Some of these stimulants are often used/misused by learners and students as cognitive performance enhancers.  Do a search on the internet and compile a report on the merits/ dangers of this practice.

 

Merits on pharmaceutical cognitive enhancement prescribed for the use of students

Pharmaceutical cognitive enhancement has been seen to help humans become “better” and overcome currently believed limitations concerning what we are able to memorise, how long we can concentrate, or how efficiently we can make decisions and adapt to challenging environments (Bostrom and Sandberg, 2009). For example, having a good memory might be generally valued and thus positive for users. And indeed, key features of humankind have been changing over the centuries due to better healthcare, vaccination or food. One hope is that PCE can amplify human capacities for more autonomous agency and complex judgments and that its intake may even result in changes of character traits that could be beneficial for users, such as improved self-confidence (Flanigan, 2013).

Dangers on pharmaceutical cognitive enhancement misuse of students

There is no safe level of drug use. Taking any type of drug always carries some risk, so it’s important to be careful.

Large doses of stimulants can lead to psychosis, seizures, and cardiovascular events. The induction of schizophrenic-like states in AMP abusers is well documented, although the onset of such states in children on prescribed doses of stimulant medication is observed far less often (Surles et al. 2002).  The most observed cardiovascular effects linked with ADHD stimulant medications include hypertension and tachycardia. In addition, cardiomyopathy, cardiac dysrhythmias, and necrotizing vasculitis have been described.  Additional potential ADRs associated with stimulant use are important to note including abdominal pain, anorexia, constipation, dizziness, dry mouth, headache, insomnia, jitteriness, irritability, nausea, and palpitations (Greydanus and Strasburger 2006). College students with ADHD who misuse prescribed stimulants also reported hyperactivity symptoms as a common adverse event.

 

 

REFERENCES:

Bostrom, N. And A. Sandberg (2009), “Cognitive enhancement: Methods, ethics, regulatory challenges”, Science and Engineering Ethics, Vol. 15/3, pp. 311-341, http://dx.doi.org/10.1007/s11948-009-9142-5.

Flanigan, J. (2013), “Adderall for all: A defense of pediatric neuroenhancement”, HEC Forum, Vol. 25/4, pp. 325-344, http://dx.doi.org/10.1007/s10730-013-9222-4.

Greydanus DE, Strasburger VC, Adolescent medicine, Prim Care. 2006 Jun; 33(2):xiii-xviii.

Surles LK, May HJ, Garry JP, “Adderall-induced psychosis in an adolescent.”, J Am Board Fam Pract. 2002 Nov-Dec; 15(6):498-500.

• Which different groups of hallucinogenic drugs are known?

PCP and LSD

• Name a few typical effects of the hallucinogenic drugs and discuss the clinical profile of a patient who had taken them.

Effects of hallucinogenic drugs:

• Dizziness.
• Vomiting.
• Euphoria.
• Nausea.
• Weakness.
• Paraesthesia.
• Blurred vision.
• Sense of well-being and relaxation.

Clinical profile of patient who had taken them:

• Change in behaviour.
• Poor skin tone.
• Lack of energy.
• Bloodshot eyes.
• Poor performance.
• Tired and run down.

• How is an over-dose of LSD dealt with? 

Intravenous administration of anticoagulants, vasodilators or sympatholytic. Supportive care and rehabilitation.

• How is an over-dose of anticholinergic drugs dealt with?

By administering a reversible acetylcholine inhibitor such as physostigmine salicylate.

Answer the following for a Blog Summary:

Select one of the following assignments for elucidation in a 15-minute address to a certain target group:

• You (as a pharmacist) are invited by the local high school to address all the teachers and learners on the topic “Alcohol, what is its effect on my body”. Focus on the effects, “pleasant” as well as “unpleasant”, how many glasses are safe? How do I know when I am starting to develop a problem? What should I then do?  Throughout, keep the age of your target group (learners) in mind!

 

ALCOHOL

• EFFECT ON BODY:
  • PLEASANT

How does alcohol make you feel good?

That aspect seems to stem from the fact that alcohol increases activity in the dopamine neurons in the mesolimbic reward pathway, as well as opioid cells that release endorphins. Both produce feelings of joy, pleasure, euphoria, depending on the type of activation. That's why drinking can be so pleasurable.

 

• • UNPLEASANT

SHORT-TERM EFFECTS OF ALCOHOL

 

Depending on how much is taken and the physical condition of the individual, alcohol can cause:

• Slurred speech
• Drowsiness
• Vomiting 
• Diarrhoea
• Upset stomach
• Headaches
• Breathing difficulties 
• Distorted vision and hearing 
• Impaired judgment 
• Decreased perception and coordination 
• Unconsciousness 
• Anaemia (loss of red blood cells) 
• Coma
• Blackouts (memory lapses, where the drinker cannot remember events that occurred while under the influence)

 

 

• HOW MANY GLASSES ARE SAFE?

Measured by units and not glasses!

With so many different drinks and glass sizes, from shots to pints and even bottles, it’s easy to get confused about how many units are in your drink. 

Units are a simple way of expressing the quantity of pure alcohol in a drink.

One unit equals 10ml or 8g of pure alcohol, which is around the amount of alcohol the average adult can process in an hour.

The number of units in a drink is based on the size of the drink, as well as its alcohol strength.

For example, a pint of strong lager contains 3 units of alcohol, whereas the same volume of low-strength lager has just over 2 units.

Knowing your units will help you stay in control of your drinking.

 

To keep health risks from alcohol to a low level if you drink most weeks:

• Men and women are advised not to drink more than 14 units a week regularly 
• Spread your drinking over 3 or more days if you regularly drink as much as 14 units a week
• If you want to cut down, try to have several drink-free days each week

Fourteen units are equivalent to 6 pints of average-strength beer or 10 small glasses of low-strength wine.

 

• HOW DO I KNOW WHEN I AM STARTING TO DEVELOP A PROBLEM

USUALLY SELF-DIAGNOSABLE

Symptoms include repeated alcohol consumption despite related legal and health issues. Those with alcoholism may begin each day with a drink, feel guilty about their drinking and have the desire to cut down on the amount of drinking.

 

PEOPLE MAY EXPERIENCE:

Whole-body: blackout, dizziness, shakiness, craving, or sweating

Behavioural: aggression, agitation, compulsive behaviour, self-destructive behaviour, or lack of restraint

Mood: anxiety, euphoria, general discontent, guilt, or loneliness

Gastrointestinal: nausea or vomiting

Psychological: delirium or fear

Also common: physical substance dependence, problems with coordination, slurred speech, or tremor

 

• WHAT SHOULD I THEN DO

If you think that you have a drinking problem, you should seek a full evaluation by a healthcare professional. There are many diagnostics tests available online that can help you self-evaluate your drinking, but none of them should substitute for professional medical advice.

Pain is used to describe uncomfortable sensations in the body that stems from activation of the nervous system. Pain has a broad range: it can range from annoying to debilitating, it may be consistent, it may start and stop frequently, it may only occur under certain conditions, it can develop suddenly and only last for a short period of time or it may be ongoing sensations that last or return over several months or even years.  Pain can also be described in many different ways: it may feel like a sharp stab or dull ache, it may be described as throbbing, pinching, stinging or even burning.  Pain may also be localized, only affecting a specific part of the body or it my by generalized like with overall body ached.

People also respond differently to pain: some have a high tolerance for pain and don not feel pain that easily/frequently and others have a low tolerance for pain and feel pain very intensely. Thus, pain is highly subjective.

The causes of pain can be due to a specific injury or medical condition or in some cases the cause of pain can even be less obvious or unknown. Illnesses and disorders that cause pain include: flu, arthritis, endometriosis and fibromyalgia. Pain can also be caused by bruises, burns, broken bones, etc.

Important principles of pain management include providing treatment that reduces the pain with minimal side effects, while still being able to maintain daily functions as well as preventing acute pain from progressing to chronic pain.

Medical attention is needed when the pain is a result of an injury or accident that may have caused damage to the body like bleeding, broken bones or a head injury. It is also needed when an acute, sharp internal pain is felt for it may be a sign of a serious problem like a ruptured appendix. Medical attention for pain is also needed when the pain is located in the chest, back, shoulders, neck or jaw together with other signs of a heart attack like shortness of breath, nausea, dizziness and weakness OR when the pain is interfering with your daily life, including the ability to sleep, work or taking part in any other activities that is enjoyed.

Classification of drugs

Selective Serotonin Re-uptake Inhibitors (SSRIs)	Fluoxetine Citalopram Escitalopram Paroxetine Sertraline
Serotonin Norepinephrine Re-uptake Inhibitors (SNRIs)	Duloxetine Venlafaxine Levomilnacipran
Selective Norepinephrine Re-uptake Inhibitors (NARIs)	Reboxetine
Tricyclic Antidepressants	Secondary amine: Nortriptyline Desimipramine Lofepramine
	Tertiary amine: Amitriptyline Imipramine Trimipramine Chlorimipramine Dothiepine Butriptyline
5-HT Receptors Modulators	Trazodone Vortioxetine
Monoamine Oxidase Inhibitors (MAOIs)	Tranylcypromine Moclobemide Selegeline
Tetracyclic and Unicyclic	Mianserin Mirtazepine Bupropione
Circadian Rhythm Regulators	Agomelatine

What do the existing drugs all have in common regarding their mechanisms of action?

The antidepressants inhibit reuptake of neurotransmitters through selective receptors, thereby increasing the concentration of specific neurotransmitter around the nerves in the brain.

How long does it take for the antidepressive effects of these drugs to appear? What is the reason for this?

• It takes approximately four to six weeks for antidepressant medications to reach their full therapeutic effect.
• n people with depression, G proteins tended to congregate in lipid rafts, areas of the membrane rich in cholesterol. Stranded on the rafts, the G proteins lacked access to a molecule called cyclic AMP, which they need in order to function. 
• AD's accumulates in the lipid rafts over time and as they do so, G proteins in the rafts decreases.
• It's likely that this effect on the movement of G proteins out of the lipid rafts towards regions of the cell membrane where they are better able to function is the reason these antidepressants take so long to work.

Difference

	TADs	SSRIs
EFFICACY	Mixed and variable blockade of NET and SERT.	Highly selective blockade of SERT Little effect on NET
SIDE EFFECTS	Sympathomimetic: tremors Anticholinergic: dry mouth CVS: orthostatic hypotension Psychosis Convulsions Metabolic: weight gain	Anticholinergic EPS Anxiety Sexual dysfunction Withdrawal syndrome GIT disturbances
SAFETY	Cause coma, cardio toxicity and convulsions	CYP inhibition

What is the action of mirtazapine?

• NaSSA (NA & Specific Serotonin Antidepressant)
• Blocks alpha 2, 5-HT2A, 5-HT3
• Blockade of inhibitory alpha 2 receptors advance both NA (auto-receptor) & 5-HT (heteroreceptor) release.
• Indirect stimulation of 5-HT1A
• Blocks 5-HT3 as well as 5-HT2

What is the action of venlafaxine?

• Moderately selective blockade of NET and SERT
• More potent for 5-HT

What is the action of agomelatine?

• Melatonin 1 and -2 agonist and 5-HT2C antagonist
• 5-HT2C antagonism: disinhibition of DA and NA release in FC (increase DA and NA release)

• Discuss the possible mechanisms of action of lithium.

Mechanism of action of lithium: Lithium influences the IP3 and DAG 2nd messenger systems by decreasing the various enzymes which are very important for conversion and re-circulation of membrane phosphoinositide’s.

• What is the therapeutic index of lithium and what is its clinical significance?

The therapeutic index of lithium is 0,5-1.5mM which is very small and therefore the dosing of lithium should be done very carefully, and blood levels must be monitored to prevent lithium toxicity.

• When is lithium used as single drug and in which cases and with which type of drugs is lithium combined?

Lithium as monotherapy is used for prophylaxis of manic and hypomanic episodes and treatment of an acute manic episode. Lithium is used in combination with antidepressants for the treatment of resistant or recurrent unipolar depression and self-mutilating or aggressive behaviour.

• Name 3 clinically significant interactions lithium may have with other drugs. Illustrate your answer with suitable examples of drugs.

The renal clearance may be decreased by thiazide diuretics, new NSAIDs, ACE inhibitors, and fluoxetine. Renal clearance of lithium is increased by theophylline and caffeine. Lithium is neurotoxic in combination with carbamazepine, calcium-blockers, losartan, methyldopa, metronidazole, and phenytoin.

• Name the major side effects of lithium.

Tremors, sedation, ataxia, aphasia, muscle weakness, fatigue, polydipsia, polyuria, nocturia, nephrogenic diabetes insipidus, thyroid enlargement, leucocytosis, oedema, weight gain, acne, alopecia, and sexual dysfunction.

• What is the status of the use of lithium during pregnancy and lactation?

Lithium has been associated with an increased incidence of congenital cardiovascular abnormalities, but the incidence is very low, keep the risk-benefit in mind. Lithium is excreted into the breastmilk in high concentrations and thus breastfeeding is not suggested.

• Name three other important indications for lithium.

Lithium as monotherapy is used for prophylaxis of manic and hypomanic episodes and treatment of an acute manic episode.

• Evaluate the following case and fully motivate your recommendations:
• Ms B. Polar (21 years, 60 kg) is a student and used the following medication for the past two months: Camcolith 600mg bd. The plasma levels after two weeks were 0.8mmol/l. She sustained a muscle injury and has been using Indocid® 75mg nocte for the past 10 days. On questioning she reveals that “she had picked up a lot of weight” and is now using some of her mother’s “water pills” in the hope of losing a few of the extra kilos. However, she complains of fatigue, that she has difficulty in keeping her eyes open in class, remains thirsty and constantly feels shaky and nauseous.

The NSAID is causes decreased clearance of the lithium and therefore can cause an increase in the patient’s weight and other side effects of lithium. I would rather recommend Tylenol, acetaminophen, for pain. It does not have any drug interactions with lithium.

1. Name an example of each of the three phenothiazine sub-families and state how they differ from one another in terms of potency and side effects.

The three phenothiazine sub-families are: Aliphatic derivatives, Piperidine derivatives and Piperazine derivatives. The aliphatic and piperidine derivatives have low potency and cause severe sedation, anti-cholinergic effects, postural hypotension and they are cardiotoxic. The Piperazine derivatives have a high potency, but it causes weaker anticholinergic effects and less sedation, less cardiovascular effects and does not cause postural hypotension.

2. Which receptors in particular are blocked by the typical antipsychotic drugs?

Antipsychotics block D2- receptors as well as H1-receptors, cholinergic receptors and alpha1-receptors (to a lesser extent).

3. How does the mechanism of action of the atypical drugs differ from that of the typical drugs?

Atypical drugs block serotonin 2A-receptors whereas typical drugs block mesolimbic D2-receptors.

4. Which of the receptors blocked by the older drugs reduce the risk of extrapyramidal side effects?

Typical drugs block D3-receptors and this causes the risk of extrapyramidal effects to reduce.

5. Which of the older drugs have a high incidence of extrapyramidal side effects? What is the reason for this?

The phenothiazines, particularly the piperazine derivatives, have a high incidence of causing extrapyramidal side effects.

6. Because of which receptor(s) blockade do the aliphatic group of drugs have a high incidence of autonomic side effects?

The blockage of cholinergic neurons by the aliphatic derivatives cause the autonomic side effects.

• Which two main groups of drugs are important in the treatment of Parkinsonism?

- Drugs that increase the activity of Dopamine.

- Drugs that lower the Cholinergic (Ach) activity.

• In what way does amantadine act as a antiparkinsonism drug?

Amantadine is a metaffinoid potentiator of dopamine, which therefore has the effect of increasing the release of dopamine, increasing the synthesis of dopamine and inhibiting the reuptake of dopamine. Can also act as an anticholinergic. Can also act as an NMDA antagonist, as it has antidyskinetic effects, which will therefore help with movement disorders of Parkinsonism. It can also act as an adenosine α2-A antagonist, which inhibits D2 function and thus results in increased dopamine.

• Discuss the mechanisms of action of the antiparkinsonism drugs that indirectly increase dopamine concentration.

• Amantadiene:

Metaffinoid potentiator of dopamine, which therefore has the effect of increasing the release of dopamine, increasing the synthesis of dopamine and inhibiting the reuptake of dopamine.

• Selective MAOB inhibitors (eg Rasagiline and Selegiline):

Selectively inhibits MAO-B enzymes that result in dopamine metabolism being suppressed and dopamine levels being high in the central nervous system.

• COMT inhibitors (eg Entacapone):

COMT metabolizes l-dopa to 3-oxygen (O) -methyl dopa (3OMD), so the increased levels of 3OMD have a poor therapeutic response with l-dopa, because they compensate for the active transport processes. Thus, by using a COMT inhibitor, it prevents competition with l-dopa and thus l-dopa's duration of action will be prolonged, peripheral metabolism will be reduced and improved bioavailability will occur.

• Which of the dopamine agonists are ergot derivatives and which are not?

Ergot derivatives: Bromocriptine

Non-ergot derivatives: Pramipexole and Ropinirole

• List the specific dopamine receptors that are stimulated by each agonist.

D2 receptor agonists:

-Ropinirole

-Bromocriptine

D3 receptor agonists:

-Pramipexole

• Which of these drugs are classified as neuron protecting drugs?  What does this mean?

Selective Monoamine Oxidase B (MAO-B) inhibitors (eg Rasagiline). This means that the MAO-B inhibitor prevents MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) from being converted to MPP + (N-methyl-4-phenylpyridium), which can therefore protect against the prevalence of Parkinsonism.

• What is the importance of monoamine oxidase B (MAO-B) selective drugs in the treatment of Parkinsonism?

MAO-B has a preference for Dopamine as a substrate, so the Dopamine concentration in the central nervous system will be increased.

• How do the COMT-inhibitors act in Parkinsonism?

COMT metabolizes l-dopa to 3-oxygen (O) -methyl dopa (3OMD), so the increased levels of 3OMD have a poor therapeutic response with l-dopa, as they compensate for the active transport processes. Thus, by using a COMT inhibitor, it prevents competition with l-dopa and thus l-dopa's duration of action will be extended, peripheral metabolism will be reduced and improved bioavailability will occur.

• How does istradephyline act?

The drug is an adenosine α2-A antagonist, which therefore inhibits D2 function. The drug can also be used as additional therapy in l-dopa / carbidopa therapy.

• Discuss the MOA of safinamide

Safinamide has a dual mechanism of action:

1. The drug increases the Dopamine activity, through the potent reversible inhibition of MAO-B, as well as the inhibition of Dopamine reuptake.

2. The drug also lowers glutamate release.

• How does the sensitivity for blockade by a LA compare regarding the following types of fibres:

(a) myelinated fibres with unmyelinated fibres; and

Small and myelinated fibers are therefore more easily blocked than large and unmyelinated fibers.

(b) pressure/touch nerves with the dorsal nerves that transmit pain impulses?

The dorsal nerves that conduct impulses are therefore more sensitive to the blockage and are thus also blocked faster than pressure / touch nerves.

• Make a list of the effects of LA on other tissues.

• Hard: The Sodium channels are blocked in the heart, thus shortening the action potential and prolonging the refractory period and thus may result in antiarrhythmic effects, usually caused by Class 1 antiarrhythmic drugs such as Lidocaine.

• Skeletal muscle: A weak blocking effect emerges. There is no clinical application.

• Cocaine: Has an effect on the state of mind, thus increasing the state of mind. May also affect central catecholamine-mediated neurotransmission, thus blocking NA reuptake.

• What is the basis for the selection of a LA?

• It depends on how long the LA will be used.

• What the LA will be used for, its clinical use.

• How long the LA lasts.

• Why are LA solutions sometimes saturated with CO₂?

It potentiates the LA, which therefore means the LA are accelerated.

• Which of the LA are typically used for surface anaesthesia?

• Cocaine

• Benzocaine

• Oxybuprocaine

• Name the major acute toxic effects of the inhalation drugs

• Nephrotoxicity

• Hematotoxicity - The drugs can produce CO, thus reducing the oxygen in the tissue.

• Hepatotoxicity - May occur due to Halothane.

• Teratogenicity - May occur due to Halothane, Enflurane, Isoflurane, Desflurane and Sevoflurane.

 

• Compile a table, listing the major effects on every system (cardiovascular, CNS, renal, hepatic and uterus) for all the inhalation anaesthetics. This table is important when it comes to the selection of drugs in certain individuals.

System	Halothane	Enflurane	Isoflurane	Desflurane	Sevoflurane	N2O
Central nervous	Rapid smooth induction, increased cerebral blood flow and increased intracranial pressure, stage 2 is therefore also absent.	There is a rapid, smooth induction. Exception: Epilepsy, due to convulsions that may occur.	Has a faster induction and recovery rate than Halothane. Exception: Do not use in patients who need to breathe spontaneously.	Faster induction and recovery than Isoflurane. Increases cerebral blood flow as well as intracranial pressure.		Weak anesthesia, but potent analgesic. May cause amnesia.
Cardiovascular	Decreased blood pressure and thus sensitizes the myocardium to arithomogenic effects of catecholamine’s.	Sensitization of the myocardium does not occur.	Less suppression than Halothane and Enflurane. No sensitization of the myocardium.	Less oppressive than Halothane and Enflurane.		No effect.
Respiratory	So there is no saliva or bronchial secretions, nor coughing.	More suppression than Halothane.	Great suppressive effect. Has a skeletal muscle relaxant effect and therefore strengthens the drug.	Has a pungent odor, irritates the respiratory tract and if used as an induction, can cause cough, shortness of breath and laryngospasms.	Less irritating in airways.	Hypoxia. No skeletal muscle relaxation.
Kidney	Reduces glomerular filtration, as well as urine flow.
Liver	Hepatotoxicity  may occur.
Uterus	Reduces muscle contractions, so external rotation of the baby may occur.