Exam II: Adrenergic Agonists Flashcards
The general term for neurotransmitters/hormones in the sympathetic nervous system is:
Catecholamines
What are the 3 major catecholamines?
Dopamine
Norepinephrine
Epinephrine
What are the 4 basic adrenergic receptors?
alpha 1
alpha 2
beta
dopamine
Alpha 1 receptors are coupled with ____ proteins and produce ____ effects
Gq proteins
Activate other enzymes, resulting in positive effects
Alpha 2 receptors are coupled with ____ proteins and produce ____ effects
Gi proteins
Decrease cAMP causing negative action
Beta receptors are coupled with ____ proteins and produce ____ effects
Gs proteins
Inc. conversion of ATP to cAMP (inc. cAMP)
Dopamine receptors are coupled with ____ proteins and produce ____ effects
Gi and Gs
D1: increase cAMP
D2: decrease cAMP
What are the 4 factors that can alter the degree to which adrenergic receptors respond to a stimulus
- Selectivity
- Regulation
- Polymorphism
- Catecholamine metabolism
What are the 4 examples of mechanisms of desensitizations?
- Altered transcription or translation of DNA and/or RNA
- Modifications of receptors
- Long term exposure to an agonist
- Interactions or messages from other receptors
How is NE terminated in the cell? (4 ways)
- NET acts as pre-synaptic pump to move NE out of synapse and back into neuron
- Movement of NE out of synaptic cleft and into bloodstream
- Metabolism b COMT
- Metabolism by MAO
What are 2 drugs that inhibit NET?
Atomoxetine (for ADHD)
Cocaine
What does COMT stand for?
catecholamine-O-methyltransferase
What does COMT metabolize?
All catecholamines (NE, Epi, DA)
What is a drug that inhibits COMT and what disease is it used to treat?
Entacapone
Treats Parkinson’s dz to inhibit metabolism of levodopa
What does MAO stand for?
Monoamine Oxidase
What does MAO metabolize?
Endogenous monoamines (NE, epi, serotonin, DA)
Define sympathomimetic
Drugs that mimic actions of NE, epi, DA
Where on the chemical structure can changes be made to sympathomimetics to alter affinity?
- Benzene Ring Substitutions
- Amino group substitutions
- Alpha carbon substitutions
- Beta carbon substitutions
Describe possible benzene ring substitutions
- Adding hydroxyl groups to C3 and C4
- Adding a hydroxyl group to either C3 or C4
- Absence of hydroxyl group on benzene ring
If a sympathomimetic has -OH groups added to C3 and C4 position of the benzene ring then what characteristics would you expect?
Maximized alpha and beta activity
Susceptible to COMT breakdown so they will have a shorter half-life
If a sympathomimetic has an -OH group added to either C3 or C4 position of the benzene ring then what characteristics would you expect?
Reduced adrenergic potency
COMT can NOT break down so inc. drug duration
If a sympathomimetic has no -OH groups on its benzene ring then what characteristics would you expect?
Lipophilic –> can enter CNS
Describe the possible amino group substitutions
Increasing the size of alkyl substitutions
Isopropyl groups on the amino nitrogen
What does increasing the size of an alkyl substitution do to the sympathomimetic drug?
Increases beta activity
The larger the group, the lower the alpha activity
What does adding an isopropyl group to the amino nitrogen do to the sympathomimetic drug?
Increases beta activity
What do substitutions to the alpha carbon of a sympathomimetic cause?
They block oxidation by MAO and therefore have a prolonged duration of action
What can adding a methyl group to the alpha carbon do?
Increases drugs ability to act as an indirect sympathomimetic and a direct sympathomimetic
What is an example of a drug with a methyl group added to the alpha carbon?
Amphetamine
The outcome of giving a drug is dependent upon 3 things:
- Selectivity for alpha and beta receptors
- Pharmacologic action at the receptors (at/antag)
- Action of body’s compensatory mechanisms to maintain homeostasis (ie: desensitization)
Where are alpha 1 receptors located in the cardiovascular system?
Vascular beds
When an alpha 1 receptor is activated in the CV system what occurs?
Arterial and venous vasoconstriction –> inc. BP, a reflexive slowing of HR, but venous return also increases which increases stroke volume and maintains CO
(CO= HR x SV)
Name a drug that activates alpha 1 receptors in CV system. What does it treat?
Phenylephrine
Maintain BP in pt w/ poor organ perfusion
Treat stuffy nose (neosenephrine)
Where are alpha 2 receptors located in the CV system?
Vascular beds and CNS
When the peripheral alpha2 receptors are activated what occurs?
Vasoconstriction – but only when given locally, IV push, or very high oral doses
When the central alpha 2 receptors are activated what occurs?
A decrease in sym. activity –> dec. BP
*Needs to be given systemically
What is a therapeutic use involving alpha 2 receptors….what drug is commonly used?
Hypertension
Clonidine
If a beta 1 receptor is activated then what CV effects will be seen:
Inc. HR –> inc. CO
If a beta 2 receptor is activated then what CV effects will be seen?
Dec. BP
What does stimulation of dopamine 1 receptors do in terms of the CV system?
Vasodilation
Dopamine also binds to ____ and ____ receptors.
Alpha and beta
A low dose of dopamine….
activates beta 2 receptors
A medium dose of dopamine….
activates beta 1 receptors
A high dose of dopamine…
activates alpha 1 receptors
What receptors are present in the lungs and what does stimulation of these receptors cause?
Beta 2 receptors –> bronchodilation
What receptors are present in the eyes and what does stimulation of these receptors cause?
Alpha receptors (in radial muscle) –> mydriasis
What receptors are present in the GU system and what does stimulation of these receptors cause?
Alpha receptors (in bladder, sphincter, prostate, etc) –> promotes urine retention and ejaculation
What receptors are present in salivary glands and what does stimulation of these receptors cause?
Beta receptors –> inc. salivation
Sympathomimetics ______ glycogenolysis in liver via ______ _________.
Increase
Beta Receptors
____ receptors increase lipolysis while ____ receptors decrease lipolysis.
Beta
Alpha 2
____ receptors increase release of renin while ___ receptors decrease release of renin
Beta 1
Alpha 2
Besides insulin and renin, what are 4 other hormones mediated by adrenergic receptors:
- Parathyroid hormone
- Calcitonin
- Thyroxine
- Gastrin
Epinephrine is an agonist at ____ and ____ receptors
alpha and beta
Epi causes a ____ in systolic BP due to _____. And it also ____ HR and CO due to _____.
Increase
Alpha 1
Increases
Beta 2
NE causes an ____ in systolic BP due to ____. It also ____ HR and CO via _____.
increased
Alpha 1
Increased
Beta 1
Phenylephrine
Direct alpha 1 agonist
Not inactivated by COMT…longer duration
Used as a decongestant and to raise BP
Midodrine
Direct alpha 1 agonist (a prodrug…its hydrolyzed form is actually the alpha 1 agonist)
Inc. BP and treats orthostatic hypotension
Name the 4 drugs that act as alpha 2 agonists and reduce blood pressure, treating HTN
“Gross Men Chew Gum”
Guanfacine
Methyldopa
Clonidine
Guanabenz
What is dexmedetomidine used for? What type of sympathomimetic drug is it?
Acts in the CNS and used for sedation of patients in the ICU setting
Direct Alpha 2 Agonist
What is an example of a direct alpha (1 and 2) agonist?
Oxymetazoline
What does oxymetazoline do?
Alpha 1 action causes vasoconstriction and used as a decongestant
Alpha 2 reduces BP
Name a non-selective beta agonist
Isoproterenol
Isoproterenol: effects and what it is used for
Vasodilation (beta 2) –> dec. BP and mean arterial pressre
Positive chronotropic and inotropic effects (beta 1) –> inc. HR and CO
Variety of effects so not really used
_____ is a beta 1 selective agonist.
Dobutamine
Describe the actions of the two dobutamine isomers
(+) isomer: Beta 1 agonist, alpha 1 antagonist
–> Inc. CO w/o increase BP
(-) isomer: Alpha 1 agonist
–> Inc. BP
*When given together = positive inotropic effect w/ little change in BP
What type of sympthomimetics are used to treat asthma and COPD?
Beta 2 selective agonists
What type of sympathomimetics are used to relax uterine smooth muscle during labor?
Beta 2 selective agonists
List the drugs used to treat asthma and COPD
“Albert Met Soloman Teaching Pilates Form”
Albuterol Metaproterenol Salmeterol Terbutaline Pirbuterol Formoterol
What is the drug (beta 2 selective agonist) used to relax uterine smooth muscle during early labor?
Ritodrine
How would one classify ephedrine (pseudoephedrine)
Mixed-acting sympathomimetic
AKA: provides effects of alpha and beta receptors
What are the two mechanisms in which indirect-acting sympathomimetics act?
- They displace stored catecholamines
2. Inhibit reuptake of released neurotransmitter by interferring w/ NET
What do amphetamines release and what is their action within in the CNS system?
Cause release of NE and DA
They are a CNS stimulant meaning they inc. mood and alertness while dec. appetite
What are the 3 amphetamine derivatives?
- Methamphetamine (crystal meth)
- Phenmetrazine
- Methyphenidate (Ritalin)
How does methyphenidate work? (aka what does it treat)
(Ritalin) reduces reuptake of NE, improving its function in the brain in order to treat ADHD
What two drugs can be used to treat patients w/ narcolepsy, obstructive sleep apnea, and shift work disorder?
What class are these drugs?
Modafinil and Armodafinil
Indirect acting sympathomimetics
Patients taking an MAO inhibitor need to be warned not to consume ______ because of _______.
tyramine containing foods (aged foods)
Potentially dangerous HTN
Describe tyramine actions
Causes release of stored catecholamines…similar actions to NE (alpha 1, alpha 2, beta 1)
4 examples of catecholamine reuptake inhibitors:
- Atomoxetine
- Subutramine
- Doluxetine
4 Cocaine
Atomoxetine
Selective inhibitor of NE reuptake w/ mostly CNS effects (maybe inc. in BP)
Used to treat ADHD
Subutramine
Serotonin and NE reuptake inhibitor
Appetite suppressant, but taken off the market recently b/c of negative CV effects
Doluxetine
Serotonin and NE reuptake inhibitor
Antidepressant
Cocaine
Inhibits peripheral reuptake of NE
In CNS, has amphetamine-like actions, more intense.
Inhibition of DA reuptake in pleasure center of brain –> leads to rapid addiction
What would be used to treat a patient w/ hypotension?
Goal: Raise BP
Use alpha 1 agonists such as NE, phenylephrine
What would you use to treat a patient in shock?
Positive inotropic agents such as dopamine and dobutamine
What would you use to treat a patient w/ hypertension?
an alpha 2 agonist such as clonidine
What would you use to treat orthostatic hypotension?
Alpha 1 agonist like midodrine
What would you use in emergency cardiac measures?
Epinephrine
Isoproterenol
What are the two goals of surgical use of sympathomimetics?
- Reduce blood loss at site of surgical manipulations
2. Slow diffusion of anesthetics away from site of administration
What drugs are used to reduce blood loss at site of surgical manipulations?
Epi or cocaine
What drugs slow diffusion of anesthetics away from site of administration?
Epi, NE, phenylephrine
What drugs are used as a sinus decongestant?
Alpha 1 agonist –> cause vasoconstriction
Phenylephrine and Oxymetazoline (Afrin)
**No more than 3 days of use due to rebound effect!!!
How are sympathomimetics used to treat anaphylaxis?
Epi activates alpha 1, beta1, and beta2 receptors to reverse symptoms of anaphylaxis
*Often use steroid or antihistamine in combination
What are the 3 ways drugs can treat ophthalmic problems?
- Alpha 1 agonists cause mydriasis –> useful for eye exam
- Alpha 1 agonists used as decongestants to reduce red eye
- Alpha 2 agonists reduce intraocular pressure of glaucoma
Three drugs used in the treatment of ADHD
- Methylphenidate (ritalin)
- Dextroamphetamine (Adderall)
- Lisdexamfetamine (Vynase)
