Term
| direct acting a2 receptor agonists |
|
Definition
-Clonidine
-Methyldopa
-Guanabenz
-Guanfacine
-Tizanidine
-Gi -x-> Adenylate Cyclase --> ATP -x-> cAMP --> reduced cAMP-dep PKA --> response & K+ flows out of opened channels |
|
|
Term
| direct acting a1 receptor agonists |
|
Definition
-Phenylephrine
-Methoxamine
-Oxymetazoline
-used in eye drops and nasal sprays
-Gq--> PIP2 --> IP3 + DAG --> Increase Ca2+ and activate PKC --> response |
|
|
Term
| direct acting non-selective B receptor agonists |
|
Definition
-Isoproterenol
-B receptors agonists act by activating Gs--> activates Adenylate Cyclase --> ATP->cAMP --> increased cAMP-dependent PKA --> response |
|
|
Term
| direct acting B1-selective receptor agonists |
|
Definition
-Dobutamine
-Dopamine
-increase heart rate |
|
|
Term
| direct acting B2 selective receptor agonists |
|
Definition
-Terbutaline
-Metaproterenol
-Albuterol
-Salmeterol
-Ritodrine
-act to relax muscles (ie - bronchioles and uterus) |
|
|
Term
|
Definition
1. Pi-pi: with phenyleprine and aromatic ring of NE
2. Ion pair: with -CO2 of Asp and -NH3+ of NE
3. H-bonds: between -OHs of serine and NE |
|
|
Term
| Selectivity at a1 adrenergic receptors |
|
Definition
|
|
Term
| selectivity at B1 adrenergic receptors |
|
Definition
|
|
Term
| selectivity at B2 adrenergic receptors |
|
Definition
I>E>>N>P
-N is less selective at B2 than at B1
-E is most nonselective at all receptors
-selectivity is completely dependent on dose; at higher doses you begin to lose selectivity
-compare selectivities by comparing EC50s |
|
|
Term
|
Definition
-potent a and B1 receptor agonist
-substrate for MAO and COMT
-parenteral administration
-used as a pressor (agents that keep BP up)
-use sodium bisulfite to prevent oxidation |
|
|
Term
|
Definition
-Potent a, B1, and B2 receptor agonist
-substrate for MAO and COMT
-parenteral administration
-use sodium bisulfite to prevent oxidation
-available as many salts: HCl, nitrate, bitartrate
-Uses: anaphylaxis, glaucoma, incombination with local anesthetics |
|
|
Term
|
Definition
-potent a1 receptor agonist
-substrate for MAO
-Administration: parenteral, oral, local
-uses: mydriasis without cycloplegia(paralysis of CM) - during eye exams, glaucoma, pressor, nasal decongestant (in place of PSE) |
|
|
Term
| Why are imidazolines more basic than simple aliphatic amines? |
|
Definition
-imidazoline cation is resonance stabilized allowing the positive charge to be spread over the entire three atom system
-imidazolines are partial a1 receptor agonists |
|
|
Term
|
Definition
-partial a receptor agonists
-increase BP
-administered locally/topically to promote vasoconstriction
-basic nature causes them to be ionized at physiological pH
-used in nasal and opthalmis decongestants
-can have tachyphylaxis/desensitization
-CNS effects at high doses; full on psychosis if OD |
|
|
Term
| Explain what Clonidine [(phenylimino)imidazolidine] does and how it can do that |
|
Definition
-selective a2 receptor agonist
-basicity is decreased (from 13.6 to 8.0) because of attachement to the dichlorophenyl ring; allows it to penetrate BBB
-activates a2 receptors in nucleus of the solitary tract (CV center) which decreases sympathetic nervous system tone
Uses: HTN (not 1st line choice because you shut system down) & opiate withdrawal (reduces symp. activation assoc w/ withdrawal) |
|
|
Term
| explain what happens when sympathetic tone is decreased |
|
Definition
-decreased HR
-decreased contractility
-decreased renin release
-decreased vasoconstriction |
|
|
Term
| What are Guanabenz and Guanfacine used for? |
|
Definition
-HTN, but not 1st line therapy
-"open-ring" imidazolidines; have decreased pKa so mostly no charge at physiological pH--> can cross BBB
-Oral administration
-Guanabenz has short 1/2 life: 6 hrs |
|
|
Term
| Explain the MOA for methyldopa |
|
Definition
-prodrug metabolized to a2 receptor agonist; acts on CNS a2s and decreases sympathetic outflow; used for HTN
-Methyldopa is oral
-methyldopate is water soluble and parenteral |
|
|
Term
| What is apraclonidine used for? |
|
Definition
-a2 agonist
-used for glaucoma
-unknown MOA |
|
|
Term
| what is tizanidine used for? |
|
Definition
-a2 agonist
-used for muscle spasticity
-disrupts muscle reflex arc |
|
|
Term
| what are the adverse effects of a2 receptor agonists? |
|
Definition
-sedation
-Na+ and water retention --> pts will also need to take diuretics
-dry mouth
-withdrawal syndrome (HTN, tachycardia, sweating); need to taper off drug |
|
|
Term
|
Definition
-nonselective B agonist
-causes brochodilation and increased CO
-metabolized by phase II and COMT; NOT MOA
-administration: oral, parenteral, local
-uses: asthma, COPD, cardiostimulant |
|
|
Term
| Metproterenol and Terbutaline |
|
Definition
-selective B2 receptor agonists
-cause bronchodilation
-cardiac effects only observed at high doses
-not metabolized by MAO and COMT (much better oral bioavailability)
-longer duration that isoproterenol
-admin: oral, parenteral, local (inhaled)
-uses: asthma, COPD; terbutaline used as tocolytic (prevents premature labor by relaxing uterine smooth muscle) |
|
|
