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
2
Q
what are the targets for direct-acting drugs?
A
receptors
ex. adrenergic receptors aka α, β and DA
3
Q
how might you increase NE signaling?
A
- agonist at adrenergic receptors**
- block reuptake transport**
- inhibit enzymatic degradation
- auto/heteroreceptors that control negative feedback
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
5
Q
how might you decrease NE signaling?
A
- adrenergic receptor antagonists**
- up regulate transporters or degradative enzymes
- block neurotransmission in general
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
7
Q
what are the key effects of α1 adrenergic receptors?
A
- vascular smooth muscle constriction in skin and splanchnic**
- radial muscle contraction = mydriasis
- bladder sphincter and prostate contraction
- increases heart force
- ejaculation
- constrict GI sphincters
8
Q
what are the key effects of α2 adrenergic receptors?
A
- inhibits NE release presynaptically** (basically autoreceptors)
- decreases SNS outflow from the brain**
- constriction of blood vessels
- decreases eye fluid production
- decrease tone, motility and secretions in the GI
9
Q
what are the key effects of β1 adrenergic receptors?
A
- increase heart rate and force**
2. increases renin release in the kidney
10
Q
what are the key effects of β2 adrenergic receptors?
A
- bronchodilator of airway smooth muscles**
- vascular smooth muscle dilation in skeletal muscles**
- increase eye fluid production
- relaxation of the detrusor in the bladder to keep bladder in
- uterus relaxation to keep baby in
- increase glycogenolysis and gluconeogenesis
11
Q
what are the key effects of β3 adrenergic receptors?
A
increase lipolysis
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
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
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
15
Q
which drugs are α1 agonists?
A
- phenylephrine
2. midodrine
16
Q
what effects do α1 agonists have?
A
- vasoconstriction of vascular smooth muscle in the skin and splanchnic
- radial muscle contraction = mydriasis
- bladder sphincter and prostate contraction
- increases heart force
- ejaculation
- constrict GI sphincters
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)
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)
- goose bumps (α1 causes piloerection)
- bradycardia
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
20
Q
which drugs are α2 agonists?
A
- clonidine
- tizanidine
- brimonidine
21
Q
what do α2 agonists do?
A
- inhibits NE release presynaptically** (basically autoreceptors)
- decreases SNS outflow from the brain**
- constriction of blood vessels
- decreases eye fluid production
- decrease tone, motility and secretions in the GI
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
23
Q
what is tizanidine?
A
α2 agonist
central-acting muscle relaxant (PO; Zanaflex®)
side effects: sedation, hypotension, dry mouth
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)
25
which drugs are β1 agonists?
dobutamine
26
what do β1 agonists do?
1. increase heart rate and force**
| 2. increases renin release in the kidney
27
what is dobutamine?
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
28
how is dobutamine administered?
β1 agonist with t1/2 = 2 minutes
continuous IV infusion must be given because the half life is so short
29
which drugs are β2 agonists?
1. albuterol
2. salmeterol
3. terbutaline
30
what do β2 agonists do?
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
31
what is albuterol?
β2 agonist
treats *acute* bronchospasm in asthma or COPD due to rapid onset of effect (inhaled, Ventolin®)
32
what is salmeterol?
β2 agonist
prophylaxis against bronchospasm in asthma or COPD, slow onset of effect (inhaled, Serevent®)
33
what is terbutaline?
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
34
what are the key side effects of β2 agonists?
1. tremor
2. tachycardia
3. metabolic effects
4. arrhythmias
35
what are the effects of D1 receptors?
1. vascular smooth muscle dilation
2. increase renal blood flow
D1 receptors are most highly expressed in periphery outside CNS
36
what are the effects of D2 receptors?
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
37
what are some of the CNS functions of dopamine signaling?
1. reward pathways
2. emotion
3. movement
4. impulse control
5. sleep
38
which drugs are D1 agonists?
fenoldopam
39
which drugs are D2 agonists?
bromocriptine
40
what is fenoldopam? what are its side effects?
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
41
what is bromocritine?
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®)
42
which dopamine pathways are involved in the treatment of Parkinson's?
niagrastriatal and tuberoinfundibulnar
43
which substances are catecholamines?
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!!
44
what are the general effects of catecholamines on the body?
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
45
what is shock?
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
what are the different types of shock?
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)
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47
what is anaphylaxis?
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
what are the clinical uses of epinephrine?
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
why is epinephrine useful in anaphylactic shock?
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
mydriasis is mediated by which receptor?
α1
so when epinephrine binds to α1 it'll cause mydriasis
51
how does epinephrine prolong the effect and reduce toxicity of local anesthetics?
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
what are the cardiovascular effects of epinephrine at low doses?
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
which receptors does epinephrine bind too?
α1, α2, β1, β2, β3
54
which receptors does norepinephrine bind too?
α1, α2, β1
55
what are the effects of norepinephrine on the body in general?
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
what are the clinical uses of norepinephrine?
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
what are the side effects of NE?
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
why would extravasation be a problem and how does an α antagonists help?
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
what are the cardiovascular effects of IV norepinephrine
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
what are the effects of isoproterenol on the body? which receptors does it bind to?
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
compare NE, Epi and isoproterenol
slide 28
62
which receptors does dopamine bind too?
D1, D2 > α1, β1
63
what are the dose-dependent effects of dopamine on the body?
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
what are the clinical uses of dopamine?
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
which drugs are indirect acting adrenergic agonist reuptake inhibitors? what is their MOA?
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
what are the uses of indirect acting adrenergic agonist reuptake inhibitors?
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
which drugs are indirect acting adrenergic agonist enzyme inhibitors? what is their MOA?
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
what is selegiline?
MAO-B inhibitor
treats Parkinson’s and depression (PO; Zelapar®)
69
what is entacapone?
COMT inhibitor
used to treat Parkinson's (PO; Comtan®)
70
which drugs are indirect acting adrenergic agonist releasers? what is their MOA?
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
what are the clinical uses of indirect acting adrenergic agonist releasers?
1. ADHD (methylphenidate PO, Ritalin®)
2. narcolepsy, although not preferred due to side effects
3. obesity (benzphetamine PO, Regimex®)
72
which drugs are mixed-acting agents? what is their MOA?
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
what are the uses of mixed-acting agents?
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
summar and key points
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
what is the main clinical use of dopamine antagonists?
antipsychotics!
76
Do adrenergic antagonists oppose the effects of endogenous catecholamines, adrenergic agonist drugs, or both?
both!
they occupy the receptor so whoever is trying to bind to the adrenergic receptor, it doesn't matter, it'll block them
77
what are some drug classes that produce off-target effects at adrenergic receptors?
TCAs
antipsychotics
antidepressants
78
what are the cardiovascular effects of blocking α1 receptors?
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
2. reflex tachycardia in response to not being able to constrict blood vessels --> drop in MAP triggers baroreceptor response to stimulate β1 receptors
79
what are the cardiovascular effects of blocking α2 receptors?
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
what are the non-cardiovascular effects of blocking α1 receptors?
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)
4. diarrhea
5. ejaculation dysfunction
81
which drugs are nonselective α blockers?
1. phentolamine
| 2. phenoxybenzamine
82
what is phentolamine?
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
what is phenoxybenzamine?
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
why is phenoxybenzamine preferred for treatment of PCC instead of phentolamine?
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
which drugs are α1 selective alpha blockers?
1. prazosin
2. terazosin
3. tamsulosin
86
what is prazosin?
α1 selective alpha blockers (α1 >>>α2)
treats HTN and PTSD related insomnia/nightmares
87
what is terazosin?
α1 selective alpha blockers (α1 >>>α2)
treats HTN and benign prostatic hyperplasia (BPH)
blockers relax prostate and allow for urine flow
88
what are the side effects of prazosin and terazosin?
they're α1 selective alpha blockers (α1 >>>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
what is tamsulosin?
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
what are first generation β adrenergic blocks? which drugs does this include?
oldest class, non-selective blockers of β receptors
1. propranolol
2. sotalol
3. pindolol
4. timolol
5. nadolol
91
what are second generation β adrenergic blocks? which drugs does this include?
β1 receptor selective blockers (“cardioselective”)
1. atenolol
2. metoprolol
3. esmolol
4. acebutolol
5. bisoprolol
6. nevbivolol
92
what are third generation β adrenergic blocks? which drugs does this include?
newest class – non-selective β receptor blockers with additional vasodilating (α1 antagonist) effects, some also have antioxidant effects
1. labetalol
2. carvedilol
93
what are the effects of blocking β1 receptors?
1. decreasing HR and contractility
fall in CO reduces BP
2. decreases renin release from kidney
net effect is loss of sodium and water in urine which lowers BP
94
what are the effects of blocking β2 receptors?
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
what are the non-cardiovascular effects of blocking β2 receptors?
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
2. decreases aqueous humor production so reduces IOP in glaucoma
3. decreases glycogenolysis in liver so it inhibits recovery from hypoglycemia (use with caution in type 1 diabetes, since they have hypoglycemic episodes)
96
what are the non-cardiovascular effects of blocking β3 receptors?
decreases lipolysis which increases triglyceride levels
97
what are the cardiac clinical uses of β blockers?
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
what is propranolol? what are its clinical uses?
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
what are the side effects of propranolol?
1. bradycardia
2. worsened asthma
3. fatigue
4. vivid dreams
5. cold hands
black box warning for cardiac ischemia after abrupt discontinuation
100
what is sotalol?
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
what is timolol?
1st generation non-selective β blocker
open angle glaucoma (drops; Timoptic®); no local anesthetic activity
systemic (PO) use: hypertension, migraine prophylaxis, MCI
102
what is nadolol?
1st generation non-selective β blocker
long duration of action
spectrum of action like timolol = HTN, migraine prophylaxis, MCI
103
what is pindolol?
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
what is atenolol, metoprolol, and bisoprolol?
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
what is nevbivolol?
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
what is esmolol?
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
what is acebutolol?
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
what is labetalol?
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
what is carvedilol?
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
what are the common and serious side effects of β blockers?
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
