Nervous system drugs Flashcards
What are cholinergic nerves?
Nerves that release acetylcholine
What are adrenerigic nerves?
Nerves that release norepinephrine
Name some adrenergic neurotransmitters. What are their important shared features?
- Epinephrine
- Norepinephrine
- Dopamine
All of the adrendergic neurotransmitters contain OH groups for H-bonding, an ammonium group, and a flat non-polar ring. All of these are important for receptor-ligand binding.
What are the different classes of CNS drugs? Give an example in each class.
- Sedative-hypnotic drugs (benzodiazepines)
- Alcohols (Ethanol)
- Anaesthetics (Desflurane)
- Anti-depressants (Tricyclics, MAOI, SSRI)
- Recreational Drugs (LSD)
- Narcotic Analgesics (morphine, heroin)
In what ways can drugs interact with normal neurotransmission?
- Competitive inhibition: no nervous impulse
- Use the neurotransmitter as a drug
- Increase/decrease degradation of the neurotransmitter
- Inhibition of neurotransmitter synthesis
- Inhibition of uptake of excess NT
In what ways can drug agonists and antagonists alter neurotransmission?
- Agonists stimulate: mimic neurotransmitter, decrease degradation, increase release rate.
- Antagonists depress: receptor block, storage decrease, increase degradation.
What are some of the organ effects of cholinergenic and adrenergic nerve impulse?
- Eye
- Nose
- Mouth
- GI tract
- Lungs
- Heart
Adrenergic nerves stimulate the sympathetic nervous system, and cholinergenic nerves stimulate the parasympathetic nervous system.
What are the receptors for adrenergic neurotransmitters and drugs? What are their receptor-ligand binding outcomes?
There are at least two receptors: alpha and beta.
- Alpha: the stimulation of alpha receptors is associated with constriction of small blood vessels in the bronchial mucosa and relaxation of intestinal tract smooth muscles. The receptor itself has an anionic site (to bind the positive ammonium group), one hydrogen bonding area, and a flat non-polar area (for the aromatic ring).
- Beta: beta receptor activation relaxes bronchial smooth muscles which cause the bronchi of the lungs to dilate. The receptor itself contains two hydrogen bonding areas (2x Serine -OH bind drug phenol -OH), anionic site (Asparagine negative group, binds positive ammonium), flat non-polar area. Ligands exhibit stronger binding to beta receptors, and ligands have a lower kD value.
The image shows this via norepinephrine binding its beta receptor.
Name some agonists and antagonists of adrenergic receptors, including:
- Alpha or beta?
- Subtype?
- Tissue affected?
How do adrenergic drugs work?
Adrenergic drugs stimulate the adrenergic nerves directly by mimicking the action of norepinephrine. Adrenergic stimulants have different modes of action:
- direct interaction with specific receptors
- indirect action by stimulating release of neurotransmitters
- or a mixed action involving both of these effects
What are ephedrine and epinephrine used to treat?
Epinephrine and ephedrine are mainly used in the treatment of bronchial asthma, a respiratory disease results from a spasmodic contraction of the smooth muscles of the bronchi.
Epinephrine and ephedrine act directly on β adrenergic receptors to relax the smooth muscles (bronchodilation). Epinephrine also exhibits an alpha receptor stimulating action, constricts the bronchial mucosa and reduces secretions.
How is asthma treated? What drugs and receptors are involved?
Ephedrine has prolonged bronchodilatory effects when bound to beta adrenergic receptors in the lungs. These drugs are sympathomimetics as they are sympathetic nervous system agonists.
The newer a preferred drug for asthma is Salmeterol, which has a longer duration of action. This is achieved due to its high lipid solubility. It to dissolves in the smooth muscle cell membrane in high concentration and the lipid membrane then serves as a ‘slow release depot’.
The bronchodilators that are specific for the β2 receptors, like Salmeterol, are the most widely used drugs for the treatment of asthma as they:
- are effective after both oral or inhaled administration
- have a long duration of action
- have significant β2 selectivity
- have effects that are maximal within 30 minutes
The amount that reaches the lungs depends on the particle size, airway geometry, and breathing pattern. Most of the inhaled drug, 80-90%, gets suspended in the mouth and pharynx (2-5 microns). Smaller particles can be exhaled, so a held breath keeps particles in lungs.
What is the difference between ephedrine and pseudo-ephedrine?
Pseudo-ephedrine (decongestant) and ephedrine are optical isomers. This means pseudoephedrine is much less potent, and binds more weakly to the beta2 receptors. This is because hydrogen bonding cannot occur between the drug and the receptor.
Outline adrenergic receptor antagonists.
Adrenergic blocking agents are drugs that selectively inhibit specific receptor sites from sympathetic stimulation.
There are several modes of action by which they can act:
- Blocking agents may interact with specific α and β receptors
- The release of norepinephrine from storage sites may be blocked
- The synthesis of norepinephrine may be inhibited
Briefly outline alpha and beta blockers.
Both can be used to treat hypertension.
- Alpha blockers: the arteriolar and venous system function is largely determined by alpha receptors. Alpha adrenergic antagonists lower blood pressure, may cause postural hypotension and reflex tachycardia (increase heart rate). Elderly people are more at risk of these side effects. Chronic use may increase blood volume.
- Beta blockers: well absorbed, low bioavailability (lots lost to metabolism), rapid distribution, high volume of distribution (more in tissue), lipophilic (can cross blood-brain barrier), 2-5 hr half-life.
