Sympathetic drugs Flashcards
Other than being taken back up into the presynaptic neuron, some NE can be broken down by _____________
Monoamine oxidase (MAO) and catechol-O-methyltransferase
An example of drug action on the synthesis of NE
Methyldopa acts as a ‘false transmitter’ that reduces NE production and creates a different metabolite that causes sympathetic inhibition.
An example of drug action on the storage of NE
Resperine blocks the uptake into storage vesicles of NE so when the stored up NE runs out there is no more left to be used.
An example of drug action on the release of NE
Bretylium blocks the release of NE at the synapse decreeing the amount available.
An example of drug action on the uptake/reuptake of NE
Imipramine inhibits reuptake of NE causing it to remain in the synapse longer.
Beta 1 agonists are often used to treat _________
Cardiac disease
Epinephrine in general is used to treat _________
Anaphylactic reactions
Beta 2 agonists are often used to treat _________
Obstructive airway disease
Alpha 2 agonists are often used for _________
Sedation/analgesia
Beta 1 antagonists are often used to treat _________
tachyarrhythmias
Alpha 1 antagonists are often used to treat _________
vasodilation (?)
Alpha 2 antagonists are often used as _________
reversals for Alpha 2 sedation
What are catecholamines?
endogenous substances that serve as hormones/neurotransmitters
**positive ionotropes (contractility)
What are 5 examples of catecholamines?
Epinephrine Norepinephrine Isoproterenol Dopamine Dobutamine
What receptors are targeted by epinephrine and what is it used for?
All adrenergic receptors. Alpha 1 - vasoconstriction Alpha 2 Beta 1 - cardiac contraction (cardiac arrest) Beta 2 - bronchodilation (anaphylaxis) Beta 3 -
Epinephrine mode of delivery?
IV, IM, SC.
NOT given orally because it is rapidly metabolized by the GI tract.
T/F Catecholamines generally cross the BBB
FALSE.
Catecholamines generally do not cross the BBB
When to be cautious using epinephrine?
Glaucoma, non-anaphylactic shock, combined with other drugs effecting the heart, Tachycardia/tachyarrhythmias.
What type of drug is epinephrine?
Catacholamine - Direct acting sympathomimetic
Norepinephrine mode of delivery?
Given intravenously.
What receptors are targeted by norepinephrine?
Mainly alpha receptors but also beta 1.
NOT beta 2.
What is norepinephrine used for?
It will increase mean arterial blood pressure, increase after load of the heart, and be a potent vasoconstrictor due to lack of beta 2 involvement.
Cautions for using norepinephrine?
Combined with other drugs effecting the heart, and avoid extravasation (injecting outside of the blood vessel could cause tissue damage).
What type of drug is norepinephrine?
Catacholamine - Direct acting sympathomimetic
What receptors are targeted by isoproterenol?
Beta 1 and Beta 2
Isoproterenol mode of delivery?
Injectable solution.
What is isoproterenol used for?
Rarely used anymore. SYNTHETIC
Increases heart contractility, increases oxygen consumption, decreases vascular resistance, and bronchiole relaxation.
Cautions using isoproterenol?
Can lead to tachycardia/tachyarrhythmias
What drug would be better to use in the short term to treat bradyarrhythmias, isoproterenol (catecholamine) or atropine (antimuscarinic)
Atropine.
Which receptors does dopamine target?
Alpha and Beta-1. Dose dependent (Alpha 1 not involved until medium dose achieved)
Dopamine mode of delivery?
IV infusion due to short half life.
What effect will dopamine have at a low dose?
Dilation of vascular beds (renal, mesenteric, etc)
What effect will dopamine have at a medium dose?
Activates alpha 1 and promotes increased contractility.
What effect will dopamine have at a high dose?
Activated alpha 1 receptors cause release of NE and vasoconstriction.
*not used for anaphylaxis as much as other catecholamines.
Cautions when using dopamine?
Combined with other drugs effecting the heart (lead to tachyarrhthymia) and avoid extravasation (injecting outside of the blood vessel could cause tissue damage).
What type of drug is dopamine?
Catacholamine - Direct acting sympathomimetic.
What receptors are effected by Dobutamine?
Beta 1 mainly
Dobutamine mode of delivery?
IV infusion due to short half life.
What is dobutamine used for?
Increased heart contractility and heart rate.
Cautions with dobutamine
Combined with other drugs effecting the heart (lead to tachyarrhthymia) and avoid extravasation (injecting outside of the blood vessel could cause tissue damage).
What kind of drug is dobutamine?
Catecholamine - Direct acting sympathomimetic.
Phenylephrine targets which receptor?
Alpha 1 agonist
Phenylephrine mode of delivery?
Oral, IV, IM, intranasal, ophthalmic
Phenylephrine can be used systemically or locally to induce __________
vasoconstriction and increase vascular resistance
Phenylephrine can be used ophthalmically to induce __________
mydriasis and and diagnose horner’s syndrome (sympathetic lesion)
Cautions when using Phenylephrine?
- Less effective in cats and horses.
- Systemic effects (increased vasoconstriction) can occur when used topically in small patients.
- Reflex bradycardia
What kind of drug is phenylephrine?
Non-catecholamine Direct acting sympathomimetic
What receptors does Brimonidine effect?
Alpha 2 agonist.
Brimonidine mode of delivery?
Topical ophthalmic
What is Brimonidine used for?
Decrease aqueous humor production to treat glaucoma despite possible mydriasis.
Similar agent to Brimonidine that is less effective and has more adverse effects
Apraclonidine
What type of drug is Brimonidine?
Non-catecholamine Direct acting sympathomimetic
What receptors do Ractopamine and Zilpaterol target?
Beta - 1, Beta - 2, BETA - 3 (beta3 involved in adipocyte lipolysis)
What are Ractopamine and Zilpaterol used for?
‘partitioning agents’ - reduce fat deposition and increase muscle deposition in late finishing meat-producing animals.
What type of drugs are Ractopamine and Zilpaterol?
Non-catecholamine Direct acting sympathomimetics
**nonselective beta agonist
What are selective beta-2 agonists and what are they used for?
Act primarily at Beta-2 receptors (Little/no involvement with beta1/3) and are used to improve ciliary function and treat bronchoconstriction.
Cautions when using selective beta 2 agonists?
Problems mainly result from any potential beta 1 effects (cardiac stimulation) or beta 2 unwanted effects (vasodilation/uterine relaxation)
What receptors do Albuterol/Salbutamol target?
Beta 2
They are selective beta 2 agonists!!
Albuterol/Salbutamol mode of delivery?
oral, aerosol, or solution for nebulization
Preferred as an aerosol as it has very good mucosal absorption and very poor oral absorption (high pKa)
What is Albuterol/Salbutamol used for?
Treating asthma in mainly horses and cats. Also mainly used in acute cases due to rapid onset.
What type of drug is Albuterol/Salbutamol?
Non-catecholamine Direct acting sympathomimetics
**selective beta 2 agonist
Why is Salmeterol combined with Fluticasone and what is it used for?
Combined selective beta 2 agonist with a steroid to treat asthma and inflammation at the same time.
What receptors does Clenbuterol target?
Beta 2
**Selective Beta 2 agonist
Clenbuterol mode of delivery?
Oral syrup for equines
What is Clenbuterol used for?
Bronchodilation and outside of the US for possible uterine relaxer.
NOT permitted in food animals.
What type of drug is Clenbuterol?
Non-catecholamine Direct acting sympathomimetics
**selective beta 2 agonist
What receptors does Terbutaline target?
Beta 2
**Selective Beta 2 agonist
Didnt really tell us what its used for, assuming bronchodilation.
Terbutaline mode of delivery?
Oral or injectable
Little to no oral availability in horses.
What type of drug is Terbutaline?
Non-catecholamine Direct acting sympathomimetics
**selective beta 2 agonist
What receptors does isoxuprine target?
Beta 2
**Selective Beta 2 agonist
What is isoxuprine used for?
Uterine relaxation and peripheral vasodilation.
Perviously thought to treat laminitis/navicular disease.
What are examples of selective beta 2 (Noncatecholamine) Direct acting sympathomimetics?
- Albuterol/Salbutamol
- Salmeterol
- Clenbuterol
- Terbutaline
- Isoxuprine
What are Indirect acting sympathomimetics used for?
Mainly used for their behavioral/CNS effects as opposed to their autonomic NS effects.
What receptors does Phenylpropanolamine (proin) target?
MIXED acting sympathomimetic and primarily works through indirectly increasing the release of NE at the bladder.
Also directly on Alpha 1.
What is Phenylpropanolamine (proin) used for?
Used to treat urinary incontinence by working at the urethral sphincter.
What drug can be used synergystically with Phenylpropanolamine (Proin)?
Estrogens - Diethylstilbestrol and Estriol.
Will increase alpha 1 expression at the urinary sphincter.
Cautions while using Phenylpropanolamine (Proin)?
Urinary retention, tachycardia, hypertension, and potentially tachyphylaxis (acute tolerance)
What type of drug is Phenylpropanolamine (Proin)?
Mixed (Indirect and Direct) acting sympathomimetic acting on the bladder.
What receptors are targeted by Ephedrine/Pseudoephedrine?
Mixed agent, so indirect release of NE and direct alpha 1 action.
What is Ephedrine/Pseudoephedrine used for?
Vasoconstriction at nasal passages (cold/flu) and used in some herbal therapies.
What type of drug is Ephedrine/Pseudoephedrine?
Mixed (Indirect and Direct) acting sympathomimetic acting on the blood vessels of the nasal passage.
What are 2 Direct acting sympatholytics that are alpha blockers?
Phenoxybenzamine and Prazosin
What receptors does Phenoxybenzamine target?
Alpha 1 and Alpha 2
Nonspecific, irreversibly binding (binding lasts 3-4 days)
Phenoxybenzamine mode of delivery?
Oral (often used for cats and needs to be compounded
What is Phenoxybenzamine used for?
Used to treat urinary retention at the smooth muscle of the internal urinary sphincter.
Also, used to treat hypertension caused by catecholamine release in pheochromocytomas (adrenal medulla tumor) - better choice for this than Prazosin.
Cautions while using Phenoxybenzamine?
Hypotension leading to tachycardia, miosis
What type of drug is Phenoxybenzamine?
Direct acting sympatholytics
Alpha blocker.
What receptors does prazosin target?
Alpa 1 agonist!
Prazosin mode of delivery?
Oral
What is Prazosin used for?
Also used to treat smooth muscle of the internal urinary sphincter (more effective than Phenoxybenzamine, but also more cardiavascular effects than Phenoxybenzamine)
What type of drug is Prazosin?
Direct acting sympatholytics
Alpha blocker.
What are some Direct acting sympatholytics that are beta blockers?
- Propanolol
- Timolol
- Metoprolol
- Atenolol
- Esmolol
- Sotalol
What receptors does Propanolol effect?
Non-selective for beta receptors
Propanolol mode of delivery?
Oral (significant first pass metabolism) or injectable.
What is propanolol used for?
Causes bradycardia (treats supraventricular tachyarrhythmias), decreases atrioventricular node conduction, treats feline hyperthyroidism, or treatment of methylxanthine chocolate toxicity.
Cautions while using propanolol?
Potential bradycardia, hypotension, and brinchospasm (bronchconstrictor - not good in asthma patients)
What type of drug is propanolol?
Direct acting sympatholytic
Beta blocker.
What receptors does Timolol target?
Non-selective for beta receptors
What is Timolol used for?
The treatment of glaucoma, decreases aqueous humor production, and miosis.
What type of drug is Timolol?
Direct acting sympatholytic
Beta blocker.
What receptors does Metaprolol effect?
Selective for beta 1
What is Metaprolol used for?
Go to drug for methylxanthine poisoning. Longer acting and faster toxin renal excertion than Propanolol.
What type of drug is Metoprolol?
Direct acting sympatholytic
Beta blocker.
What receptors does Atenolol effect?
Selective for beta 1
What is Atenolol used for?
Used for the same purposes as propanolol but does not have beta 2 effects on the lungs making it safer for patients with asthma.
What type of drug is Atenolol?
Direct acting sympatholytic
Beta blocker.
What receptors does Esmolol effect?
Selective for beta 1
What is Esmolol used for?
Injectable therefore short duration of acting makes it useful as a testing response to beta-blocker therapy)
What type of drug is Esmolol?
Direct acting sympatholytic
Beta blocker.
What receptors does Sotalol effect?
Non-selective for beta receptors
Class III antiarrhythmic
What is Sotalol used for?
An anti-arrhthymic to manage ventricular tachyarrythmias.
What is Carvedilol?
Non-selective beta-1 antagonist and selective alpha 1 antagonist.
What are indirect acting sympatholytics?
Alter synthesis, storage, or release of NE
What does Reserpine do and what type of drug is it?
It is an indirect acting sympatholytic that blocks vesicular monamine transporters reducing the uptake of NE into vesicles reducing its storage.
Used as a calming agent in horses.
What is Co-Transmission?
Transmitters that work alongside ACh or NE
Cotransmitters of NE include:
- VIP
- GnRH
- GABA (MAIN INHIBITORY NT OF THE CNS)
- 5-HT (seratonin)
- dopamine
Clicker Question:
Both Atropine and Glycopyrrolate are commonly used to treat bradycardia. Which of the following is TRUE regarding comparison of these two drugs?
A. Atropine is Direct acting while Glycopyrrolate is Indirect acting.
B. Atropine can be given IV but Glycopyrrolate can only be given SC.
C. Atropine crosses the BBB but Glycopyrrolate does not.
D. Atropine has a slower onset and a longer duration of action than Glycopyrrolate.
C. Atropine crosses the BBB but Glycopyrrolate does not.
Clicker Question:
Tropicamide is commonly used in ophthalmology for what purpose?
A. To dilate the pupil for retinal (fundic) examination.
B. To improve aqueous drainage in treatment of glaucoma
C. To prevent lens luxation
D. To prevent cyclopegia.
A. To dilate the pupil for retinal (fundic) examination.
Because shorter acting than atropine.
Clicker Question:
Regarding Dobutamine, which of the following statements is true?
A. It is best administered orally
B. It is primarily a Beta-1 adrenergic agonist
C. Its net effect is to decrease cardiac contractility
D. It should be given chronically on a daily basis for maximum chronological effect.
B. It is primarily a Beta-1 adrenergic agonist
