Adrenergics/Anti-Adrenergics Flashcards
Indirect Acting Sympatho-mimetics
Cocaine
Tricyclic Anti-depressants (TCAs)
Amphetamines
Non-amphetamines
Atomoxetine
Modafinil
Cocaine and Tricyclic Anti-Depressants (TCAs)
Inhibit reuptake NE transporter (NET) in various locations (intentionally vs. unintentionally)
Amphetamines
Central Stimulant for ADHD
Centrally inhibit NET to increase attentiveness
-can also release stored monogamies
Amplification of SANS effects via increased monoamine receptor activation
Cocaine
Centrally:
Stimulate pre-synaptic NE release + inhibit NET +inhibit reuptake of domaine (DA) and serotonin (5HT)
Peripherally:
-stimulate pre-synaptic NE release and inhibits neuronal reuptake of both NE and E
Topically:
-Decreased nerve permeability to sodium (local anesthetic)
Therapeutic Use:
- Topical Local anesthetic (sodium channel inhibitor)
- seen primarily in the operating room
Illicit Use
- stimulating effect->robust SANS activation with mild local anesthetic effects (depending on route of admin)
- vasoconstriction: increased alertness: enhanced reward
- no reversal agents
Amphetamine based stimulant
MOA: Promote release of NE primarily and DA (at high dose) from pre-synaptic storage into synapse
-also blocks NE/DA reuptake—>less significant effect
Uses:
ADHD, obesity, narcolepsy, binge eating
ADRs:
Increased SBP/DBP, tachyardia, lost/reduced appetite, weight loss, dry mouth, constipation, teeth grinding, abdominal pain, insomnia,
-cautious uses in Tourette’s - may exacerbate tics
-cautious use in cardiac compromise -tachycardia
-growth inhibition in children ?
Non-Amphetamines based Stimulants
MOA: Similar effect/use of amphetamines but mediated primarily by DA reuptake (less NE effects)
Similar ADRs but generally less pronounced (especially cardiac)
Methylphenidate (Ritalin) and Dexmethylphenidate
Atomexetine
Thought to involve NET reuptake inhibition
Non stimulant for treatment of ADHD
Modafinil
Increase NE/DA/5HT/Glu
Decreases GABA
Uses: narcolepsy, circadian rhythm disturbances
Indirect Acting Sympatholytics
Anti-adrenergic without directly blocking the receptors
-not commonly used anymore
Metyrosine and Reserpine
Metyrosine
Inhibits tyrosine hydroxylase (rate-limiting step in catecholamine synthesis) in an effort to decrease excess production/activity
Benefit seen in pheochromocytoma
Reserpine
- Inhibits VMAT, reuptaken monoamines metabolized by MOA
- Anti-hypertensive effect (drug no longer used to hypertension given safer alternatives)
Selective Alpha-1 Agonists
Midodrine
Phenylephrine
Pseudoephedrine
Oxymetazoline
Naphazoline
Midodrine
Treats Orthostatic Hypotension
Phenylephrine
Cough cold
IV vasopressor
Eye drops
Pseudoephedrine
Decongestant for cough and cold
Oxymetazoline (Afrin)
Nasal Spray
Rhinitis Medicamentosa:
- cannot use Afrin for more than 3 days, shrinks the nasal mucous
- become dependent
- leads to rebound congestion
Alpha-1 Subtypes
1A: prostrate smooth muscle contraction
1B/1D: vascular smooth muscle contraction (blood vessels)
-1D: bladder neck
Antagonize 1A/1D=BPH relief (Benign Prostrate Hypertrophy)
- less pressure on urethra
- increased urinary flow
Selective Alpha-1 Antagonists
Prazosin
Doxazosin ; Terazosin
Tamsulosin ; Alfuzosin
Silodosin
ADRs:
- erectile dysfunction and abnormal ejaculation
- dizziness/syncope, hypotension, reflex tachycardia for prazosin, doxazosin, Terazosin (less selective)
- first dose phenomenon
Prazosin
Use primarily in PTSD nightmares
Doxazosin and Terazosin
Block all alpha-1 subtypes —>can use for BPH and or for HTN
Tamsulosin and Alfuzosin
For treatment of BPH
More selective for alpha-1A receptors on prostate/urethra
Less cardiac effect
May want to use them in people with BP problems
Silodosin
More selective for alpha-1A
Treatment for BPH
Least hypotensive
Less cardiac effect
Selective Alpha 2 Agonists
Clonodine
Tizanidne
Guanfacine
Dexmedetomidine
Brimonidine
Apraclondine
Methyldopa
Clonidine and Tizanidine
HTN
ADHD
Withdrawal
Muscle spasticity (t»c)
Guanfacine
ADHD in Pediatrics
Older drug for HTN
Dexmedetomidine
IV sedative with Sympatholytic/analgesic properties
Brimonidine and Apraclonidine
Eye drops for glaucoma
Less aqueous humor production
Methyldopa
Favorable agent for HTN pregnancy
Non Selective Alpha Antagonists
Vasodilation while increasing cardiac output
-benefit seen in diagnosis/treatment of pheochromocytoma
Phenoxybenzamine (oral) or Phentolamine (IV/IM)
- Phentolamine is paranteral and has shorter duration of action—>more inpatient uses
- treatment of extravasation (potential dermal necrosis due to extensive use) from IV alpha-1 agonists=phentolamine can treat this
ADRs:
-Nasal Congestion, myosis(constriction of the pupal), orthostatic hypotension
Selective Beta-1 Agonist
Dobutamine
- positive inotropic effects»> chronotropic effects
- IV; requires dose titration to desired effect
Therapeutic use (short-term)
- cardiogenic shock; septic shock
- acute congestive HF
Selective Beta-1 Antagonists
Metoprolol succinate Atenolol Nebivolol** Bisoprolol ** Acebutolol Betaxolol Esmosol
- At high doses, may become non-selective
- *generally maintain selectivity at higher doses
Selective Beta 2 Agonists
SABA: short acting
-albuterol and levalbuterol
LABA: long acting
- formoterol, salmeterol, olodaterol, aformoterol, indacaterol
- Terbutaline (oral tablets/parenteral)
Local administration ideal
PK differences between agents
Selective for beta-2 receptors» beta-1 receptors
Non-selective Beta Agonists
Isoproterenol
- primarily used for beta-1 effect (positive inotrope)
- used largely replaced by dobutamine
Metaproterenol
- primarily used for beta-2 effect
- asthma/COPD, bronchospasm
Non-selective Beta Antagonists
Nadolol
Propranolol
Carteolol, Timolol, Levobunolol, Metipranolol->ophthalmic
Sotalol
Prindolol
Therapeutic Uses:
- Gluacoma; ocular hypertension (ophthalmic)
- Migraine Prophylaxias; tremors; stage fright (propranolol)
- Hypertension; atrial fibrillation; arrhythmias
- Portal hypertension; esophageal varicose, bleeding prophylaxis (nadalol)
- decrease portal vein pressure, decrease blood flow
B-3 Receptor
Primarily theorized actions include lipolysis in adipose tissue and thermogenesis in skeletal muscle
Receptors found in gallbladder, heart, colon, CNS, brown adipose tissue and BLADDER
Expressed in DETRUSOR MUSCLE OF BLADDER
ACTIVATION results in RELAXATION of detrusor muscle
Selective Beta 3 Agonist
MIRABEGRON
On the DETRUSOR muscle
MIRABEGRON -uses
Used for symptoms of overactive bladder (OAB), urinary incompetence, urgency and frequency
Increased bladder capacity during storage phase
Mirabegron ADRs
BP elevations
Tachycardia
- mostly due to losing selectivity at higher doses
- it is an alternative to anti-muscarinics for OAB
