ANWSER
Question 1:
(a) What are the causes of epilepsy?
Answer:
Epilepsy can be caused by genetic factors, brain trauma, infections (e.g., meningitis, encephalitis), developmental disorders (e.g., autism), brain tumors, stroke, or metabolic imbalances. In some cases, the cause remains unknown (idiopathic epilepsy).
(b) How is convulsion different from epilepsy?
Answer:
Convulsion refers to a sudden, involuntary muscle contraction or series of contractions, often due to fever, electrolyte imbalance, or other transient conditions. Epilepsy is a chronic neurological disorder characterized by recurrent, unprovoked seizures due to abnormal brain activity.
(c) Describe status epilepticus.
Answer:
Status epilepticus is a life-threatening condition where seizures last longer than 5 minutes or occur in rapid succession without recovery between episodes. It requires emergency treatment to prevent brain damage or death.
(d) Provide mechanism(s) of action for the following drugs:
i. Phenobarbital: Enhances GABAergic inhibition by binding to GABA-A receptors, increasing chloride influx and hyperpolarizing neurons.
ii. Phenytoin: Blocks voltage-gated sodium channels, stabilizing neuronal membranes and reducing abnormal electrical activity.
iii. Felbamate: Modulates NMDA receptors (blocks) and potentiates GABA-A receptors.
iv. Tiagabine: Inhibits GABA reuptake by blocking GAT-1 transporters, increasing synaptic GABA levels.
v. Vigabatrin: Irreversibly inhibits GABA transaminase, preventing GABA breakdown and increasing its concentration.
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Question 2:
The neuropharmacology of drugs involves modification or mimickery of endogenous neurotransmission. Discuss this statement using specific examples and at least four (4) ways by which drugs can accomplish this.
Answer:
Drugs alter neurotransmission by:
1. Receptor Agonism/Antagonism:
– *Example:* Morphine (ΞΌ-opioid agonist) mimics endogenous endorphins.
2. Enzyme Inhibition:
– *Example:* SSRIs (e.g., fluoxetine) block serotonin reuptake by inhibiting SERT.
3. Modulating Ion Channels:
– *Example:* Phenytoin blocks sodium channels to prevent seizure propagation.
4. Neurotransmitter Release/Storage Interference:
– *Example:* Amphetamines increase dopamine release by reversing DAT transport.
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Question 3:
(a) In a tabular format give clinical differentiations between acute and chronic pains.
Answer:
| Feature | Acute Pain | Chronic Pain |
|——————|————————————-|————————————-|
| Duration | Short-term (<3β6 months) | Persistent (>3β6 months) |
| Cause | Tissue injury (e.g., surgery) | Ongoing disease (e.g., arthritis) |
| Purpose | Protective (signals harm) | Maladaptive (no biological benefit)|
| Treatment | NSAIDs, opioids | Antidepressants, physical therapy |
(b) Write short notes on nociceptive pain.
Answer:
Nociceptive pain arises from tissue damage, activating nociceptors. It is classified as somatic (localized, e.g., cuts) or visceral (diffuse, e.g., organ pain).
(c) What is the role of Bradykinin in pain mediation?
Answer:
Bradykinin binds to B1/B2 receptors, sensitizing nociceptors and promoting inflammation by increasing prostaglandin release (via COX activation).
(d) Morphine is a potent analgesic agent but its widespread use is limited by abuse. Briefly discuss this statement.
Answer:
Morphineβs high efficacy in pain relief is overshadowed by risks of dependence, tolerance, and addiction due to ΞΌ-opioid receptor activation in reward pathways.
(e) Aspirin use has been linked to gastropathy, explain gastropathy as related to side-effect of Aspirin.
Answer:
Aspirin inhibits COX-1, reducing protective prostaglandins (e.g., PGI2) in the gastric mucosa, leading to erosion, ulcers, and bleeding (gastropathy).
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Question 4:
(a) Discuss fully the monoamine theory of depression and enumerate some of its shortcomings.
Answer:
The theory posits that depression results from deficits in serotonin (5-HT), norepinephrine (NE), or dopamine. *Shortcomings:*
– Not all patients respond to monoamine-targeting drugs.
– Delayed onset of antidepressants contradicts acute monoamine changes.
– Ignores neuroplasticity (e.g., BDNF) and glutamatergic involvement.
(b) Describe the tricyclic antidepressants (TCAs) under:
(i) Mechanism(s) of action with a simple annotated sketch:
TCAs block SERT and NET, increasing synaptic 5-HT and NE. *Sketch:* [Reuptake inhibition diagram].
(ii) Common adverse effects:
Anticholinergic effects (dry mouth), sedation, cardiotoxicity (QT prolongation).
(iii) Two (2) examples with their corresponding structures:
– *Amitriptyline:* Tertiary amine TCA.
– *Nortriptyline:* Secondary amine metabolite.
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Question 6:
Discuss selective serotonin reuptake inhibitors (SSRIs) under the following:
i. Mechanism(s) of action with annotated sketch:
SSRIs (e.g., fluoxetine) block SERT, increasing 5-HT in the synapse. *Sketch:* [SERT blockade diagram].
ii. Major advantages compared to the TCAs and the MAOIs:
– Fewer anticholinergic/cardiac side effects than TCAs.
– No dietary restrictions (unlike MAOIs).
– Better safety profile in overdose.
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Question 5:
i. List the main five possible reasons why benzodiazepines were used to replace barbiturates:
1. Safer overdose profile (less respiratory depression).
2. Lower abuse potential.
3. Fewer drug interactions (e.g., minimal enzyme induction).
4. More selective GABA-A modulation (Ξ±-subunit specificity).
5. Better tolerability (milder sedation).
ii. Discuss the clinical uses of Barbiturates:
– Anesthesia (thiopental), epilepsy (phenobarbital), euthanasia (rare).
iii. Briefly discuss the mechanism of action of Ramelteon and eszopiclone:
– *Ramelteon:* Melatonin receptor agonist (MT1/MT2) regulating sleep-wake cycles.
– *Eszopiclone:* GABA-A receptor modulator (non-benzodiazepine).
iv. List the four major adverse effects of lithium carbonate as mood-stabilizing drug:
1. Tremors.
2. Nephrogenic diabetes insipidus.
3. Hypothyroidism.
4. Teratogenicity (pregnancy).