Drugs for Seizures and other Conditions

Other Sedative- Hypnotics Drugs 1\. Z-drugs ZOLPIDEM, ESZOPICLONE, ZALEPLON \*MOA:binds in BZD =which controls sleep/ wakefulness \*DOC for insomnia \*replaced older benzodiazepines for the treatment of insomnia 2\. Melatonin and Related Drugs \* neuroendocrine hormone synthesized in the pine...

Other Sedative- Hypnotics Drugs 1\. Z-drugs ZOLPIDEM, ESZOPICLONE, ZALEPLON \*MOA:binds in BZD =which controls sleep/ wakefulness \*DOC for insomnia \*replaced older benzodiazepines for the treatment of insomnia 2\. Melatonin and Related Drugs \* neuroendocrine hormone synthesized in the pineal gland A. MELATONIN is released before the onset of sleep and produces drowsiness that facilitates sleep. USES b\. treatment of insomnia in shift-change workers -- Graveyard shift B. RAMELTEON (Rozerem) \*acts selectively at melatonin receptors \* approved to treat sleep -- onset insomnia Advantages - No abuse liability - No rebound insomnia 3\. Chloral Hydrate \* older hypnotic that is largely obsolete today \* active metabolite : TRICHLOROETHANOL \* occasionally used for preanesthetic sedation in PEDIATRIC patients 4\. Antihistamines (1^st^ generation) \*DIPHENHYDRAMINE, HYDROXYZINE and DOXEPIN -- insomnia and mild anxiety 5\. BUSPIRONE -treatment of chronic anxiety and produces an anxiolytic effect without causing marked sedation, amnesia, tolerance, dependence, muscle relaxation. 6\. Propranolol \- Treatment of stage fright or acute situational or performance anxiety ANTIEPILEPTIC DRUGS \*Seizure -- abnormal discharge of neurons in the brain. \* Epilepsy -- recurrent, unprovoked seizure. Types of Seizures 1\. Focal Seizures a\. Simple -- no loss of consciousness \- tingling or twitching b\. Complex -- loss of consciousness \- behavioral changes 2\. Generalized Seizures a\. Tonic -- Clonic \- most dramatic \- tonic -- stiffening \- clonic -- muscle contraction alternating with relaxation. b\. Absence Seizures \- primarily affect children \- loss of consciousness c\. Atonic Fall \- loss of tone d\. Myoclonic Seizure \- muscle jerks e\. Status Epileticus \- seizures that lasts longer than 5 minutes f\. Febrile Seizure g\. Epilepsy or Seizure in Pregnancy \- Levetiracetam \- IM MgSO4 -- for eclampsia DRUGS FOR PARTIAL AND GENERELIZED TONIC-CLONIC SEIZURES 1\. CARBAMAZEPINE \* PRODRUG : OXCARBAZEPINE \* DOC -- Partial Seizure, Tic Douloureux ( trigeminal neuralgia ) S/E \*Blood Dyscracias \*Teratogenic \*Passes in breast milk \*Stimulate ADH release \* Steven -- Johnson Syndrome (SJS) 2\. PHENYTOIN \* PRODRUG : FOSPHENYTOIN \* Hydantoin derivative formaly called DIPHENLHYDANTOIN \* DOC for partial seizures A/E - Interferes folate metabolism - Vitamin D metabolism - Collagen metabolism - SJS 3\. VALPROATE \* DOC for tonic clonic seizures \* BROAD SPECTRUM Antiepileptic drug \* FORMS \- Valproic acid = free acid form \- Valproate sodium = sodium salt of valproic acid \- Divalproex sodium = mixture of valproic acid and valproate sodium S/E - Hepatotoxicity ( less than 2 years old) - SPINA BIFIDA 2^nd^ LINE FOR PARTIAL SEIZURE AND GENERALIZED TONIC- CLONIC SEIZURES 1\. PHENOBARBITAL \* PRODRUG : PRIMIDONE -- phenobarbital and phenylethylmalonamide (PEMA) \- act as GABA A receptor agonist \- DOC for FEBRILE SEIZURE or Status Epilepticus in Children ADJUNCT DRUGS FOR PARTIAL SEIZURES 1\. LAMOTRIGINE \* effective adjunct drugs for treating partial seizures in Adults and children. \* treatment in LENOX GASTRO SYNDROME or LENOX GASTAUT SYNDROME -- characterized by multiple types of seizures in pt with mental retardation and other neurologic abnormalities. S/E - Cerebellar dysfunction , drowsiness and rash - SJS - Aseptic meniningtis (rare) 2\. Topiramate \* sulfamate -- substituted monosaccharide \* TERATOGENIC : Cleft palate in Children 3\. Clobazam \* Adjunct treatment of seizures in children and adults with LGS \*Orphan Drug 4\. FELBAMATE \* treatment of Partial seizures refractory to other drugs \*problem: fatal aplastic anemia and acute hepatic failure 5\. Levetiracetam and Brivaracetam \*bind to synaptic vehicle protein (SV2A), reducing vesicular packaging of GABA and impeding neurotransmission across synapses. 6\. Perampanel -- AMDA blockers 7\. Clorazepate 8\. Gabapentin \*treatment of post-herpetic neuralgia \* PRODRUG: GABAPENTIN ENACARBIL \- restless leg syndrome 9\. Pregabalin \* treatment of neuropathic pain \* 1^st^ treatment of FIBROMYALGIA / POST LEG SYNDROME 10\. EZOGABINE \* AKA RETIGABINE \- sodium and chloride channel opener 11\. Vigabatrin \- Block GABA enzyme 12\. TIAGABINE \- GAT -- 1 inhibitor (GABA reuptake inhibition) DRUGS FOR GENERALIZED ABSENCE, MYOCLONIC or ATONIC SEIZURES 1\. ETHOSUXIMIDE \* inhibits the T-type calcium channels \*little toxicity, causes dizziness, drowsiness, gastric distress and nausea \* DOC for ABSENCE SEIZURE in CHILDREN \*in absence seizure, DO NOT USE A.CARBAMAZEPINE B.PHENYTOIN C.GABAPENTIN DRUGS FOR STATUS EPILEPTICUS - OLD DOC : LORAZEPAM - ALTERNATIVE: DIAZEPAM - NEW DOC : MIDAZOLAM \*if uncontrolled by Benzo or phenytoin, use FOSPHENYTOIN \*if highly resistant cases, use GENERAL ANESTHESIA DRUGS FOR PARKINSON'S DISEASE T- TREMOR R-RIGIDITY A-AKINESIA/BRADYKINESIA P-POSTURAL INSTABILTY S-SHUFFLING GAET INTERACTIONS LEVODOPA + MAOIs = Hypertensive Crisis LEVODOPA + Antipsychotic (typicals) = antagonist LEVODOPA + B6 = higher Dopamine conversion LEVODOPA + PROTEINS = transport process alterations LEVODOPA AKA DIHYDROXYPHENYLALANINE OTHER DRUGS for ANTI-PD 1\. AMANTADINE \*antiviral and anti-PD \*MOA = dopamine releaser A/E \*SEDATION, RESTLESSNESS, VIVID DREAMS, LIVEDO RETICULARS ANESTHETIC AGENTS STEPS /STAGES IN ANESTHESIA 1\. CORTICAL- ANALGESIA 2\. DELIRIUM -- NEURONAL EXCITATION 3\. SURGICAL -- RESPIRATORY AND SKELETAL MUSCLE RELAXATION 4\. MEDULLARY -- RESPIRATION DEPRESSION 2 TYPES OF ANESTHETIC AGENTS 1\. LOCAL ANESTHETICS -- block conduction nerve impulses S/E - CNS STIMULATION -- tremors - Drowsiness, sedation - High dose -- seizure or coma A.1 ESTER TYPE LOCAL ANESTHETICS +-----------------------+-----------------------+-----------------------+ | SHORT ACTING "PE" | INTERMEDIATE ACTING | LONG ACTING | | | "BC" | | +=======================+=======================+=======================+ | A. PROCAINE -- 1^st^ | A. COCAINE -- 1^st^ | A. TETRACAINE --long | | synthetic LA | naturally LA | DOA of all ester | | | | | | \*NOT AVAILABLE | \- VASOCONSTRICTOR | | +-----------------------+-----------------------+-----------------------+ | B. CHLOROPROCAINE | B. BENZOCAINE -- | | | | TOPICAL ANESTHETIC | | +-----------------------+-----------------------+-----------------------+ A.2 AMIDE TYPE LOCAL ANESTHETICS +-----------------------------------+-----------------------------------+ | INTERMEDIATE ACTING | LONG ACTING | +===================================+===================================+ | A. LIDOCAINE -- most widely used | A. BUPIVACAINE -- for labor and | | local anesthetic | delivery | | | | | \- safe for pregnant | \- can cause cardiotoxic (most) | | | | | \- soln, ointment, spray, gel, | | | patch | | +-----------------------------------+-----------------------------------+ | B. PRILOCAINE -- congener of | B. LEVOBUPIVACAINE | | lidocaine | | | | \- use for epidural anesthesia | | \- converted to methemoglobin | for labor and delivery | | | | | | \- less cardiotoxic | +-----------------------------------+-----------------------------------+ | EMLA -- LIDOCAINE + PRILOCAINE | C. ROPIVACAINE | | | | | = CIRCUMCISION | \- less potent | | | | | Toxic = methemoglobimia | \- adv: cause fewer cases of | | | cardiac toxicity | | Tx: methylene blue | | +-----------------------------------+-----------------------------------+ | | D. DIBUCAINE -- limited for pain | | | and itchiness | | | | | | E. ETIDOCAINE | +-----------------------------------+-----------------------------------+ B. GENERAL ANESTHETICS \* loss of consciousness a\. MINIMUM ALVEOLAR CONCENTRATION (MAC) \*most potent -- methoxyflurane( 0.16%) \*least potent -- nitrous oxide (100%) b\. BLOOD -- GAS PARTITION COEFFICIENT (BGPC) \*highest BG ratio : METHOXYFLURANE , \*lowest BG ratio : DESFLURANE (0.42%) Example drugs 1\. NONHALOGENATED DRUGS a\. NITROUS OXIDE (laughing gas) \*the only nonhalogenated anesthetic gas used today \*produces greater analgesia than do the other inhalational anesthetics \* NO cardiovascular or respiratory depression \* use in minor surgery A/E \*megaloblastic anemia \* produces mild euphoria 2\. HALOGENATED ANESTHETICS \*halogenated anesthetics replaced older, volatile liquid anesthetics ADVANTAGES \*more rapid rate of induction and recovery \* lower incidence of postoperative nausea and vomiting \*not flammable DISADVANTAGES - Dose dependant respiratory and cardiovascular depression - Cause uterine relaxation - Relatively little analgesia or skeletal muscle relaxation. Examples 1\. HALOTHANE \- the most potent inhalational agent NOW \- disadvan: slow onset and recovery Sensitizes the heart to catecholamines more than other anesthetics HEPATOTOXICITY -- Malignant hyperthermia ( treatment: Dantrolene) 2\. ENFLURANE AND ISOFLURANE \- more rapid induction and recovery than halothane \- less metabolic degradation and produce little cardiac arrhythmia DISADVA: \*cause more respiratory depression APPLICATION - ENFLURANE -- ASTHMA -- least hepatotoxic - ISOFLURANE -- NEUROSURGERY 3\. DESFLURANE AND SEVOFLURANE \*have more rapid rate of induction and recovery than other halogenated anesthetics DESFLURANE- irritating to the respiratory tract SEVOFLURANE -- close to an ideal anesthetic -- preferred for children \*rapid and smooth induction and recovery \* causes little cardiovascular or other organ system toxicity 3\. PARENTERAL ANESTHETICS 1\. BARBITURATES -- thiopental, methohexital 2\. BENZODIAZEPINES --midazolam 3\. OPIOIDS (FENTANYL) FENTANYL + DROPERIDOL = neuroleptanesthesia, twilight sleep FENTANYL + Nitrous OXIDE + DROPERIDOL = neuroleptanalgesia 4\. PROPOFOL \*induction anesthesia, presurgery \* PRODRUG : FOSPROPOFOL \* milk of AMNESIA 5\. ETOMIDATE \*rapid induction to induce anesthesia or for conscious sedation \* no cardiovascular 6\. KETAMINE \*blocks NMDA DISADVAN: unpleasant effects during recovery, including delirium, hallucinations and irrational behavior \*most often used in pediatric patients.