Tricyclic antidepressants

Secondary amines: Nortriptyline, desimipramine and lofepramine

Tertiary amines: Amitriptyline, imipramine, trimipramine, chlorimipramine, dothiepine and butriptyline.

Monoamine oxidase inhibitors

Irreversible non-selective monoamine oxidase inhibitors: Tranylcypromine

MAO type A-Inhibitors: Moclobemide

MAO type B-Inhibitors: Selegiline(deprenil) and rasagiline

Selective serotonin re-uptake inhibitors(SSRIs)

Flouxetine, paroxetine, fluvoxamine, sertraline, citalopram and escitalopram

           Serotonin-Noradrenalin re-uptake inhibitors(SNRIs)

Venlafaxine and duloxetine 

Selective Noradrenalin re-uptake inhibitors(NARIs)

Reboxetine

Tetracyclic and unicyclic antidepressants

Tetracyclic: Mianserin and mirtazapine

Unicyclic: Bupropion

5-HT₂ modulators

Trazodone and vortioxetine

Circadian Rhythm regulators

Agomelatine

2. Most of them increase the concentration of 5-HT and NE.
3. It takes 3-5 weeks until Antidepressants target our DNA, in particular the genes that code for the serotonin transporter. They make these genes less active, so fewer serotonin transporter molecules are available in the brain and thus it takes longer for the clinical effect to be seen.
4. EFFICACY

TADs are serotonin-noradrenalin re-uptake inhibitors and thus they are less specific and less efficacious as antidepressants.

SSRIs are specific for the serotonin receptors and thus they are more efficacious as antidepressants.

SIDE EFFECTS

TADs

H1 blockade leads to sedation and weight gain. Sympathomimetic effects e.g tachycardia and agitation. Anticholinergic effects such as blurred vision and constipation. Cardiovascular effects such as orthostatic hypotension. Psychosis and mania as well as convulsions.

SSRIs

Insomnia, tremors, GIT disturbances, headache, decreased libido, sexual dysfunction, anxiety(acute) and withdrawal syndrome.

SAFETY

The side effect profile of TADs is very severe and broad and thus TADs are relatively unsafe. SSRIs are relatively safe based on their side effect profile with certain doses and only become unsafe at excessively high doses or when used with drugs like MAOIs.

5. -    Mirtazepine blocks the alpha-2, 5-HT_2A, and the 5-HT₃ receptors. Mirtazepine also blocks the H₁ and the alpha-1 receptors.

• Venlafaxine inhibits NE and 5-HT re-uptake
• Agomelatine is an agonist on the MT1/MT2 receptors and an antagonist on the 5-HT_2C receptors.

1. Lithium inhibits the enzymes that are involved in the recycling of neuronal membrane phosphoinositides. This leads to the depletion of the second messenger source, PIP₃ which then leads to a decrease in the generation of IP₃ and DAG.
2. 0.6-1.4 mEq/L. This therapeutic index is relatively small and requires plasma level monitoring to ensure effective and safe dosing.
3. Lithium is used as monotherapy in the manic phase of bipolar disorder. Lithium and lamotrigine, clonazepam or lorazepam are used for the treatment of bipolar depression in patients who didn’t respond to monotherapy.
4. The use of diuretics(thiazides), NSAIDs, ACEIs and fluoxetine decrease lithium’s renal clearance and thus increasing the lithium levels and causing toxicity.

Theophyllin and caffeine increase lithium excretion.

Typical antipsychotic drugs can worsen EPS when used with lithium.

5. Tremor, choreoathetosis, motor hyperactivity, ataxia, dysarthria, aphasia, sedation, thyroid gland hypofunction, thyroid enlargement, polyuria, polydipsia, nocturia, nephrogenic diabetes insipidus, oedema and weight gain.
6. Renal clearance of lithium increases during pregnancy and decreases back to normal levels after delivery. A patient whose serum lithium concentration is in a good therapeutic range during pregnancy may develop toxic levels after delivery. Lithium is transferred to nursing infants through breast milk, in which it has a concentration of about one third to one half of that serum. Lithium toxicity in newborns is manifested by lethargy, cyanosis, poor suck and moro reflexes, and perhaps hepatomegaly.
7. Recurrent depression, acute major depression and schizoaffective disorder.
8. The concurrent use of Camcolith and Indocid is the cause of the side effects that the patient is experiencing. The Indocid contains indomethacin which is a NSAID. NSAIDs decrease the renal clearance of lithium and thus this causes lithium accumulation and thus toxicity and causes things like weight gain and fatigue.

1. Aliphatic derivatives: Chlorpromazine

Piperidine derivatives: Thioridazine

Piperazine: Fluphenazine

The aliphatic and piperidine derivatives have a low potency, low EPS, high sedation, high anticholinergic and alpha-lytic effects and cardiotoxicity. The piperazine derivatives have a high potency and EPS but have low sedation, low anticholinergic and alpha-lytic effects and low cardiotoxicity.

2. The D2- and 5HT2A-receptors are blocked but they have a higher affinity for the D2-receptors, hence they are blocked to a higher extent that the 5-HT2A receptors.
3. The typical antipsychotics have a higher block the D2-receptors to a higher extent, while the atypical antipsychotics block the 5-HT2A-receptors to a higher extent.
4. The 5-HT2A-receptors.
5. Piperazine derivatives of phenothiazines, thioxanthenes, butyrophenones, pimozide. This is due to the fact that they have a high potency for the D2-receptors.
6. Alpha-1 and muscarinic receptors.  

Chamomile, Kava kava, passionflower, lavender, valerian, Galphimia glauca and cannabidiol have all been shown to have efficacy in anxiety.

Valerian, passionfruit, glycine, lavender and melatonin have shown efficacy in treating insomnia.

1. Pka value: With barbiturates, they are weak acids and have a pka-value of 7.2 and they are eliminated faster due to alkalinisation.

Lipophilicity: Drugs with a high lipophilicity enter the CNS rapidly and this gives them the ability to be used as induction agents in anaesthesia.

2. Redistribution means that something is distributed to another area from the area it was initially distributed to. For example, thiopental’s CNS effects are terminated through rapid distribution to other high perfused areas such as the skeletal muscles, the heart and the kidney.
3. First step is dealkylation, then it is followed by oxidation (phase 1 reaction) through the cytochrome P450 enzymes. The metabolites are subsequently conjugated (phase 2 reactions) to form glucuronides that are excreted in the urine.
4. Chlordiazepoxide, Diazepam, Prazepam, clorazepate and ketazolam. Their active metabolites contribute to the extended duration of action as they are converted into pro-drugs in which they can only show their pharmacological effects when they are in their active form.
5. Oxazepam, lorazepam, temazepam and lormetazepam. These drugs are given in their active form.

 6.  Stimulation of drug-metabolizing capacity; usually manifested in the liver by increased synthesis of smooth endoplasmic reticulum (which contains high concentrations of phase 1 enzymes). These drugs will have marked sedative, hypnotic and anxiolytic effects after the phase 1 reaction

1. The loss of the ability to create new memories or not being able to remember the events that occurred during the action of the drug. Benzodiazepines cause anterograde amnesia.
2. Benzodiazepines decrease the time it takes to fall asleep and increases the total sleep duration (only in patients who normally sleep less than 6 hours per night).
3. Midazolam, diazepam and lorazepam.
4. Clonazepam, lorazepam and diazepam.
5. Carbamates act as cholinesterase inhibitors and thus this leads to the accumulation of ACh which causes skeletal muscle relaxation. Benzodiazepines bind to GABA receptors and potentiate GABA’s effects causing sedation and hypnosis that lead to skeletal muscle relaxation.
6. At normal therapeutic doses, they cause a decrease in the heart rate and cause bronchoconstriction. At high therapeutic doses, they can cause severe cardiovascular and respiratory depression.

1. Dopamine agonists and anticholinergic drugs
2. It increases the synthesis of dopamine, the release of dopamine and prevents dopamine re-uptake.
3. MAO B Inhibitors prevent the metabolism of dopamine by MAO B. Amantadine and istradefyllin are Adenosine A2A antagonist and prevent adenosine from metabolising dopamine. COMT inhibitors prevent COMT from converting levodopa to 3-O-methyldopa.
4. Bromocriptine is a dopamine agonist and pramipexole and ropinirole are not.
5. Bromocriptine and ropinirole are dopamine 2 agonists and pramipexole is a dopamine 3 agonist.
6. Pramipexole and Rasagiline. Pramipexole acts as a scavenger for hydrogen peroxide and Rasagiline prevents MPTP-mediated Parkinson’s.
7. They have neuroprotective effects and they decrease disease progression.
8. COMT inhibitors act by preventing the conversion of levodopa to 3-O-Methyldopa. They decrease fluctuations, improve response and prolong on-times.
9. Istradefyllin acts by antagonizing denosine A2A.
10. Safinamide is a MAO B inhibitor that increases dopamine levels by preventing re-uptake and also decreases glutamate release.

1. Myelinated fibres are blocked more easily than unmyelinated fibres. Activated pain fibres fire rapidly; thus, pain sensations appear to be selectively blocked by local anaesthetics.

2. a. These drugs can be used in the heart as group 1 antiarrhythmic drugs.

2.b Most local anaesthetics also have weak blocking effects on the skeletal muscles but this hasn’t been found to have any use clinical application.

2.c The mood elevation that is caused by cocaine reflects action on dopamine and amine-mediated synaptic transmission in the CNS rather than local anaesthetic effect on the membranes.

3. The type of procedure required, the type of tissue they can be used on and the duration of the effect required.
4. CO2 acts a buffer and this then potentiates the effects of the local anesthetic.
5. Benzocaine, cocaine and oxybupirocaine.

ACUTE SIDE EFFECTS

• Post-operative hepatitis is seen with the use of Halothane.
• Fluoride is released during the metabolism of methoxyflurane, enflurane and sevoflurane and may cause renal insufficiency.
• Prolonged exposure to Nitrous oxide decreases methothianine activity thus leading to megaloblastic anemia.
• Susceptible patients may develop malignant hyperthermia when general anesthetics are used together with neuromuscular blockers, especially Succinylcholine.

• Phenobarbitone, phenytoin and carbamezapine. The contraceptive levels may be reduced by these strong inducers thus leading to the failure of the contraceptive drugs. Non-enzyme inducing drugs or drugs that do not have any interactions and are excreted via the kidney such as gabapentin.
• Yes, they can.
• Neonates have a relatively slow metabolism of anti-epileptic drugs because their metabolic systems are underdeveloped at the time. Babies and children have a faster metabolism than adults. Geriatrics require a low dose because the level of function of their metabolism has deteriorated.
• In drugs that have a narrow therapeutic index, when using the combination of valproate and lamotrigine and when phenytoin undergoes zero-order kinetics