L4 Adrenergic Agonist and Antagonist Flashcards
what are the Direct acting- selective drugs
a1- phenylephrine
a2-clonidine
b1-dobutamine
b2-terbutamine
what are the direct acting- non selective drugs
a1a2-oxymetazoline
b1b2-isoproterenol
a1a2b1b2-epinephrine
a1a2b1-norepinephrine
what is the mixed acting drug
a1a2b1b2-ephedrine
what are the indirect acting- releasing agents drugs
-amphetamine
-tyramine
what are the indirect acting-uptake inhibitor
cocaine
what are the indirect acting- MOA inhibitor
Seleliline
what are the indirect acting- COMT Inhibitor
entacapone
what drug when uses causes response that are NOT REDUCED WITH PRIOR TREATMENT for the direct acting selective and non selective drugs
RESERPINE OR GUANETHEDINE WHICH DEPLETE NE
What drugs cause the response to be potentiated for direct acting selective and non selective drugs
COCAINE, RESERPINE AND GUANETHEDINE
what drug when uses causes response that are REDUCED WITH PRIOR TREATMENT for the mixed- acting drug
RESERPINE AND GUANETHEDINE
what drug causes response to be abolished by prior treatment for indirect acting-releasing agent amphetamine and tyramine
RESERPINE AND GUANETHEDINE
what is the main agonist for the a1 b1 b2 receptor
NE
where is the alpha 1 receptor primarily found
blood vessels
Agonist and Antagonist of alpha 1
- Agonist: NE
- Antagonist: Phentolamine
(and phenoxybenzamine, which is used to treat hypertension, MOA is vasodilation
Any drug that looks like NE and causes VC and increase in BP
what is the effect of a tumor of the adrenal gland
causes excessive production of NE and EPi, the treatment would be to administer phentolamine because it inhibits NE from binding to the synapse so blood pressure is reduced.
where is alpha 2 receptors found
presynaptic nerve terminals of postganglionic nerve
Control the release of neurotransmitters
Agonist and Antagonist for Alpha 2
Agonist: NE
* Antagonist: none
Quanidine (stimulate a2 receptor, used to treat hypertension)
- Feedback mechanism and therefore decrease release of NE or dec BP
predominant alpha-adrenergic agonist responses are
- Vasoconstriction and CNS stimulation
- Primarily located on smooth muscle. vasculature or blood vessels and prostate
what is the function of NE transporter(NET)
carries NE into the cytoplasm of nerve cell
what is the function of VMAT
which carry NE into the vesicle
what is the effect of cocaine
blocks the NET protein, inhibits the NE reuptake
NE stays in the synapse cleft longer causing prolonged sympathetic activity
what is the effect of reserpine
-used to treat hypertension
-inhibits VMAT
prevents the refilling of vesicles of NE’, MAO in cytosil will breakdown the NE
where is Beta 1 primarily located
heart
Stimulate B1 will case increase in heart rate
where are beta 2 receptors primarily located
smooth muscle of the bronchioles, arterioles, and visceral organs, skeletal muscle, activates glycogenolysis
Stimulate B2 relax smooth muscle and cause bronchodilation or vasodilation
The beta-adrenergic agonist response results in
- Bronchial, GI, and uterine smooth muscle relaxation
- Glycogenolysis (B-receptor activation leading to activation of glycogen phosporylase which is rate limiting step in glycogenolysis)
- Cardiac stimulation
what is the effect of dopamine(adrenergic receptor)
Stimulated by dopamine (inc HR)
* Causes dilation of the following blood vessels, resulting in INCREASED blood flow
* Renal
* Mesenteric * Coronary
* Cerebral
what are the 3 adrenergic receptors
Alpha
Beta
Dopamine
Effects of beta 1 at different locations
cardiac muscles- Increased contractility
AV Node- Increased heart rate
SA Node- Increased heart rate
Effects of beta 2 at different locations
Blood vessels- dilation
Muscle- Decreased motility
Bronchial- dilation, relaxation
uterus- relaxation
Effects of Alpha 1 at different locations
Blood vessels- constriction
bladder Sphincters- constriction
uterus- constriction
what examples cathecholamines molecules
-dopamine
-Norepinephrine (Norepinephrine)
-Epinephrine
-Isoproterenol (Isuprel)
-Dobutamine
where does cathechloamines binds
adrenergic receptors
what is the half life of catheclolamines
20 secs
what is the parent compound of catecholamines
Phenylethylamine(benzene ring without the OH on c3 and C4) is considered the parent compound which sympathomimetic drugs are derived
describe the chemical structure of catecholamines
-benzene ring with OH on c3 and c4
-ethylamine side chain
How does increasing the size of the amino group affect the catecholamine structure
increase the alpha and beta receptor activity when groups are added at the (Beta carbon)
how is the half life increased for catecholamines
altering the structure by adding groups to the (alpha carbon)
Epinephrine
50%- Alpha
50%-Beta
Norepinephrine
95%- Alpha
5%- Beta/Dopamine
Isoproterenol
5%- Alpha
95%- Beta phenylephrine, Dobutamine
Examples of noncatecholamines
-Ephedrine
-Phenylephrine
-Albuterol
-Methoxamine
-Amphetamine
can catecholamine be administered orally
-no
it can be administered orally when the OH group on the benzene ring is removed.
what is the rate limiting step in catecholamine synthesisq
Tyrosine——Tyrosine Hydroxylase—–> DOPA
What is the major metabolite of NE/ EPI
-Vanillymandelic Acid (VMA), via MAO and COMT enzyme
-is the major metabolite found in the urine
Describe the tyramine like effect
Drug interaction of MAOI with tyramine foods (beer, fava beans, cheese, yeast red wine…) will result in hypertensive crisis
-Tyramine inhibits MAO is NE is not degraded in the synapse, so the increased amount of NE binding to alpha 1 receptor causes BP to increase drastically
-also tyramine produces tyrosine which is the substrate for catecholamine production so this increase NE production
Patient on MAOI must avoid tyramine containing foods
* Broad beans, fava beans
* Cheese, natural or aged, cheddar gruyere, stilton * Chicken liver
* Chocolate
* Sausage
* Smoked herring
* Snails
* Wine
* yeast
- Increased force of contraction
(positive inotropic effect)
Increased heart rate
(positive chronotropic effect)
Increased conduction through the AV node
(positive dromotropic effect)
One Therapeutic Use of Adrenergic Agents:
Anorexiants: adjuncts to diet in the short-term management of obesity
Examples: benzphetamine phentermine
dextroamphetamine Dexedrine
One Therapeutic Use of Adrenergic Agents:
Bronchodilators: treatment of asthma and bronchitis
Examples:
albuterol
isoetharine
metaproterenol
ephedrine
isoproterenol
salmeterol
epinephrine
levalbuterol
terbutaline
Bronchodilators- * Isoproterenol
Non selective B1, B2 agonist
* Most potent
* Indication: Bronchodilator
* Inhaler rapid onset
* Side effect: cardiac arrhythmia, due to B1 being stimulated
Bronchodilator-Isoethraine
- Inhaler
- B1, B2
- Indication: Bronchodilator
Bronchodilator-Terbutaline
- Prototype oral
- B2 selective
- PO, sc, inhaler, iv
- PO long duration
- Will cause caridac arrhythmia only art higher doses
- SE: skeletal m tremor, restlessness
-used to decrease uterine contraction to slow down the laboring process.
Ritoridine
- B2 agonist
- Relaxes uterine smooth muscle
- Indication: premature labor
- May also use Terbutaline
One Adrenergic Agents: Therapeutic Uses
Reduction of intraocular pressure and mydriasis (pupil dilation): treatment of open-angle glaucoma
Examples: epinephrine and dipivefrin
One Adrenergic Agents: Therapeutic Uses
Nasal decongestant:
* Intranasal (topical) application causes constriction of dilated arterioles and reduction of nasal blood flow, thus decreasing congestion.
Examples: epinephrine, ephedrine, pseudoephedrine,naphazoline phenylephrine
tetrahydrozoline
Nasal decongestants
-Phenylepherine
-Pseudophedrine
* Oral or nasal drops
* A1 agonist VC of mucosa in
nostrils
* “rebound nasal stuffiness” * Ischemia of nostrils
* Topical SE like cocaine
* CNS stimulation
Nasal Decongestants Inhalers
- Oxymetazoline LA (Afrin) * Xylometazoline LA
- Tetrahydrazoline
- Propylhexadrine
- Phenylproponolamine
Vasoconstrictors- Norepineherine (levaterenol, noradrenaline)
- NE-like
- Indicated for vascular shock
- Vasopressor
Vasoconstrictors- Epinepherine
-stimulates the a1 b1 b2 receptor
* VC and cardiac stimulant
* Increase in BP secondary to cardiac
* Indicated for anaphylaxsis ie insect bite, drug allergy
* Not as potent as levaterenol
* Will elevate BP by causing VC,
Inc HR
* SE: cardiac arrhythmias
Vasoconstrictors-Ephedrine
- Mau Huang
- Oral form of epi
- Resist breakdown by GI mucosa
- A1, B1, B2
- Indication: asthma attack (dilate airway)
- Derivative of pseudoephedrine (difficult to get in pharmacy)
- CNS stimulation
Vasoconstriction- * Metaraminol iv
- Vasopressor
- Indirect acting amine
Vasoconstriction-* Mephenteramine iv
- Vasopressor
- Direct and indirect
- LA (long lasting)
Phenmetrazine is a
anorexant
Methylphenidate is a
Attention deficient disorder
Pemoline is a
Attention deficient disorder
Cocaine
- Local anestetic
- MOA: inhibit reuptake at noradrenergic synapses, inhibit dopamine
ru pleasure center - Enters CNS and causes amphetamine like effect * Routes: smoked, snorted, injection
Salmeterol
is indicated for PREVENTION of bronchospasms, not management of acute symptoms.
Non selective alpha blocker
Phenoxybenzamine
Phentolamine
Selective alpha 1 blocker
Prazosin
Doxazosin
Tamsulosin
Terazosin
-All except Tamsulosin is used to treat hypertension
selective alpha 2 blocker
Mirtazapine
Yohimbine
What are 2 drugs that are alpha and beta blocker
carvedilol
labetalol
Alpha 1 Antagonist
- Phentolamine (not a prodrug)
-competitive inhibitor- reversible binding - Imidazole, a1
- SE: a2, mild Ser, H1
- Reduce periperhal vascular resistance
- Cardiac stimulation due to baroreflex
- iv
- Tx: Pheochromocytoma
- Phenoxybenzamine (a prodrug)
-Covalently bond to a receptor-irreversible binding - a1 blockade LA
- SE: same
- Little fall in BP in normal patients only when BP is high
- po
- Tx; Pheochromocytoma
Alpha 1 Antagonists
- Prazosin, terazosin, doxazosin (HTN) * Tolazoline (PVD?)
- Tamulosin, Alfuzosin a1a (BPH)
Side Effects of Alpha blockers
Cardiovascular:Palpitations, orthostatic hypotension, tachycardia, edema, dysrhythmias, chest pain
CNS: Dizziness, headache, drowsiness, anxiety, depression, vertigo, weakness, numbness, fatigue
Gastrointestinal: Nausea, vomiting, diarrhea, constipation, abdominal pain
Other: Incontinence, nose bleeding, tinnitus, dry mouth, pharyngitis, rhinitis, nasal stuffiness, inhibit
What molecules does beta blockers compete with
- Compete with norepinephrine and epinephrine
What receptors does Nonspecfic beta blockers block
block both beta1 and beta2 receptors
Beta Blockers Cardiovascular effects
- Reduction in cardiac output
- Reduction of renin release from Juxtaglomerular cells of kidney
- Central action to reduce sympathetic activity
Beta Blockers
Metabolic and Endocrine Effects
-glycogenolysis is partially inhibited after B-2 receptor blockade(b2 blocker inhibits glycolysis)
What is the outcome of giving a diabetic patient a non seclective beta blocker
the beta 2 being blocked would cause the inhibition of glycogenolysis, which reduces the glycogen level, plus the administration of insulin further reduce the glucose level and leads to hypogylcemia.
What is the outcome of giving a asthmatic patient a non seclective beta blocker
the blockage of beta 2 receptor will cause bronchoconstriction, resulting in difficulty to breathe
Beta Blockers Specific agents
- Propranolol prototype B-blocker
- Metoprolol and atenolol B1-selective
- Nadolol long duration of action
- Timolol: nonselective, use: glaucoma
- Levobunolol (nonselective), Betaxolol (b1-selective) use: glaucoma
- Pindolol, acebutolol, carteolol, bopindolol, oxprenolol, celiprolol, penbutolol, partial B agonist activitiy, less bradycardia, ISA uncertain, less lipid abnprmalities ie VLDL
Esmolol (Beta Blocker)
ultra-short acting B1-selective blocker, short T1/2, iv infusion, use: supraventricular arrhythmias, arrhythmias associated with thyrotoxicosis, perioperative HTN, myocardial ischemia acutely ill
Acetbutolol (Beta Blocker)
PVC= Premature Ventricular Contraction
-membrane stablizing drug= activity at the myocardium, so the drug has arrthymic properties
Sotalol
ventricular arrhythmias and atrial fibrillation
Beta blockers that also cause vasodilation
- Labetalol , racemic mixture of two chiral isomers non selective beta blocker with alpha 1 blocking activity (less than Phentolamine)
- Nebivolol B1 selective antagonist that causes vasodilation through and endothelium dependent mechanism
- Carvedilolol (drug interactions due to inhibition CYP2D6 activity ie Quinidine and Fluoxetine) Medroxalol. Bucindolol, nonselective b blocker with capacity to block a1
what is rebound hypertension
the use of a Beta blocker causes an increase in NE overtime, when a patient stop taking the beta blockers abruptly, the increase amount of NE binds to the receptor which causes drastic increase in blood pressure
