AUTONOMIC DRUGS II:

ADRENERGIC AGONISTS & ANTAGONISTS low dose: dopamine receptors

Francis R. Capule, RPh moderate dose: β receptors
high dose: α receptors
SYNTHESIS & RELEASE OF NOREPINEPHRINE (NE)
d. Dobutamine (Dobutrex)
1. Synthesis - heart failure
- tyrosine  dihydroxyphenylalanine or DOPA  S/E: HTN, palpitations, arrhythmia
dopamine
- rate-limiting step is hydroxylation of tyrosine 2. α Agonists
- metyrosine inhibits the rate-limiting step
α1 Agonists:
2. Uptake into Vesicles 1. Phenylephrine (Neo-Synephrine, Dimetapp)
- dopamine enters vesicle - nasal decongestant, shock, mydriatic
- Dopamine  NE S/E: HTN
- reserpine inhibits transport into vesicle
2. Phenylpropanolamine (Neozep, Decolgen,
3. Release Tuseran, Disudrin, Sinutab)
- Ca causes release of NE - nasal decongestant
- guanethidine & bretylium block NE release S/E: HTN
- amphetamine, methamphetamine, ephedrine, &
tyramine cause NE release 3. Pseudoephedrine (Sudafed)
- nasal decongestant
4. Binding to receptor S/E: HTN

5. Removal 4. Methoxamine
- methylated by catechol O-methytransferase (COMT) - hypotension
- oxidized by monoamine oxidase (MAO) S/E: HTN
- reuptake by neuron: cocaine & TCAs inhibit reuptake
- urine metabolites: vanillylmandelic acid (VMA), α2 Agonists:
metanephrine, normetanephrine 1. Clonidine (Catapres)
- treatment of HTN
SE: withdrawal induced rebound HTN

2. Methyldopa (Aldomet)
- prodrug
- active: α-methyldopamine & α-methylNE
- HTN in pregnancy
SE: (+) Coomb’s test

3. β Agonists

β2 Agonists:
- Salbutamol (Ventolin), Terbutaline (Bricanyl),
Metaproterenol
- asthma
- terbutaline: premature labor / tocolytic (↓ uterine
contraction)
S/E: stimulates β 1 at high doses: palpitations,
tremors

β1 & β 2 Agonist:
- Isoproterenol
- cardiac arrest
ADRENERGIC AGONISTS / SYMPATHOMIMETICS S/E: HTN, palpitations, arrhythmia

Direct-Acting Indirect-Acting
- directly bind to the receptor - promotes NE release

1. α, β Agonists 1. Tyramine
- red wine, beer, cheese, chocolates
- can cause HTN in depressed patients taking MAOI
a. Epinephrine
- aka adrenaline 2. Amphetamine, Metamphetamine
- anaphylaxis (bronchodilator) - attention deficit hyperactivity disorder (ADHD),
- cardiac arrest appetite suppression
- given with local anesthetics (prolongs effect) S/E: HTN, palpitations, dependence, insomnia,
S/E: HTN, palpitations, arrhythmia psychosis
b. Norepinephrine (Levophed)
- shock / hypotension Mixed (Direct-Acting & Indirect-Acting)
S/E: HTN, palpitations, arrhythmia
1. Ephedrine
c. Dopamine (Docard) - alkaloid from ma huang (Ephedra sinica)
- shock / hypotension - urinary incontinence, bronchospasm, hypotension,
- heart failure nasal congestion, narcolepsy
- renal failure to increase blood flow S/E: HTN, palpitations, arrhythmia, insomnia
S/E: HTN, palpitations, arrhythmia

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2. Metaraminol
- hypotension
S/E: HTN, palpitations, arrhythmia

ADRENERGIC ANTAGONIST / BLOCKERS

Direct-Acting
- directly blocks receptors

α Blockers

1. α1 Blockers
- Prazosin, Doxazosin, Terazosin
- HTN
- benign prostatic hyperplasia (BPH): bladder
relaxation, prevents urinary retention
S/E: orthostatic hypotension especially after the first
dose

2. α2 Blocker
- Yohimbine
- impotence (penile injection)
3. α1 & α2 Blockers

1. Phenoxybenzamine
- HTN due to pheochromocytoma (tumor of adrenal
medulla (overproduction & release of epinephrine &
NE))
S/E: postural hypotension

2. Phentolamine
- pheochromocytoma-associated HTN
S/E: postural hypotension
β Blockers

1. β1, β 2 Blockers
- Propranolol, Timolol, Nadolol, Pindolol, Labetalol,
Carvedilol
- HTN
- hyperthyroidism, MI, angina, arrhythmia, migraine
prophylaxis, panic attacks
- glaucoma: Timolol, Nadolol (↓ aqueous humor
production)
S/E:
Bronchoconstriction (C/I for asthmatic patients)

2. β1 Blockers
- Bisoprolol, Betaxolol, Esmolol, Atenolol, Acebutolol,
Metoprolol, Celiprolol
- BEAMC
- HTN
- blocks β 2 receptors at high doses

Indirect-Acting
- blocks release of NE

1. Guanethidine
- HTN
- rarely used

2. Reserpine
- alkaloid from Rauwolfia serpentina
- HTN
- rarely use

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