Pharmacology: Peripheral Acting Drugs

Study Notes

Peripherally acting drugs have their primary mechanism of action outside of the central nervous system (CNS), usually due to being excluded from the CNS by the blood-brain barrier.
By being excluded from the CNS, drugs may act on the rest of the body without producing side-effects related to their effects on the brain or spinal cord.

The nervous system consists of the central nervous system (CNS) and the peripheral nervous system (PNS).
The PNS consists of efferent nerves and afferent nerves.
Efferent nerves transmit signals from the CNS to the periphery, while afferent nerves transmit signals from the periphery to the CNS.
The PNS is further divided into the somatic nervous system and the autonomic nervous system.
The autonomic nervous system is divided into the sympathetic nervous system, parasympathetic nervous system, and enteric nervous system.
The sympathetic nervous system is responsible for the "fight or flight" response, while the parasympathetic nervous system is responsible for the "rest and digest" response.

Neurotransmitters are chemical messengers in the body that transmit signals from nerve cells to target cells.
There are over 50 chemical neurotransmitters in the nervous system, including acetylcholine (Ach), norepinephrine (NA), dopamine, serotonin, histamine, and GABA.
Neurons are named by the neurotransmitter they release, such as cholinergic neurons that release Ach and adrenergic neurons that release NA.

Cholinergic receptors are classified into muscarinic receptors and nicotinic receptors.
Muscarinic receptors are further classified into M1, M2, and M3 receptors.
Muscarinic receptor agonists, such as pilocarpine, have parasympathomimetic actions, including:
- Contracting smooth muscle (e.g., gut, bladder, pupil)
- Increasing glandular secretion (e.g., salivary, sweat)

Anticholinesterases, such as neostigmine, are cholinesterase inhibitors that potentiate the action of Ach.
They have parasympathomimetic actions, including:
- Increased peristalsis
- Increased secretions
- Bradycardia
- Bronchoconstriction
- Decreased intraocular pressure
Anticholinesterases are used to treat myasthenia gravis and to reverse non-depolarizing neuromuscular block.

Muscarinic antagonists, such as ipratropium, are used to treat bronchoconstriction and mucus secretion.
They act by competitively antagonizing the action of Ach on muscarinic receptors.

Adrenergic receptors are classified into alpha (α) and beta (β) receptors.
Alpha receptors are further classified into α1 and α2 receptors, while beta receptors are further classified into β1 and β2 receptors.
Alpha receptor agonists, such as phenylephrine, have actions including:
- Vasoconstriction
- Nasal decongestion
- Dilatation of the pupil
Beta receptor agonists, such as dobutamine, have actions including:
- Increased cardiac output
- Increased contractility
- Bronchodilation
Beta receptor antagonists, such as atenolol, have actions including:
- Decreased cardiac output
- Decreased renin release
- Decreased CNS-mediated sympathetic activity

Histamine antagonists, such as cyclizine, are used to treat hypersensitivity reactions.
They act by competitively inhibiting the action of histamine on H1 receptors.
Sedating antihistamines, such as cyclizine, have anticholinergic actions, including:
- Dry mouth
- Blurred vision
- Constipation
- Urine retention
Non-sedating antihistamines, such as loratadine, do not cross the blood-brain barrier and therefore do not have sedative adverse effects.

H2 antagonists, such as famotidine, are used to treat gastric and duodenal ulcers and gastro-oesophageal reflux disease.
They act by selectively and reversibly inhibiting the action of histamine on H2 receptors on parietal cells.