PHARM Chapter 10 - Adrenergic Pharmacology Flashcards
ME of Alpha-Methyltyrosine
Inhibit tyrosine hydroxylase, the rate-limiting enzyme in the catecholamine biosynthesis pathway
Uses of Alpha Methyltyrosine
Pheochromocytoma-associated hypertension
Structural analogue of tyrosine
Alpha-Methyltyrosine
Pheochromocytoma
Tumor of the enterochromaffin cells of the adrenal medulla that produces norepinephrine and epinephrine
Inhibitors of Catecholamine Storage
Reserpine, Guanethidine, Guanadrel, Amphetamine, Methylphenidate, Pseudoephedrine
ME of Reserpine, Guanethidine, Guanadrel, Amphetamine, Methylphenidate, Pseudoephedrine
Inhibitors of catecholamine storage in vesicles - results in short-term increase in release of catecholamines from the synaptic terminal but long term depletion of available pool of catecholamines
Uses of Reserpine
Hypertension
Uses of Guanethidine and Guanadrel
Hypertension
Uses of Amphetamine and Methylphenidate
ADHD
Narcolepsy (Amphetamine)
Uses of Pseudoephedrine
Allergic rhinitis
Nasal Congestion
Irreversibly inhibits VMAT - results in vesicles that lose the ability to concentrate and store norepinephrine and dopamine
Reserpine
Used experimentally to assess whether effect of drug requires its concentration in presynaptic terminals
Reserpine
Low vs. High Dose of Reserpine
Low: causes neurotransmitter leak into cytoplasm where catecholamine is destroyed by MAO
High: rate of transmitter leak can be sufficiently high to overwhelm MAP in presynaptic neuron - has transient sympathetic effect
Why is Reserpine not used therapeutically?
Associated w/ severe depression
Concentrates in transmitter vesicles and displaces norepinephrine, leading to gradual depletion of norepinephrine
Guanethidine and guanadrel
Effect of Guanethidine and Guanadrel on Cardiac sympathetic nerves
Reduced cardiac output
Effect of Guanethidine and Guanadrel on sympathetic nerves
Leads to symptomatic hypotension following exercise
How does Guanethidine enter neurons
Actively transported by NET, concentrates in vesicles and displaces norepinephrine
1) Displace endogenous catecholamines from storage vesicle
2) weakly inhibit MAO
3) block catecholamine reuptake mediated by NET and DAT
Amphetamine and Methylpenidate
Carries risk of dependence and tolerance
Amphetamine and Methylpenidate
Binds to postsynaptic adrenergic receptors, but has little agonist action at alpha or beta adrenoceptors
Amphetamine
Used as OTC decongestant
Pseudoephedrine
Ephedrine used for the treatment of
persistent hypotension
Herbal source of ephedrine
ma huang
Dietary amine that is ordinarily metabolized by MAO in GI tract and liver
Tyramine
Fermented foods such as red wine and aged cheese possess high concentrations of
Tyramine
In patients taking MAOIs tyramine is absorbed in gut, transported in blood, and taking up sympathetic neurons where it is transported into synaptic vesicles by ____ to cause _____
VMAT
acute displacement of vesicular norepinephrine and massive non-veiscular release of norepinephrine from the nerve terminal via reversal of NET
Tyramine is hydroxylated into a metabolite, ____ which is better able to _____
octopamine
Be stored at high concentrations in the vesicles
ME of Cocaine
Inhibits voltage-gated sodium channels in excitable cell membranes
Inhibits norepinephrine transport (NET)-mediated reuptake of catecholamines - potentiates catecholamine action
Uses of Cocaine
Mucosal and opthalmic local anesthetic, diagnosis of Horner’s syndrome pupil
Major side effect of Cocaine
Cariotoxicity and euphoria
ME of Amitriptyline and Imipramine
Inhibit reuptake of 5-Ht and NE from the synaptic cleft by blocking reuptake transporters, causes enhancement of postsynaptic responses
Inhibit norepinephrine transporter (NET)-mediated reuptake of catecholamines, potentiating catecholamine action
Uses of Amitriptyline and Imipramine
Depression, Pain syndromes, nocturnal enuresis (imipramine)
Tricyclic antidepressants that affect cardiac sodium channels in a quinidine-like manner, leading to potentially lethal conduction delays
Amitriptyline and Imipramine
Can precipitate mania in patients w/ bipolar disorder
Amitriptyline and imipramine
Monoamine Oxidase (MAO) Inhibitors
Phenelzine Iproniazid Tranylcypromine Clorgyline Brofaromine Befloxatone Moclobemide Selegiline
ME of Phenelzine Iproniazid Tranylcypromine Clorgyline Brofaromine Befloxatone Moclobemide Selegiline
Inhibit MAO - increases catecholamine levels by blocking catecholamine degradation
Block deamination of monoamines by inhibiting the functional flavin moiety of MAO; increase the 5-HT and NE available in the cytoplasm of presynaptic neurons, which leads to increased uptake and storage of 5-HT and NE in synaptic vesicles and to some constitutive leakage of monoamines into the synaptic cleft
Uses of Phenelzine Iproniazid Tranylcypromine Clorgyline Brofaromine Befloxatone Moclobemide Selegiline
Depression
A1 adrenergic agonists
Methoxamine
Phenylephrine
oxymetazoline
tetrahydrozoline
ME of A1 adrenergic agonists
selectively activate A1 adrenergic recpetors to increase peripheral vascular resistance
Uses of methoxamine
hypotension and shock
Uses of Phenylephrine, oxymetazoline, tetrahydrozoline
Opthalmic hyperemia
nasal congestion
hypotension (phenylephrine only)
Which A1 adrenergic agonist has very limited clinical use in treatment of shock
methoxamine
Contraindication of A1 adrenergic agonists
severe hypertension and narrow angle glaucoma (not methoxamine)
SE of phenylephrine, oxymetazoline, tetrahydrozoline
cardiac arrythmia, hypertension
Afrin and Visine are what type of drugs and what do they treat
A1 adrenergic agonists - nasal congestion and opthalmic hyperemia
What is used intravenously in treatment of shock
phenylephrine
alpha-adrenergic antagonists
penoxybenzamine phentolamine prazosin terazosin doxazosin tamsulosin yohimbine
ME of alpha adrenergic antagnoists
block endogenous catecholamines from binding to A1 and A1 adrenoceptors - causing vasodilation, decreased blood pressure and decreased peripheral resistance
Uses of penoxybenzamine and phentolamine
pheochromocytoma associated hypertension and sweating
Blocks A1 and A2 receptors irreversibly
phenoxybenzamine
reversible, nonselective alpha-adrenoceptor antagnoist
phentolamine
SE of phentolamine
coronary artery disease
Uses of prazosin, terazosin, doxazosin
hypertension, benign prostatic hyperplasia
nonsubtype-selective antagonists of A1 receptors in arterioles and veins
prazosin, terazosin, doxazosin
why do patients have to remain supine w/ first dose of prazosin, terazosin, doxazosin
severe postural hpotension
SE of prazosin, terazosin, doxazosin
pancreatitis, hepatotoxicit, systemic lupus eruthematosus
uses of tamsulosin
benign prostatic hyperplasia
why is tamsulosin different?
subtpe-selective A1a receptor antagonist that has more specificity towards smooth muscle in GU tract - lower incidence of orthostatic hypotension
uses of yohimbine
organic and psychogenic impotence
SE of yohimbine
bronchospasm, nervousness, tremor, anxiety, agitationq
A2-selective antagonist that leads to increased release of norepinephrine, stimulates cardiac B1-receptors and peripheral vascular A1 receptors
yohimbine
What does yohimbine inadvertently release
increased insulin due to blockade of A2 receptors in pancreatic islets
Suffix for B-adrenergic antagonists
olol
ME of B-adrenergic antagonists
block B-adrenergic receptors
block B1 and B2 receptors equally
propranolol, nadolol, timolol
Ocular formation used in the treatment of glucagoma
timolol, levobunolol, carteolol
Uses of propranolol, nadolol, timolol, prenbutolol, levobunolol, careolol
hypertension, angina, heart failure, phenocrhromocytoma
SE of propranolol, nadolol, timolol, prenbutolol, levobunolol, careolol
bronchospasm AV block, bradyarrythmia
Uses of labetalol, carvedilol, pindolol, acebutolol
hypertension, angina
what additional sideeffect does labetalol have
hepatotoxicity
block A1, B1, and B2 receptors
labetalol and carvedilol
partial agonist at B1 and B2 receptors, preferred in hypertensive patients who have bradycardia or decreased cardiac reeserve
pindolol
partial agonist at B1 adrenoceptors, no effect on B2 receptors
acebutolol
Uses for esmolol, metoprolol, atenolol, betaxolol, nebivolol
hypertension, angina, heart failure, thyroid storm (esmolol)
B1 selective adrenergic antagonists
esmolol, metoprolol, atenolol
extremely short half life (3-4) used for emergency B-blockade
esmolol
has ancillary property of promoting vasodilation via NO release from endothelial cells
nebivolol
MAOI approved for treatment of Parkinsons
selegiline
concomitant use of MAOIs and SSRIs contraindicated because
it can cause serotonin syndrome
A2 receptor agonist that lowers blood pressure by acting in brainstem vasomotor centers to suppress sympathetic flow
clonidine
A2 receptor that can cause sedation and respiratory depression
dexmedetomidine
endogenous enzymes catalyze its metabolism which is then released by adrenergic nerve terinal which it acts presynaptically as A2 antagonist
a-Methyldopa
antihypertensive drug in pregnancy
a-methyldopa
diastolic bp is a __ effect, whereas systolic bp is a __ effect
B2, B1
used intravenously for heart failure and as diagnostic agent in ischemic heart disease
dobutamine
ME of dobutamine and isoproterenol
increase cAMP by activating G protein coupled adrenergic recpetors, acting at cardiac B1 adrenergic receptors to have positive inotropic, chronotropic, and lusitropic effects
uses of dobutamine
short term treatment of cardiac decompensation secondary to depressed contractility (cardiogenic shock)
overall effect of dobutamine is predominantly on __ and modestly on ___
B1 and B2
uses for isoproterenol
emergency treatment of arrythmias, atropine-resistant hemodynamically significant bradycardia, heart block and shock, bronhospasm
ME of metaproterenol, terbutaline, albuterol/salbutamol
agonists at B-adrenergic receptors on airway smooth muscle, act through stimulatory G protein to cause relaxation and bronchodilation
Uses of metaproterenol, terbutaline, albuterol/salbutamol
asthma/copd
Selective agonists at B2 receptors
metaproterneol, terbutaline, albuterol/salbutamol
