNS penetration

ex. epinephrine and dopamine

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13
Q

what’s the bioavailability of noncatecholamines?

A

they have an absence of one or both OH groups on the ring – catecholamines look like a cat with the two OH groups!

higher PO bioavailability

longer duration of action

can enter CNS

ex. amphetamine, phenylephrine

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14
Q

what is the term that quantifies affinity of a drug for its receptor?

A

potency

Kd = dissociation constant

higher affinity = lower Kd

the lower the amount of the drug you need to block 50% of the receptor, the higher the potency

but as concentrations increase, drugs will begin binding to other targets as well

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15
Q

which drugs are α1 agonists?

A
  1. phenylephrine

2. midodrine

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16
Q

what effects do α1 agonists have?

A
  1. vasoconstriction of vascular smooth muscle in the skin and splanchnic
  2. radial muscle contraction = mydriasis
  3. bladder sphincter and prostate contraction
  4. increases heart force
  5. ejaculation
  6. constrict GI sphincters
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17
Q

what is phenylephrine?

A

α1 agonist

treats rhinitis (OTC nasal spray; Afrin®)

treats eye redness, irritation (OTC 0.12% eye drops; Refresh®)

mydriatic for ophthalmology (Rx 2.5% eye drops; Glaucon®)

so at low doses it treat eye redness but at a high enough dose it’ll dilate your pupils!

also treats hypotension resulting from vasodilation associated with septic shock or anesthesia (IV)

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18
Q

what is midodrine?

A

α1 agonist

treats orthostatic hypotension (PO; Orvaten®) via vasoconstriction effects

some side effects:
1. urine retention (α1 constricts prostate, bladder sphincter)

  1. goose bumps (α1 causes piloerection)
  2. bradycardia
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19
Q

how do α1 agonist cause bradycardia?

A

α1 agonist constrict blood vessels which increases BP and consequently activates baroreceptors which acutely oppose the change in BP

this results in decreased CO, peripheral resistance and HR = bradycardia!

so the α1 agonist are constricting blood vessels and the baroreceptors drop the HR to try and counteract it

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20
Q

which drugs are α2 agonists?

A
  1. clonidine
  2. tizanidine
  3. brimonidine
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21
Q

what do α2 agonists do?

A
  1. inhibits NE release presynaptically** (basically autoreceptors)
  2. decreases SNS outflow from the brain**
  3. constriction of blood vessels
  4. decreases eye fluid production
  5. decrease tone, motility and secretions in the GI
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22
Q

what is clonidine?

A

α2 agonist

hypertension (adjunct treatment); acts centrally to reduce SNS outflow (transdermal or PO; Catapres®)

medically supervised opioid withdrawal (reduces physical symptoms e.g., sweating, cramping, chills)

analgesic effects for severe pain (epidural)

treats symptoms of ADHD, tic disorders (Kapvay®)

rapid discontinuation –> rebound hypertension

side effects: dry mouth, sedation

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23
Q

what is tizanidine?

A

α2 agonist

central-acting muscle relaxant (PO; Zanaflex®)

side effects: sedation, hypotension, dry mouth

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24
Q

what is brimonidine?

A

α2 agonist

treats glaucoma - reduces IOP by decreasing aqueous humor production and stimulating its outflow (eye drops; Alphagan P®)

treats eye redness by constricting vessels in the eye (OTC eye drops; Lumify®)

side effects: drowsiness, conjunctivitis and eye itching, dry mouth

no mydriasis (no α1 effect on iris)

administered 3-4x daily (not first choice for glaucoma due to ocular side effects, dose frequency)

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25
Q

which drugs are β1 agonists?

A

dobutamine

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26
Q

what do β1 agonists do?

A
  1. increase heart rate and force**

2. increases renin release in the kidney

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27
Q

what is dobutamine?

A

β1 agonist

short-term use as inotropic support in decompensated congestive heart failure, ACLS

used in stress echocardiogram testing in patients who cannot exercise because it makes your heart feel like it’s doing a lot of work

minimal β2 effects allow increase in cardiac output with less reflex tachycardia (relative to nonselective β agonists)

t1/2 is 2 minutes

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28
Q

how is dobutamine administered?

A

β1 agonist with t1/2 = 2 minutes

continuous IV infusion must be given because the half life is so short

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29
Q

which drugs are β2 agonists?

A
  1. albuterol
  2. salmeterol
  3. terbutaline
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30
Q

what do β2 agonists do?

A
  1. bronchodilator of airway smooth muscles**
  2. vascular smooth muscle dilation in skeletal muscles**
  3. increase eye fluid production
  4. relaxation of the detrusor in the bladder to keep bladder in
  5. uterus relaxation to keep baby in
  6. increase glycogenolysis and gluconeogenesis
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31
Q

what is albuterol?

A

β2 agonist

treats acute bronchospasm in asthma or COPD due to rapid onset of effect (inhaled, Ventolin®)

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32
Q

what is salmeterol?

A

β2 agonist

prophylaxis against bronchospasm in asthma or COPD, slow onset of effect (inhaled, Serevent®)

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33
Q

what is terbutaline?

A

β2 agonist

treats asthma (inhaled, PO)

also used to stop premature labor, limited acute short-term use as a tocolytic (2nd line treatment, off-label, IV or SC

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34
Q

what are the key side effects of β2 agonists?

A
  1. tremor
  2. tachycardia
  3. metabolic effects
  4. arrhythmias
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35
Q

what are the effects of D1 receptors?

A
  1. vascular smooth muscle dilation
  2. increase renal blood flow

D1 receptors are most highly expressed in periphery outside CNS

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36
Q

what are the effects of D2 receptors?

A
  1. inhibits NE release from presynaptic neuron
  2. decreases renin release from kidney
  3. decrease aldosterone release from adrenal glands
  4. decrease prolactin release from pituitary gland
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37
Q

what are some of the CNS functions of dopamine signaling?

A
  1. reward pathways
  2. emotion
  3. movement
  4. impulse control
  5. sleep
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38
Q

which drugs are D1 agonists?

A

fenoldopam

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39
Q

which drugs are D2 agonists?

A

bromocriptine

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40
Q

what is fenoldopam? what are its side effects?

A

D1 agonist

short-term use for severe hypertension (IV, Corlopam®)

adverse effects: dose-related tachycardia, hypokalemia, increased IOP in glaucoma

it causes tachycardia because it causes vasodilation which decreases BP and has baroreceptor reflex which try and compensate with increased HR

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41
Q

what is bromocritine?

A

D2 agonist

treatment of Parkinson’s disease as adjunct to levodopa (PO, Parloset®)

treatment of hyperprolactinemia

treatment of type 2 diabetes, possibly by effects on circadian rhythms (PO, Cycloset®)

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42
Q

which dopamine pathways are involved in the treatment of Parkinson’s?

A

niagrastriatal and tuberoinfundibulnar

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43
Q

which substances are catecholamines?

A

NE and DA are neurotransmitters

epinephrine (adrenaline) is a hormone

all are catecholamines!!

these all have poor bioavailability since they’re catecholamines because they’re metabolized extensively by COMT in the blood and have a short duration of action so you have to give them parenterally!!

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44
Q

what are the general effects of catecholamines on the body?

A
  1. metabolic effects: put glucose into circulation
  2. regulate hormone secretion (insulin, renin)
  3. CNS effects only observed at highest doses (feelings of nervousness, impending doom)

poor drug-like properties (nonselective effects, PK profile), but have potent cardiovascular effects

main uses are in treatment of shock and heart failure

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45
Q

what is shock?

A

Shock is a life-threatening condition that occurs when blood flow is insufficient

lack of oxygen and nutrients can cause permanent damage to organs

46
Q

what are the different types of shock?

A
  1. cardiogenic shock (due to heart problems)
  2. hypovolemic shock (caused by too little blood volume)
  3. obstructive shock (cardiac tamponade, tension pneumothorax)
4. distributive shock:
septic shock (due to infections), neurogenic shock (from damage to the nervous system), anaphylactic shock (caused by allergic reaction)
47
Q

what is anaphylaxis?

A

allergens in the blood activate mast cells which increase in vascular permeability and a widespread constriction of smooth muscle

fluid leaving the blood causes BP to drop drastically

48
Q

what are the clinical uses of epinephrine?

A
  1. treatment of choice for anaphylactic shock and related IgE-mediated reactions (IM, SC; EpiPen®)
  2. treatment of hypotension in shock (IV)
  3. mydriatic for intraocular surgery (topical)
  4. prolongs effect and reduces toxicity of local anesthetics (injection)
  5. off-label uses including local hemostasis, cardiac arrest, and acute severe asthma that does not respond to β agonist
49
Q

why is epinephrine useful in anaphylactic shock?

A

if epinephrine binds to:

β2 receptors it’ll relieve bronchospasm by dilating bronchioles

α1 receptors it’ll relieve mucous membrane congestion by vasoconstriction

α + β1 receptors it’ll help with hypotension by vasoconstriction and increasing HR, respectively

50
Q

mydriasis is mediated by which receptor?

A

α1

so when epinephrine binds to α1 it’ll cause mydriasis

51
Q

how does epinephrine prolong the effect and reduce toxicity of local anesthetics?

A

when epinephrine binds to α receptors it leads to vasoconstriction which reduces local anesthetic diffusion away from the site of administration and keeps it more contained

so then localization of the anesthetic also prolongs its effect because it stays where you want it and it reduces toxicity because it prevents the anesthetic from entering into systemic circulation!

52
Q

what are the cardiovascular effects of epinephrine at low doses?

A

epinephrine binds to β2 with higher affinity than α receptors in general so epinephrine will cause vasodilation via β2 activation instead of vasoconstriction because β2 activation predominates –> you get a decrease in peripheral resistance

β1 activation will cause an increase in pulse rate

also CO = HR*SV

since HR increased and SV increased due to increase contractility from β1 effects, you’ll have an increase in CO

53
Q

which receptors does epinephrine bind too?

A

α1, α2, β1, β2, β3

54
Q

which receptors does norepinephrine bind too?

A

α1, α2, β1

55
Q

what are the effects of norepinephrine on the body in general?

A

produces increased contractility and heart rate as well as vasoconstriction, thereby increasing systemic blood pressure and coronary blood flow

clinically, alpha effects (vasoconstriction) are greater than beta effects (inotropic and chronotropic effects)

56
Q

what are the clinical uses of norepinephrine?

A
  1. aintenance of blood pressure in cardiogenic and septic shock (IV infusion; Levophed®)

vasopressors (epinephrine, dobutamine, vasopressin) are useful in patients who remain hypotensive despite adequate fluid resuscitation

57
Q

what are the side effects of NE?

A

adverse reactions: bradycardia, arrhythmia, anxiety, headache

warnings: extravasation - NE (and DA and EPI) is a vesicant; ensure proper needle placement; can correct with phentolamine (an α antagonist)

58
Q

why would extravasation be a problem and how does an α antagonists help?

A

extravasation of vesicants causes tissue damage, ischemia and necrosis so you don’t want them to get outside the blood vessel!!

α antagonists dilates blood vessels to try and restore blood supply and wash it out of the tissue

59
Q

what are the cardiovascular effects of IV norepinephrine

A

there’s a huge increase in peripheral resistance because of α1 and α2 activation causing vasoconstriction – plus NE doesn’t activate β2 receptors either so there’s no vasodilation!

because of this, systolic and diastolic pressure increases and so does MAP

since MAP increases, there’s a baroreceptor reflex so you get decreased HR to try and counteract increased BP – even though there’s β1 agonist effects, short term the baroreceptor reflex is what predominates

60
Q

what are the effects of isoproterenol on the body? which receptors does it bind to?

A

β1 and β2

vasodilation from β2 that drops peripheral resistance and MAP and you get reflex tachycardia in addition to β1 effects that are turning up HR

61
Q

compare NE, Epi and isoproterenol

A

slide 28

62
Q

which receptors does dopamine bind too?

A

D1, D2 > α1, β1

63
Q

what are the dose-dependent effects of dopamine on the body?

A

low doses: D1 activation predominates (↑ cAMP mediates vasodilation in renal, splanchnic, coronary, cerebral vessels; promotes natriuresis, increases urine output)

moderate doses: β1 receptors are also activated (renal blood flow still increased, but also HR, cardiac contractility and CO increase; peripheral resistance may decrease)

high doses: α receptors activated (vasoconstriction, increased BP)

64
Q

what are the clinical uses of dopamine?

A
  1. adjunct in the treatment of shock (e.g., MI, heart surgery, renal failure, cardiac decompensation) that persists after fluid volume replacement; helps maintain organ perfusion (IV infusion; Dopastat®)
  2. inotropic support in heart failure (off-label)
65
Q

which drugs are indirect acting adrenergic agonist reuptake inhibitors? what is their MOA?

A
  1. cocaine
  2. atomoxetine
  3. duloxetine

MOA: inhibition of the transporter responsible for removing NE from the synapse after release (increases NE concentrations in synapse, and thus increases adrenergic receptor activation)

66
Q

what are the uses of indirect acting adrenergic agonist reuptake inhibitors?

A
  1. cocaine produces euphoria by blocking DA reuptake; also blocks Na+ channels to produce local anesthesia and produces vasoconstriction via increase in NE (topical; Goprelto®)
  2. treatment of ADHD (atomoxetine PO; Strattera®)
  3. antidepressant (duloxetine PO; Cymbalta®)
67
Q

which drugs are indirect acting adrenergic agonist enzyme inhibitors? what is their MOA?

A
  1. selegiline
  2. entacapone

MOA: inhibition of enzymes that metabolize NE in the nerve terminal (monoamine oxidase; MAO) and in liver and kidney (catechol-o-methyl transferase; COMT)

MAO degrades ~20% of NE that returns via NET

COMT rapidly and extensively clears NE from blood (t ½ < 1 minute)

68
Q

what is selegiline?

A

MAO-B inhibitor

treats Parkinson’s and depression (PO; Zelapar®)

69
Q

what is entacapone?

A

COMT inhibitor

used to treat Parkinson’s (PO; Comtan®)

70
Q

which drugs are indirect acting adrenergic agonist releasers? what is their MOA?

A
  1. amphetamines

NE transporter usually pumps NE into the presynaptic cell and then VMAT packs NE into vesicles so that they’re ready to be released again

with amphetamines, they act as substrates for reuptake transporters (e.g., DAT, NET, SERT) and they competitively inhibit reuptake of NE!

once they’re in the presynaptic terminal, they also inhibit VMAT, preventing filling of vesicles with NE

this causes catecholamine buildup in cytoplasm, which
causes uptake transporters to reverse direction and pump intracellular catecholamines into the synaptic cleft independently of action-potential-induced release

71
Q

what are the clinical uses of indirect acting adrenergic agonist releasers?

A
  1. ADHD (methylphenidate PO, Ritalin®)
  2. narcolepsy, although not preferred due to side effects
  3. obesity (benzphetamine PO, Regimex®)
72
Q

which drugs are mixed-acting agents? what is their MOA?

A
  1. ephedrine
  2. pseudoephedrine
  3. phenylephrine

they enter neurons via NET and displace stored NE (structurally similar to amphetamines)

they’re α and β agonist (phenylephrine α only)

they’re lipophilic and enter the CNS; not metabolized by MAO or COMT

eliminated in urine; elimination can be increased by acidifying urine

73
Q

what are the uses of mixed-acting agents?

A
  1. nasal decongestion (OTC; e.g., Sudafed®)
  2. ephedrine-like drugs (phenylpropane-olamines) were used for narcolepsy and appetite suppression; now banned)
  3. pseudoephedrine used as precursor to make methamphetamine (purchase limits)
74
Q

summar and key points

A

Sympathomimetic drugs include direct- and indirect-acting agents

α1 agonists main uses are related to vasoconstriction (locally, and treating hypotension) and mydriasis; vasoconstriction can result in bradycardia (baroreceptor response)

α2 activation generally opposes SNS effects, including centrally; wide range of effects including treatment of hypertension, pain, withdrawal, ADHD – also treats glaucoma

β1 agonist (dobutamine) – inotropic effects useful in heart failure

β2 agonists are used for asthma – main effect is bronchodilation, but also produces some adrenergic side effects despite local administration

Endogenous catecholamines act at many receptors, poor drug-like properties, but are useful in shock and other emergency conditions

Sympathetic activity can be increased indirectly by inhibiting enzymes that degrade NE, transporters that remove NE from synapse, and agents that cause spilling of NE into synapse (most clinical uses relate to CNS effects of these agents)

75
Q

what is the main clinical use of dopamine antagonists?

A

antipsychotics!

76
Q

Do adrenergic antagonists oppose the effects of endogenous catecholamines, adrenergic agonist drugs, or both?

A

both!

they occupy the receptor so whoever is trying to bind to the adrenergic receptor, it doesn’t matter, it’ll block them

77
Q

what are some drug classes that produce off-target effects at adrenergic receptors?

A

TCAs

antipsychotics

antidepressants

78
Q

what are the cardiovascular effects of blocking α1 receptors?

A
  1. vasodilation: manifests as reduced PVR and MAP, headaches, nasal congestion
  2. orthostatic hypotension (blocks α1 vasoconstricting element of baroreceptor response)

gravity causes pooling in the lower limbs which decreases preload and stroke volume and causes CO and MAP to decrease and you could pass out – normally when this happens your baroreceptors pick up on this but with α1 blockers you can’t vasoconstriction to counteract the blood pooling

  1. reflex tachycardia in response to not being able to constrict blood vessels –> drop in MAP triggers baroreceptor response to stimulate β1 receptors
79
Q

what are the cardiovascular effects of blocking α2 receptors?

A

when you’re blocking that negative feedback you end up with more sympathetic activity and more release of NE and further stimulation of β1 receptors so you end up with even more tachycardia

80
Q

what are the non-cardiovascular effects of blocking α1 receptors?

A
  1. miosis
  2. effects in urinary sphincter, and prostate to help relieve urinary retention
  3. vasodilation in specific tissues

with systemic administration, dilation in nasal tissues can causes stuffiness – can be injected into penis (along with smooth muscle relaxant) to enable erection (not 1st line)

  1. diarrhea
  2. ejaculation dysfunction
81
Q

which drugs are nonselective α blockers?

A
  1. phentolamine

2. phenoxybenzamine

82
Q

what is phentolamine?

A

nonselective α blocker

used to be used as a test for pheochromocytoma (PCC)

  1. reverses accidental extravasation with vasopressor infusions (e.g., NE)
  2. reverses local anesthetic effects by dilating blood vessels (sub-mucosal injection, OraVerse®)
83
Q

what is phenoxybenzamine?

A

nonselective α blocker (α1 > α2)

treats HTN in preoperative pheochromocytoma (PCC) patients

binds covalently to α receptors!!!!**

this irreversible α blockade is preferred over reversible for treatment of PCC

84
Q

why is phenoxybenzamine preferred for treatment of PCC instead of phentolamine?

A

phenoxybenzamine is an irreversible α blocker because it covalently binds to α receptor

since PCC can involve the release of large bursts of catecholamines, using an irreversible antagonists means that even when huge quantities of agonists are added into the body this irreversible antagonists won’t be overcome

85
Q

which drugs are α1 selective alpha blockers?

A
  1. prazosin
  2. terazosin
  3. tamsulosin
86
Q

what is prazosin?

A

α1 selective alpha blockers (α1&raquo_space;>α2)

treats HTN and PTSD related insomnia/nightmares

87
Q

what is terazosin?

A

α1 selective alpha blockers (α1&raquo_space;>α2)

treats HTN and benign prostatic hyperplasia (BPH)

blockers relax prostate and allow for urine flow

88
Q

what are the side effects of prazosin and terazosin?

A

they’re α1 selective alpha blockers (α1&raquo_space;>α2)

  1. significant risk of orthostatic hypotension, esp. with first dose or dose increases
  2. produce less reflex tachycardia than nonselective a-blockers (little α2 blockade)
89
Q

what is tamsulosin?

A

α1 selective alpha blocker (α1A > other α1 subtypes)

treats benign prostatic hyperplasia (BPH) symptoms

minimal effects on BP; less risk of hypotension –> this is because α1A receptors are found in the prostate! so when you block them specifically, you keep normal activation everywhere else! so it’s a great drug for BPH

90
Q

what are first generation β adrenergic blocks? which drugs does this include?

A

oldest class, non-selective blockers of β receptors

  1. propranolol
  2. sotalol
  3. pindolol
  4. timolol
  5. nadolol
91
Q

what are second generation β adrenergic blocks? which drugs does this include?

A

β1 receptor selective blockers (“cardioselective”)

  1. atenolol
  2. metoprolol
  3. esmolol
  4. acebutolol
  5. bisoprolol
  6. nevbivolol
92
Q

what are third generation β adrenergic blocks? which drugs does this include?

A

newest class – non-selective β receptor blockers with additional vasodilating (α1 antagonist) effects, some also have antioxidant effects

  1. labetalol
  2. carvedilol
93
Q

what are the effects of blocking β1 receptors?

A
  1. decreasing HR and contractility

fall in CO reduces BP

  1. decreases renin release from kidney

net effect is loss of sodium and water in urine which lowers BP

94
Q

what are the effects of blocking β2 receptors?

A

reduces dilation of blood vessels in skeletal muscles

with baroreceptor response to decreased BP, only α receptors will be activated (since β2 blocked), leading to rise in peripheral resistance

95
Q

what are the non-cardiovascular effects of blocking β2 receptors?

A
  1. bronchoconstriction

increase in airway resistance particularly in asthma patients

β1selective antagonists are better in asthma, but no β blockers are completely selective; all should be used with caution

  1. decreases aqueous humor production so reduces IOP in glaucoma
  2. decreases glycogenolysis in liver so it inhibits recovery from hypoglycemia (use with caution in type 1 diabetes, since they have hypoglycemic episodes)
96
Q

what are the non-cardiovascular effects of blocking β3 receptors?

A

decreases lipolysis which increases triglyceride levels

97
Q

what are the cardiac clinical uses of β blockers?

A
  1. Chronic stable angina (chest pain due to reduced blood flow to heart) - β blockers are first line therapy, due to reduction in myocardial oxygen demand
  2. after acute MI - beta blocker therapy reduces infarct size and early mortality when started early and lowers the risk of death when continued long term
  3. supraventricular and ventricular arrhythmia – β blockers (class II antiarrhythmics) decrease SA node automaticity and AV node conduction speed, and affect ion channels
  4. hypertension – as adjunctive therapy; not first-line due to inferior protection against stroke compared to other agents
  5. heart failure – some β blockers are useful in reducing mortality
98
Q

what is propranolol? what are its clinical uses?

A

1st generation non-selective β blocker

low, dose-dependent bioavailability

lipophilic, crosses BBB

  1. migraine - used as prophylaxis treatment (mechanism unknown)
  2. thyroid storm – blocks SNS effects and conversion of T4 to T3
  3. reduces tremor (SNS activity enhances skeletal muscle tremor)
  4. anxiety – reduces physical symptoms of anxiety (stage fright) at low doses
  5. angina, hypertension, arrhythmias, MI
99
Q

what are the side effects of propranolol?

A
  1. bradycardia
  2. worsened asthma
  3. fatigue
  4. vivid dreams
  5. cold hands

black box warning for cardiac ischemia after abrupt discontinuation

100
Q

what is sotalol?

A

1st generation non-selective β blocker

used only in arrhythmia, mechanism also includes ion channel blockage

black box warning: life threatening ventricular tachycardia associated with QT interval prolongation

101
Q

what is timolol?

A

1st generation non-selective β blocker

open angle glaucoma (drops; Timoptic®); no local anesthetic activity

systemic (PO) use: hypertension, migraine prophylaxis, MCI

102
Q

what is nadolol?

A

1st generation non-selective β blocker

long duration of action

spectrum of action like timolol = HTN, migraine prophylaxis, MCI

103
Q

what is pindolol?

A

1st generation partial β agonist activity

used in hypertension, and as adjunct for depression treatment (potentiates effects of older antidepressants possibly via 5HT1A autoreceptor antagonism)

less likely to cause bradycardia and altered plasma lipids

104
Q

what is atenolol, metoprolol, and bisoprolol?

A

2nd generation β1 selective β blocker

all are useful for standard CV applications: angina, hypertension, arrhythmias, MI

metoprolol has some local anesthetic effect and is also used in migraine prophylaxis

105
Q

what is nevbivolol?

A

2nd generation β1 selective β blocker

used only in HTN

most selective for β1 but metabolites are less selective

also vasodilators via NO production in endothelial cells

106
Q

what is esmolol?

A

2nd generation β1 selective β blocker

ultra short duration of action (metabolized rapidly by plasma esterases, t½ = 10 min)

administered by infusion, reaches steady-state rapidly, effects end rapidly with termination of infusion

used in acutely ill patients in hypertensive emergency, thyroid storm, ventricular tachycardia

107
Q

what is acebutolol?

A

2nd generation β1 selective β blocker

partial β agonist activity
Local anesthetic effects

less likely to cause bradycardia and altered plasma lipids

effective for typical CV applications (hypertension, angina), and thyrotoxicosis

108
Q

what is labetalol?

A

3rd generation α1 and β blocker

produces hypotension, but less tachycardia than phentolamine and other α blockers

used in acute aortic dissection, to decrease aortic pressure and shear stress

BP management in acute ischemic stroke, acute severe hypertension, hypertensive emergency, eclampsia / pre-eclampsia, subarachnoid hemorrhage

basically it’s used in horrible situations….

109
Q

what is carvedilol?

A

3rd generation α1 and β blocker

gets cleared by CYP2D6 so people who have low 2D6 and are poor metabolizers can have 10x higher blood concentrations

antioxidant effects; prevents LDL oxidation

110
Q

what are the common and serious side effects of β blockers?

A

COMMON: bradycardia and hypotension, fatigue, sexual dysfunction

SERIOUS: many β blockers carry black box warnings regarding precipitation or worsening of CHF, and significant negative chronotropy

you don’t want to abruptly withdraw because it can exacerbate ischemic symptoms because when you put a drug in the system that’s always pushing homeostasis in one direction, your body makes more and more B receptors to try and counteract the effects of the drugs blocking B receptors

so if you suddenly stop a B blocker you have a TON of receptors that are sensitive to maximize NE input and you get a rebound effect where you have significant tachyarrhythmia, MI or cardiac death

Cardio Week 1 (15 decks)

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