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Anti-depressantsDepression- due to decrease in levels of excitatory amines or NT

-NT & amine: serotonin-alteration of mood & characterized by intense feelings of sadness, worry, anxiety,

hopelessness, despair& inability to experience pleasure in usual activities-produce disturbances in thought-the ptx may lose weight & libido

Drugs for tx of depression: Thymoleptics-improve mood by increasing catecholamine stores1)Amine Re-uptake inhibitors

a.Nonselective NE 5HT Re-uptake Inhibitorsb.SSRIsc.SNRIs

2)Monoamine Oxidase Inhibitorsa.Nonselective MAO A & MAO B Inhibitorsb.Selective MAO A Inhibiors

1)Amine Re-uptake Inhibitorsa.NonselectiveMOA: block/inhibit the re-uptake of the amines after release from the presynaptic neuron

: blocking of 5HT, -adrenergic, histamine, muscarinic receptorsResult: enhanced or increased response of NE & 5HT

1 st generation: TCAs: Imipramine Amitriptyline NortriptylineDoxapine Despiramine

2 nd generation: HCAs: Amoxapine BupropionMaprotyline Trazodone

Pharmacokinetics:-well absorbed from the GIT-lipophilic; therefore, well absorbed, widely distributed, long half lives-metabolized by hydroxylation, N-demethylation & conjugation with glucuronic acid-demethylated metabolites of amitriptyline & imipramine exert antidepressant

property-excretion of metabolites via kidney

Pharmacologic effects:-sedation when given to non-depressed person-for depressed ptx elevation of mood after 2-3 weeks or 1 month-antihistaminic action- adrenergic blocking property-antimuscarinic action

Other Therapeutic uses:-for panic disorders-Imipramine used to control enuresis in children

SE:1.antimuscarinic effects/anticholinergic effects>amitriptyline- highest incidence of anticholinergic effect

Caution: ptx with glaucoma & BPH2.CV: cardiac overstimulation, arrhythmias, tachycardia, increased heart rate>caution: cardiotoxic3. -adrenergic blocking orthostatic hypotension & reflex tachycardia

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4.sedation5.Manic excitement can occur in ptx with bipolar disorders>caution: use in manic depressive patients6.weight gain

DI:1) TCAs + adrenergic drugs = increased sympathomimetic effects2) TCAs + ethanol/ other CNS depressants = toxic sedation3) TCAs + MAOis = hypertensive crisis

b.SSRIs- Selective Serotonin Re-uptake Inhibitors-advantages over TCAs:

:fewer anticholinergic effects:lower CV toxicity

Sertraline FluoxetineParoxetine Fluvoxamine

Pharmacokinetics:-Fluoxetine well absorbed after PO administration

- undergoes extensive hepatic biotransformation to active metabolitenorfluoxetine

- half-life: 1-3 days fluoxetine- half- life: 7-15 days norfluoxetine- onset of action: 1-3 weeks after therapy is started

DI:Fluoxetine- potent inhibitor of P450 affects metabolism of:

-Neuroleptic drugs-TCAs- -adrenergic antagonists-antiarrhythmic drugs

Therapeutic uses:-bulimia nervosa/anorexia/obesity-obsessive-compulsive disorder-PMS-alcoholism-panic attacks

SE:1.loss of libido 5.weight loss9.mania2.delayed ejaculation 6.anorexia3.seizures 7.insomnia

4.tremors 8.anxietyc.SNRIs- Serotonin- Norepinephrine Re-uptake Inhibitors

-primarily affect serotonin re-uptake-lower incidence of anticholinergic effect & CV toxicity compared to TCAs but higher

than that of SSRIs-clinical effectiveness compared to 2 other drugs

Venlafaxine Nefadozone Trazodone

Therapeutic uses:1.clinical depression

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2.anxiety3.OCD4.ADHD

***SSRIs & SNRIs = cause GI irritation>advise the patient to take the drug with food or milk to avoid GI irritation

2)Monoamine Oxidase InhibitorsMOA: irreversibly inactivating MAO by forming stable complexes with MAO, preventing oxidativedeamination of

Biogenic amines (NE, 5HT & DA)Result: increased conc of amines in the brain, intestines, heart & bloodAntidepressant effect: -due to INCREASE in NE, 5HTMAO A- deaminates 5HT & NEMAO B- DA

a.Nonselective MAO A & MAO BHydrazide derivatives: Isocarboxazid

PhenelzineIproniazid = hepatotoxic

Nonhydrazide: Tranylcypromineb.Selective MAO A

Moclobemide

Pharmacokinetics of MAOis:-ALL MAOis are rapidly absorbed from the GIT but the therapeutic response occurs after 2-3 weeks

***Tranylcypromine- has an amphetamine-like action release NE rapid action(48hrs)-hydrazides inactivated by acetylation for genetically slow acetylators, dose must be lowered-enzyme regeneration terminates the effect of MAOis (but after weeks of stopping drug intake)-switching to another antidepressant drug needs a 2 week MAOi free interval-switching from MAOis to SSRIs or vice versa: takes 6 weeks of washout period

Pharmacologic effects:(1) CNS effect- for narcolepsy (sleep disorder)(2) CV effects- hypertensive crisis(3) Hepatic effect- interfere with the detoxification of many drugs

>enhance the action of: anesthetics, sedatives, narcotics, TCAs

SE/adverse effects:1) Hepatocellular damage2) Excessive CNS stimulation resulting to insomnia & convulsions3) Overdosage: agitation, headache, hallucination, convulsions, hypotension or

hypertension>since the effects are lengthy, ptx should be observed in the hospital for at least 1 week

4) Sedation

5) Cardiomyopathies

arrhythmiasPrecautions for MAOi:

a.do not administer MAOi with tyramine-rich foods = hypertensive crisisb.do not administer MAOi with SSRI = serotonin syndrome

-hyperthermia, rigidity, myoclonusc.do not administer MAOi with TCAs = hyperpyrexia, convulsions, comad.PPA/dextromethorphan/EPI

Uses: DEPRESSION1) + psychomotor retardation (inactivity)/sleep disturbance/poor appetite/wt loss

DOC: TCAs

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2) + significant anxiety/hypochondriac/extreme phobias DOC: MAOis

3) + increase appetite DOC: SSRI

4) Acute panic attacks5) + Obsessive- compulsive disorder/ phobic-anxiety syndromes/ chronic pain

DOC: TCAs6) OC, obesity, alcoholism

Therapeutic Advantages of Antidepressants:1)Low potential for anticholinergic effects: Maprotiline (HCAs)

SSRIs & SNRIsNon-selective MAOis

Therapeutic Disadvantages of Antidepressants:1)Anticholinergic effects & arrhythmias = TCAs/HCAs2)High potential for orthostatic hypotension = Amitriptyline, Doxepin, Nonselective MAOis3)Sedation = TCAs/HCAs except Desipramine & Protriptyline

= Trazodone

Anxiolytics: Sedative, HypnoticsSedative= calming effect ; Hypnotics = sleep-inducing effect (artificial)

Anxiety- unpleasant state of tension, apprehension or uneasiness-fear that seems to arise from an unknown sourceSx: tachycardia palpitations

sweating **sympathetic activation is involvedtrembling

Drugs: Anxiolytics/Minor Tranquilizers/Sedatives/Hypnotics-antianxiety agents exert sedative and hypnotic effect & some skeletal muscle relaxant

property-have a habituation and physical dependence-have lower incidence of adverse effects than antipsychotic agents

Classes: (1) benzodiazepines(2) barbiturates(3) miscellaneous: buspirone, meprobamate, zolpidem(4) Nonbarbiturate/ nonbenzodiazepine sedatives

Benzodiazepines- DOC due to high therapeutic index- Most widely used anxiolytics

MOA: bind to GABA receptors = GABAergic effect: when GABA receptors are activated, chloride channels open Cl ions enter the cell

membranehyperpolarization of cell inhibition of activity

Classification:

1)SA (3-8hrs)Midazolam Triazolam

2)IA (10-20hrs) Tremazepam EstazolamAlprazolamLorazepamOxazepam

3)LA (1-3days)DiazepamClonazepamPrazepam

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FlurazepamChlordiazepoxideChlorazepateQuazepam

Pharmacokinetics1)rapidly absorbed after PO administration since its lipophilic (cross BBB & unionized

form)2)distributed throughout the body3)plasma levels reflect brain level4)longer acting drugs form active metabolites with long half-lives5)metabolized by P450 to more active metabolites

>parent drug + active metabolite exert combined therapeutic action6)excreted in urine as glucuronides or oxidized metabolites

Uses: basis of therapeutic use is the duration of action1)Reduction of anxiety = at low doses

Diazepam- prolonged txAlprazolam- short and long term tx of panic disorders

2)Sedative/Hypnotic tranquilizers = all are sedative but at higher doses, producehypnosis

Tx: sleep disorders (Flurazepam, Temazepam, Triazolam)3)Muscle relaxant- to relax the spasticity of skeletal muscles

adjuncts in anesthesia (anesthetic premedication)-as muscle relaxants for muscle spasm in cerebral palsy

4)Anticonvulsant = Tx: seizure disorders: status epilepticus in adults = Diazepam-increase the seizure threshold

5)For alcohol withdrawal syndrome = Chlordiazepoxide/ chlorzepate/ diazepam/oxazepam

SE:1.excessive CNS depression if given with other drugs that cause sedation

>ex: alcohol, barbiturates, antipsychotics, opioid analgesics2.anterograde amnesia Lorazepam (ATIVAN)3.drowsiness & confusion most common4.motor incoordination (ataxia)5.menstrual irregularities6.cognitive impairment = decrease long term memory & acquisition on new

knowledge7.hypothermia- if Diazepam is given for status epilepticus in children8.rebound insomnia- Triazolam

>Triazolam has the most rapid elimination leading to rapid development of tolerance,

EARLY MORNING INSOMNIA, daytime anxiety, along with amnesia & confusion

Dependence: Psychological or Physical>will only develop if BZDs are given in high doses over a prolonged period of time

Withdrawal symptoms:-more withdrawal problems = drugs that are more potent & rapidly eliminated-examples: Lorazepam & Triazolam

>confusion/ psychosis>anxiety/ tension>restlessness/ agitation/ insomnia>malaise>anorexia>diaphoresis

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>seizures>strange smells/ metallic taste>nausea & vomiting

Antidote: Flumazenil (GABA receptor antagonist)- given IV only-onset is rapid-duration is short: half-life = 1 hour-Remedy: frequent adm to maintain reversal of LA BZDs-disadv: May induce withdrawal sx in ptx dependent on BZD

:May cause seizures if BZDs is used to control seizure disorder-SE: dizziness, N&V, agitation

Advantage of BZDs: Overdose is seldom lethal unless given with CNS depressants

Barbiturates- parent compound: barbituric acid- derived from the dehydration of urea & malonicacid

-Barbituric acid has no depressant effect on the CNS-formerly, the mainstay of tx used to sedate patient or to induce sleep-replaced by BZDs, due to:

Narrow TI

Tolerance develops quicklyHave high potential for physical dependence & abuseVery severe withdrawal symptomsInduce drug metabolizing enzymesComa in toxic doses

MOA: bind & stimulate GABA receptors:there is a picrotoxin site associated with the GABA receptor where barbiturates bind:greater affinity of a Barbiturate for picrotoxin binding site = greater potency:less selective than BZDs

Classification: based on duration of action1)USA (30 mins)

IV adjuncts to anesthesia Thiopental ThiamylalMethohexital

2)SA (2hrs) sleep-inducing hypnotics

PentobarbitalSecobarbitalHexobarbital

3)IA (3-5hrs) hypnotics . . . but have a hangover liability

AmobarbitalButabarbital

4)LA (6hrs) hypnotics and sedatives, antiepileptics but . . . have hangover

PhenobarbitalBarbital

Pharmacokinetics:1.Absorbed from the stomach, small intestines, rectum, and IM sites2.Readily cross the placental barrier

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3.Distributed widely4.Duration of action of a barbiturate depends on:

a)rate of metabolic/hepatic degradationb)degree of lipid solubilityc)extent of protein binding, which reduces renal excretion

5.LA barbs.- metabolized in the liver by slow oxidation6.USA- highly lipid soluble; have short onset & duration of action

a)high lipid-solubility allows rapid transport across BBBb)removal of USA barbs from brain occurs via redistribution to other tissues

***redistributed in the body from brain splanchnic areas skeletal muscle adiposetissues

(movement causes short duration of action for USA)7.Barbs & metabolites- renal route of excretion

Effects/Uses:1)Depress CNS at all levels>barbiturate + CNS depressant = marked depression2)Sedative- hypnotic>as hypnotic, decrease the time for REM sleep3)Anticonvulsant- tx: seizure disorders

DOC for status epilepticus in children- Phenobarbital>ALL barbs suppress convulsant activity4)Tx of hyperbilirubinemia in neonates to prevent Kernicterus>ability of barbs to stimulate liver glucoronyl transferase5)Adjuncts to anesthesia- USA barb.

SE:1.Physical dependence/addiction2.CNS effect- drowsiness, impaired conc, mental & physical sluggishness3.Drug hangover- produces a feeling of tiredness after the patient awakes

-impaired ability of the ptx to function normally for many hours afterwaking

-nausea & dizziness4.oversedation5.overdose: seizures, coma, respiratory depression6.very narrow therapeutic index7. rebound insomnia8.enzyme inducer- Phenobarbital

>results in increased degradation of the barb, ultimately leading to barbtolerance

>cause increased inactivation of other drugs (anticoagulants, phenytoin,digitoxin,

theophylline & glucocorticoids) decrease effect of drugs9.barbiturate-induced porphyria

Contraindicated:1)Ptx with acute intermittent porphyria.2)Ptx taking drugs which are primarily metabolized by CYP-450

***Porphyrias- are group of disorders caused by deficiencies of enzymes involved insynthesis of heme

Heme-chemical compound that carries oxygen & makes blood red-synthesized largely in the bone marrow for the manufacture of Hb

What happens in porphyria?- deficiency of the enzyme/s in the production of hemeleads to accumulation of heme precursors (delta-aminolevulinic acid,

porphobilinogen,

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porphyrins) in the tissues-excess porphyrins = photosensitivity-excess of the other 2 = nerve damage

***Acute Intermittent Porphyria-hepatic porphyria that causes neurologic symptoms-common in women-Sx abdominal pain, N&V, constipation or diarrhea, tachycardia, hypertension,

sweating,restlessness-causes: Drugs: Barbs, anti-seizure agents, sulfonamide ABCs

Hormones: progesterone, related steroidsDiet: low calorie, low carbo, large amount of alcoholCrash Diets

Acute Barbiturate Overdosage: results to coma, severe respiratory depression, hypotension, leading to CV collapse &renal failure

Treatment of Overdosage:1)Primary tx: support respiration & circulation2)Purging of the contents of the stomach3)Promote excretion of drugs by alkalinization of urine & induce dieresis4)Hemodialysis

Anxiolytics: Miscellaneous1.Buspirone

MOA: partial agonist at 5HT 1A receptor (no GABA effect)SE: tachycardia/palpitationsCharacteristics:

a)no muscle relaxant activityb)no anticonvulsant propertyc)no hypnotic activity

Advantages:a)no marked sedation/ no additive CNS depressant effect/ does not interact with

ethanol or otherCNS depressant drugs

b)no rebound anxietyc)no withdrawal symptomsd)minimal/ low addiction potential

Pharmacokinetics:a)rapidly & completely absorbed from GITb)undergoes extreme first-pass effectc)highly protein boundd)partly excreted in the urine

e)half-life = 4.8hrsUse: for short-term treatment of generalized anxiety (therapeutic effect seen after 1-2weeksor 2-4weeks)

>not used for situational anxiety (ex. Dental surgery)

2.ZolpidemMOA: GABAergic effect but nonBZDAdvantage over BZD: no risk of tolerance/dependenceCharacteristics/advantages:

a)no anticonvulsant activityb)no muscle relaxant activityc)no withdrawal symptoms

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d)exhibits minimal rebound insomniae)little or no tolerance with prolonged use

Pharmacokinetics:a)rapidly absorbed from GITb)rapid onset of actionc)half-life = 3hrs

SE:-nightmares -GI upset-agitation -dizziness-headache -daytime drowsiness-diarrhea -memory problems after taking drug

DI:Avoid alcohol & other CNS depressants due to potentiation of increased CNS

depressant effect.

3.Chloral hydrate - - - inexpensivePharmacokinetics:a)metabolized in the liver by alcohol dehydrogenase to trichloroethanol produces CNS

effectb)trichloroethanol is oxidized to trichloroacetic acidc)trichloroacetic acid glucuronide conjugation renal excretion

Effect: induces sleep in 30mins & lasts about 6hrsUses:

a.safe hypnotic drug, inducing sleep in 30mins & lasting about 4-6hrsb.mainly used in children & elderly & is most effective when used for 1-3 nights to tx

transient insomniaSE/Adverse Effects:

a.DF: liquid preparation- bad tasting; disagreeable odor mixed with flavored syrup, juice

b.irritating to GITc.addiction

DI: chloral hydrate + alcohol = Mickey Finn marked CNS depression

4.ParaldehydeEffects: produces hypnosis in about 15mins, lasting for 4-8hrsRoute of administration: PO, parenterally, rectallyUses: exclusively for ptx undergoing alcohol withdrawal

For ptx with hepatic or renal failure since its eliminated via lungsAdverse effects/SE: strong odor, disagreeable taste, GI irritationDI: Disulfiram

5.AntihistaminesEx: diphenhydramine doxylamine Hydroxyzine chlorpheneramine

Hydroxyzine antihistamine + anti-emetic activity-low tendency for habituation-useful for ptx with anxiety & has history of drug abuse-used for sedation prior to dental surgery or procedure

6.EthanolPharmacokinetics:

Metabolized in the liverEthanol aldehyde acetic acid

Disulfiram blocks oxidation of aldehyde to acetic acid

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-accumulation of aldehyde causes: flushing, tachycardia, hyperventilation,nausea

7. Meprobamate-was developed in order to reduce tolerance & addiction with Barbs-however, it was just as addicting & dangerous to BarbsSE/Adverse effects/Overdose:

a.CNS depressionb.CV collapsec.respiratory depression deathd.dependence & drug abuse

DI: other CNS depressants

AntiParkinsons DrugsParkinsonism- disorder caused by death of group of brain cells

-causes progressive neurologic disorder of muscle movements (tremors, rigidity,bradykinesia)

-cause: reduction of the activity of dopamine due to destruction in substantia nigra &corpus striatumDrugs:

1)Dopaminergic Agonistsa.Levodopa & carbidopa = Sinemet b.Bromocriptine ergot derivativec.Selegiline- MOA: selective MAO-B inhibitord.Pergolide- ergot derivativee.Amantadine- MOA: enhances synthesis & release

2)Anticholinergics/Antimuscarinica.Benztropineb.Trihexyphenidylc.Biperiden

3)Antihistaminesa.Diphenhydramine

Epilepsy- recurrent seizure disorder-sudden, excessive, disorderly discharge of cerebral neurons-seizures contractions; uncontrolled involuntary muscle movement-causes: a)primary or idiopathic epilepsy

b)secondary epilepsy: tumor, head injuries, meningeal infection, rapid alcoholwithdrawal,

trauma, metabolic imbalance hypoglycemiahyponatremiahypercalcemiahypomagnesimia

-Classification of Epilepsy:

1.Partial (Focal) Seizuresa) Simple Partial (jacksonian type)-convulsions on single limb or muscle group or half of body-abnormal electrical activity is confined to a single part in the brain-no loss of consciousness-occurs at any age

b)Complex Partial-loss of consciousness-before the age of 20

c)with secondary generalization-a part affected then progress to whole body involvement

2.Generalized seizures

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-convulsive or nonconvulsive-immediate loss of consciousness-begins locally, rapidly spreads through both hemispherea)GTC (Generalized Tonic-Clonic)-Grand mal-most common & most dramatic-tonic = increase in the tone of muscles-clonic = jerky movements-frothy secretion of mouth-upward rolling of the eyeballs

b) Absence or Petit mal-more common in children (3-5 yrs old until puberty)-ptx has blank stares & has rapid eye-blinking lasting for 3-5secs-no convulsions

c)Myoclonic-short episodes skeletal muscle convulsions-may reoccur for several minutes-occur at any age-often results from permanent neurologic damage

d)Febrile seizures in children/ Infantile spasms-3months to 5yrs develop seizures due to high fever-consist of generalized tonic-clonic convulsions of short duration-benign & do not cause death, neurologic damage, injury, or learning disorder-rarely require medication

e)Status Epilepticus-rapidly recurrent seizures-Emergency case

Anti-epileptic DrugsMOA: reduce seizures by- a)blocking the initiation of the electrical discharge from the focal area

b)prevent the spread of the abnormal electrical discharge to other areasof brainChoice of anti-epileptic drugs: --specific for the type of seizure

1. For Grand mala) Phenytoin- DOC: adultsb)carbamazepinec) Phenobarbital- DOC: childrend)Primidonee)Valproic acid

2. For Petit mal

a) Ethosuximide- DOCb)Valproic acidc)Clonazepam

3. Myoclonic seizuresa) Clonazepam- DOCb)Valproic acid

4. Status epilepticusa)Phenytoinb) Diazepam- IV = DOC: adultc) Phenobarbital= DOC: childd)Lorazepam

5. Partial seizures

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a)Phenytoinb)Carbamazepinec)gabapentind)felbamatee)Primidonef)Lamotigrine

6. Partial with secondary generalizationa) Valproic acid- DOCb)Felbamatec)gabapentind)Lamotigrine

Barbiturates (Phenobarbital)Pharmacologic effects/MOA1.limits the spread of seizure discharges in the brain2.elevates the seizure threshold3.potentiates the inhibitory effect of GABA-mediated neurons

SE:1.sedation, ataxia, nystagmus, vertigo, acute psychosis2.physical & psychological dependence3.depress cognitive performance in children4.N&V5.agitation & confusion6.rebound seizures

Pharmacokinetics:1.well absorbed PO2.freely penetrates the brain3.75% of the drug is inactivated by CYP-450; rest excreted unchanged by kidney4.POTENT INDUCER OF CYP-450

Deoxybarbiturates (Primidone- prototype)Pharmacokinetics & uses:1.close resemblance to the barbs structurally & in anticonvulsant activity2.well absorbed from GIT3.poor protein binding4.two metabolites responsible for activity:

Phenobarbital- grand mal & simple partialPEMA- phenylethylmalonamide- complex partial

Hydantoins (Phenytoin, Mephenytoin, Ethytoin)-ALL are highly liposoluble & are water insoluble

Phenytoin(diphenylhydantoin)-most common prescribed drug in this classMOA: stabilizes the depolarization of neuronal membrane by a decrease in the influx of NA+Pharmacokinetics

1)slow PO absorption, but once it occurs, distribution is rapid & brain conc are high2)chronic adm: given PO3)IV adm in stat epilepticus4)largely protein bound5)metabolized in the liver6)excreted first in the bile, then in the urine7)at low doses, half-life = 24hrs

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8)increase in dose, metabolizing system becomes saturated increase in plasmaconc of the drug

TOXIC!SE

1.GI irritation given with meals2.blood dyscrasias3.CNS depression (nystagmus) & CV collapse if exceeds 50mg/min4.Hypersensitivity reactions: SJS & SLE

stop Phenytoin adm if a rash occurs5.Hepatitis6.Coarsening of the facial features occur in children7.megaloblastic anemia due to interference of Vit B12 metabolism8.behavioral changes: confusion, hallucination, drowsiness9.inhibition of ADH release10.hyperglycemia & glycosuria due to inhibition of insulin release11.Gingival hyperplasia- gums tend to grow over teeth12.Hirsutism13.Increased collagen proliferation14.increase in bone growth15. Fetal hydantoin syndrome

-teratogenic effects: cleft lip/palate, mental deficiency, slow growth, congenitalheart disease

DI1) Inhibition of phenytoin metabolism by:

Chloramphenicol, dicumarol, cimetidine, sulfonamide, isoniazid2) Stimulation of phenytoin metabolism by:

carbamazepine3) Increase in metabolism of other drugs by phenytoin

Phenytoin- inducer of CYP 450Affected drugs: antiepileptics, anticoagulants, OC, quinidine, doxycycline,

cyclosporineMexiletine, methadone, levodopa

Management of therapy: Never stop treatment abruptly.

Succinimides (Ethosuximide, methsuximide, phensuximide)EthosuximideMOA: reduces propagation of abnormal electrical activity in the brain by GABA effectPharmacokinetics:

1.well absorbed PO; not bound to plasma protein2.25% excreted unchanged in urine; 75% converted to inactive metabolite3.metab in liver by CYP-450

SE/adverse effects:1.GI irritation, N&V

2.drowsiness, lethargy, dizziness3.restlessness, agitation, anxiety4.inability to concentrate5.hypersensitivity reaction: SJS6.urticaria7.blood dyscrasias: leucopenia, aplastic anemia, thrombocytopenia8.Psychotic episodes9.Photophobia

Benzodiazepines-safest & most free from severe side effects of all the anti-epileptic drugsMOA: enhance GABA effect

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SE: 1)sedation2)drowsiness/ dizziness3)fatigue4)ataxia

Drugs: Diazepam-IV, Clorazepate, Clonazepam

Carbamazepine-chemically related to the TCAsMOA: reduces propagation of abnormal impulses in the brain by blocking Na+ channels,

thereby inhibitingRepetitive action potentials

Use: also used in the tx: trigeminal neuralgia (CN V- facial nerve): in manic-depressive states

-anticonvulsant action similar to phenytoinPharmacokinetics

1.slowly absorbed after PO2.enters brain highly lipophilic3.induces CYP-450 in the liver; its half-life decreases with chronic adm

DI: inhibition of hepatic metabolism of carbamazepine by cimetidine, diltiazem,erythromycin,

isoniazid,propoxypheneAdverse effects/SE:

1.N&V, vertigo, drowsiness2.bone marrow depression, including aplastic anemia3.Congestive heart failure4.atropine-like symptoms; blurred vision5.kidney & liver toxicity6.stupor, coma, respiratory depression

Management of therapy:1)Ptx should have liver function tests.2)If the ptx is concurrently taking Carbamazepine & any drug that inhibits its

metabolism.LOWER the dose of carbamazepine to avoid its TOXIC effects.

Valproic acid (dipropylacetic acid)-used as a solvent in the screening of compounds for antiepileptic activity;

it was found out to possess antiseizure actionMOA: inhibition of GABA transaminase, the enzyme responsible for breakdown of GABAPharmacokinetics:

1)rapidly absorbed from the GIT2)90% protein bound: 3% excreted unchanged; the rest is activated to active

metabolites in the liver3)metabolized by CYP-450; glucuronides are excreted in the urine

SE/adverse effects:1.N&V, anorexia2.sedation, ataxia, tremor3.hepatotoxic & pancreatitis4.rash5.alopecia6.menstrual disturbances7.bleeding time may increase due to thrombocytopenia & inhibition of platelet

aggregation8.teratogenicity

DI: causes 40% rise in plasma Phenobarbital conc

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Felabamate-structurally similar to meprobamateMOA: blocks repetitive neuronal firing by decreasing in Na+ influx (depolarization)Adverse effect: aplastic anemia

Gabapentin & Lamotigrine-new drugs

Gabapentin- analogue of GABA-does not bind to plasma proteins; excreted unchanged through kidneys

Lamotigrine- MOA: blocks Na+ channels & prevents repetitive firing-metabolized in the liver-half-life is decreased by enzyme-inducing drugs (carbamazepine, phenytoin);

increased byValproic acid

-SE: rash