1. Mechanism of action of lithium: Lithium influences the IP3 and DAG 2^nd messenger systems by decreasing the various enzymes which are very important for conversion and re-circulation of membrane phosphoinositides.
2. The therapeutic index of lithium is 0,5-1.5mM which is very small and therefore the dosing of lithium should be done very carefully, and blood levels must be monitored to prevent lithium toxicity.
3. Lithium as monotherapy is used for prophylaxis of manic and hypomanic episodes and treatment of an acute manic episode. Lithium is used in combination with antidepressants for the treatment of resistant or recurrent unipolar depression and self-mutilating or aggressive behavior.
4. The renal clearance may be decreased by thiazide diuretics, new NSAIDs, ACE inhibitors, and fluoxetine. Renal clearance of lithium is increased by theophylline and caffeine. Lithium is neurotoxic in combination with carbamazepine, calcium-blockers, losartan, methyldopa, metronidazole, and phenytoin.
5. Tremors, sedation, ataxia, aphasia, muscle weakness, fatigue, polydipsia, polyuria, nocturia, nephrogenic diabetes insipidus, thyroid enlargement, leucocytosis, edema, weight gain, acne, alopecia, and sexual dysfunction.
6.  Lithium has been associated with an increased incidence of congenital cardiovascular abnormalities, but the incidence is very low, keep the risk-benefit in mind. Lithium is excreted into the breastmilk in high concentrations and thus breastfeeding is not suggested.
7.  Lithium as monotherapy is used for prophylaxis of manic and hypomanic episodes and treatment of an acute manic episode.
8. The NSAID is causes decreased clearance of the lithium and therefore can cause an increase in the patient’s weight and other side effects of lithium. I would rather recommend Tylenol, acetaminophen, for pain. It does not have any drug interactions with lithium.

1. The three phenothiazine sub-families are Aliphatic derivatives, Piperidine derivatives, and Piperazine derivatives. The aliphatic and piperidine derivatives have low potency and cause severe sedation, anticholinergic effects, postural hypotension, and they are cardiotoxic. The Piperazine derivatives have high potency, but it causes a weaker anticholinergic effect and less sedation, less cardiovascular effects, and does not cause postural hypotension.
2. Antipsychotics block D2- receptors as well as H1-receptors, cholinergic receptors, and alpha1-receptors. (> alpha 1 receptors)
3. Atypical drugs block serotonin 2A-receptors. Typical drugs block mesolimbic D2-receptors.
4. Typical drugs block the D3-receptors and this causes the risk of extrapyramidal effects to reduce.
5. The phenothiazines, particularly the piperazine derivatives, have a higher incidence of causing extrapyramidal side effects.
6. The blockage of cholinergic neurons by the aliphatic derivatives causes autonomic side effects.

1. Dopamine agonists and MOA-B inhibitors.
2. Amantadine is a NMDA-antagonist that has anti-dyskinetic effects.
3. MOA-B inhibitors inhibits the MOA-B enzyme that metabolizes DA this increases the dopamine stores in neurons and inhibits the uptake of dopamine in the neurons.
4. Ergot derivative: bromocriptine. Non-ergot derivatives: ropinirole, pramipexole and apomorphine.
5. Pramipexole: direct agonist at D3 receptors. Ropinirole: agonist on D2 receptors. Bromocriptine: partial agonist on D2 receptors. Apomorphine: Activates D2-receptors and to a lesser extent D1-receptors.
6. Rasagiline and selegiline are neuroprotective drugs.
7. MOA-B inhibitors inhibit the MOA-B enzyme that metabolizes DA, increasing the dopamine stores in neurons and inhibits the uptake of dopamine in the neurons.
8. COMT-inhibitors inhibit the COMT-enzyme that converts L-dopa to 3-O-methyl dopa. 3-O-methyl dopa produces a weak therapeutic response with L-dopa because it competes with L-dopa for the active transport process. Thus, COMT-inhibitors will decrease the metabolism of L-dopa and increases its duration of action.
9. Istradefyllin is an Adenosine A2a-antagonist. The antagonist interferes with GABA releasing and controls ACh and DA release and will also facilitate DA receptor signaling.
10. Safinamide is used to increase DA activity as it is a potent antagonist of MAO-B. It also inhibits DA uptake in the neurons and decreases glutamate release. It is reversible.

1. Myelinated and unmyelinated fibres:
   1. Unmyelinated fibres and smaller myelinated fibres are blocked more efficiently by local anaesthetics than larger myelinated fibres. Thus, unmyelinated fibres are more sensitive to the effects of local anaesthetics.
   2. when a-type fibres are blocked, proprioception, touch, pressure, and motor fibres are influenced. These are the final type of fibres to be blocked by local anaesthetics, these fibres are therefore not that sensitive to local anaesthetics.
2. Local anaesthetics affect the cardiovascular tissue by causing cardiac depression. It also affects the central nervous system by producing light-headedness, visual and auditory disturbances.
3. A local anaesthetic is chosen for the type of procedure that is being done, the type of tissue that the local anaesthetic must be used on and the duration of the numbing effect that is needed.
4. Carbon dioxide acts as a buffer to the local anaesthetic. This reduces the pain of the injection and gives a faster onset of action. It also raises the effective concentration of the nonionized form of the local anaesthetic, this is beneficial as only the nonionized form can cross the plasma membrane to have an effect. Thus, the onset time of the regional block will be shortened.

Local anaesthetics used for surface anaesthesia include: oxybuprocaine, benzocaine and cocaine

Major acute toxicities of inhalation anesthetics : 

• nephrotoxicity 
• hematotoxicity 
• malignant hyperthermia 
• hepatoxicity 
• nausea and vomiting

• phenobarbitone, phenytoin, carbamazepine, oxcarbazepine, topiramate. 
  • The patient can fall pregnant, or the patient's hormone levels will not be regulated, the contraceptive might not reach the therapeutic effective levels to prevent ovulation.
  • Drugs that are safe to use with oral contraceptives: Valproate, Lamotrigine, Gabapentin, Levetiracetam, Vigabatrin. 
•  Yes, oral contraceptives can decrease serum levels of anti-epileptic drugs. 
• In neonates, the metabolism of these drugs is slower than in adults. In babies and children, the drugs are faster metabolized than in adults. The metabolism in geriatrics patients is slower than in an adult because their liver and renal functions are not optimal.
• It is indicated so the patient's tolerance for the drugs can be monitored. The test helps to identify possible allergies, interactions, infections, and other abnormalities. This may affect the choice in medicine. The test is also used to monitor the liver and renal functions, to monitor the medicine metabolism. 

1. Alcohol tolerance may result from ethanol-induced up-regulation in response to the continued consumption of alcohol. Alcohol dependence may result from overactivity of the same pathway after the ethanol effect starts vanishing and  before the system has time to return to a normal state.  GABA is believed to play an important role in tolerance. 
2. It can cause metabolic consequences because of the ethanol oxidation in the liver, liver injury that is caused by the toxicity of the metabolic byproducts of alcohol as well as inflammation caused by these products.  Chronic alcohol consumption can also cause dysregulation of fatty acid oxidation and synthesis, and activation of the innate immune system. 
3. Wernicke-Korsakoff-syndrome is caused by a thiamine deficiency and is characterized by the paralysis of external eye muscles, ataxia, and a confused state that can lead to a coma and/or death. This is rarely seen in the absence of alcoholism. It is treated with parenteral thiamine. 
4. Fetal alcohol syndrome is caused by chronic maternal alcohol abuse during pregnancy. It is associated with teratogenic effects which include mental retardation and congenital malformations. Alcohol rapidly crosses the placenta and causes the fetal blood to reach the same concentration as that of the mother. This triggers apoptotic neurodegeneration which causes neuronal and glial migration in the developing nervous system. 
5. In acute alcohol consumptions, the most important enzymes are mostly alcohol dehydrogenase and MEOS that mostly work when concentrations are too high. In chronic alcohol consumption, the MEOS are the predominant active enzymes and their activity is induced by chronic alcohol consumption and which increases alcohol metabolism.
6. Aspirin, Paracetamol, Vasodilators, Hypoglycemic drugs

1. Alcohol metabolism follows zero-order kinetics. The body will only be able to metabolize alcohol until all NAD enzymes are saturated and then the feeling of intoxication starts. 
2. Alcohol is metabolized via two pathways. 

• Alcohol dehydrogenase 
• MEOS, these enzymes convert alcohol to acetaldehyde, which is then converted to acetate through the aldehyde dehydrogenase enzyme.

3.  Drugs that influence the metabolism of acetaldehyde to acetate include disulfiram, cephalosporins, and hypoglycemics.  They inhibit aldehyde dehydrogenase and this means acetaldehyde cannot be converted to acetate.  This excessive acetaldehyde in the body causes nausea, headache, hot flushes, and fever. 

• What does anterograde amnesia mean and which drugs can cause this effect? 
  • Patients struggle to remember things that happened during the drug's duration of action. These drugs include Adco-alzam, Ativan, Azor, Brazepam, Bromaze, Demetrin,Lexotan
• Name the effects of the sedative-hypnotic drugs on the normal sleep pattern and explain their significance to the patient. 
  • Barbiturates cause sedation because of increased suppression of NS. 
  • Benzodiazepines help patients to fall asleep faster, which lengthens the time that a patient can sleep. BDs in high dosages decrease REM sleep. These drugs are significant to the patient as it helps with sleeplessness and insomnia. They help a patient sleep longer. 
• Which of the sedative-hypnotic drugs are used as a supplementary therapy in anesthesia? Can you explain why? 
  • Barbiturates
  • Diazepam
  • Lorazepam
• Which of the sedative-hypnotic drugs are used as anticonvulsants? 
  • Clonazepam
  • Lorazepam
  • Clobazam 
  • Diazepam 
• What is the mechanism of the muscle-relaxing effects of some of the carbamates and the BDs?
  •  The mechanism of action of the carbamates and the BDs is they inhibit multiple synaptic reflexes. They have Metacoid mechanisms. Barbiturates extend the period of chloride channel opening. Benzodiazepines increase the frequency of chloride channel opening. 
• Discuss the effects of the sedative-hypnotic drugs on the respiratory and cardiovascular systems.
  • Sedative-hypnotic drugs decrease the cardiovascular and respiratory systems. They ,therefore, decrease respiratory and cardiovascular disease

1. Voltage-gated ion channels and ligand-gated ion channels 

2. Voltage-gated: 

• responds to changes in membrane potential 
• they are in a high concentration on the axons of nerve cells
• they open sodium, potassium, and calcium channels  

Ligand-gated: 

• responds to neurotransmitters
• they are found on presynaptic and postsynaptic cell bodies 
• they can either function as ionotropic or metabotropic 

3. Ionotropic receptors opens ion channels by working directly on them, whereas metabotropic receptors use signal transduction mechanisms when there is metabolic change with the help of 2nd messengers. 

4. Ionotropic receptors include GABA-A, Nicotinic, EAA, and 5-HT3. Metabotropic receptors work with transduction systems that rely on the formation of 2nd messengers. Adenylyl cyclase systems and Phospholipase C systems are transduction systems. 

Adenylate cyclase receptors include negative( D2, α2,5-HT1 A+B , M2 ) and positive( ß1 + 2, D1) receptors, which convert ATP to cAMP. cAMP activates various protein kinase enzymes. 

Phospholipase C receptors are positive and include α1, 5-HT2 M1, H1 receptors. This system converts PIP2 to IP3 and/or DAG. IP3 and DAG function as second messengers.  

5. EPSP: Excitatory postsynaptic potentials that are generated by the opening of Sodium or Calcium channels. Exp: Nicotinic, EEA, and 5-HT3 receptors 

IPSP: Inhibitory postsynaptic potentials that are generated by the opening of potassium or chloride channels. Exp: GABA-A 

6. An influx of calcium into the presynaptic membrane causes NT release from the synaptic vesicles into the synaptic cleft. The NT can then diffuse and bind to the postsynaptic membrane, this will produce an effect. Calcium is essential for  NT release and ultimately for the effect.