2008 Pharm Exam 1 Seizures/Anticonvulsants

Seizures = hyperactivity of NMDA receptor (glutamate) Drugs = encourage inactivatins of Na/Ca channels Na channel Blockers Phenyltoin: Use= chronic tonic seizure Contraindication: myoclonic seizure Mechanism: reduces potentiation from seizure focus (blocks Na channel), oral absorbtion * cant be injected, (other form fosphenytoin injected instead) * gingival hyperplasia Carbamazepine/oxcarbazepine: Use: Tonic clonic, neuralgia Contra: myoclonic Mech: Inactivates voltage gated Na, oral absorption

Na/Ca channel Blockers Lamotrigine: Use: complex, myoclonic Mech: more potent Na blocker than phenyltoin, also ca blocker Leviteracetam: Use: complex partial seizure and tonic clonic Mech: na/ca vesicles Valproic acid/valproate: Use: Tonic clonic and Epson(mild) seizures, neuralgia Contra: hepatic disease Mech: inactivates Na/ca(t-type) channels

Ca channel Blockers Ethosuximide: Use: Myoclonic Contra: tonic clonic Zonisamide: Use: myoclonic seizures Mech: blocks Ca channels Ca channel blocker (PAIN) Gabapentin: Use: neruropathic pain Mech: binds to subunit of voltage gater Ca channel Pregabalin: Same as gabapentin (but higher affinity) Gabaergic Drugs Phenobarbital: Use: tonic clonic Mech: opens cl- channel to inactivate entire cell Na/Ca/Gaba Topiramate: Use: partial seizures Mech: GABA, blocks AMPA, blocks NA channels Felbamate: Use: tonic clonic, partical seizures Mech: NMDA receptor

Psycosis
(Parkinson)Da release from s. nigra (D2 receptor caudate) = inhibits movement (psycosis) Da = frontal cortex neurotransmitter -motor side effects due to D2 antagonists Typical Antipsycotics Thioridazine - High sedative / High anticholenergic = low motor side effects - D2 antagonist Haloperidol - D2 selective antagonist - low sedative/ low anticholenergic = High motor side effects Atypical Antipsycotics Risperidone - Atipical - strong 5HT2 antagonist, strong d2 - less side effects than typicals Clozapine - Atipical - Strong 5HT2 antagonist, weak d2 - Motor side effects * Agranulocytosis Olanzapine - Atipical - strong 5HT2 (serotonin) antagonist, weak D2 -No motor side effects\ - used instead of clozapine (No agranulocytosis) Aripiprazole - Atipical - New antipsychotic - D2 Agonist (lowers nigra dopamine release), D2 Antagonist (post synaptic straital) - No Motor side effects

Parkinsons
-(Parkinson)Da release from s. nigra (D2 receptor (caudade)=inhibit motion suppression -= movement -Ach + glutamate(caudate)= activate movement suppression= no movement DA replacement Drugs L dopa + carbidopa (sinemet)

- Dopamine substitute (kinda) - side effects: orthostatic hypotension, dyskinesia

Entacapone

- blocks l-dopa metabolize in blood - extend life of (sinemet)

Anticholenergics Benzatropine

- enhance motion -Early PD - low TI * side effect = SLUD

DA Agonists Bromocriptine

- D2 receptor agonist, early and late PD - side effect = fibrosis, hallucinations

Misc Drugs Amantadine

-new antiviral -enhances DA release(s. nigra), block glutamate and ACH in caudate)
Selegiline

- inhibits DA metabolism (stays in brain longer) - side effect = reacts w/ SSRIs and tricyclics -mild effects and expensive
Apomorphine

-rescues frozen person -powerful d1/d2 agonist

Benzos

- reduce tremors

Autonomic Drugs
Muscarinic Agonists - parasympathetic (AHC release) - cause vasodilation via NO receptors -side effects; DUMBBLES Pilocarpine: used to stimulate salivary flow for patients w/xerostomia Cevimeline: used to stimulate salivary flow for patients w/xerostomia Bethanechol: Indirectly acting cholinomimetics - inhibitors of anticholinesterases (cause build-up of ACH) - affects PNS, SNS, skeletal muscle - reverse neuromuscular junction blockers Donepezil: Alzheimers treatment Neostigmine: myasthenia gravis treatment (no brain entry) Physostigmine: uncharged at in body (can get into brain - treatment of atropine poison ( ACH competes w/atropine for muscarinic receptor, so, more ACH in terminal means more stimulus) Cholinergic Blocking Agents (Muscarinic Antagonists) - blocks sympathetic postganglionic AHC receptors and sympathetic muscarinic receptors in sweat glands. - may cause xerostomia Atropine/Scopolamime: CNS effects of parkinsons disease Ipatropium/Tiotroipium: COPD patients, decrease secretions Tolterodine: incontinence Diphenhydramine: OTC sleep aid, antihistamine, motion sickness treatment Neuromuscular Junction Blockers - block ACH effect on skeletal muscle - barroreceptor mediated heart rate changes blocked Nicotine Varenicline: smoking cessation (partial nicotine agonist=can act as antagonist) - side effects= nausea, vomiting Mecamylamine: blocks ganglionic transmission (smoking cessation) - orthostatic hypotension, xerostomia

Sympathomimetic Agents Epinephrine: A1, A2, B1, B2 Norepinephrine: A1, A2, B1 Isoproterenol: B1, B2 Dopamine: D1, D2 (A1, B1 in high doses) Agents acting directly on adrenergic receptors Phenylephrine: A1 agonist - Vasoconstriction, pupil dialation - used in local anesthetics (vasoconstrictor) *safer for cardiac patients - metabolized by MAO (dont use w/patients taking MAO inhibitors) Levonordephrine (Clonidine and alphaphamethyl norepinephrine): A2 agonist - acts on CNS vasomotor center (decrease sympathetic output) - hypotension, sedation, Vasoconstriction (peripheral blood vessles) Dobutamine: B1 agonist - stimulate cardiac tissue (increase heart rate Albuterol: B2 agonist - relaxation of vascular, bronchiole, uterine smooth muscle - acute asthma treatment Salmetrol: B2 agonist - chronic asthma treatment (slow acting and long-term) Dopamine: Multi receptor agonist - increase cardiac output (B1 activity) - increase kidney arteriole vasodilation Indirectly acting agents: Amphetamine and Tyramine - act via NE realease (can get into CNS, unlike injected NE)

Sympatholytics - occupy receptor, but lack efficacy (dont elicit response) Alpha Adrenoceptor Antagonists Prazosin + Tamsulosin -block effects of endogenous NE and EPI -decrease vascular resistance (easier for heart) - increase urinary outflow - block A1 vasoconstrictors (levonordefrin) *Orthostatic hypotension Beta Adenoceptor Antagonists - reduce cardiac output - may result in bronchiole constriction (aggravate asthma) Propranodol: non-selective beta receptor blockers Metoprolol: selective B1 blocker Carvedilol: A1 and Beta receptors Agents acting sympathetic nerve endings - can be sympatholytics or sympathomimetics Guanadrel/Bretylium/Reserpine: inhibit nerve action potential, inhibits storage of NE in vesicles (sympatholytic) - general loss of SNS * Orthostatic hypotension Cocaine: blocks reuptake of NE (sympathomimetic) MOA inhibitors: decrease NE biosynthesis, decreased SNS function * orthostatic hypotension - Dont take w/tyramine (= sudden release of NE = Very high BP)

Antidepressants
- receptor desensitization takes several weeks (body rebounds to decrease receptor #) Clomipramine: Tricyclic, Unipolar depression, OC disorder -NE reuptake inhibitor/desensitize receptor - side effects: orthostatic hypotension, SLUD, dry mouth * interacts w/sedatives Phenelzine: MAO inhibitor, Unipolar depression -blocks breakdown NE, 5HT, DA/desensitize receptors - side effects: convulsions if OD * Dont take w/tyramine foods, antihistamine, decongestant = hypertension crisis Sertraline SSRI, Unipolar depression - selective serotonin (5HT) reuptake inhibitor/desensitize receptors - side effects: safe anti depressant (cant really OD) Venlafaxine: SNRI, Unipolar depression (take 2-3x daily) - serotonin/NE, desensitize receptors - side effects: hypertension (mild) Buproprion: Atipical, unipolar depression and psychomotor retardation/nicotine addiction - Dopamine/Seratonin reuptake inhibitor/desensitize receptor - side effects: nervousness/insomnia, dont react well with other sedatives Lithium: Bipolar depression/Mania -modifies NE and 5HT transmission -side effects: muscle fatigue, ataxia * NSAIDs reduce renal excretion of Li (toxic)

Anxiolytic-Sedatives - most act on GABA receptor

the brains main inhibitor (cl- channel)

Benzodiazapine - Dose dependent CNS depressants - Anxiety drug of choice - safe alone but lethal w/booze - long acting = hangover (metabolites can be active and longer lasting than original drug) - short action = rebound Oral Benzos Triazolam: short term pre-surgical sedatio - oral benzo (short term 2-hrs) - rebound anxiety Alprazolam: anxiety/insomnia - medium lasting oral benzo ( 6-20 hrs ) Diazapam: anxiety and Insomnia - Oral benzo (long lasting 14-90 hrs) - no cardiac or respitory depression - side effects: dependence with long term use Midazolam: preanesthetic sedation (dentistry) - short acting/water soluble IV benzo (GABA receptor agonist) -no major respitory/cardiac depression -rebound anxiety/insomnia when drug wears off Flumazenil: Benzo reverser (brings patient out of Benzo sedation) - GABA receptor antagonist

Barbituates Thiopental: short-term surgical anesthesia - ultra short acting barbiturate (lipid soluble = enters brain fast then enters fat stores) - major respitory and cardiac depression in OD, hangover intoxification (leach from fat stores) Secobarbital: short-term insomnia - intermediate acting oral barbiturate (GABA agonist) - side effects: diminishing TI over time (tolerance to ED, not LD), hangover effect, physical withdrawal and dependence from long-term use Phenobarbital: Epileptic seizures w/o tolerance - long acting oral barbiturate (GABA receptor agonist) - slowly metabolized by liver = long lasting - side effects: major respitory and cardiac depression in OD Other Sedative Diphenhydramine/Hydroxyzine: Insomnia, runny nose - anticholinergic action - no side effects Meprobamate: Anxiety/Insomnia - Barbituate-like action, but cant produce surgical anesthesia - 50s women sedatives (Stepford Wives) - side effects: Low TI Chloral Hydrate: Liquid sedative (mild anesthetic) - rapid onset, short duration - side effects: Low TI * used for child dental appts Nitrous Oxide: Anesthesia - no cardiac or respitory suppression Melatonin: Insomnia, Jet lag - mild hypnotic, changes circadian rhythm Non Sedating Anxiolytic Buspirone: anxiolytic effect only (no sedation), takes several weeks to work - 5HT agonist (reduces transmission) - no major effects Zolpidem: Z Drug. Insomia only - act on GABA receptor (like benzos) - side effects: mild psych dependence * Do not take z-drugs w/ Benzos = bad mix