Noradrenergic Transmission Flashcards
1
Q
What allows for termination of acetylcholine?
A
ACh-esterase
- 150 ms
2
Q
What allows for termination of norepinephrine?
A
- Reuptake
- Monoamine oxidase
- Catechol-O-Methyltransferase
3
Q
What are the types of adrenergic receptors?
A
- α1 α2
- β1 β2
- Dopamine
- Sympathomimetic vs sympatholytic
4
Q
Can adrenergic receptors be downregulated/desensitized?
A
Yes!
- Congestive Heart Failure (CHF)
- Acidosis
- Hypoxia
5
Q
What does the alpha-1 adrenergic receptor do?
A
- Vasoconstriction
- Blood pressure increased
- Mydriasis
- Urinary sphincter constriction
6
Q
Where does the alpha-1 adrenergic receptor act and what is it’s function?
A
- peripheral vascular bed
- excitatory
7
Q
What does the alpha-2 adrenergic receptor do?
A
- Inhibitory
- In the vasculature
- Inhibition of NE and ACh
- Decreased sympathetic tone
- Decreased BP
- Sedation
8
Q
What does the beta-1 adrenergic receptor do?
A
- Cardiac excitation
- Increased rate, contractility,
conduction - excitatory
9
Q
What does the beta-2 adrenergic receptor do?
A
- Bronchodilation
- Smooth muscle relaxation
- Skeletal muscle vasodilation
- Decreased vascular resistance
- inhibitory
10
Q
What does the dopamine adrenergic receptor do?
A
- Resistance vessel vasodilation
— Renal
— Splanchnic
— Coronary
— Cerebral
11
Q
What are the catecholamines?
A
- dopamine (DA)
- norepinephrine (NE)
- epinephrine
12
Q
Where is dopamine (DA) produced?
A
brain
kidney
13
Q
Where is norepinephrine (NE) produced?
A
Sympathetic nerve endings
14
Q
Where is epinephrine produced?
A
Adrenal medulla
15
Q
What are the direct acting sympathomimetics?
A
- Norepinephrine
- Epinephrine
- Dopamine
- Dobutamine
- Phenylephrine
- Milrinone
- Vasopressin
- Alpha-2 selective agonists (Clonidine, Dexmedetomidine, Guanfacine, Methyldopa)
16
Q
What is the function of norepinephrine?
A
- Endogenous
- Primary neurotransmitter at sympathetic nerve endings
- Maintenance of sympathetic tone
- ⬆BP
- No cardiac output changes
- Minimal chronotropic changes
- Increased coronary blood flow
- Caution with prolonged infusions
17
Q
What is the function of epinephrine?
A
- Endogenous
- Only released by adrenal medulla
- Stress preparation
- ⬆ coronary blood flow
- Caution prolonged infusions
18
Q
What is the function of dopamine?
A
- Endogenous
- NE precursor
- Dose-specific effects
— Low dose (0.5 – 3 mcg/kg/min)
— Intermediate (3 – 10 mcg/kg/min)
— High (10 – 20 mcg/kg/min)
19
Q
What is the function of dobutamine?
A
- Synthetic
- Augments myocardial contractility
- Dose-dependent increase in stroke volume (SV) and cardiac output (CO)
- Alpha agonist AND antagonist
- Beta-mediated vasodilation (low dose)
- High dose increases myocardial O2 consumption
20
Q
What is the function of phenylephrine?
A
- Synthetic
- All alpha, no beta
- Not a catechol derivative, not metabolized by COMT
- Can lead to baroreceptor mediated decrease in HR
- Push dose pressor
21
Q
What is the function of milrinone?
A
- Phosphodiesterase-3 inhibitor
- Inhibits breakdown of cAMP
— Positive inotropy - Potent vasodilator
- Increased diastolic relaxation
— Reduced preload and afterload - Good in the setting of receptor downregulation
22
Q
What is the function of vasopressin?
A
- AKA: antidiuretic hormone
- Stored in posterior pituitary
— Released when plasma osmolality increases or BP drops - V1 and V2 receptor agonist
- Neutral to negative impact on CO
- Dose dependent SVR and vagal tone increase
- Not affected by pH
22
Q
What is the function of alpha-2 selective agonists?
A
- Drop BP by reducing sympathetic tone
- Effective antihypertensive
- Class effect = sedation
Clonidine
Dexmedetomidine
Guanfacine
Methyldopa
23
Q
What receptors does norepinephrine act on?
A
α1
β1
β2
24
What receptors does epinephrine act on?
α1 @ higher doses
β1 @ lower doses
β2 @ lower doses
25
What receptors does dopamine act on?
α1
β1
β2
26
What receptors does dobutamine act on?
**β1**
β2
α1
27
What receptors does phenylephrine act on?
α1
28
What receptors does milrinone act on?
**β1 “like effect”**
β2 “like effect"
29
What receptors does vasopressin act on?
α1 “like effect”
30
What is the mechanism for indirect acting sympathomimetics?
- Displacers
- Reuptake inhibition
31
What are the indirect acting sympathomimetics?
- amphetamine like agents
--- Amphetamine
--- Methylphenidate (Ritalin)
--- Modafinil (Provigil)
- Catecholamine reuptake inhibitors
--- Straterra
--- Cocaine
32
What are the functions of amphetamine?
- Rapid CNS uptake
- Stimulant
- Effects mediated by NE and DA
33
What are the functions of methylphenidate (ritalin)?
- Amphetamine variant
- Similar effect and abuse potential
- Use: ADD-spectrum
- Caution - UDS
34
What are the functions of modafinil (provigil)?
- Psychostimulant
- Totally different from amphetamine
- NE, DA reuptake inhibition
- NE, DA, 5-HT3, glutamate increase; GABA decrease
- Use: narcolepsy
35
What are the functions of straterra?
- Selective NE reuptake inhibition
- No CV effects
- Clonidine-like effect
- Use: ADD
36
What are the functions of cocaine?
- Local anesthetic, peripheral sympathomimetic
- Reuptake inhibition, especially dopamine
- Excited delirium
- Avoid concurrent beta blockade
- Use: epistaxis
37
What is beta-2 agonism used for?
- Key to management of acute asthma
- Common “allergy” in dentistry
--- 7.9%
- Triggered by allergens, stress, food,
drugs
- Angioedema = similar but different
38
What is used for acute managment of asthma (short acting beta agonists; SABA)?
Albuterol
Levalbuterol
Terbutaline
39
What is used for longterm managment of asthma (long acting beta agonists; LABA)?
Formoterol
Salmeterol
40
Can you use long acting beta agonists such as Formoterol and Salmeterol for an acute asthma attack?
No
- Have to be used with steroids
41
How do you manage a patient with asthma while doing dentistry?
- Minimize likelihood of exacerbation
- Talk to your patient to learn their management strategies
- Instruct pt. to bring albuterol inhaler to all appointments
- Decrease stressors
42
What do you do in an emergency with a patient with asthma?
- Supplemental O2
- Consider epinephrine
--- 0.3 mg IM (or use EpiPen)
43
What drugs should you avoid with an asthma patient?
- No ASA or NSAIDS
- Avoid histaminic drugs
- Avoid antihistamines
- Avoid cholinergics
44
What are the two types of alpha antagonists?
- Reversible
--- Concentration dependent
--- Duration dependent on t1/2
- Irreversible
--- Body has to generate new receptors
--- Drug effect can persist even after drug is cleared
45
What are the pharmacologic effects of alpha antagonists?
- Cardiovascular
--- α1 blockade blocks vasoconstriction
--- Orthostatic hypotension
- Other
--- Miosis, nasal stuffiness
--- Decreased resistance to urinary flow
46
What are the alpha receptor antagonists?
- phentolamine
- prazosin
- terazosin
- doxazosin
- tamsulosin
47
What is the function of phentolamine?
- Blocks α1 and α2
- Decreased PVR and cardiac stimulation
- Can lead to CV adverse reactions
48
What is the function of prazosin, terazosin, and doxazosin?
- Selective α1
- Arterial and venous vascular smooth muscle relaxation and prostate relaxation
- 50% bioavailability
--- First pass effect
- T1/2
- Prazosin: 3h
- Terazosin: 9h
- Doxazosin: 22h
49
What is the function of tamsulosin?
- Competitive α1 blocker
- High bioavailability
- More specific to prostate
- Less orthostatic hypotension
50
What are beta receptor antagonists?
- Antagonize effects of catecholamines and beta agonists
- Differ in affinity for β1 and β2
- β1 specificity decreases as dose increases
- End in -lol
51
What are the types of beta receptor antagonists?
- Betaxolol
- Esmolol
- Acebutolol
- Metoprolol
- Atenolol
- Nebivolol
52
What is the function of esmolol?
- Beta-1 selective
- Short t1/2
- Quick onset
- Requires central line for administration
- Great for tight BP control
53
What is the function of labetalol?
- Beta and alpha blockade
-- 3:1 oral
--- 7:1 IV
- Dose dependent duration of action
--- up to 20 hours
54
____ specific drugs safer for asthmatic patients
β1
55
Caution with non-specific
β-blockers and...
epi
