• Which different groups of hallucinogenic drugs are known?

LSD and PCP

• Name a few typical effect of the hallucinogenic drugs and discuss the clinical profile of a patient who had taken them.
  • Dizziness.
  • Sleeplessness
  • Euphoria.
  • Dry mouth
  • Paraesthesia.
  • Blurred vision.
  • Sense of well-being and relaxation.
  • Numbness
  • Impulsiveness
  • Increase in body temperature and heart rate

Clinical profile of patient who had taken them:

• Change in behaviour.
• Impaired judgement
• Alertness
• Agitated
• Blood shot eyes

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

A Benzodiazepine is given to reduce the agitation and to protect patient against convulsions. 

Supportive care and rehabilitation

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

Physostigmine (ACE inhibitor)

 

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 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?  Throughout, keep the age of your target group (learners) in mind!

ALCOHOL

PLEASANT EFFECTS

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.

 UNPLEASANT EFFECTS

Depending on individual and their intake of alcohol:

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

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

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 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.

Pain is described as an uncomfortable sensory and emotional experience associated with tissue damage (actual or potential). Pain occurs in an acute(renal colic) and chronic form (cancer pain).

Pain is caused by a specific injury or medical condition while in other instances it may be idiopathic.

Pin thus may originate due to headaches, toothache, sore throat, stomach cramps, muscle cramps, cuts, burns, bruises etc while other forms may originate as a result of illnesses, such as the flu, arthritis, endometriosis, and fibromyalgia. “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).

“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). Certain people have a higher tolerance to pain than others.

The principles of pain management lie on the basis of providing treatment that reduces the pain while minimising the side effects and being able to allow patients to life with a good quality of life. It is also important that maintain acute pain so that it doesn’t progress to a state of 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: 23 June 2021.

Gabbey, A.E.  2021 .Everything You Need To Know About Pain.  https://www.healthline.com/health/pain#treatment  Date of access: 23 June 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: 23 June 2021.

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

TCA’S	MAOI’S	SSRI’S	SNRI’S	NARI’S	Tetracyclic and Unicyclic	5-HT antagonist
Tertiary amine: Impramine Amitriptyline Trimipramine Chlorimipramine Secondary amine Nortriptyline Desimipramine	Phenelzine Isocarboxazid Tranylcypromine Selegiline Moclobemide	Fluoxetine Sertraline Citalopram Paroxetine Escitalopram	Venlafaxine Duloxetine Desvenlafaxine	Reboxetine	Bupropion Mirtazapine Amoxapine Maprotiline	Trazodone Nefazodone Vortioxetine

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

They al 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 even thou the increase in monoamine concentrations can bw seen within hours after administration due to the action that of the anti-depressants that still needs to be altered in the brain.

• 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?

Blockade of α2, 5-HT2A, 5-HT2c and 5-HT3 receptors. It also blocks H1 and α1 and causes the indirect stimulation of 5-HT1A

• What is the action of venlafaxine?

Blockade of 5-HTand NA re-uptake(more potent for 5- HT than for NA).

Moderately selective blockade of SERT and NET

• What is the action of agomelatine?

Antagonist: 5-HT2C

Agonist: Melatonergic R’s – MT1 & MT2 &NA release.

• Discuss the possible mechanisms of action of lithium.

Lithium suppresses IP3 and DAG second messenger systems by decreasing various enzymes important for conversion and re-circulation of phosphoinositides thus leading to an effect on monoamine and cholinergic neurotransmission

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

It has a narrow therapeutic index of 0.5-1.5Mm ,anything >2mM = toxic

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

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

Combination therapy: 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 diuretic, NSAID, ACE inhibitor and fluoxetine it increases lithium levels and leads to toxicity.

In combination with caffeine, it increases renal excretion of lithium

In combination with a typical APs it worsens EPS.

• Name the major side effects of lithium.

GIT disturbance ,increase in QT Intervals ,Tremors, sedation, ataxia, aphasia, muscle weakness, fatigue, polydipsia, polyuria, nocturia, nephrogenic diabetes insipidus, thyroid enlargement, leucocytosis, oedema weight gain, acne, alopecia, sexual dysfunction.

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

Category D drug. The use of lithium during lactation is not encouraged.

• 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.

NSAIDS and the water pills that the patient is taking is increasing levels of lithium making it toxic and can be the reason for her side effects thus it explains the side effects she has been experiencing. Therefore I suggest is a replacement of the medication for the injury with something such as Cyclobenzaprine (antispasmodic) or paracetamol to help relieve the pain. Stopping the water pills and increasing physical activity and following correct eating habits may assist in the weight loss. The other symptoms that she is facing are side effects of using lithium.

• 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.

1. Aliphatic sidechain: Chlorpromazine
2. Piperidine sidechain: Periciazine
3. 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?

Mesolimbic D2 Receptors

• 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 mesolimbic DA 2 receptors.

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

Benzamides block D₂ (selectively) and D₃ receptors. The risk of extra pyramidal side effects is reduced due to the limbic localisation of the D₃ receptors. Furthermore, Aliphatic side-chain typical drugs such as Chlorpromazine compounds have a low potency and few extra pyramidal side effects

• 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.

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

Autonomic side effects occurs as a result of Muscarinic and α1 blockade effects.

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

Drugs that increase Dopamine Activity ( L-dopa and dopamine agonists)

Drugs that decrease Anti-cholinergic Activity (Anti cholinergic)

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

It serves as a mettafinoid Potentiator of Dopamine by increasing its release and synthesis and blocking its reuptake. It 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 work to increase extracellular Dopamine levels in the striatum by suppressing metabolism

COMT-Inhibitors work to inhibit COMT in the periphery thus decreasing peripheral metabolism as it inhibits the formation of 3-OMD.

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

Ergot derivative: Bromocriptine 

Non-ergot derivative: Pramipexole and Ropinirole

• 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?

Drugs such as Rasagiline are seen as neuroprotective as they prevent 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?

These drugs 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 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

It increases the activity of dopamine as it is a potent reversible MAO-B inhibitor an inhibits dopamine re-uptake .It also decreases glutamate release.

• How does the sensitivity for blockade by a LA compare regarding the following types of fibres:
  1. myelinated fibres with unmyelinated fibres

Unmyelinated fibres and smaller myelinated fibres are blocked more efficiently by local anaesthetics than larger myelinated fibres therefore these unmyelinated fibres are more sensitive to local anaesthetics block

1. 2. 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.

CVS: Acts as a class 1 anti-arhythmic drug, slow upstroke of sodium dependant Action potentials and prolongation of QRS duration

Skeletal Muscle: weak blocking action of no clinical application

Cocaine : elevates mood and influences the catecholamine mediated neurotransmission

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

A  Local Anaesthetic is selected based on

• • 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 od 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?

Cocaine ,Benzocaine and Oxybuprocaine

• 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: Increased cerebral blood flow and  intracranial pressure. Fast smooth muscle induction. ANS: Bradycardia CVS: Depress normal cardiac contractility. Decrease BP ad atrial mean pressure. Sensitized myocardium for arrhythmic effects of catecholamines. Respiratory System: Saliva, bronchial secretions, or cough not induced thus Cn be a drug of choice if patient has airway issues Musculo-Skeletal: Skeletal muscle effects in stage 3. Increases action on non-depolarizing muscle relaxants (competitive antagonist) Decreases action on depolarizing muscle relaxant. Post-operative shaking causes hypoxia (decrease O2 flow to the tissue) Uterus: Decrease muscle contraction and was used to assist in labour delivery 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 Pungency effect thus less suitable for induction of anesthesia esp.  in patients with active bronchospasm
Isoflurane	CNS: Faster induction and recovery compared to halothane CVS: Less decrease in blood pressure than Halothane and Enflurane. No sensitization of myocardium. Respiratory System: Suppressing effect enhances by skeletal muscle relaxing effects
Desflurane	CNS: Faster induction and recovery phase than Isoflurane Increase cerebral blood flow and intracranial pressure CVS: Less depressing than enflurane and halothane Respiratory System: Pungent smell causes an irritation in airways when 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: Fast recovery phase 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

• 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? 

Drugs that affect metabolism of the Pill: Perampenel (decreases levonorgestrel-containing contraceptives) and Phenobarbitone, phenytoin , carbamazepine and oxcarbazepine all decrease the effectiveness of the oral contraceptive pill leading to increased pregnancies and the possibility of teratogenic effects in these pregnancies.

Drugs that are safe to use in combination is Valproate, Lamotrigine, Gabapentin, Levetiracetam and Vigabatrin.

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

Yes, oral contraceptives can decrease serum levels of drugs such as Lamotrigine and Valproate.

• How does age affect the kinetics of these drugs (from neonates to old age)?

Neonates have a slower metabolism and should therefore receive lower dosages. Babies and children have a faster metabolism than adults and should receive higher dosages. For geriatric patient’s lower dosages are required due to slower metabolism and decreased renal function.

• In which cases is plasma blood level monitoring indicated?

Where protein binding takes place and in certain diseases that may affect protein binding, these cases are with chronic kidney failure, liver diseases, hypoalbuminemia, burns, pregnancy, malnutrition, age and where displacement drugs are involved. In these instances, plasma blood level monitoring is required.

Brand, L. 2021. Antiepileptic drugs. Study unit 4 [PowerPoint Presentation]. Unpublished lecture notes on eFundi, FKLG312. Potchefstroom: NWU