Adrenergic Drugs (Exam 1) Flashcards
Picture of Sympathetic (Adrenergic) and Parasympathetic (Cholinergic) Nervous System
Norepinephrine
Main adrenergic mediator (Sympathetic)
-Purpose is to maintain a constant internal environment
Epinephrine
- Also known as adrenaline
- Fight or flight
Synthesized and released from the adrenal medulla
Dopamine
Reward system contributes to survival
-Feel good, food, sex, drugs
*Abusive drugs release dopamine
Examples: amphetamine, opiates, nicotine, caffeine
Autonomic Nervous System breakdown
- CNS Outflow
- Ganglia
- Pre/post-ganglionic fiber length
- Postganglionic fiber distribution
- Response to stimulation
- Postganglionic neurotransmitter
Catecholamines (adrenergics)
Epinephrine, Norepinephrine, and dopamine
-Rapid onset of action/brief duration of action
Not orally active
Direct adrenergic agonist
Compounds that mimic the action of epinephrine
Ex. dopamine (binds to dopinergic, alpha, and beta receptors)
Indirect acting compounds
Release norepinephrine, which acts on the adrenergic receptors
Ex. amphetamine, tyramine (wine/cheese/sausage) or methylphenidate (Ritalin)
Mixed acting compounds
Have two actions:
1) Direct action to stimulate the receptors
2) Indirect action to release NE, which also acts on the receptors
Ex. pseudoephedrine (Sudafed)
What are the enzymes involved in adrenergic neurons? Cholinergic?
Adrenergic: MAO and COMT
Cholinergic: acetylecholinesterase
What is biosynthesis of catecholamines? (photo)
What is the rate limiting enzyme?
Tyrosine hydroxylase (Tyrosine to Dopa)
What can cause the accumulation of tyramine in humans?
MAO inhibitors
Consumption of food/beverages containing it (Wine/sausage/cheese)
When in the pre-synaptic neuron, what prevents MAO from breaking down all the adrenergic catecholamines (dopamine/NE)?
Dopamine and NE are stored in nerve vesicles, which prevent MAO from breaking them down
-Reserpine is an old drug that would prematurely release them from their vesicles, where they would be broken down and the neuron would be unable to release them upon arrival of an action potential (major side-effect: depression)
Catecholamine Release Sequence
Tyramine transported into a nerve ending by a Na+-dependent carrier
Converted to dopamine and transported into the vesicle by VMAT
Converted in the vesicle into NE by dopamine beta hydroxylase
NE physiologically released from nerve terminal (Dependent on Ca++ and an action potential)
What are some substances that can inhibit the recycling of NE back into the pre-synaptic neuron?
Cocaine and tricyclic anti-depressants (amitriptyline, nortriptyline, doxepin, etc.)
-Acts as an indirect agonist, inhibiting NET from bring NE back in and prolonging NE’s presence in synaptic cleft
Catecholamine Termination
Active reuptake (90%)
- NET carries NE back into the pre-synaptic neuron cell cytoplasm
Simple Diffusion (10%)
- NE diffuses into surrounding glial cells and smooth muscles, where it is eventually metabolized (plasma or liver)
What are examples of MAO inhibitors and what have they been used for?
- Phenelzine, selegiline, tranylcypromine, isocarboxazid
- Treat Parkinson’s disease (since NE/dopamine isn’t being metabolized by MAOs)
- Old treatment for depression; not used anymore
*Tyramine can cause a hypertensive crisis while using these
What should be generally associated with a1 receptors? How about ß2 receptors?
a1: Vasoconstriction
ß2: Vasodilation
Alpha1 receptor
- Location (2)
- Function (6)
Adrenergic
Located on blood vessels and smooth muscle (GI, mucosa, skin)
Control vasomotor tone (BP), vasoconstriction, pupil dilation (mydriasis)
Increased: peripheral resistance, BP, and closure of internal sphincter of bladder
Alpha2 receptor
- Location
- Function
Adrenergic
-Located at terminal ending of NE-releasing neurons
Stimulation will inhibit release of:
1) NE (via negative feedback)
2) Insulin
ß1 receptor
- Location (3)
- Function (3)
Adrenergic
- Located in Brain, heart and kidneys
1) Tachycardia - Increased:
2) Myocardial contractility
3) Renin secretion (which ultimately increases BP)
ß2 receptors
- Location (3)
- Function (7)
-Located in the lung, pancreas and smooth muscle
Vasodilation, bronchodilation, relaxed uterine smooth muscle
Slight decrease in peripheral resistance (counters a1)
Increased:
1) muscle/liver glycogenolysis
2) glucagon release
3) insulin secretion
Affinity of NE and Epinephrine for receptors (tie in Local Anesthetics)
NE: 90% alpha
Epi: 50:50* (Prefer alpha at high concentrations)
*Problematic if ß1 receptor (heart concerns)
For local anesthetics we want:
1) Localized high dose: vasoconstricts to keep LA @ site
2) Systemic low dose: minimal vasodilation/heart concerns; therefore it is critical that we have negative aspiration
Dopamine receptors
- Locations (4)
- Type and function (2)
-Located in CNS, kidney, heart and vasculature
DA1-like: control movement, cognitive function
- Positive inotropic effect (CV function; stronger contractions)
- Decreased renin and Na+ reabsorption (Decr. BP)
- Vasodilation (vasculature)
DA2-like: control movement, cognitive function, and prolactin secretion
Ropinorole
What receptor does it have affinity for? What is its function?
Ropinirole (Requip)
DA2 in brain (dopamine agonist)
Treatment of Parkinson’s and restless-leg syndrome
What is an example of a dopamine-antagonist? What is its function?
haloperidol (Haldol) and chlorpromazine (Thorazine)
Depleting DA in CNS; anti-psychotics
What are the receptor types in the eye for the radial muscle (iris) and the ciliary muscle?
Radial muscle: alpha1
Ciliary muscle: ß2
What are the adrenergic responses for the radial muscle (iris) and ciliary muscle in the eye?
Radial muscle: Mydriasis pupil dilation
Ciliary muscle: Relaxation for distant vision
*Note the sphincter muscle is the complement to the radial muscle, causing pupil constriction upon cholinergic impulse
What are the cholinergic responses for the sphincter and ciliary muscle in the eye?
Sphincter muscle: Miosis (pupil constriction)
Ciliary muscle: contraction for near vision
*Note radial muscle is complementary to sphincter muscle during adrenergic stimulation
Heart Responses to Autonomic Nerve Impulses (chart)
What receptor type is found for all heart receptors listed?
ß1 receptor
Blood Vessel Responses to Autonomic Nerve Impulses (chart)
- Coronary BVs
- Skin/mucosa BVs
- Skeletal muscle BVs
- Cerebral BVs
- Pulmonary BVs
- Abdominal viscera BVs
- Veins
- Salivary gland BVs
Coronary: ß2 predominates
Skin/mucosa: alpha1
Skeletal muscle BVs: ß2 predominates
Cerebral: alpha
Pulmonary: Alpha predominates
Abdominal: both alpha and ß2
Veins: Alpha predominates
Salivary glands: alpha
Summarize adrenergic activity in blood vessels (based on receptor type)
Alpha recptors constrict (skin/kidney/abdomen)
Beta receptors dilate (skeletal muscle/coronary artery)
Summarize CV effects of Catecholamines in therapeutic doses (Epi, NE, and Isoproterenol)
Epi: A1=A2; B1=B2
NE: All A, low ß
Isoproterenol: All ß, low A
Lung, Stomach, Intestine, Gallbladder, and Kidney Responses to Autonomic Nerve Impulses (chart)
- Bronchial muscle
- Stomach motility/tone
- Stomach sphincters
- Intestinal motility/tone
- Intestinal sphincters
- Kidney
-Bronchial muscle: ß2
-Stomach motility/tone: ß2 predominates
-Stomach sphincters: Alpha
-Intestinal motility/tone: ß2 predominates
-Intestinal sphincters: Alpha
-Kidney: ß1
Summarize Adrenergic and Cholinergic activity in the GI Tract
Cholinergic: Rest and Digest= increased motility and secretion
Adrenergic: Fight or Flight= reduced motility and sphincter contraction
Bladder, Sex Organs, Skin, and Adrenal Medulla Responses to Autonomic Nerve Impulses (chart)
Bladder (detrusor)
Bladder (trigone/sphincter)
Sex organs
Skin (piloerection)
Sweat glands
Bladder (detrusor): ß
Bladder (trigone/sphincter): alpha
Sex organs: alpha
Skin (piloerection): alpha
Sweat gland: alpha
*Note Skin piloerection is solely adrenergic (no cholinergic impulses)
Liver, Pancrease, Fat Cells and Glands Responses to Autonomic Nerve Impulses (chart)
- Liver
- Pancreas (Acini)
- Pancreas (Islets of langerhans)
- Fat Cells
- Salivary glands
- Liver: ß2
- -Pancreas (Acini): Alpha*
-Pancreas (Islets of langerhans): ß2 predominates
-Fat Cells: Both
-Salivary glands: Both
Summarize Adrenergic activy on salivary glands
Cholinergic: thin secretions (more)
Adrenergic: thick secretions (less)
*Adrenergic agonists cause xerostomia
What is critical in adrenergic activity in the CNS? What is the root cause? Where are side effects at toxic levels and what are they?
The ability to cross the Blood Brain Barrier (BBB)
-Hydroxyl groups are the root cause
At toxic levels, individuals experience severe CNS and CV side effects: nervousness/excitation/headache/tremor/cerebr. hemhorrage; hypertension/arrythmias/pulm. edema
Alpha Agonists
Phenlyephrine: A1
*Clonidine
*Dexmedetomidine
*Guanfacine
*Methyldopa
*=a2 predominates
What are the mixed alpha and beta agonists?
NE (Levophed): a1=a2; ß1>>ß2
Epinephrine: a1=a2; ß1=ß2
Beta agonists
dobutamine: ß1
isoproterenol
albuterol/metaproteren**ol/levalbuterol/pirbuterol/salmeterol/formoterol/arformeterol/terbutaline**
*Note: ß2 agonists all end in -ol (EXCEPT terbutaline)
Dopamine Agonists
dopamine: D1=D2>>ß>>alpha
fenoldapam: D1 (vasodilator used in anti-hypertensive crisis)
Mixed Action Agonists
ephedrine (alpha, ß2)
pseudoephedrine (alpha, ß2)
amphetamine & dextroamphetamine (Adderall)
dextroamphetamine (Dexedrine)
Controlled Substance classification for Adderall?
alpha (CNS) & adrenergic agonists
- Class 2 controlled substance (Adderall)
- Use for weight loss (NE depresses appetite)
Off-label uses: Narcolepsy & ADHD
atomoxetine (Strattera)
Controlled Class of drug?
alpha (CNS) & adrenergic agonists
non-stimulant; selectively inhibits reuptake of NE with little or no activity at neuronal receptor sites
Class IV
diethylpropion (Tenuate)
alpha (CNS) & adrenergic agonists
Bath salts
methamphetamine (Desoxyn)
Alpha (CNS) & adrenergic agonist
methylphenidate (Ritalin; Concerta)
dexmethylphenidate (Focalin)
Controlled Substance classification?
Alpha (CNS) & adrenergic agonists
-Blocks the reuptake of NE and dopamine and increases their release into extraneural space
(weight loss and better concentration; ADHD; narcolepsy; depression in elderly adults)
Both Class 2 controlled substances
*Release more NE than dopamine, therefore making them a lower probability for abuse
modafanil (Provigil)
armodafinil (Nuvigil)
central Alpha (CNS) & adrenergic agonist
- -Psychostimulants for nacrolepsy, shift work sleep disorder, obstructive sleep apnea, and off-label ADHD*
- increases NE, dopamine, seratonin, and glutamate
phentermine (Adipex-P; Suprenza)
Alpha (CNS) agonist
-Stimulates the hypothalamus to release NE and dopamine from neurons
sodium oxybate (Xyrem)
GABA receptor & adrenergic agonist
-sodium salt of gamma-hydroxybutyrate
tyramine
alpha, ß1; adrenergic agonist
Therapeutic uses of the following drugs:
Therapeutic uses of the following drugs:
Therapeutic uses of the following drugs:
albuterol
arformoterol
epinephrine
formoterol
levalbuterol
metprolerenol
pirbuterol
salmeterol
terbutaline
Bronchial asthma, COPD
-oral ß2 agonists are less effective, produce more adverse effects and have slower onset of action than the same drugs given by aersol inhalation
-Stimulation of ß2 relaxes bronchial smooth muscle (bronchodilators)
*terbutaline also stops uterine contractions and is used to prevent pre-term labor
-zoline
Alpha1 agonist (used as a decongestant)
-Constricts arteriolar network, decreasing blood flow to edematous area and improving breathing
Therapeutic Uses of the following drugs:
Common Cold/Decongestion
Therapeutic use of the following drugs:
Opthalmic uses (to dilate the pupils through the alpha1 receptor in the iris)
Dexmedetomidine (Precedex)
*Important!*
selective Alpha 2 agonist
Used for anesthetic and sedative properties
*Inhibits NE release by binding to receptors in the brain stem
*High doses can result in vasoconstriction
clonidine (Catapres)
guanfacine
Also stimulate alpha 2 brain receptors (in addition to controlling hypertension)
*Both drugs cause sedation
Off Label uses:
- ADHD
- Hyperkinesis
Overdose of Adrenergic Agonists/CNS stimulants Signs
Dilated Pupils
Shallow Respirations
Increase in BP/HR
Hyperactive tendon reflex
Nervousness/Insomnia to excitation/hallucination
Convulsion
Methylxanthines
-What are they?
What is their mechanism of action and function?
-What are examples?
Non-adrenergic stimulants
-Block adenosine (alpha 1 and 2b) receptors in the brain
Function: stimulates respiratory center sensitivity to CO2; prevent apnea (adenosine involved in constriction of airway smooth muscle/bronchoconstriction); diuresis (water/Na+ loss); Increased lipolysis/glycogenolysis/gluconeogenesis; Induces release of epinephrine from adr. medulla (- side-effect)
-Caffeine/theophylline
What enzyme is inhibited by methylxanthines? What enzyme is inhibited by beta agonists?
Methylxanthines: Phosphodiesterase
Beta agonists: Adenylate cyclase
Where does Caffeine have the highest impact? Theophylline?
CNS Respiration
Weak Diuretic
Bronchial Relaxation (bronchodilation)
Heart (positive inotropic/chronotropic effects)
Caffeine: CNS Respiration
Theophylline: Bronchodilation
What is the #1 drug used in neonates?
Caffeine
What are some of the special considerations for methylxanthine therapeutic use?
- Pregnancy: may delay blood flow to the placenta, thus harming the fetus (decrease or eliminate consumption during this period)
- Common side-effects are benign breast lumps, GI reflux, and anxiety
Why would you utilize another option than a methylxanthine for treatment of obstructive lung disorders (asthma, emphysema) or apnea?
Because it has a tight therapeutic index so other options are better
Side effects: Cardiac/CNS stimulation; nausea, vomiting, diarrhea, headache, insomnia, and irritability (tachycardia and arrythmias can occur at higher levels than 35 mcg/mL)
What is aminophyline (IV) used for?
Reversal agent for adenosine (Adenoscan) and regadenoson (Lexiscan)
