Doctors prescribe medicines like Adderall and Ritalin to treat conditions like attention deficit hyperactivity disorder (ADHD). Sometimes, people who don't have these conditions take other people's medicines because they think they'll help them focus while doing schoolwork. These drugs are stimulants. They can increase alertness, energy, heart rate, breathing rate, and blood pressure for a short time. Study drugs don't actually increase learning or thinking ability, though. If you suddenly stop using this medication, you may have withdrawal symptoms such as depression, suicidal thoughts, or other mental/mood changes Though it helps many people, this medication may sometimes cause addiction. AHDH drugs works by increasing the amount of dopamine released in the striatum, a key region in the brain related to motivation, action and cognition higher levels of dopamine make both humans and rodents more motivated to perform physically demanding tasks.

https://kidshealth.org/en/teens/study-drugs.html#:~:text=What%20Are%20Study%20Drugs%3F,them%20focus%20while%20doing%20schoolwork.

https://www.radboudumc.nl/en/news/2020/ritalin-enhances-your-ability-to-do-tasks-by-making-you-more-motivated

• 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.

- Alter consciousness such that the individual senses things that are not present. They induce, often in an unpredictable way, perceptual symptoms, including shape and colour distortion

- depersonalization, hallucinations, distorted time perception

- They also produce somatic symptoms dizziness, nausea, paresthesias, and blurred vision.

- Flashbacks

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

• Benzodiazepine for convulsions and agitation
• Supportive care and rehabilitation

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

• Physostigmine

Alcohol Suppresses CNS function; Potentiates GABA effects which are calming effects. it Inhibits glutamate’s effects on NMDA Receptors which affect your learning & memory. It then causes an increase 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.

 unpleasant effects  could include:

• Slurred speech
• Drowsiness
• Vomiting 
• Diarrhoea
• Upset stomach
• Headaches
• Breathing difficulties 
• Distorted vision and hearing 
• Impaired judgment 
• Decreased perception and coordination 
• Unconsciousness 
• Anaemia
• Coma

• Alcohol is Measured by units and not glasses 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. Knowing your units will help you stay in control of your drinking.

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

Once you notice that you have a repeated alcohol consumption habit and 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: blackout, dizziness, shakiness, craving, or sweating, aggression, agitation, compulsive and self-destructive behaviour, or lack of restraint, anxiety, euphoria, general discontent, guilt, or loneliness, nausea or vomiting, delirium or fear as well as physical substance dependence, problems with coordination, slurred speech, or tremor.

• What should I then do:

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.

Prepare a short “lecture” of no 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. 

Pain is an Uncomfortable, subjective sensory and emotional experience. It can be Associated with actual or potential tissue damage. Acute pain can be seen as skin, bone, joint, muscle, connective tissue pain. Visceral can be pain in the internal organs, e.g. large intestine and pancreas. Chronic functional and neuropathic pain can be fibromyalgia, IBS, tension-type headache Neuropathic can be nerve damage, postherpetic neuralgia, diabetic neuropathy. Pain intensity can be measured from 0 to 10, from 0 being no pain to 10 being Excruciating pain. Pain can also have a character sharp, dull aching or burning. This can be recognised by tissue damage which has nociceptors which send signals from the tissue to spinal cord to the brain. The brain responds to pain by the motor pathway. Endorphins and enkephalins are released when in pain help regulate and reduce pain. Sensitivity and efficacy of the brain circuit determines how much pain you feel. That’s how people have different perceptions of pain.

Brand, L. 2021. Opioid analgesics and antagonists. SU. 11 [PowerPoint Presentation]. Unpublished Lecture Notes on eFundi, FKLG 312. Potchefstroom, NWU.

Katzung, B.G. 2018. Basic and Clinical Pharmacology. 14^th ed. United States of America: McGraw-Hill Education

• Using your textbooks, draw up a classification of the drugs that are used as antidepressants.
  • Tricyclic antidepressants-

                             Tertiary amine:

• Impramine
• Amitriptyline
• Trimipramine
• Chlorimipramine

                               Secondary amine:

• Nortriptyline

• Desimipramine

• • Monoamine oxidase inhibitors - Phenelzine, Tranylcypromine, Selegiline, Moclobemide

• • Selective Serotonin reuptake inhibitors-Fluoxetine, Sertraline, Citalopram, Paroxetine, Escitalopram

• • Serotonin and noradrenalin reuptake inhibitors- Venlafaxine, Duloxetine, Desvenlafaxine

• • Selective noradrenalin reuptake inhibitors-Reboxetine

• • Tetracyclic and Unicyclic AD’s-Bupropion, Mirtazapine, Amoxapine, Maprotiline

• • Serotonin Receptor Modulator-Trazodone, Nefazodone, Vortioxetine
  • Circadian rhythm regulators- Agomelatine

• What do the existing drugs all have in common regarding their mechanisms of action?
  • They all promote monoamine activity by increasing NA and 5-HT levels at the central synapse (re-uptake inhibition, degradation inhibition or the blockage of the presynaptic α2 receptor)

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

The onset of the drug is very slow and can take up to 6-8 weeks for effects to be seen. In people with depression G-proteins tend to cluster in the patches in brain cell membrane rich in cholesterol called lipid rafts. When stuck on this raft G-proteins lack access to molecules called CAMP which is necessary to work and transmits signals of serotonin.

• How do the TADs and the selective serotonin reuptake inhibitors (SSRI’s) differ in respect of?

• • Efficacy- TAD’s: needs to be titrated to the minimum effective dose

               SSRI’s: can be started on the full dose

• • Side effects-
  • TAD’s: sedation, tremors, insomnia, disturbed vision, dry mouth, urinary retention, confusion, orthostatic hypotension, dysrhythmias convulsions, weight gain and sexual dysfunction. 
  • SSRI’s: Insomnia, tremors, GIT disturbances, headache, ↓ libido, sexual    dysfunction, anxiety (acute), EPS, withdrawal syndrome. ↓ appetite, non-sedating, acute increase in 5-HT synaptic activity initially causes acute anxiety, later 5-HT decreases again

Safety?

-TAD’s: Not safe in overdose but it is commonly the drug used for suicide.

-SSRI’s: safer with regards to overdose.

• What is the action of mirtazapine?

Blocks:

• a2: Increases NA & Increase 5-HT release
• 5-HT2A: antidepressant effect
• 5-HT3: anxiolytic; decrease nausea
• H1 & a1
• Indirect stimulation of 5-HT_1A: anxiolytic

• What is the action of venlafaxine?

Blocks both 5-HT and NA re-uptake; more potent for 5-HT than for NA

• What is the action of agomelatine?

MT1 and MT2 receptor agonist; also 5-HT2C antagonist with antidepressant properties

Brand, L. 2021. Antidepressants. SU. 10 [PowerPoint Presentation]. Unpublished Lecture Notes on eFundi, FKLG 312. Potchefstroom, NWU.

Katzung, B.G. 2018. Basic and Clinical Pharmacology. 14^th ed. United States of America: McGraw-Hill Education

• Discuss the possible mechanisms of action of lithium.

• Mediated by Li+
• Suppresses IP3 & DAG 2^nd messenger systems by decreasing various enzymes important for conversion & re-circulation of membrane phosphoinositide’s

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

narrow therapeutic index of 0.5-1.5mM, anything more than 2mM = toxic

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

Single Drug: prophylaxis of manic and hypomanic episodes and for treatment of acute mania.

Combined: treatment of resistant depression and aggressive behaviour

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

• In combination with a Thiazides, NSAID, ACE inhibitor and fluoxetine it increases lithium levels and leads to toxicity.
• In combination with xanthine’s, can increases renal excretion of lithium and decrease its effect.
• In combination with antipsychotic drugs, it worsens EPS.

• Name the major side effects of lithium.

• Tremor
• Sedation
• Ataxia, aphasia, m weakness, fatigue, choreoathetosis, motor hyperactivity
• Polyuria, polydipsia & nocturia
• Oedema
• Hypothyroidism
• Li-induced diabetes insipidus
• Transient acneiform eruptions
• Leucocytosis
• Folliculitis, Acne, Alopecia
• Sexual dysfunction
• Increase weight
• Renal dysfunction & Dysrhythmias

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

• The use of lithium during lactation is not encouraged. Pregnancy category D

• Name three other important indications for lithium.

• Bipolar disorder
• Schizoaffective disorder
• Major depression

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 patient has increasing levels of Lithium because of the use of the NSAIDS and water pills creating toxic levels of Lithium which could explain the side effects she is facing. Therefore, I would prescribe another drug for her muscle injury such as paracetamol or Mephenesin. Stopping the water pills and a correct monitored diet could help with the weight loss. Lithium could be causing the fatigue thirstiness and other side effects

Brand, L. 2021. Antipsychotic drugs and lithium salts. SU. 9 [PowerPoint Presentation]. Unpublished Lecture Notes on eFundi, FKLG 312. Potchefstroom, NWU.

Katzung, B.G. 2018. Basic and Clinical Pharmacology. 14^th ed. United States of America: McGraw-Hill Education

• 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 sidechain: Chlorpromazine
• Piperidine sidechain: Periciazine
• Piperazine sidechain: Fluphenazine, Perphenazine, Trifluoperazine, Prochlorperazine.

Aliphatic and piperidine compounds:

• •  low potency, little EPS
  •  severe sedation
  •   strong anti-cholinergic effects,
  •   strong α-lytic effects (postural hypotension),
  •    cardiotoxic

 Piperazine derivatives:

• • high potency, more EPS,
  •  weaker anti-cholinergic side effects
  •  weaker α-lytic effects,
  •  less sedation
  •  less cardiovascular (CVS) side effects

• Which receptors in particular are blocked by the typical antipsychotic drugs?
  • D2 Receptors in the mesolimbic pathway

• How does the mechanism of action of the atypical drugs differ from that of the typical drugs?
  • Atypical drugs: block 5-HT_2A receptors more than D₂. 
  • Typical drugs: block DA 2 receptors in the mesolimbic

• Which of the receptors blocked by the older drugs reduce the risk of extrapyramidal side effects?
  • Benzamides such as sulpiride and amisulpride block D₂ and D₃ receptors. The risk of extra pyramidal side effects is reduced due to the limbic localisation of the D₃ receptors.

• Which of the older drugs have a high incidence of extrapyramidal side effects? What is the reason for this?
  • Extrapyramidal side effects are caused by the blockade of D2 receptors in the nigrostriatal pathway which occurs potently by drugs of the piperazines derivatives. Piperazine drugs such as Fluphenazine, perphenazine, trifluoperazine, prochlorperazine

• Because of which receptor(s) blockade do the aliphatic group of drugs have a high incidence of autonomic side effects?
  • Autonomic side effects occur as a result of Muscarinic and α1 blockade effects.

Brand, L. 2021. Antipsychotic drugs and lithium salts. SU. 9 [PowerPoint Presentation]. Unpublished Lecture Notes on eFundi, FKLG 312. Potchefstroom, NWU.

Katzung, B.G. 2018. Basic and Clinical Pharmacology. 14^th ed. United States of America: McGraw-Hill Education

• Which two main groups of drugs are important in the treatment of Parkinsonism?
  • Drugs that increase Dopamine Activity which are L-dopa and dopamine agonists
  • Drugs that decrease Anti-cholinergic Activity, Anti cholinergic drugs

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

It acts as a Metaffinoid potentiator of DA. It increases DA release & synthesis and Block DA reuptake. Its further acts as an adenosine A2 Antagonist as well as an NMDA Antagonist.

• Discuss the mechanisms of action of the antiparkinsonism drugs that indirectly increase dopamine concentration.
  • MAO-B Inhibitors. These drugs work to increase extracellular Dopamine levels in the striatum by suppressing metabolism of dopamine.
  • COMT-Inhibitors. These work to inhibit COMT in the periphery therefore decreasing peripheral metabolism as it inhibits the formation of 3-OMD, in turn increase the concentration of dopamine in the brain.

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

Bromocriptine: ergot derivative

Pramipexole & Ropinirole:  not ergot derivatives

• List the specific dopamine receptors that are stimulated by each agonist.
  • Bromocriptine and Ropinirole: D2 Agonist
  • Pramipexole: D3 Agonist

• Which of these drugs are classified as neuron protecting drugs?  What does this mean?
  • Pramipexole is known as neuroprotective – delay disease progression prevents the degeneration of dopamine neurons due to constant stimulation

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

Allow for Dopamine neurons to be constantly stimulated without allowing for degeneration as they are neuroprotective.

• How do the COMT-inhibitors act in Parkinsonism?

These drugs extend the action of L-dopa by decreasing the peripheral metabolism and increasing the bioavailability of dopamine in the brain and inhibiting the formation of the 3-OMD metabolite.

• How does istradephyline act?

It functions as an adenosine A_2A Antagonist by blocking the adenosine receptor, improve D2 function & also acts as an antiviral

• Discuss the MOA of safinamide

Has a Dual MOA:

Increases DA activity as it is a potent reversible MAO-B inhibitor and inhibits DA reuptake.

Decrease Glutamate release

Brand, L. 2021. Parkinsonism & other movement disorders. SU. 8 [PowerPoint Presentation]. Unpublished Lecture Notes on eFundi, FKLG 312. Potchefstroom, NWU.

Katzung, B.G. 2018. Basic and Clinical Pharmacology. 14^th ed. United States of America: McGraw-Hill Education

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

• Myelinated fibres with unmyelinated fibres

Smaller and myelinated fibers easier blocked than larger and unmyelinated fibers therefore these myelinated fibres are more sensitive to local anaesthetics block.

• Pressure/touch nerves with the dorsal nerves that transmit pain impulses?

Blocking A-type fibres influences proprioception, touch, pressure and motor fibres. However, these fibres are blocked last by local anaesthetics and are therefore not as sensitive to local anaesthetics.

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

Heart: Acts as a class 1 anti-arhythmic drug

Skeletal Muscle: weak blocking action of no clinical application

Cocaine: elevates mood and influences the catecholamine mediated neurotransmission(inhibits NA reuptake)

• What is the basis for the selection of a LA?
  • the type of procedure
  • the type of tissue that the drug must act on
  • the duration of the numbing effect that is required in that tissue.

• Why are LA solutions sometimes saturated with CO₂?

CO₂ acts as a buffer which reduces the pain of the injection and assists in a faster onset of action for the drug by increasing the effective concentration of the non-ionized form.

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

             Benzocaine, Cocaine and Oxybuprocaine

Brand, L. 2021. Local Anaesthetics. SU. 6 [PowerPoint Presentation]. Unpublished Lecture Notes on eFundi, FKLG 312. Potchefstroom, NWU.

Katzung, B.G. 2018. Basic and Clinical Pharmacology. 14^th ed. United States of America: McGraw-Hill Education

• Compile a table, listing the major effects on every system (cardiovascular, CNS, renal, hepatic and uterus) for all the inhalation anaesthetics?

DRUG	EFFECT
Halothane	CNS: Fast smooth muscle induction. Stadium 2 is absent. This includes excitement delirium, loss of consciousness and amnesia uneven breathing. Increased cerebral blood flow can lead to intracranial pressure ANS: Bradycardia CVS: Decreased Blood pressure Sensitized myocardium for arrhythmic effects of catecholamines. Respiratory System:  No Saliva, bronchial secretions, or cough Musculo-Skeletal: Skeletal muscle effects in stage 3. Increases action on non-depolarizing muscle relaxants Decreases action on depolarizing muscle relaxant. Post-operative shaking causes hypoxia, decrease O2 flow to the tissue Uterus: Decrease muscle contraction Liver: Hepatoxicity
Enflurane	CNS: Fast smooth muscle induction. Convulsions may occur don’t use in epileptics CVS: No myocardium sensitization less than Halothane  Respiratory System: More depression than halothane
Isoflurane	CNS: Faster induction and recovery than halothane CVS: Less decrease in blood pressure than Halothane and Enflurane. No sensitization of myocardium. Respiratory System: Potent decrease of the respiratory system. Suppressing effect enhances by skeletal muscle relaxing effects
Desflurane	CNS: Faster induction and recovery phase than Isoflurane. Increase cerebral blood flow which can lead to intracranial pressure CVS: Less depressing than enflurane and halothane Respiratory System: Strong smell causes an irritation in the airways. If used for induction May lead to coughs, laryngospasms and shortness of breath.
Sevoflurane	All effects are same as desflurane except Respiratory System: Less irritating than desflurane
Nitric Oxide	CNS: Weak anaesthetic effects. Potent analgesic effects Respiratory System: May cause hypoxia and needs to be used in combination with oxygen

Name the major acute toxic effects of the inhalation drugs.

• Nephrotoxicity
• Hematotoxicity
• Malignant hyperthermia
• Hepatotoxicity
• Hypoxia

Brand, L. 2021. General anesthesia. SU. 5 [PowerPoint Presentation]. Unpublished Lecture Notes on eFundi, FKLG 312. Potchefstroom, NWU.

Katzung, B.G. 2018. Basic and Clinical Pharmacology. 14^th ed. United States of America: McGraw-Hill Education