St. Johnsons wort

Can help to reduce anxiety, it is suggested that hyperforin plays a role in acting on messengers in our nervous system on the part that regulates mood.

Melatonin

Are secreted 9pm and lasts until 4am

• Improves onset of sleep duration
• Quality of sleep
• Increase REM
• Effective for drug-induced (B-blocker) insomnia
• If taken at desired bedtime

• Improves morning alertness
• Improves quality of sleep

Hops, Lemon Balm, Skullcap, Passionflower, Rosenroot and Chamomile: reduce anxiety

Components namely bacalin and bacalein in Skullcap are GABA agonists and potentiates GABA activity.

Lemon balm Increases GABA

Rosenroot – 340mg for 10weeks can reduce GAD

Essential oils: Lavender, Chamomile

By calming the fight and flight response it helps to improve the quality of sleep

Valerian

 Helps with insomnia by having a sedative effect on the brain and our nervous system

Ashwagandha

Have a calming effect on the brain

Kava kava

Has the same effect as alcohol on the brain by making a person feel happy and relaxed

CBD

Studies are made about using CBD for anxiety and sleep disorder but more tests are needed to confirm it

Bibliography

Alramadhan E, Hanna MS, Hanna MS, Goldstein TA, Avila SM, Weeks BS. Dietary and botanical anxiolytics. Med Sci Monit. 2012;18(4):RA40-RA48. doi:10.12659/msm.882608

Webmd.com. 2020. Accessed 6 March 2021. https://www.webmd.com/  Accessed 6 March 2021.

Herbs. 2020. Herbs to help you sleep.Pukkaherbs.com. https://www.pukkaherbs.com/us/en/wellbeing-articles/herbs-to-help-you-sleep.html. Accessed 6 March 2021.

Katzung, B.G. 2018. Basic & Clinical Pharmacology. 14^th ed. New York: McGraw-Hill Education

Liu L, Liu C, Wang Y, Wang P, Li Y, Li B. Herbal Medicine for Anxiety, Depression and Insomnia. Curr Neuropharmacol. 2015;13(4):481-493. doi:10.2174/1570159x1304150831122734

Richards, L., 2020. Herbs for anxiety: 9 calming options.  Medicalnewstoday.com. https://www.medicalnewstoday.com/articles/herbs-for-anxiety Accessed 6 March 2021.

What does anterograde amnesia mean and which drugs can cause this effect?

Anterograde amnesia is when someone is unable to remember things they did or events that take place, while the drug’s effects was still active in their body.

Benzodiazepines (midazolam) cause this effect

Name the effects of the sedative-hypnotic drugs on the normal sleep pattern and explain their significance to the patient.

When pharmacological treatment is needed to sleep, drugs are used to ensure rapid onset of sleep and prolongation of stage 2

When using drugs will see that:

• Time to fall asleep is reduced
• Time slept is increased (only if you (as patient) are not able to get more than 6 h of sleep)
• BDs don’t have a large effect on Rem sleep but:

• It increases the duration of phase 2 NREM
• Increase duration of phase 4 NREM

• Zolpidem decreases REM sleep and has a small effect on slow sleep wave
• The newer hypnotics namely like Zolpidem the decreases the latency to persistent sleep
• Patients must keep in mind that they can develop tolerance if use for longer than 1-2 weeks.

Which of the sedative-hypnotic drugs are used as a supplementary therapy in anaesthesia?  Can you explain why?

IV administration of Diazepam, lorazepam and midazolam are used in combination with other drugs in anaesthesia

Some barbiturates like thiopental or methohexital (work well because of short time of action and useful in recovery from anaesthesia)

These medications are used to put patients asleep so surgery can be done.

Which of the sedative-hypnotic drugs are used as anticonvulsants?

BDs

• Clonazepam
• Nitrazepam
• Lorazepam
• Diazepam

Barbiturates

• Phenobarbital
• Methabarbital

What is the mechanism of the muscle-relaxing effects of some of the carbamates and the BDs?

They have inhibitory effects on polysynaptic reflexes and internuncial transmission

When a large dose is administered it can reduce transmission at the neuromuscular junction

Discuss the effects of the sedative-hypnotic drugs on the respiratory and cardiovascular systems.

CVS and respiratory effects are more distinct when it is adminestered intravenously.

It can cause pulmonary depression in people with COPD or asthma.

Dose-related with some (with BDs only when used in combination with other drugs): it can cause medullary depression that can be fatal

Cardiovascular depression also a possibility if people struggle with heart diseases, hypovolemic states etc.

Toxic doses: Depression of myocardial contractility and vascular tone may appear by to central and peripheral effects due to facilitation of the actions adenosine  that leads to a circulatory collapse.

Bibliography

Brand, L. 2021. FKLG Study unit 2: Sedative-hypnotic drugs. Potchefstroom: NWU, Potchefstroom campus.

Katzung, B.G. 2018. Basic & Clinical Pharmacology. 14^th ed. New York: McGraw-Hill Education

What factors may affect the absorption and distribution of sedative-hypnotic drugs? What is the clinical significance thereof?

Lipophilicity plays a big role because it determines how fast  a drug will be absorbed and start to work (onset  of action), because the BBB is lipophilic; for example like thiopental and triazolam that is quickly absorbed and starts to show effect rapidly.

What is meant by redistribution and what is the significance thereof?

Redistribution means that the drug moves form the brain to other tissues (mostly occur with lipid soluble drugs) and it means that a drug is not eliminated right away but creates a depo-effect when it is distributed from the other tissues (for example adipose tissue).

How are the BDs metabolized? Name the various steps in the process.

It occurs via hepatic microsomal enzymes in the liver

Steps:

1. Dealkylation – where active metabolites are formed
2. Oxidation – where active metabolites are also formed and dependent on metabolism by Cytochrome P450 enzymes
3. Conjugation – where metabolite is rendered inactive so it can be excreted by the kidneys

Which BDs are converted to active metabolites? What is the significance thereof?

• Diazepam
• Chlorazepate
• Prazepam
• Chlordiazepoxide
• Ketazolam

Formation of active metabolites can lead to prolonging the duration the drug will be active in the system

It can also cause cumulative effects when multiple doses are adminestered

Which BDs are not dependent on the cytochrome P450 oxidative enzymes for metabolism? What are the advantages thereof?

• Oxazepam
• Lorazepam
• Temazepam
• Lormetazepam

The elderly, people with liver cirrhosis and neonates whose cytochrome P450 is not working optimally can use these drugs

What is enzyme induction? Which of the sedative hypnotic drugs are known for this? What is the clinical significance of enzyme induction?

It is when the activity of an enzyme for example is enhanced to decrease bioavailability of a drug and increases its clearance thus, reduces its effectiveness.

Barbiturates increase enzyme action when used for long duration of time

Brand, L. 2021. FKLG Study unit 2: Sedative-hypnotic drugs. Potchefstroom: NWU, Potchefstroom campus.

Katzung, B.G. 2018. Basic & Clinical Pharmacology. 14^th ed. New York: McGraw-Hill Education

Zevin, S., 2019. Cytochrome P450 Inducer - an overview | ScienceDirect Topics. Sciencedirect.com. https://www.sciencedirect.com/topics/medicine-and-dentistry/cytochrome-p450-inducer#:~:text=Cytochrome%20P%2D450%20enzyme%20inducers,St.&text=Grapefruit%20juice%2C%20which%20inhibits%20some,of%20some%20dihydropyridine%20calcium%20antagonists. Accessed 6 March 2021.

Which types of ion channels are found on the nerve cell membranes?

• Voltage-gated ion channels
• Ligand-gated ion channels

Name 3 differences between voltage-gated and ligand-gated ion channels.

Compare ionotropic and metabotropic receptors.

Ionotropic receptors

• They respond to chemical NTs that bind to receptor subunits present in structure.
• Binding to this receptor causes direct opening of a channel
• Important for fast synaptic transmission, thus effects do not last long

Metabotropic receptors

• They are G-protein coupled receptors that acts when there is direct action of G-proteins on the ion channel or when there is G-protein-enzyme activation that leads to formation of second messengers.
• There are 7 transmembrane G-proteins
• When a neurotransmitter binds to the metabotropic receptor it does not lead to direct gating of a channel
• Effects of activation lasts longer.

Classify the CNS receptors into ionotropic and metabotropic and know the transduction mechanism of each receptor.

Ionotropic

• GABA_A
• Nicotinic
• Glutamate

• NMDA
• Kainate
• AMPA

• 5-HT₃

Metabotropic

• Adrenergic

• α₁                                                                          (Phospholipase C)
• α₂                                             (Adenyl cyclase)
• ß₁₊₂                                                                     (Adenyl cyclase)

• Dopaminergic

• D₁                                                                         (Adenyl cyclase)
• D₂

• Serotonergic

• 5-HT₁ (A B C D)                      (adenyl cyclase)
• 5-HT₂                                                                (Phospholipase C)
• 5-HT_4-7

• Cholinergic

• Muscarine(M_2-4)                      (Adenyl cyclase)
• M₁₊₃₊₅                                                               (Phospholipase C)

• GABA_B
• EXCIT AA R

• MGluR1 (adenyl cyclase)       - mGluR8 (Phospholipase C)            

• BD
• H₁                                                                                   (Phospholipase C)

Explain the difference between an EPSP and an IPSP and give examples of each

EPSP (Excitatory postsynaptic potential)

• Membrane potential is depolarized
• Produced by the opening of Na and Ca channels and the closing of some K channels
• When Nicotinic receptor is stimulated by Ach the membrane potential is depolarized, sodium channels open and excitatory postsynaptic potential originates.

IPSP (Inhibitory postsynaptic potential)

• Membrane potential is hyperpolarized
• Produced by the opening of Cl and K channels
• When GABA-A is stimulated the membrane-potential is hyperpolarized chloride channels open.

What is the role of calcium in the development of a synaptic potential?

Calcium plays an important role in developing a synaptic potential, because the influx of calcium into the post-synaptic terminal triggers the release of NO from the vesicles for example so it can move back to the presynaptic membrane so the process can start again, thus it will exert an influence on the release of the neurotransmitter.