Noradrenergic Transmission Flashcards
What allows for termination of acetylcholine?
ACh-esterase
- 150 ms
What allows for termination of norepinephrine?
- Reuptake
- Monoamine oxidase
- Catechol-O-Methyltransferase
What are the types of adrenergic receptors?
- α1 α2
- β1 β2
- Dopamine
- Sympathomimetic vs sympatholytic
Can adrenergic receptors be downregulated/desensitized?
Yes!
- Congestive Heart Failure (CHF)
- Acidosis
- Hypoxia
What does the alpha-1 adrenergic receptor do?
- Vasoconstriction
- Blood pressure increased
- Mydriasis
- Urinary sphincter constriction
Where does the alpha-1 adrenergic receptor act and what is it’s function?
- peripheral vascular bed
- excitatory
What does the alpha-2 adrenergic receptor do?
- Inhibitory
- In the vasculature
- Inhibition of NE and ACh
- Decreased sympathetic tone
- Decreased BP
- Sedation
What does the beta-1 adrenergic receptor do?
- Cardiac excitation
- Increased rate, contractility,
conduction - excitatory
What does the beta-2 adrenergic receptor do?
- Bronchodilation
- Smooth muscle relaxation
- Skeletal muscle vasodilation
- Decreased vascular resistance
- inhibitory
What does the dopamine adrenergic receptor do?
- Resistance vessel vasodilation
— Renal
— Splanchnic
— Coronary
— Cerebral
What are the catecholamines?
- dopamine (DA)
- norepinephrine (NE)
- epinephrine
Where is dopamine (DA) produced?
brain
kidney
Where is norepinephrine (NE) produced?
Sympathetic nerve endings
Where is epinephrine produced?
Adrenal medulla
What are the direct acting sympathomimetics?
- Norepinephrine
- Epinephrine
- Dopamine
- Dobutamine
- Phenylephrine
- Milrinone
- Vasopressin
- Alpha-2 selective agonists (Clonidine, Dexmedetomidine, Guanfacine, Methyldopa)
What is the function of norepinephrine?
- 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
What is the function of epinephrine?
- Endogenous
- Only released by adrenal medulla
- Stress preparation
- ⬆ coronary blood flow
- Caution prolonged infusions
What is the function of dopamine?
- 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)
What is the function of dobutamine?
- 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
What is the function of phenylephrine?
- Synthetic
- All alpha, no beta
- Not a catechol derivative, not metabolized by COMT
- Can lead to baroreceptor mediated decrease in HR
- Push dose pressor
What is the function of milrinone?
- 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
What is the function of vasopressin?
- 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
What is the function of alpha-2 selective agonists?
- Drop BP by reducing sympathetic tone
- Effective antihypertensive
- Class effect = sedation
Clonidine
Dexmedetomidine
Guanfacine
Methyldopa
What receptors does norepinephrine act on?
α1
β1
β2
What receptors does epinephrine act on?
α1 @ higher doses
β1 @ lower doses
β2 @ lower doses
What receptors does dopamine act on?
α1
β1
β2
What receptors does dobutamine act on?
β1
β2
α1
What receptors does phenylephrine act on?
α1
What receptors does milrinone act on?
β1 “like effect”
β2 “like effect”
What receptors does vasopressin act on?
α1 “like effect”
What is the mechanism for indirect acting sympathomimetics?
- Displacers
- Reuptake inhibition
What are the indirect acting sympathomimetics?
- amphetamine like agents
— Amphetamine
— Methylphenidate (Ritalin)
— Modafinil (Provigil) - Catecholamine reuptake inhibitors
— Straterra
— Cocaine
What are the functions of amphetamine?
- Rapid CNS uptake
- Stimulant
- Effects mediated by NE and DA
What are the functions of methylphenidate (ritalin)?
- Amphetamine variant
- Similar effect and abuse potential
- Use: ADD-spectrum
- Caution - UDS
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
What are the functions of straterra?
- Selective NE reuptake inhibition
- No CV effects
- Clonidine-like effect
- Use: ADD
What are the functions of cocaine?
- Local anesthetic, peripheral sympathomimetic
- Reuptake inhibition, especially dopamine
- Excited delirium
- Avoid concurrent beta blockade
- Use: epistaxis
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
What is used for acute managment of asthma (short acting beta agonists; SABA)?
Albuterol
Levalbuterol
Terbutaline
What is used for longterm managment of asthma (long acting beta agonists; LABA)?
Formoterol
Salmeterol
Can you use long acting beta agonists such as Formoterol and Salmeterol for an acute asthma attack?
No
- Have to be used with steroids
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
What do you do in an emergency with a patient with asthma?
- Supplemental O2
- Consider epinephrine
— 0.3 mg IM (or use EpiPen)
What drugs should you avoid with an asthma patient?
- No ASA or NSAIDS
- Avoid histaminic drugs
- Avoid antihistamines
- Avoid cholinergics
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
What are the pharmacologic effects of alpha antagonists?
- Cardiovascular
— α1 blockade blocks vasoconstriction
— Orthostatic hypotension - Other
— Miosis, nasal stuffiness
— Decreased resistance to urinary flow
What are the alpha receptor antagonists?
- phentolamine
- prazosin
- terazosin
- doxazosin
- tamsulosin
What is the function of phentolamine?
- Blocks α1 and α2
- Decreased PVR and cardiac stimulation
- Can lead to CV adverse reactions
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
What is the function of tamsulosin?
- Competitive α1 blocker
- High bioavailability
- More specific to prostate
- Less orthostatic hypotension
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
What are the types of beta receptor antagonists?
- Betaxolol
- Esmolol
- Acebutolol
- Metoprolol
- Atenolol
- Nebivolol
What is the function of esmolol?
- Beta-1 selective
- Short t1/2
- Quick onset
- Requires central line for administration
- Great for tight BP control
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
____ specific drugs safer for asthmatic patients
β1
Caution with non-specific
β-blockers and…
epi
