• 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.

Reference list:

Brand, L.Prof.  2021.  Study Unit 12: Drug dependance.  Unpublished lecture notes on efundi, FKLG 312.  Potchefstroom: NWU.  [PowerPoint presentation].

Katzung, B. G.  2018.  Basic & Clinical Pharmacology.  14^th ed.  California, San Francisco: McGraw-Hill Companies, Inc.

You (as a pharmacist) are invited by the local high school to address all the teachers and learners on the topic “Alcohol, what really 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? 

Pleasant effects of alcohol on the body:

According to Burnett (2016), pleasant effects of alcohol occur due “the fact that alcohol increases activity in the dopamine neurons in the mesolimbic reward pathway, as well as opioid cells that release endorphins”.  These produce feelings of:

• Joy.
• Pleasure.
• Euphoria: feeling happy.

The unpleasant effects of alcohol on the body:

According to Luo (2018), the unpleasant effects of alcohol on the body is as follows:

• Digestive and endocrine glands: too much alcohol can cause abnormal activation of digestive enzymes produced by the pancreas. These enzymes can lead to inflammation known as pancreatitis, this can be a long-term condition and cause complications.

• Inflammatory damage: long term consumption of alcohol damages the liver, and interferes with the livers ability to break down and remove substances. This increases your risk for chronic liver disease and inflammation.

• Sugar levels: the pancreas regulates the sugar levels in your body, when your pancreas and liver do not function properly, you can develop low blood sugar.
• Central nervous system: slurred speech is the first sign you had too much to drink. “Alcohol can cause more damage to your central nervous system, and you may experience numbness and tingling sensations in your feet and hands. Alcohol makes it difficult for your brain to maintain long-term memories. It also reduces your ability to think clearly and make rational choices. Frontal lobe damage can occur over time, this area of the brain is responsible for emotional control, short-term memory, and judgement, in addition to other functions. Chronic and severe alcohol abuse can also cause permanent brain damage. This can lead to Wernicke-Korsakoff syndrome, a brain disorder that affects memory”.
• Digestive system: drinking alcohol can cause damage to your digestive tract and prevent your digestive system from metabolising food, absorbing essential minerals and vitamins, this can lead to malnutrition. Difficulty absorbing vitamins and minerals can cause anaemia.  
• Circulatory system: alcohol affects your heart and lungs. Heart complications include, high blood pressure, stroke, heart attack and heart disease.
• Immune system: drinking heavily can reduce your body’s natural defence system, this makes it more difficult to fight off infection.

How many glasses of alcohol is safe?

According to Buddy (2021), generally for men 4 or fewer drinks per day, but less than 14 drinks per week is considered safe for men. For women, 3 or fewer drinks per day, but less than 7 drinks per week is considered safe for women.

How do I know when I am starting to develop a problem?

According to Galbicsek (2021), you may cover your alcohol abuse by drinking in private and isolating yourself from people.

The most common signs of alcohol abuse is as follows (Galbicsek, 2021):

• Signs of irritability.
• Extreme mood swings.
• Choosing alcohol over other responsibilities.
• Becoming isolated from family and friends.
• Drinking alone.
• Feeling hungover when not drinking.
• Changing appearance and group of people you socialise with.
• Making excuses to drink anytime of the day.
• Experiencing blackouts and memory loss.

What should I do then?

• Participate in a recovery program (rehab).
• Support groups, such as Alcohol Anonymous.
• There are certain medications that will help you to stop drinking alcohol, such as disulfiram.

(Galbicsek, 2021).

Reference list:

Buddy, T.  2021.  How Much Alcohol Is Safe to Drink? https://www.verywellmind.com/alcohol-how-much-is-too-much-67238  Date of access: 1 June 2021.   

Burnett, D.  2016.  Drink and be merry: Why alcohol makes us feel good, then doesn’t?

https://www.theguardian.com/science/brain-flapping/2016/nov/29/drink-and-be-merry-why-alcohol-makes-us-feel-good-then-doesnt  Date of access: 1 June 2021

Luo, E.K.  2018.  The Effects Of Alcohol on Your Body. https://www.healthline.com/health/alcohol/effects-on-body#Immune-system  Date of access: 1 June 2021.

Prepare a short “lecture” of not longer than 5 minutes (200 words), explaining to a patient what pain is, its possible causes, why different people experience pain differently and what the generally important principles of pain management and referral involve. The videos above will also be of value to complete this assignment. 

What is pain?

Pain is an uncomfortable sensory and emotional experience associated with tissue damage (actual or potential). You get acute pain, such as a migraine and chronic pain such as cancer pain.

Causes of pain:

Pain is in many cases caused by a specific injury or medical condition. In other instances, the cause of the pain may be unknown.

Some common causes of pain include: headache, toothache, sore throat, stomach cramps, muscle cramps, cuts, burns, bruises and fractures in bone

Many illnesses, such as the flu, arthritis, endometriosis, and fibromyalgia, can cause pain. “Depending on the underlying cause, you may develop other symptoms as well. For example, these may include fatigue, swelling, nausea, vomiting, or mood changes” (Gabbey, 2021).

Why different people experience pain differently?

“The reason why some people are more sensitive than others comes down to how our body modulates pain, from the skin to the brain, and the structure of the brain itself”. Sensory receptors, known as nociceptors,  detect an unpleasant stimuli. “These are transformed into pain signals that are then conducted throughout the central nervous system” (Brancatisano, 2016). Some people have a high tolerance for pain while other people don’t.

Principles of pain management:

• Providing treatment that reduces the pain with few side effects.
• While being able to maintain daily activities as well as preventing acute pain from progressing to chronic pain.

Referral:

‘Injuries that cause immediate swelling and severe pain, those that create popping or crunching noises, or those that cause an inability to support weight are all situations where you need prompt medical attention. Leaving the injury despite the pain may cause additional damage” (Valley Pain Centers, 2021) .

References:

Brancatisano, E.  2016.  Why Do Some People Feel Pain Differently? https://www.huffingtonpost.com.au/2016/10/10/why-do-some-people-feel-pain-differently_a_21577905/#:~:text=The%20reason%20why%20some%20people,nociceptors)%20detecting%20an%20unpleasant%20stimuli.  Date of access: 27 May 2021.

Gabbey, A.E.  2021 .Everything You Need To Know About Pain.  https://www.healthline.com/health/pain#treatment  Date of access: 27 May 2021.

Valley Pain Centers.  2021.  How Long Should You Power Through Pain Before Seeking Medical Help?  https://www.valleypaincenters.com/blog/how-long-should-you-power-through-pain-before-seeking-medical-help#:~:text=Injuries%20that%20cause%20immediate%20swelling,pain%20may%20cause%20additional%20damage.  Date of access: 27 May 2021.

• Using your textbooks, draw up a classification of the drugs that are used as antidepressants.
  1. SSRIs:

• Fluoxetine
• Sertraline
• Citalopram
• Paroxetine
• Fluvoxamine
• Escitalopram

• 2. SNRIs:
• Venlafaxine
• Desvenlafaxine
• Duloxetine
• Milnacipran

1. 3. TRICYCLIC ANTIDEPRESSANTS (TCAs):

Tertiary amine:

• Amitriptyline
• Imipramine
• Trimipramine
• Chlorimipramine
• Dothiepine
• Butriptyline

Secondary amine:

• Nortriptyline
• Desimipramine
• Lofepramine

• 4. TETRACYCLIC AND UNICYCLIC DRUGS:
• Bupropion
• Mirtazapine
• Amoxapine
• Maprotiline

• 5. 5-HT ANTAGONISTS:
• Trazodone
• Nefazodone
• Vortioxetine

• 6. MOAIs:
• Phenelzine
• Isocarboxazid
• Tranylcypromine
• Selegiline
• Moclobemide

• 7. NORADRENALINE RECEPTOR INHIBITORS (NARIs):
• Reboxetine
  8. CIRCADIAN RHYTHM REGULATOR:
• Agomelatine

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

Multipotent actions on numerous monoaminergic receptors due to non-specific increase in serotonin or noradrenaline.

• How long does it take for the anti-depressive effects of these drugs to appear? What is the reason for this?

It takes 6-8 weeks for antidepressant agents to start being effective. This is due to the time it takes to have an effect on the serotonin receptors; either decreasing the number of 5-HT receptors or desensitizing the 5-HT receptors.

• How do the TADs and the selective serotonin reuptake inhibitors (SSRI’s) differ in respect of:
  1. efficacy
  2. side effects
  3. safety?

• What is the action of mirtazapine?

Blockade of alpha 2, 5HT2A, 5HT2C and 5HT3 receptors.

• What is the action of venlafaxine?

Serotonin and norepinephrine transporter antagonism. 

• What is the action of agomelatine?

Blockade of 5HT2C receptors with simultaneous stimulation of MT1/MT2 receptors (melatonergic receptors).

References:

Brand, L.Prof.  2021.  Study Unit 10:Antidepressants.  Unpublished lecture notes on efundi, FKLG 312.  Potchefstroom: NWU.  [PowerPoint presentation].

Katzung, B. G.  2018.  Basic & Clinical Pharmacology.  14^th ed.  California, San Francisco: McGraw-Hill Companies, Inc.

1. Discuss the possible mechanisms of action of lithium.

The MOA of lithium is not well defined.

The drug inhibits several enzymes involved in the recycling of neuronal membrane phosphoinositides.

This action may result in depletion of the second messenger source, phosphatidylinositol bisphosphate (PIP2), which, in turn, would decrease generation of inositol trisphosphate (IP3) and diacylglycerol (DAG).

These second messengers are important in amine neurotransmission, including that mediated by central adrenoceptors and muscarinic receptors.

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

0.5 – 1.5 mM; >2 mM is toxic.

Lithium is used to stabilize mood swings of bipolar disorders, and sometimes used for people with depression who are not responding to other medications.

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

Monotherapy: lithium is used for bipolar disorders

Combination therapy with lithium: valproate and carbamazepine for psychiatric symptoms.

Olanzapine and quetiapine for acute mania

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

• Dehydration, diuretics (e.g. thiazides), NSAID’s, ACE inhibitors and fluoxetine all increase lithium ion levels and causes toxicity.
• Theophylline, caffeine increase the renal excretion of lithium ions.
• Neurotoxic effects when lithium is used in combination with carbamazepine, calcium ion blockers, losartan, methyldopa, metronidazole and phenytoin.
• Traditional Anti-Parkinson’s drugs worsen EPS in combination with lithium.  

5. Name the major side effects of lithium.

• Tremors
• Sedation
• Ataxia
• Aphasia
• Muscle weakness
• Fatigue
• Polidipsia
• Poliuria
• Nocturia
• Nephrogenic diabetes insipidus (lithium ions interferes with kidney’s ability to concentrate urine)
• Thyroid enlargement
• Leucocytosis
• Edema
• Weight gain
• Acne
• Alopecia
• Sexual dysfunction

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

Not safe for use during pregnancy and breastfeeding.

The risks to your baby breastfeeding are heart defects. Taking lithium in early pregnancy can increase the risk that your baby's heart might not develop properly.

7. Name three other important indications for lithium.

• Bipolar disorders.
• Schizophrenia.
• Depression.

8. 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.

Camcolith 400 mg tablets contain lithium carbonate, which is used to treat and prevent mania or mania depressive illness and depression in adults. For acute symptoms the target plasma therapeutic concentration is 8-12 mEq/L (mmol/L) and maintenance is 0.4-0.7 mEq/L (mmol/L). The plasma levels of Ms Polar is 0.8 mmol/L which is higher than the maintenance plasma therapeutic concentration of lithium. This can be due to changes in body water of Ms Polar, due to use of NSAID such as Indocid®.

Indocid® is used for pain, swelling and joint stiffness caused by arthritis or gout. It is an anti-inflammatory drug (NSAID).

Indocid®can increase the lithium ion levels and cause adverse side effects, such as weight gain, fatigue, sedation, polydipsia (thirsty) and tremors.

The “water pill” which is a diuretic, she is taking will not help to elevate her symptoms, it will in fact worsen her symptoms, since diuretics increase the lithium ion levels and will cause adverse side effects. .

Therefore, Ms Polar must be prescribed another anti-psychotic drug that does not cause drug interactions with her NSAID and she must stop taking the “water pill”.

Reference list:

Brand, L.Prof.  2021.  Study Unit 9:Anti-psychotic Drugs and Lithium.  Unpublished lecture notes on efundi, FKLG 312.  Potchefstroom: NWU.  [PowerPoint presentation].

Katzung, B.G.  2018.  Basic & Clinical Pharmacology.  14^th ed.  California, San Francisco: McGraw-Hill Companies, Inc.

Katzung, B.G., Kruidering-Hall, M. & Trevor, A.J. 2015.  Katzung and Trevor’s Pharmacology Examination and Board Review. 11^th ed. California, San Francisco: McGraw-Hill Companies, Inc.

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.

• Aliphatic side chain:

Example: chlorpromazine.

Low potency and little EPS.

Severe sedation.

Strong anti-cholinergic effects.

• Piperidine side chain:

Example: thioridazine.

Low potency and little EPS.

Severe sedation.

Strong anti-cholinergic effects.

• Piperazine side chain:

Example: fluphenazine.

High potency and more EPS.

Less sedation.

Weaker anti-cholinergic effects.

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

Mesolimbic dopamine 2 receptor are blocked.

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

Atypical drugs are serotonin 2A blockers, more than dopamine 2 receptor blockers, and also strong blocking effects of muscarinic 1 receptor, histamine 1 receptor and alpha 1 receptor.

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

Dopamine 2 receptors are blocked and this reduces the risk of extrapyramidal side effects.

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

Piperazine compounds, because it has a high potency and high affinity for dopamine 2 receptors.

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

Muscarinic receptor blockade.

Reference list:

Brand, L.Prof.  2021.  Study Unit 9: Anti-psychotic Drugs and Lithium.  Unpublished lecture notes on efundi, FKLG 312.  Potchefstroom: NWU.  [PowerPoint presentation].

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

• Drugs that increase dopaminergic activity.
• Drugs that decrease cholinergic activity.

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

• Metaffinoid potentiator of DA (↑ in DA activity)

-  ↑ DA release

-  ↑ DA synthesis

-  Blocks reuptake of DA

• NMDA antagonist (anti-dyskinetic effects)
• Adenosine A2a Antagonist

-  Adenosine Inhibits D2 receptors.\By blocking the adenosine receptor, improve D2 function.

Improved rigidity, tremors, bradykinesia.

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

These drugs do not require enzymatic conversion to an active metabolite. They do not act directly on the post synaptic dopamine receptors. They have no potentially toxic metabolites. 

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

• Pramipexole
• Pergolide
• Bromocriptine
  • Non ergot derivative:
    • • Ropinirole
      • Rotigotine

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

• Pramipexole: D3
• Ropinirole: D2
• Rotigotine: D1, D2 and D3
• Bromocriptine: D2
• Pergolide: D1 and D2

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

• MAO- B inhibitor: Rasagiline 
• This means it increases the DA stores in neurons.

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

They work adjunctive to Levodopa. MAO-B inhibitors prolong duration of effect of levodopa. Therefore should be used with caution.

• How do the COMT-inhibitors act in Parkinsonism?

COMT metabolises L-dopa to 3-OMD. Increased plasma levels of 3OMD leads to a weak therapeutic response with L-dopa.

3-OMD competes with L-dopa for active transport.

• How does istradephyline act?

Inhibits D2 function, thus by antagonising adenosine, prevent its inhibition of dopamine function. Add on therapy to L-dopa/carbidopa experiencing on-off episodes.

• Discuss the MOA of safinamide

MOA: Novel dual MOA

1. ↑ DA activity
   • -  Potent reversible inhibition of MAO-B
   • -  Inhibition of DA uptake
2. ↓ Glutamate release

Reference list:

Brand, L.Prof.  2021.  Study Unit 8: Parkinsonism.  Unpublished lecture notes on efundi, FKLG 312.  Potchefstroom: NWU.  [PowerPoint presentation].

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

1. Myelinated fibres with unmyelinated fibres:

Smaller myelinated fibers are blocked much easier in comparison to the larger unmyelinated fibers, which are much less sensitive to blockade by the local anaesthetics.

2. Pressure/touch nerves with the dorsal nerves that transmit pain impulses:

Activated pain fibers fire rapidly, therefore pain sensation may be selectively blocked by local anaesthetics. Fibers that are located in outside of the thick nerve bundles are blocked sooner than the fibers located in the middle of thick nerve bundles. This is because they are exposed too higher concentrations of the anaesthetic much earlier.

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

Heart:

• LA have Class I anti-arrhythmic drug effects.
• Sodium channels in heart tissue is blocked.
• Resulting in cardiac depression.

Skeletal muscle:

• Weak blocking effects
• No clinical application.

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

A local anaesthetic is chosen due to the following factors:

• The type of procedure that is being done
• The type of tissue that the local anaesthetic should be used on
• The duration of the numbing effect that is needed

• Why are LA solutions sometimes saturated with CO₂?

The carbon dioxide acts as a buffer to the local anaesthetic. This will potentiate the effects of the local anaesthetic.

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

These drugs move through gums and reach nerves.

Reference list:

Brand, L.Prof.  2021.  Study Unit 6: Local Anaesthesia.  Unpublished lecture notes on efundi, FKLG 312.  Potchefstroom: NWU.  [PowerPoint presentation].

• 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.

• Name the major acute toxic effects of the inhalation drugs.

• Nephrotoxicity
• Hematotoxicity
• Malignant hyperthermia 
• Hepatotoxicity

Reference list:

Brand, L.Prof.  2021.  Study Unit 5: General Anaesthesia.  Unpublished lecture notes on efundi, FKLG 312.  Potchefstroom: NWU.  [PowerPoint presentation].

• Which of the anti-epileptic drugs affect the metabolism of the Pill (oral contraceptive) and what are the implications of this? Which drugs are safe to use in combination with the Pill? 

• Phenobarbitone
• Phenytoin
• Carbamazepine
• Oxcarbazepine
• Topiramate
•  Perampenel (decreases levonorgestrel-containing contraceptives).

All these medication decreases the pill effectiveness. This may cause unexpected pregnancies and teratogenic effects.

Drugs that are safe to use with the Pill:

• • Valproate
  • Lamotrogine
  • Gabapentin
  • Leviteracetam
  • Vigabatrin.

• Can oral contraceptives also affect the effectivity of the anti-epileptic drugs?

Yes, oral contraceptives decrease Lamotrigine and Valproate serum levels. This can result in seizures.

• How does age affect the kinetics of these drugs (from neonates to old age)?
  • Neonates have a slow metabolism, so must receive lower dosages.
  • Babies and children have a faster metabolism than adults, so they receive higher dosages.
  • Geriatric patients have a slow metabolism and decreased renal function, so they should receive lower dosages.

• In which cases is plasma blood level monitoring indicated?

Plasma blood level monitoring is required, where protein binding takes place. Anti-epileptic drugs that does affect protein binding:

• • Gabapentin
  • Ethosuximide
  • Topiramate.

Certain diseases which may affect protein binding and require plasma blood level monitoring:

• • Kidney failure
  • Liver diseases
  • Hypoalbuminemia

Other conditions/instances that require plasma blood level monitoring

 : burns, pregnancy, malnutrition, age

Reference list:

Brand, L.Prof.  2021.  Study Unit 4:Anti-Epileptic Drugs.  Unpublished lecture notes on efundi, FKLG 312.  Potchefstroom: NWU.  [PowerPoint presentation].