Adrenergics/Anti-Adrenergics

Question 1

Indirect Acting Sympatho-mimetics

Answer 1

Cocaine

Tricyclic Anti-depressants (TCAs)

Amphetamines

Non-amphetamines

Atomoxetine

Modafinil

Question 2

Cocaine and Tricyclic Anti-Depressants (TCAs)

Answer 2

Inhibit reuptake NE transporter (NET) in various locations (intentionally vs. unintentionally)

Question 3

Amphetamines

Answer 3

Central Stimulant for ADHD

Centrally inhibit NET to increase attentiveness
-can also release stored monogamies

Amplification of SANS effects via increased monoamine receptor activation

Question 4

Cocaine

Answer 4

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

Question 5

Amphetamine based stimulant

Answer 5

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 ?

Question 6

Non-Amphetamines based Stimulants

Answer 6

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

Question 7

Atomexetine

Answer 7

Thought to involve NET reuptake inhibition

Non stimulant for treatment of ADHD

Question 8

Modafinil

Answer 8

Increase NE/DA/5HT/Glu

Decreases GABA

Uses: narcolepsy, circadian rhythm disturbances

Question 9

Indirect Acting Sympatholytics

Answer 9

Anti-adrenergic without directly blocking the receptors
-not commonly used anymore

Metyrosine and Reserpine

Question 10

Metyrosine

Answer 10

Inhibits tyrosine hydroxylase (rate-limiting step in catecholamine synthesis) in an effort to decrease excess production/activity

Benefit seen in pheochromocytoma

Question 11

Reserpine

Answer 11

• Inhibits VMAT, reuptaken monoamines metabolized by MOA

- Anti-hypertensive effect (drug no longer used to hypertension given safer alternatives)

Question 12

Selective Alpha-1 Agonists

Answer 12

Midodrine

Phenylephrine

Pseudoephedrine

Oxymetazoline

Naphazoline

Question 13

Midodrine

Answer 13

Treats Orthostatic Hypotension

Question 14

Phenylephrine

Answer 14

Cough cold

IV vasopressor

Eye drops

Question 15

Pseudoephedrine

Answer 15

Decongestant for cough and cold

Question 16

Oxymetazoline (Afrin)

Answer 16

Nasal Spray

Rhinitis Medicamentosa:

• cannot use Afrin for more than 3 days, shrinks the nasal mucous
• become dependent
• leads to rebound congestion

Question 17

Alpha-1 Subtypes

Answer 17

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

Question 18

Selective Alpha-1 Antagonists

Answer 18

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

Question 19

Prazosin

Answer 19

Use primarily in PTSD nightmares

Question 20

Doxazosin and Terazosin

Answer 20

Block all alpha-1 subtypes —>can use for BPH and or for HTN

Question 21

Tamsulosin and Alfuzosin

Answer 21

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

Question 22

Silodosin

Answer 22

More selective for alpha-1A

Treatment for BPH

Least hypotensive

Less cardiac effect

Question 23

Selective Alpha 2 Agonists

Answer 23

Clonodine

Tizanidne

Guanfacine

Dexmedetomidine

Brimonidine

Apraclondine

Methyldopa

Question 24

Clonidine and Tizanidine

Answer 24

HTN

ADHD

Withdrawal

Muscle spasticity (t»c)

Question 25

Guanfacine

Answer 25

ADHD in Pediatrics Older drug for HTN

Question 26

Dexmedetomidine

Answer 26

IV sedative with Sympatholytic/analgesic properties

Question 27

Brimonidine and Apraclonidine

Answer 27

Eye drops for glaucoma Less aqueous humor production

Question 28

Methyldopa

Answer 28

Favorable agent for HTN pregnancy

Question 29

Non Selective Alpha Antagonists

Answer 29

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

Question 30

Selective Beta-1 Agonist

Answer 30

Dobutamine - positive inotropic effects>>> chronotropic effects - IV; requires dose titration to desired effect Therapeutic use (short-term) - cardiogenic shock; septic shock - acute congestive HF

Question 31

Selective Beta-1 Antagonists

Answer 31

``` Metoprolol succinate Atenolol Nebivolol** Bisoprolol ** Acebutolol Betaxolol Esmosol ``` * At high doses, may become non-selective * *generally maintain selectivity at higher doses

Question 32

Selective Beta 2 Agonists

Answer 32

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

Question 33

Non-selective Beta Agonists

Answer 33

Isoproterenol - primarily used for beta-1 effect (positive inotrope) - used largely replaced by dobutamine Metaproterenol - primarily used for beta-2 effect - asthma/COPD, bronchospasm

Question 34

Non-selective Beta Antagonists

Answer 34

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

Question 35

B-3 Receptor

Answer 35

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

Question 36

Selective Beta 3 Agonist

Answer 36

MIRABEGRON On the DETRUSOR muscle

Question 37

MIRABEGRON -uses

Answer 37

Used for symptoms of overactive bladder (OAB), urinary incompetence, urgency and frequency Increased bladder capacity during storage phase

Question 38

Mirabegron ADRs

Answer 38

BP elevations Tachycardia * mostly due to losing selectivity at higher doses - it is an alternative to anti-muscarinics for OAB