Review of Pharmacology - 9E (2015)

Review of Pharmacology
Indirectly Acting Sympathomimetics
These drugs act by increasing the release of NA in the synaptic cleft or by inhibiting the
reuptake of NA. These agents enter the neuronal cytoplasm by the same transporter that is
responsible for the reuptake of NA. From the cytoplasm, these drugs enter the storage vesicles and
displace and release the stored NA (because each vesicle has fixed storage capacity). Released
NA activates adrenergic receptors. On repeated dosing at short intervals, tachyphylaxis (rapid
development of tolerance) is seen with these drugs.
• Tyramine is normally present in certain foods and can lead to cheese reaction in patients
taking MAO inhibitors
• Methylphenidate is the preferred drug for the treatment of attention deficit hyperkinetic
disorder (ADHD). Other drugs used for this indication are amphetamines, atomoxetine
and pemoline. Pemoline has been withdrawn due to life threatening hepatotoxicity.
• Amphetamines are addictive substances and can result in tolerance and dependence.
As these are basic drugs, urinary acidification (with NH 4
Cl) is employed for the
treatment of their toxicity. On the other hand, amphetamine addicts use sodium
bicarbonate to obtain the “kick”.
• Modafinil is approved for treatment of narcolepsy, in shift workers, to relieve fatigue in
multiple sclerosis and as an adjunt in obstrutive sleep apnea.
Autonomic Nervous System
Mixed Action Sympathomimetics
These drugs enhance the release of NA (like indirectly acting drugs) apart from activating α
and β receptors directly. Ephedrine and pseudoephedrine are present in the cold remedies
for nasal decongestant and bronchodilator action. Ephedrine can also be used for the
treatment of bronchial asthma. It is the vasopressor of choice in pregnancy because due to β 2
mediated vasodilatory action, it does not interfere with placental circulation [methoxamine,
mephetermine and other selective α 1
agonists can cause placental vasoconstriction and
compromise fetal circulation].
Sympatholytic Drugs
These drugs may act by blocking α and/or β-adrenergic receptors.
ALPHA BLOCKERS
Nonselective α-Blockers
Phenoxybenzamine is an irreversible antagonist whereas phentolamine and tolazoline are reversible
blockers of α 1
and α 2
receptors. These agents result in vasodilation and postural hypotension (due
to antagonism of vasoconstrictor α 1
receptors). Reflex increase in sympathetic discharge and
increased sympathetic outflow (due to blockade of α 2
receptors) are responsible for marked
tachycardia seen with the use of these agents. Use of these drugs before adrenaline results in
vasomotor reversal of Dale. Intravenous injection of adrenaline normally causes increase
in blood pressure (α effect) followed by prolonged fall (β 2
effect). If it is administered after
giving α blockers, only fall in BP is seen (vasomotor reversal of Dale).
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