CNS Unlocked

‫صيــادلـــــــــــــــــــــــه بتخدمــــــــــــــك د‪ /‬شريـــف مدكــور ‪ .‬د‪ /‬حســـــام زيدان ‪ ..
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‫‪CNS‬‬
‫صيادلـــــــــــــــــــــــــة بتخدمـــــــــــــــــك‬
01015694262 ‫ أحــمد فـــــــــرج‬/‫ د‬.. ‫ حســـــام زيدان‬/‫ د‬. ‫ شريــــف مدكــور‬/‫صيــادلـــــــــــــــــــــــه بتخدمــــــــــــــك د‬
Drugs Affecting the Central Nervous System

➢ Introduction
Most drugs that affect the central nervous system (CNS) act by altering some step in the neurotransmission process.
Drugs affecting the CNS may act presynaptic ally by influencing the production, storage, release, or termination of action of
neurotransmitters.
Other agents may activate or block postsynaptic receptors.
The basic Functioning of Neurons in the CNS is

transmission of information in both the CNS and in the periphery involves the release of neurotransmitters that diffuse
across the synaptic cleft to bind to specific receptors on the postsynaptic neuron. the recognition of the neurotransmitter by
the membrane receptor of the postsynaptic neuron triggers intracellular changes.
In the CNS, receptors in most synapses are coupled to ion channels. Binding of the neurotransmitter to the postsynaptic
membrane receptors results in a rapid but transient opening of ion channels.
Open channels allow specific ions inside and outside the cell membrane to flow down their concentration gradients. The
resulting change in the ionic composition across the membrane of the neuron alters the postsynaptic potential, producing
either depolarization or hyperpolarization of the postsynaptic membrane, depending on the specific ions and the direction of
their movement.
Drugs for Neurodegenerative Diseases

Neurodegenerative disorders that respond to drug therapy: Parkinson Disease, Alzheimer Disease, Multiple sclerosis
Parkinson Disease
Parkinsonism is a progressive neurological disorder of muscle movement, characterized by tremors, muscular rigidity,
bradykinesia, and postural and gait abnormalities.
The disease is correlated with destruction of dopaminergic neurons in the substantia nigra with a consequent reduction of
dopamine actions.
Many of the symptoms of Parkinsonism reflect an imbalance between the Excitatory cholinergic neurons and the Greatly diminished number of
inhibitory dopaminergic neurons.
Therapy is aimed at restoring dopamine in the basal ganglia and antagonizing the excitatory effect of cholinergic neurons,
thus reestablishing the correct dopamine/acetylcholine balance.
Anti-Parkinson drugs:
1) Levodopa and carbidopa
Levodopa is a metabolic precursor of dopamine, Dopamine does not cross the blood brain barrier, but its immediate precursor, levodopa, is actively
transported into the CNS and converted to dopamine.
Carbidopa
a dopamine decarboxylase inhibitor, diminishes the metabolism of levodopa in the periphery, thereby increasing the availability of levodopa to the
CNS. The addition of carbidopa lowers the dose of levodopa needed by four- to five-fold and, consequently, decreases the severity of adverse
effects arising from peripherally formed dopamine.
Ingestion of meals, particularly if high in protein, interferes with the transport of levodopa into the CNS. Thus, levodopa should be taken on an empty
stomach, typically 30 minutes before a meal.
Adverse effects include:

Anorexia, nausea, and vomiting occur because of stimulation of the chemoreceptor trigger zone.
Tachycardia as a result of dopaminergic action on the heart, Hypotension may also develop.
Domperidone is used as an anti-emetic drug for vomiting coursed by anti-Parkinson drug.
Metoclopramide not used, it can worse the extrapyramidal side effects.
Interactions:
o The vitamin pyridoxine (B6 ) increases the peripheral breakdown of levodopa and diminishes its effectiveness.
o Concomitant administration of levodopa and nonselective monoamine oxidase inhibitors (MAOIs), such as phenelzine, can produce a hypertensive
crisis caused by enhanced catecholamine production.
2) Selective MAO-B inhibitors
Selegiline and Rasagiline, selective MAO-B inhibitors used in tablets dosage form in ttt of Parkinson (transdermal patch for depression).
MAO type B, the enzyme that metabolizes dopamine.
3)Catechol-O-methyltransferase inhibitors
Normally, the methylation of levodopa by catechol-O-methyltransferase (COMT) to 3-O-methyldopa is a minor pathway for levodopa metabolism.
However, when peripheral dopamine decarboxylase activity is inhibited by carbidopa, a significant concentration of 3-O-methyldopa is formed that
competes with levodopa for active transport into the CNS. Entacapone and tolcapone (Hepatotoxic) selectively and reversibly inhibit COMT.
Inhibition of COMT by these agents leads to decreased plasma concentrations of 3-O-methyldopa, increased central uptake of levodopa, and greater
concentrations of brain dopamine.
4)Dopamine receptor agonists

This group of antiparkinsonian compounds includes Bromocriptine, Ropinirole, Pramipexole, Rotigotine and Apomorphine. However, these drugs are
ineffective in patients who have not responded to levodopa.
Apomorphine is an injectable dopamine agonist that is used in severe and advanced stages of the disease to supplement oral medications.
Adverse effects severely limit the utility of the dopamine agonists.
The side effects include: Hallucinations, Confusion, Delirium, nausea, and Orthostatic hypotension are more common
5)Amantadine
It was accidentally discovered that the antiviral drug amantadine has an antiparkinsonian action.
Amantadine has several effects on a number of neurotransmitters implicated in parkinsonism, including increasing the release of dopamine, blocking
cholinergic receptors, and inhibiting the N-methyl-D-aspartate (NMDA) type of glutamate receptors.
Amantadine cause type of pigmentation “ Livedo reticularis pigmentation “
Mechanism of action of Amantadine as an antiviral drug: interfere with viral protein function and inhibit uncoating of the virus particles.
6)Antimuscarinic agents
The actions of Benztropine and Trihexyphenidyl are similar. they work by correct the imbalance in the dopamine/acetylcholine activity.
These agents can induce mood changes, confusion and mydriasis.

Alzheimer Disease
A disease characterized by loss of cortical neurons, particularly cholinergic neurons. Current therapies aim to either improve cholinergic
transmission within the CNS or prevent excitotoxic actions resulting from overstimulation of NMDA-glutamate receptors in selected areas of the
brain.
1) Acetylcholinesterase inhibitors
It is postulated that inhibition of acetylcholinesterase (AChE) within the CNS improves cholinergic transmission, at least at those neurons that are still
functioning.
The reversible AChE inhibitors approved for the treatment of Alzheimer disease include Donepezil, Galantamine and
Rivastigmine.
Rivastigmine is the only agent approved for the management of Dementia associated with Parkinson disease.
Common adverse effects include nausea, diarrhea, vomiting, and anorexia, tremors, bradycardia, and muscle cramps.
2) NMDA Receptor Antagonist

Stimulation of glutamate receptors in the CNS appears to be critical for the formation of certain memories. However, overstimulation of glutamate
receptors, particularly of the NMDA type, may result in excitotoxic effects on neurons and is suggested as a mechanism for neurodegenerative or
apoptotic (programmed cell death) processes.
Binding of glutamate to the NMDA receptor assists in the opening of an ion channel that allows Ca 2+ to enter the neuron. Excess intracellular Ca 2+
can activate a number of processes that ultimately damage neurons and lead to apoptosis.
Memantine is an NMDA receptor antagonist. It acts by blocking the NMDA receptor and limiting Ca 2+ influx into the neuron, such that toxic
intracellular levels are not achieved. memantine is often given in combination with an AChE inhibitor.
➢ For all stages of Alzheimer disease:

DOC: Donepezil
➢ For moderate to Sever Alzheimer disease:
DOC: Memantine +/- Donepezil
Herbal used for Alzheimer: Ginko biloba

Benzodiazepine used in Alzheimer: (DACL) Diazepam, Alprazolam, Clonazepam and Lorazepam
Multiple Sclerosis
MS is an autoimmune inflammatory demyelinating disease of the CNS.
Corticosteroids (for example, dexamethasone and prednisone) have been used to treat acute exacerbations of the disease.
Chemotherapeutic agents, such as cyclophosphamide and azathioprine, have also been used.
Fingolimod is the 1st line oral drug used in MS. it alters lymphocyte migration, resulting in fewer lymphocytes in the CNS.
Must be discontinued 2 months before getting pregnant and during pregnancy.
Anxiolytic and Hypnotic Drugs

Anxiety: a fear that arises from either a known or an unknown source
Because many antianxiety drugs also cause some sedation, they may be used clinically as both anxiolytic and hypnotic
(sleep-inducing) agents.
Anixiolytic ,Hypnotics
1-Buspirone
The actions of buspirone appear to be mediated by serotonin (5-HT1A) receptors.
Buspirone considered as 2nd
Line after SSRIs
2-Barbiturates
They have been largely replaced by the benzodiazepines, primarily because barbiturates induce tolerance and physical
dependence.
Mechanism of action: The sedative–hypnotic action of the barbiturates is due to their interaction with GABAA receptors, which
enhances GABA transmission. Barbiturates potentiate GABA action on chloride entry into the neuron by prolonging the duration
of the chloride channel openings. In addition, barbiturates can block excitatory glutamate receptors. These molecular actions lead
to decreased neuronal activity.
Therapeutic uses of barbiturates: Anesthesia, Anticonvulsant and Sedative/hypnotic.
3-Benzodiazepines
Benzodiazepines are widely used anxiolytic drugs. They have largely replaced barbiturates in the treatment of anxiety and
insomnia, because benzodiazepines are generally considered to be safer and more effective.
BZDs include Alprazolam, Oxazepam, Diazepam, Lorazepam, Clonazepam and Halazepam
Mechanism of action: Benzodiazepines modulate GABA effects by binding to a specific, high-affinity site.
Therapeutic uses of Benzodiazepine Muscle relaxant, Anticonvulsant, Reduction of anxiety and Sedative/hypnotic.
Benzodiazepine Antidote : Flumazenil.
4-Zolpidem
The hypnotic zolpidem binds to and potentiate GABAA receptors. It has a rapid onset of action and short elimination half-life
(about 2 to 3 hours). The drug provides a hypnotic effect for approximately 5 hours.
5-Eszopiclone.
Effective for insomnia for up to 6 months. Eszopiclone is rapidly absorbed. Half-life is approximately 6 hours.
Adverse events with eszopiclone include: anxiety, dry mouth, headache, peripheral edema, and unpleasant taste.
6-Melatonin receptor agonists
Melatonin is a hormone secreted by the pineal gland that helps to maintain the normal sleep–wake cycle
Ramelteon is selective agonist for melatonin receptors
Should be considered as a first line agents.
SSRIs (such as Escitalopram or Paroxetine) or Serotonin/Norepinephrine reuptake inhibitors (such as venlafaxine or duloxetine)
may be used.
Study Questions
1) Which one of the following statements is correct regarding benzodiazepines?
A. Benzodiazepines directly open chloride channels.
B. Benzodiazepines show analgesic actions.
C. Clinical improvement of anxiety requires 2 to 4 weeks of treatment with benzodiazepines.
D. All benzodiazepines have some sedative effects.
Correct answer = D. Although all benzodiazepines can cause sedation, the drugs labeled “benzodiazepines”. Benzodiazepines enhance the binding of GABAA to its
receptor, which increases the permeability of chloride.
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2) A 68-year-old female patient is demonstrating signs and symptoms of insomnia, especially difficulty falling asleep. She is afraid of taking a medication that can
negatively affect her memory and concentration, as she is still working as a bookkeeper. She has been taking temazepam for the past 4 days and has noticed a
memory problem and would like to discontinue this medication. Which medication is most appropriate to treat the insomnia and minimize the risk for cognitive
impairment?
A-Diphenhydramine
B. Zolpidem
C. Alprazolam
D. Ramelteon
Correct answer = D. All of these agents, except ramelteon, have been associated with cognitive impairments, including memory impairment. Diphenhydramine likely
causes its cognitive problems from its anticholinergic and antihistaminergic effects. Zolpidem and alprazolam are well-known causes of cognitive impairment.
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3) An 18-year-old woman is admitted to the emergency room after an accidental overdose of alprazolam. She is unconscious and not considered a regular user of any
medications or illicit drugs. Which treatment could be used to reverse the effect of the alprazolam overdose?
A-Diazepam
B. Ramelteon
C. Flumazenil
D. Naloxone
Correct answer = C. Flumazenil is only indicated to reverse the effects of benzodiazepines via antagonism of the benzodiazepine receptor.
Antidepressants
The symptoms of depression are feelings of sadness and hopelessness, as well as the inability to experience pleasure in usual activities, changes in
sleep patterns and appetite, loss of energy, and suicidal thoughts.
Most antidepressant drugs potentiate, either directly or indirectly, the actions of norepinephrine and/or serotonin (5-HT) in the brain.
Conversely, the theory proposes that mania is caused by an overproduction of these neurotransmitters.
1-Tricyclic Antidepressants
The TCAs inhibit norepinephrine and serotonin reuptake into the presynaptic neuron .
The TCAs include the tertiary amines: imipramine, amitriptyline, clomipramine and trimipramine.
Imipramine is used as an alternative to desmopressin in the treatment of bed-wetting in children.
CLOMIPRAMINE IS MORE USED FOR OBSESSIVE- COMPULSIVE DISORDER.
Secondary amines Includes: Desipramine, Nortriptyline and Protriptyline, They Are relatively selective inhibitors of Norepinephrine reuptake.
Adverse effects:
- Blockade of muscarinic receptors leads to blurred vision, urinary retention, constipation, and aggravation of angle-closure glaucoma.
- These agents affect cardiac conduction similar to quinidine and may precipitate life-threatening arrhythmias in an overdose situation.
-The TCAs also block α-adrenergic receptors, causing orthostatic hypotension, dizziness, and reflex tachycardia.
-Sedation is related to the ability of these drugs to block histamine H1 receptors.

2-Monoamine Oxidase Inhibitors

Monoamine oxidase (MAO) is a mitochondrial enzyme found in nerve and other tissues. In the neuron, MAO functions as a
“safety valve” to oxidatively deaminate and inactivate any excess neurotransmitters (for example, norepinephrine, dopamine,
and serotonin) that may leak out of synaptic vesicles when the neuron is at rest.
-Most MAOIs, such as phenelzine (non selective MAO inhibitor) form stable complexes with the enzyme, causing irreversible
inactivation. This results in increased stores of norepinephrine, serotonin, and dopamine within the neuron and subsequent
diffusion of excess neurotransmitter into the synaptic space.
-Selective MAO-B inhibitor such as Rasgiline and Selegiline causing reversible inactivation of MAO. selective MAO-B inhibitors
used in tablets dosage form in ttt of Parkinson (transdermal patch for depression).
(MAO type B, the enzyme that metabolizes dopamine).
These drugs inhibit not only MAO in the brain but also MAO in the liver and gut that catalyzes oxidative deamination of drugs and
potentially toxic substances, such as tyramine, which is found in certain foods. Because tyramine displaces norepinephrine from
storage vesicls, SO TYRAMINE PRODUCT SHOULD BE DISCONTINUED WHEN TAKEN MAOIs.
Drug Switching:
From any antidepressent to MAOIs: 2 weeks washout period.

From any antidepressant to Fluoxetine: 4-5 weeks washout period.
3-Selective Serotonin Reuptake Inhibitors

Citalopram, Escitalopram, Fluoxetine, Paroxetine and Sertraline.
Because they are relatively safe in overdose, the SSRIs have largely replaced TCAs and monoamine oxidase inhibitors (MAOIs) as the
drugs of choice in treating depression.
SSRIs typically take at least 2 weeks to produce significant improvement in mood, and maximum benefit may require up to 12 weeks
or more.
Therapeutic uses: Obsessive–Compulsive Disorder, Panic Disorder, Anxiety Disorder and bulimia nervosa (only fluoxetine is approved
for bulimia).
All SSRIs are safe in epileptic patient
The DOC for pregnant and breastfeeding woman is Sertraline
Contraindication of SSRIs: SSRIs have the potential to cause serotonin syndrome, especially when used in the presence of MAOIs.
Linezolid ( MAOIs drug) if used with SSRIs Serotonin syndrome may occur.
Serotonin syndrome characterized by:

Hyperthermia, muscle rigidity, sweating, myoclonus (clonic muscle twitching), and changes in mental status and vital signs.
The most famous side effect can occur with SSRIs is: sexual dysfunction, which can be overcomed by Atypical antidepressant (like
mirtazapine and Bupropion).
4-Serotonin-Norepinephrine Reuptake Inhibitors
Venlafaxine and Duloxetine inhibits the reuptake of both serotonin and norepinephrine and thus are termed SNRIs.
SNRIs have the potential to cause serotonin syndrome, like SSRIs, also sexual dysfunction can occur.
Duloxetine
used for neuropathic pain caused by diabetes, and it is metabolized mainly in the liver to inactive metabolites and should be
avoided in patients with liver dysfunction.
5-Atypical Antidepressants
The atypical antidepressants are a mixed group of agents that have actions at several different sites. This group includes
bupropion, mirtazapine and trazodone.
Bupropion
Bupropion is also useful for decreasing cravings and attenuating withdrawal symptoms of nicotine in patients trying to quit
smoking.
DOC for obese depressed patients
Side effects of Bupropion may include: Dry mouth, Sweating, Nervousness, Tremor, and a Dose-dependent increased risk for
seizures, so
Use of bupropion should be avoided in patients at risk for seizures.
It has a very low incidence of sexual dysfunction, and used in sexual dysfuntion developed after SSRIs.
Mirtazapine
It is sedating because of its potent antihistaminic activity, it does not interfere with sexual function like the SSRIs.
sedation, increased appetite, and weight gain frequently occur, so it is used for thin depressed patients.
Treatment of Mania and Bipolar Disorder

1) Lithium
Drug of choice for acute mania and Bipolar disorder
Lithium is effective in treating 60% to 80% of patients exhibiting mania, the mode of action is unknown.
The therapeutic index of lithium is extremely low, and lithium can be toxic.
Common adverse effects may include :
headache, dry mouth, polydipsia, polyuria, polyphagia, GI distress, fine hand tremor, dizziness, fatigue, dermatologic reactions, sedation
and hypothrodism.
Adverse effects due to higher plasma levels may indicate toxicity and include:
ataxia, slurred speech, tremors, confusion, and convulsions.
Thyroid function may be decreased and should be monitored.
Lithum should be taken with food to decrease nausea, and remember to be hydrate.
Lithium is renally eliminated, and though caution should be used when dosing this drug in renally impaired patients, it may be the best
choice in patients with hepatic impairment.
Toxicity of lithium: caused by hyponatremia.

Because lithium cause decreasing in CrCl and increase BUN and causing hypothyroidism, monitoring renal and thyroid every 6-12 months is
required.
Convulsion caused by lithium toxicity is treated by phenobarbital or propofol.
Treatment of lithium toxicity (antidote): Sodium Polystyrene Sulfonate or NaHCO3
2) Other drugs
Several antiepileptic drugs, including Carbamazepine, Valproic acid, and Lamotrigine are approved as mood stabilizers for bipolar disorder.
Lamotigine and levetiracetam used for pregnant manic woman
Study Questions
1-A 55-year-old teacher was diagnosed with depression. After 6 weeks of therapy with fluoxetine, his symptoms improved, but he complains of sexual dysfunction.
Which of the following drugs might be useful for management of depression in this patient?
A-Sertraline
B. Citalopram
C. Mirtazapine
D. Lithium
Correct answer = C. Mirtazapine is largely free from sexual side effects. However, sexual dysfunction commonly occurs with SSRIs (sertraline and citalopram), as well as
with TCAs and SNRIs. Lithium is used for the treatment of mania and bipolar disorder.
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2-A 25-year-old woman has a long history of depressive symptoms accompanied by body aches and pain secondary to a car accident.
Which of the following drugs might be useful in this patient?
A-Fluoxetine
B. Sertraline
C. Phenelzine
D. Duloxetine
Correct answer = D. Duloxetine is an SNRI that can be used for depression accompanied by symptoms of pain. SSRIs (fluoxetine and sertraline) and MAOIs (Phenelzine)
have little activity against pain syndromes
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3-A 51-year-old woman with symptoms of major depression also has angle-closure glaucoma. Which antidepressant should be avoided in this patient?
A-Amitriptyline
B. Bupropion
C. Mirtazapine
D. Fluvoxamine
Correct answer = A.
Because of its potent antimuscarinic activity, amitriptyline should not be given to patients with glaucoma because of the risk of acute increases in intraocular pressure.
The other antidepressants all lack antagonist activity at the muscarinic receptor.
4-A 36-year-old man presents with symptoms of compulsive behavior. He realizes that his behavior is interfering with his ability to accomplish his daily tasks but
cannot seem to stop himself. Which drug would be most helpful to this patient?
A-Desipramine
B. Paroxetine
C. Amitriptyline
D. Selegiline
Correct answer = B.
SSRIs are particularly effective in treating obsessive–compulsive disorder, and paroxetine is approved for this condition. The other drugs are less effective in the
treatment of obsessive–compulsive disorder.
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5-Which mood stabilizer is completely renally eliminated and may be beneficial for patients with hepatic impairment?
A-Valproic acid
B. Carbamazepine
C. Lithium
D. Risperidone
Correct answer = C. Lithium is the only agent for bipolar disorder that does not require hepatic metabolism and, thus, may be dosed without issue in a
hepatically impaired patient. However, if the patient had renal impairment, the lithium dosage would have to be adjusted.
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A. 6-Which antidepressant agent has significant α1 receptor antagonism and, thus, is a poor choice in an elderly female with depressive symptoms due to a higher
risk of falls related to orthostatic hypotension?
A. Venlafaxine
B. Bupropion
C. Escitalopram
D. Amitriptyline
Correct answer = D.
Venlafaxine, bupropion, and Escitalopram have very little effect on decreasing blood pressure (no α1 receptor antagonism) and are considered acceptable choices for
treatment of depression in the elderly. Amitriptyline is associated with a high risk for orthostasis in the elderly and should be avoided due to its adverse effect profile.
Antipsychotic Drugs
The antipsychotic drugs are used primarily to treat schizophrenia, but they are also effective in other psychotic and manic states. Antipsychotic drugs are not curative
and do not eliminate chronic thought disorders, but they often decrease the intensity of hallucinations and delusions and permit the person with schizophrenia to
function in a supportive environment.
❖ Mechanism of action
❖ 1. Dopamine antagonism, All of the first-generation and most of the second-generation antipsychotic drugs block D2 dopamine receptors in the brain and the
periphery
❖ 2. Serotonin receptor–blocking activity,
Most of the second-generation agents exert part of their action through inhibition of serotonin receptors (5-HT). but it is also a weak dopamine D2 receptor antagonist.
FIRST-GENERATION ANTIPSYCHOTICS
First-generation antipsychotics are more likely to be associated with movement disorders known as extrapyramidal symptoms
(EPS), particularly drugs that bind tightly to dopaminergic neuroreceptors, such as haloperidol. these drugs have antiemetic
effects that are mediated by blocking D2
Movement disorders are somewhat less likely with medications that bind less potently, such as Chlorpromazine .
First generation (Typical antipsychotic), Used for treatment of +ve symptoms only
Chlorpromazine cause Pigmentary on Retina and Cornea.
Clozapine, Aripiprazole, Olanzapine, Risperidone and Quetiabine

The second-generation antipsychotic drugs (also called “atypical” antipsychotics) have a lower incidence of EPS than the first-
generation agents but are associated with a higher risk of metabolic adverse effects, such as diabetes, hypercholesterolemia, and
weight gain. Second generation used for both +ve and –ve symptoms
General Notes
Some of the antipsychotics, particularly, Chlorpromazine, Clozapine, and Olanzapine, Produce Anticholinergic effects.
These effects include

Blurred vision, Dry mouth (the exception is clozapine, which increases salivation), Confusion, and inhibition of gastrointestinal and
urinary tract smooth muscle, leading to constipation and urinary Retention.
Quetiapine used as Antipsychotic drug for Parkinson Patients.
Valbenazin used for tardive dyskinesia caused by some Antipsychotic .
Benztropine used for Extrapyramidal effect caused by some antipsychotic.
Clozapine is the only antipsychotic medication that has a black box warning and a risk of agranulocytosis in approximately 1% of
the patients treated.
❖ Study Questions
❖ 1-An adolescent male is newly diagnosed with schizophrenia. Which antipsychotic agent may have the best chance to improve his apathy and blunted affect?
❖ A. Chlorpromazine
B. Fluphenazine
C. Haloperidol
D. Risperidone
❖ Correct answer = D.
Risperidone is the only antipsychotic on the list that has some reported benefit in improving the negative symptoms of schizophrenia. All of the agents have the
potential to diminish the hallucinations and delusional thought processes (positive symptoms).
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❖ 2-Which of the following antipsychotic agents is considered to be the most potent and thus have the highest risk of extrapyramidal symptoms?
❖ A. Thioridazine
B. Haloperidol
C. Quetiapine
D. Chlorpromazine
❖ Correct answer = B. Among the older, conventional, or typical antipsychotics on this list, haloperidol is the most potent and would thus be expected to have the
highest incidence of EPS.
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3-Which antipsychotic agent is most associated with the possibility of a hematological dyscrasia such as agranulocytosis in a patient being treated for
schizophrenia?
A. Chlorpromazine
B. Buspirone
C. Lithium
D. Clozapine
❖ Correct answer = D.
Correct answer = D. Clozapine is the only antipsychotic medication that has a black box warning and a risk of agranulocytosis in approximately 1% of the patients
treated. This requires regular monitoring of white blood cell counts.
Drugs for Epilepsy

A number of causes, such as illicit drug use, tumor, head injury, hypoglycemia, meningeal infection, and the rapid withdrawal of
alcohol from an alcoholic, can precipitate seizures.
In cases when the source of a seizure can be determined and corrected, medication may not be necessary.
In other situations, anti seizure medications may be needed when the primary cause of the seizures cannot be corrected.
Mechanism of action of Antiseizure medications Drugs

Reduce seizures through mechanisms such as blocking voltage-gated channels (Na + or Ca 2+ ), enhancing inhibitory γ-aminobutyric acid (GABA)
impulses and interfering with excitatory glutamate transmission.
Sodium Channel Blockers (Na+ ): -

1-Phenytoin, Fosphenytoine
• It is effective for treatment of focal and generalized tonic–clonic seizures and in the treatment of status epilepticus.
• Strong correlation between the plasma level and its effect
• Dose: phenytoin sodium 100 mg = 92 mg of phenytoin base
• Side effects of phenytoin: Gingival hyperplasia, nystagmus (rapid involuntary movement of eye), hirsutism, acne, and Purple glove syndrome
2-Carbamazepine (used also for trigeminal neuralgia),
3-Oxecarbamazapine
4-Lamotrigine (Rash Dependent Dose)
GABA Enhancing Agent (GABA): -

- Barbiturate (primidone is the prodrug of phenobarbital), Phenobarbital is used primarily in the treatment of status epilepticus when other agents fail.
- Benzodiazepine (BZDs)
- Valproic acid, Divalproex sodium is a combination of sodium valproate and valproic acid that is converted to valproate ion in the gastrointestinal tract. It was
developed to improve gastrointestinal tolerance of valproic acid.
Ethosuximide
reduces propagation of abnormal electrical activity in the brain, most likely by inhibiting T-type calcium channels. It is most effective in treating absence
seizures.
Gabapentin
is an analog of GABA. However, it does not act at GABA receptors, enhance GABA actions or convert to GABA.
Topiramate
Has multiple mechanisms of action. It blocks voltage-dependent sodium channels, reduces high-voltage calcium currents and may act at glutamate (NMDA) sites.
topiramate is effective for use AS a first-line medication for generalized tonic–clonic seizures .
It is also approved for prevention of migraine.
Adverse effects include: weight loss, Renal stones, glaucoma, oligohidrosis (decreased sweating, Zonisamide also), and hyperthermia have also been reported.
Treatment of Neuropathic Pain:

• 1st: Duloxetine, Pregabalin
• Others: Gabapentin, Venlafaxine
Antiepileptic For Pregnant:

Levetiracetam, lamotrigine
Antiepileptic For Breastfeeding:

Levetiracetam
Antiepileptic Need Renal Adjustment:

Topiramate, Contraindicated with Alcohol, Metabolic Acidosis and Metformin.
Antiepileptic in absence seizures (Petit):

Ethosuximide
Antiepileptic for older + (AOT):
Alprazolam, Oxazepam, Triazolam
Status epilepsy :
In status epilepticus, two or more seizures occur without recovery of full consciousness in between episodes. Status epilepticus is life threatening and requires
emergency treatment usually consisting of parenteral administration of a fast-acting medication such as a benzodiazepine, followed by a slower- acting medication such
as phenytoin, fosphenytoin, divalproex, or levetiracetam.
• 1st BZD: IV Diazepam, Lorazepam, midazolam

• 2nd: phenytoin, valproic acid, levetiracetam
N:B Fastest Diazepam (D form Drive), Longest Lorazepam (longest from L), Strongest Clonazepam
Study Questions
1-A child is experiencing absence seizures that interrupt his ability to pay attention during school and activities. Which therapy is most appropriate for this patient?
A. Ethosuximide
B. Carbamazepine
C. Diazepam
D. Watchful waiting
Correct answer = A. The patient has had many seizures that interrupt his ability to pay attention during school and activities, so therapy is justified. Carbamazepine may
make the seizures more frequent. Diazepam is not indicated for absence seizures.
---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
2-A patient with focal seizures has been treated for 6 months with carbamazepine but, recently, has been experiencing breakthrough seizures on a more frequent
basis. You are considering adding a second drug to the antiseizure regimen. Which of the following drugs is least likely to have a pharmacokinetic interaction with
carbamazepine?
A-Topiramate
B. Tiagabine
C. Levetiracetam
D. Lamotrigine
Correct answer = C. Of the drugs listed, all of which are approved as adjunct therapy for refractory focal seizures, only levetiracetam does not affect the
pharmacokinetics of other antiepileptic drugs, and other drugs do not significantly alter its pharmacokinetics.
-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
Which is a first-line medication for generalized tonic–clonic seizures?
A-Ethosuximide
B- Felbamate
C. Vigabatrin
D. Topiramate
Correct answer = D.
Topiramate is a broad-spectrum antiseizure medication that is indicated for primary generalized tonic–clonic seizures.
Anesthetics
For patients undergoing surgical or medical procedures, different levels of sedation can provide important benefits to facilitate
procedural interventions.General anesthesia is a reversible state of central nervous system (CNS) depression, causing loss of
response to and perception of stimuli.
The state of general anesthesia can be divided into three stages: induction, maintenance, and recovery.
Mechanism of Action:
At clinically effective concentrations, general anesthetics increase the sensitivity of the γ-aminobutyric acid (GABA) receptors to
the inhibitory neurotransmitter GABA. This increases chloride ion influx and hyperpolarization of neurons.
Inhaled Anesthesia:
- Halothane
- Nitrous oxide (laughing gas), Can cause anemia.
- isoflurane (liver toxic)
Intravenous Anesthesia:
- Propofol (1st choice)
Milk like appearance
Contraindication: in patient with allergy of egg & soy products
- Ketamine: Benefit in hypovolemic patient

increase Bp, CO, CSF pressure, bronchodilator
Local Anesthesia:
- Lidocaine: ( Systematic antiarrhythmic) Locally: anesthetic
- Articaine, Ropivacaine
Q,A
Q A
DOC of Neuromuscular block in Spinal Anesthesia Tetracaine
Choroid plexus
Which place produce spinal fluid
Atracurim
Neuromuscular blocker used in renal or hepatic failure
Neuromuscular blocker has the lowest half-life

Succinylcholine
Bevacizumab (anti-cancer)
Bevacizumab used for peritoneal
Age related muscular degeneration
carcinoma
Malignant hypothermia complication of General anesthesia

Picrotoxin
Patient with respiratory depression from anesthesia, what is drug for post anesthesia Used as central nervous system
respiratory depression stimulate, antidote.
Lumber puncher (LP) Contraindicated in seizure and

intercranial pressure (ICP)
Opioids
Because of their analgesic property, opioids are commonly combined with other anesthetics. The most commonly used opioids is
Fentanyl, because they induce analgesia more rapidly than morphine.
Heroin and morphine: Miosis “Pointed Pupil”

Cocaine: Mydriasis
Narcotic addiction: Methadone (treatment)
Narcotic toxicity or overdose: Naloxone (Antidote)
Analgesic and consider narcotic but dispense normally: Methadone, Ketorolac
Morphine in Neonate: IV
Fentanyl:
IV: Adjunct to Anesthetic
Patch: Chronic pain
CNS Stimulants
Amphetamine
The effects of amphetamine on the CNS and peripheral nervous system are indirect.
That is, both depend upon an elevation of the level of catecholamine neurotransmitters in synaptic spaces.
Methamphetamine is a derivative of amphetamine.
Methylphenidate
Methylphenidate has CNS stimulant properties similar to those of amphetamine and is often used in the treatment of ADHD.
The pharmacologically active isomer, dexmethylphenidate, is also used for the treatment of ADHD.
Therapeutic uses of amphetamine and Methyphenidate
Attention deficit hyperactivity disorder (ADHD)
Narcolepsy
Appetite suppression
Drug used for ADHD and non stimulant: Atomoxetine
AUTISM
Treatment by: Dimethyl glycine
Vaccines which cause autism (thimerosal “Mercury” containing Vaccine)

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‫صيــادلـــــــــــــــــــــــه بتخدمــــــــــــــك د‪ /‬شريـــف مدكــور ‪ .‬د‪ /‬حســـــام زيدان ‪ ..

‬د‪ /‬أحــمد فـــــــــرج ‪01015694262‬‬

Drugs Affecting the Central Nervous System

The basic Functioning of Neurons in the CNS is

Drugs for Neurodegenerative Diseases

Adverse effects include:

4)Dopamine receptor agonists

These agents can induce mood changes, confusion and mydriasis.

2) NMDA Receptor Antagonist

➢ For all stages of Alzheimer disease:

Herbal used for Alzheimer: Ginko biloba

Anxiolytic and Hypnotic Drugs

Imipramine is used as an alternative to desmopressin in the treatment of bed-wetting in children.

CLOMIPRAMINE IS MORE USED FOR OBSESSIVE- COMPULSIVE DISORDER.

-Sedation is related to the ability of these drugs to block histamine H1 receptors.

2-Monoamine Oxidase Inhibitors

From any antidepressent to MAOIs: 2 weeks washout period.

3-Selective Serotonin Reuptake Inhibitors

Serotonin syndrome characterized by:

Treatment of Mania and Bipolar Disorder

Toxicity of lithium: caused by hyponatremia.

Clozapine, Aripiprazole, Olanzapine, Risperidone and Quetiabine

These effects include

Quetiapine used as Antipsychotic drug for Parkinson Patients.

Valbenazin used for tardive dyskinesia caused by some Antipsychotic .

Benztropine used for Extrapyramidal effect caused by some antipsychotic.

Drugs for Epilepsy

Mechanism of action of Antiseizure medications Drugs

Sodium Channel Blockers (Na+ ): -

2-Carbamazepine (used also for trigeminal neuralgia),

4-Lamotrigine (Rash Dependent Dose)

GABA Enhancing Agent (GABA): -

Treatment of Neuropathic Pain:

Antiepileptic For Pregnant:

Antiepileptic For Breastfeeding:

Antiepileptic Need Renal Adjustment:

Antiepileptic in absence seizures (Petit):

• 1st BZD: IV Diazepam, Lorazepam, midazolam

- Ketamine: Benefit in hypovolemic patient

DOC of Neuromuscular block in Spinal Anesthesia Tetracaine

Neuromuscular blocker has the lowest half-life

Malignant hypothermia complication of General anesthesia

Lumber puncher (LP) Contraindicated in seizure and

Heroin and morphine: Miosis “Pointed Pupil”

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