CNS Drugs

• Paradoxical disinhibition
• Sedation, anxiolysis, anticonvulsant + muscle relax
• Hypnosis
• Anesthesia (BDZs start plateau here)
• Meduallary depression-->resp depression
• Coma
• Death

• Ligand gated Cl- channel
• 5subunits
• alpha- GABA
• beta- Barbituates
• gamma-Benzodiazepines

• GPCR--> K+ efflux
• (just like M2 in SA and AV node!)
• only agonist- Baclofen

• BDZ overdose antidote!
• -block both BZ1 and BZ2 receptor sites! (both GABAa receptor gamma subunit subtypes)

does NOT reverse Barbituate or Alcohol overdose

• Sedative-hypnotic
• Potentiate GABA (GABAa)
• (shift sigmoid log-response curve to Left!)
• Increase frequency of Cl channel opening
• Decrease REM sleep
• most have long half-lives, active metabolites
• less risk of resp depression than Barbituates, alcohol

• USE- Anxiety, Spasticity
• Status epilepticus (Lorazepam, Diazepam)
• Detox for alcohol withdrawal
• night terrors, sleepwalking
• General anesthetic (amnesia, muscle relax)
• Hypnotic (insomnia)

• BZ1--> sedation
• BZ2-->antianxiety, anterograde amnesia

SE- dependence, additive CNS depression with alcohol

• Oxazepam
• Temazepam
• Lorazepam

• Temazepam
• Oxazepam
• Midazolam (shortest, only IV)

• Good for insomnia!
• But has Highest addiction potential

• Diazepam
• Lorazepam
• Midazolam

Good for emergency withdrawal states (alcohol) and Seizures (except Midazolam)!

• BDZ, Potentiate GABA
• (shift sigmoid log-response curve to Left!)
• Increase frequency of Cl channel opening
• Has active metabolite, long half life

USE- Anxiety, Panic, Phobias

SE- dependence, additive CNS depression with alcohol

• BDZ, Potentiate GABA
• (shift sigmoid log-response curve to Left!)
• Increase frequency of Cl channel opening
• Has many active metabolites, so long acting
• Diazepam-->Nordiazepam-->Oxazepam
• has IV!

• USE- Anxiety, preOp sedation, muscle relaxant (UMN-spasticity)
• Withdrawal states (esp. Alcohol)
• can use for Seizures (but prefer Lorazepam)

SE-dependence, additive CNS depression with alcohol

• BDZ, Potentiate GABA
• (shift sigmoid log-response curve to Left!)
• Increase frequency of Cl channel opening
• NO active metabolites, but still long acting
• has IV!

• USE- anxiety, preOP sedation,
• Status Epilepticus (IV)!!

SE-dependence, additive CNS depression with alcohol

• BDZ, Potentiate GABA
• (shift sigmoid log-response curve to Left!)
• Increase frequency of Cl channel opening

Shortest Half life (mins)!! so use only IV!

USE- PreOP sedation, Anesthesia IV

• SE-dependence, additive CNS depression with alcohol

• BDZ, Potentiate GABA
• (shift sigmoid log-response curve to Left!)
• Increase frequency of Cl channel opening

• Short half life! No active metabolites
• so good for insomnia!

USE- sleep disorders

SE-dependence, additive CNS depression with alcohol

• BDZ, Potentiate GABA
• (shift sigmoid log-response curve to Left!)
• Increase frequency of Cl channel opening

• Short half life! NO active metabolites
• so good for insomnia!

USE- sleep disorders

SE-dependence, additive CNS depression with alcohol

BDZ (see other cards)

• Sedative-hypnotic
• Prolong GABA activity (GABAa)
• Increase duration of Cl- channel activity
• Bind gamma subunit
• GABA mimetic activity at HIGH DOSE --> resp depression-->coma-->death
• Inhibit Complex I on ETC--> decr ATP
• INDUCE Cyp450!! (incr Vmax!)

USE- Sedative for Anxiety, Seizures, Insomnia, Induction of Anesthesia (Thiopental)

• SE- dependence, additive CNS depression with Alcohol, Resp/CV depression-->coma/death, Induce Cyps!!
• DO NOT USE IN PORPHYRIAS!! -activate D-ALA synthase, worsen the buildup of metabolites in Porphyrias (enzyme deficiency downstream of ALA-synthase)

• Chronic use-->tolerance
• Cross-tolerance between BDZ, Barbituates, Ethanol
• Psychologic (craving) + Physical dependence
• Abuse liability BDZ< Barbituates or Ethanol

• Rebound insomnia
• Rebound anxiety
• Seizures (if Lorazepam or Diazepam was used as antiepileptic)

• Anxiety
• Agitation
• Life-threatening Seizures!
• Delirium (w/ alcohol)

Manage withdrawal with long acting BDZs (Diazepam, Lorazepam)

Additive with other CNS depressants! (anesthetics, antihistamines, opiates, beta-blockers, alpha-agonists)

Barbituates INDUCE Cyps-->induce breakdown of lipid soluble drugs (OPC, Cabamazepine, Phenytoin, Warfarin..)

• Barbituate
• Prolong GABA activity
• Increase duration of Cl- channel activity
• GABA mimetic activity at HIGH DOSE --> resp depression-->coma-->death
• Inhibit Complex I on ETC--> decr ATP
• INDUCE Cyp450!! (incr Vmax!)
• LONG ACTING

USE- Seizures, safe in pregnancy!

• SE- dependence, additive CNS depression with Alcohol, Resp/CV depression-->coma/death,
• Induce Cyps!!
• DO NOT USE IN PORPHYRIAS!! -activate D-ALA synthase, worsen the buildup of metabolites in Porphyrias (enzyme deficiency downstream of ALA-synthase)

• Barbituate
• Prolong GABA activity
• Increase duration of Cl- channel activity
• GABA mimetic activity at HIGH DOSE --> resp depression-->coma-->death
• Inhibit Complex I on ETC--> decr ATP
• INDUCE Cyp450!! (incr Vmax!)
• Short acting!

USE- Induction of Anesthesia

• SE- dependence, additive CNS depression with Alcohol, Resp/CV depression-->coma/death,
• Induce Cyps!!
• DO NOT USE IN PORPHYRIAS!! -activate D-ALA synthase, worsen the buildup of metabolites in Porphyrias (enzyme deficiency downstream of ALA-synthase)

• Barbituates
• Prolong GABA activity
• Increase duration of Cl- channel activity
• GABA mimetic activity at HIGH DOSE --> resp depression-->coma-->death
• Inhibit Complex I on ETC--> decr ATP
• INDUCE Cyp450!! (incr Vmax!)

USE- Sedative for Anxiety, Seizures, Insomnia

• SE- dependence, additive CNS depression with Alcohol, Resp/CV depression-->coma/death,
• Induce Cyps!! DO NOT USE IN PORPHYRIAS!! -activate D-ALA synthase, worsen the buildup of metabolites in Porphyrias (enzyme deficiency downstream of ALA-synthase)

• Non-BDZ hypnotics
• BZ1 agonist! -->sedation
• Less effect on cognition/memory (BZ2)
• Less addictive
• Short duration

USE- Sleep disorders only

• SE-ataxia, headache, confusion
• modest day-after psychomotor depression

• Non-BDZ hypnotics
• BZ1 agonist! -->sedation
• Less effect on cognition/memory (BZ2)
• Less addictive
• Short duration

USE- Sleep disorders only

SE-ataxia, headache, confusionmodest day-after psychomotor depression

• Non-BDZ hypnotic
• 5-HT_1A partial agonist
• partial agonist (agonist alone, blocker w/ full agonist)
• NO effect on GABA
• nonsedative!! no addition, no tolerance, no interaction with alcohol!

USE- generalized anxiety disorders (takes 1-2wks to work)

• CNS depression
• metabolic acidosis

Ethylene glycol--->Alcohol dehydrogenase-->Aldehyde dehydrogenase-->Oxalic acid

• CNS depression
• Severe anion gap metabolic acidosis
• Acute tubular necrosis + Oxalate crystals

Rx- Fomepizole (block alcohol dehydrogenase)

• (wood alcohol contaminant)
• Methanol-->alcohol dehydrogenase-->Formaldehyde-->aldehyde dehydrogenase-->Formic acid

• CNS depression, respiratory failure
• Severe anion gap metabolic acidosis
• Blindness!

Rx-Fomepizole

• Ethanol-->alcohol dehydrogenase (cytoplasm)-->Acetaldehyde->acetaldehyde dehydrogenase (mitochon)-->Acetic Acid-->Acetyl-CoA--> glycerol-3P
• NADH made every step!
• Build up of Acetaldehyde--> hangover!
• Acetaldehyde dehydrogenase needs Thimine and Folate!
• -headache, hypotension, inactivate Folate, decrease Thiamine

• CNS depression
• Metabolic acidosis
• Acetaldehyde toxicity

steps: incr sociability-->gait-->delay rxn time-->ataxia-->impaired mental status-->coma-->death

Alcohol damages Liver, Pancrease, Heart and Brain!

• Fasting hypoglycemia
• -Acetaldehyde-->decrs Thiamine-->decrs Gluconeogenesis
• -incres NADH-->make Pyruvate-->lactic acid, so deprive Pyruvate for gluconeogenesis.
• Faty liver + lipemia (mallory bodies)
• -Incrs NADH, Acetyl-CoA
• Acute, Chronic Pancreatisis
• Muscle wasting (low glu--> incrs proteolysis)
• Gout (lactate competes with urate for excretion)
• Mallory Weis, Borhaaves' Syndrome
• Beri Beri
• Wernicke Korsakoff
• Dilated Cariomyopathy
• Risk of squamous cell carcinoma of esophagus
• Risk of Linitis Plastica

• Note: Give IV Thiamine before giving glucose!
• b/c Thiamine cofactor for carb-metabolism->fiving just glucose may cause hyperosmolar coma!

Acetaldehyde dehydrogenase blocker

• USE-given to increase neg feedback for alcoholics
• build up of acetaldehyde-->make you feel like shit (hangover)

Disulfram-like effects: headache, hypotension, nausea, vomit

-azoles

• Metronidazole
• Cephalosporines (Cefoperazone. Cefotetan)
• Chlorpropamide (sulfonylurease)
• Griseofulvin (antifungal)

• Decrs axon conduction by blocking Na influx
• -Phenytoin, Carbamazapine
• Increase inhibition by GABA
• -Barbituates, BDZ
• Decrease excitation by Glutamate
• -Lamotrigine, Topiramate, Felbamate
• Decrease presynaptic T-type Ca channel (in thalamus)- Ethosuximide, Valproic Acid

• Partial: simple or complex
• -no loss of consciousness
• USE- Valproic Acid, Phenytoin, Carbamazepine

• General- global brain, all lose consciousness
• General- Tonic Clonic
• -Grand mal seizure
• USE- Phenytoin, Carbamazepine, Valproic acid

• General-Absence
• -moment of CNS depression!
• CNS depressants like BDZ, Barbituates will worsen it!
• USE- Ethosuximide, Valproic acid

• Status Epilepticus
• -epilepsy prolongs over 30 mins-->danger of glutamate toxicity, hydroping braing swelling, respiratory compromise
• -need IV-anticonvulsants!
• USE- IV BDZ: Lorazepam, Diazepam
• -prophylactic: Phenytoin or Fosphenytoin(parenteral, water soluble)

• anticonvulsant
• -block axonal Na channels (inactivated state, like Class Ib antiarrhythmics)
• -increase refractory period, inhibit glutamate release
• -prevent seizure prolongation

• USE- 1st line for Tonic Clonic seizure! (any seizures except absence!!)
• -prophylaxis for Status Epilepticus

Zero-order kinetics! (constant amount cleared per time-->nonlinear kinetics of dose vs plasma conc) reach toxic dose faster

• SE-Induce Cyps (don't use in Porphyria), Gingival hyperplasia +hirsutism, Nystagmus, ataxia, diplopia, sedation, SLE-like syndrome.
• -Osteomalacia (decrs Vit D), megaloblastic anemia (decr GI conjugase-->decr Folate absorp), Aplastic anemia (SLE-like HST rxn)
• Teratogenic!-cleft lip, palate (fetal hydantoin syndrome)

• anticonvulsant
• -block axonal Na channels (inactivated state, like Class Ib antiarrhythmics)
• -increase refractory period, inhibit glutamate release
• -prevent seizure prolongation

• USE- 1st line for Tonic Clonic seizure (any seizure except absence!)
• - Trigeminal neuralgia (DOC!)
• - manic phase of Bipolar

• SE-Induce Cyps (incrs its own metabolism-may req higher doses later)
• -Exfoliative Dermatitis (Steven-Jphnson's syndrome) + incrs ADH secretion (dilutional hyponatremia!-SIADH)
• -Osteomalacia + Megaloblastic anemia + Aplastic anemia
• Teratogenic- clepft lip/palate, spina bifida

• anticonvulsant
• -block inactivated Na channels (like Phenytoin)
• -block GABA tansaminase (block GABA breakdown)
• -blocke T-type Ca-channel

• USE- any seizures including Absence seizures!
• -Mania of Bipolar, Migraines

• INHIBIT Cyps (opposite of Phenytoin, Carbamazapine..)
• SE-Hepatotoxicity, Thrombocytopenia
• Pancreatitis , Alopecia (hair loss- opposite of Phenytoin), weight gain, tremor
• Teratogenic- Spina bifida (Phenytoin-cleft lip/palate)
• do NOT use in pregancy!

• anticonvulsant
• -block T-type Ca channels in thalamus

USE- Absence seizures! (DOC)

• SE-GI distress, fatigue, headache, urticaria,
• Stevens-Johnson Syndrome!

Prodrome of malaise + fever--> rapid onset red rash (oral, ocular, genital)

rash progresses to epidermal necrosis and sloughing

• anticonvulsants are additive with other CNS depressants! -alcohol, opiates, antihistamines..
• Avoid abrupt withdrawal-->ppt seizures
• Decrs efficacy of OPCs (b/c most induce Cyps)-use Valproic acid that inhibits Cyps if on OPCs
• Phenobarbital-safe during pregnancy

• anticonvulsant
• block vol-Na channels AND glutamate receptors

USE- adjunct to other seizure drugs

• SE- Hepatotoxicity + aplastic anemia (Felbamate)
• - Stevens-Johnson syndrome (Lamotrigine)

• anticonvulsant
• -GABA analog (enhance GABA effects)
• -inhibit HVA Ca-channels

• USE- Seizures, neuropathic pain (peripheral neuropathy)
• -Bipolar

SE- Sedation, ataxia

• anticonvulsant
• -block Na channels
• -enhance GABA

USE- Partial seizures and Tonic Clonic

SE- Sedation, Mental-dulling, Kidney stones, weight loss

• Barbituate, anticonvulsant
• Prolong GABA activity

• INDUCE Cyp450!! (incr Vmax!)
• LONG ACTING

USE- Seizures, safe in pregnancy!

• SE- dependence, sedation, tolerance, Induce Cyps!!
• DO NOT USE IN PORPHYRIAS!!

• Benzodiazepines
• Potentiate GABA (incrs frequency of open)

• USE- DOC for Status Epilepticus!
• -b/c IV
• -seizures of eclampsia (1st line is MgSO4)
• -Lorazepam has simpler kinetics (no active metabolite and long acting)

SE- Sedation, tolerance, dependence (see Benzos)

• anticonvulsant
• -inhibit GABA reuptake

USE- Partial seizures

• anticonvulsant
• -irreversibly inhibit GABA transaminase-> incr GABA

USE- Partial seizures

• anticonvulsant
• -unknown mech

USE- Partial seizure , Tonic clonic

• Lipid soluble (cross BBB) or be Actively transported.
• -inhaled anesthetics potency depends on Lipid solubility!

• MAC= amount req to anesthetize 50% patients
• -measure of potency
• -Drugs w/ LOW solubility in blood (less lipid soluble) = more protein bound, less free "gas' form= rapid induction, recovery (ex) N2O

-Drugs with HIGH solubility in blood (more lipid soluble)= low MAC, high potency. Slower induction!

• - more lipid soluble= lower MAC, greater potency
• -MAC values are additive (why use combo)
• -MAC lower in elderly! so use lower dose
• -MAC lower in combo with opiates, sedative hypnotics.

• Blood:Gas
• Blood= protein bound drug
• Gas= free, active drug (goes to brain)

higher blood solubility= slower anesthesia (b.c more protein bound)

• Low B/G--> fast onset, fast recovery! (ex) N2O
• High B/G --> slow onset, slow recovery! -likes to accumulate. (ex) Haloethane

-Lungs: high rate + depth of ventilation= high gas tension

-Blood: high solubility= high Blood/Gas partition coefficient= high solubility= More gas req to saturate blood= slower onset!

-Tissue (ex. Brain): high AV concentration gradient= high solubility= high gas req to saturate tissue= slower onset!

• inhaled anesthetic
• -HIGH MAC (104%) = LOW potency
• -LOW bood:gas ratio (low protein bound)
• -LOW blood and lipid solubility
• -fast induction and recovery
• -NO metabolism. Just breath out

USE- Great induction of anesthesia

SE- Diffusional hypoxia (Henry's law: dec partial-P O2), spontaneous abortions, expansion of trapped gas

• inhaled anesthetic
• -LOW MAC (0.8%)= HiGH potency
• -HIGH blood: gas ration (high protein bound)
• -High lipid, blood solubility
• -slow induction, slow recovery
• -likes to build up! (slow metabolism)

USE- anesthesia: heart depression, resp depression, nausea/emesis, incr cerebral blood flow (decrease cerebral metabolic demand)

• SE- CV: sensitize heart to NE, EPI--> arrhythmias
• Hepatotoxicity (additive!) Malignant hyperthermia
• (see next cards)

• Nephrotoxicity
• Malignant hyperthermia

• Proconvulsant
• Malignant hyperthermia

• Barbituate, IV-anesthetic
• -highly lipid soluble, high potenty
• -rapid entry to brain- rapid onset
• -short acting due to redistribution!

• USE- INDUCTION of anesthesia
• -short surgery
• -decrease cerebral blood flow

• BDZ, IV-anesthetic
• Potentiate GABA
• -Shortest Half life BDZ (mins)!!
• so use only IV!

• USE- preOP sedation, Adjunctive to Gaseous anesthetic & narcotics
• -most commonly used drug for ENDOSCOPY
• (b/c sedation + amnesia)

• SE- severe post-op resp depression, additive CNS depression with alcohol
• -RX overdose with Flumazenil!

• IV anesthetic
• -looks like milk!
• -Potentiate GABAa
• -CNS, Cardiac depressant
• -rapid onset

• USE- rapid induction + maintenance anesthesia
• -short procedures
• -antiemetic! less postop nausea than thiopental

• IV- anesthetic, Opiate
• depress respiratory function
• -has central analgesic fuction! (different from anesthesia)

• USE- Inuduction + maintenance of anesthesia
• -used with other anesthetics dur general anesthesia

SE- resp depression

• arylcyclohexylamine, IV-anesthetic
• -PCP (phencyclinidine) analog "angel dust"
• -block NMDA-receptor

• USE- dissociative anesthetic
• -Induction of anesthesia, esp used alot in Kids

• SE- CV stimulation, delirium, hallucinations, disorientation, Nightmares, incerase ICP (increase cerebral blood flow)
• DO NOT use in head trauma.

• Provide regional anesthesia
• -are ALL weak bases (R-NH2--> R-NH3+)
• MECH:
• 1. unionized weak base diffuse into nerve terminal
• (need alkaline pH to be unionized & lipid soluble)
• 2. gets ionized by acidic environment inside the cell
• 3. block inactivated Vol-Na channel (like Class Ib antiarrhythmic)

NOTE: infected tissue is more acidic! so must use MORE anesthetic b/c they'll be ionized and less will get in the nerve terminals

• Esters: Cocaine, Procaine, Benzocaine, Tetracaine
• -NO "i" before "-caine"
• -metabolized by esterases in tissue, plasma
• -must worry about slow vs fast metabolizers

• Amides: Lidocaine, Bupivacaine, Mepivacaine
• -"i" before "-caine"
• -metabolized by liver amidases
• -pt must have good liver function

• -smaller diameter & high firing rate fibers are more sensitive to local anesthetics!
• (reach effective conc faster, more inactivated channels)
• small diameter> larger diameter (size matters more)
• myelinated> unmyelinated

• B, C fibers> A-delta> A-beta, gamma> A-alpha
• small myelinated> small unmyelinated> large myelinated> large unmyelinated

• B= preganglionic autonomic
• C= dull pain
• A-delta= sharp pain
• Pain> temp> touch> pressure (lose last)

• Neurotoxicity (CNS excitation)
• Cardiotoxicity (esp. Bupivacaine)
• Arrhythmia (esp. cocaine)
• Hypertension, Hypotension
• Allergies with Ester anesthetics! (PABA-drugs)
• -like Sulfonamide hypersensitivity, PABA-drugs cause skin allergies.
• -use Amide locals if pt has PABA allergy!!!

NOTE: Sulfonamides actually also have PABA structure! both Sulfa- and PABA- allergy!!

• locals administerd with Alpha-agonists--> vasoconstrict
• - decrease local anestheic spread into systemic
• -prolong effects + decrease toxicity

NOTE: do NOT need alpha-agonist adjuvant with Cocaine!- inhibit Na-channel + inhibit reuptake of NE--> indirect alpha-agonist--> vasoconstrict

• natural Vol-Na channel blocker
• -in Puffer fish
• -block activated channels--> block Na entry

NOTE: "TTX-sensitive channel" = classic vol-Na channel!

• natural Vol-Na channel blocker
• -in algae! "red-tide" in southern cali
• -block activated channels--> block Na entry
• -can aerosolize

• neuromuscular blocking agents!
• -block Nicotinic receptor (Nm- only SKM)
• -Two Ach bind each to two alpha subunits to open Na channel--> depol
• -2 types:
• 1. Nondepolarizing: competative-
• D-Tubocurarine, Atracurium, Mivacurium, Pancuronium, Vecuronium, Rocuronium
• 2. Depolarizing: non-competative- Succinylcholine

USE-anesthesia protocols, intubation

• Competative nicotinic blocker
• -"-curium"
• -prototype: D-Tubocurarine
• -reversible with AchE inhibitors (Neostigmine)
• -Progressive paralysis (face, limbs, resp muscle)
• -NO CNS effects

NOTE: b/c need 2 Ach binding to open the nicotinic channel, we only need ONE molecule of drug to prevent channel opening.

• -skeletal muscle relaxant
• Prototype of nondepolarizing , competative nicotinic receptor blocker
• -reversible with AchE inhibitors (Neostigmine)
• -Progressive paralysis (face, limbs, resp muscle)
• -NO CNS effects

• skeletal muscle relaxant
• -depolarizing , competative nicotinic receptor blocker
• -reversible with AchE inhibitors (Neostigmine)
• -Progressive paralysis (face, limbs, resp muscle)
• -NO CNS effects (SKM only)

• -rapid recovery
• -safe in liver or renal disease, b/c spontaneously breakdown to Laudanosine. (Hoffmann degredation)

SE- Laudanosine can cause seizures!

• skeletal muscle relaxant
• -nondepolarizing , competative nicotinic receptor blocker
• -reversible with AchE inhibitors (Neostigmine)
• -Progressive paralysis (face, limbs, resp muscle)
• -NO CNS effects (SKM only)

• -very short duration
• -metabolized by plasma cholinesterases

SE- watch out for slow metabolizers!

• skeletal muscle relaxants
• -nondepolarizing , competative nicotinic receptor blocker
• -reversible with AchE inhibitors (Neostigmine)
• -Progressive paralysis (face, limbs, resp muscle)
• -NO CNS effects (SKM only)

• Skeletal muscle relaxant
• -Depolarizing, non-competative nicotinic receptor agonist!
• -2 phases:
• I: depol--> fasciculation-->prolonged depol--> flaccid paralysis
• II: desensitization

• -cannot reverse with AchE-inhibitors- actually worsen phase I, no effect on II.
• -Short duration, hydrolzyed by pseudocholinesterases

• SE-watch for slow metabolizers
• -Hypercalcemia
• -Hyperkalemia-->worsen depol
• -Malignant hyperthermia (Rx w/ Dantrolene)

life-threatening syndrome assoc w/ use of SKM relaxants, esp. Succinylcholine and inhalation anesthetics (except N2O)

Succinylcholine-->depol muscle-->contract, need lot of ATP-->increase ETC, O2consumption, metabolic rate--> metabolic acidosis + heat!!--> trigger SNS to cool--> tachycardia, arrhythmia, hyperkalemia, HTN

Genomic susceptability: mutation in Ryanodine receptor or L-type Ca channel in SKM--> abnormal high Ca storage--> massive response to Succinylcholine.

Rx- Dantrolene

antidote for Malignant Hyperthermia, Neuroleptic malignant syndrome

-block Ca release from SER of SKM

• USE- malignant hyperthermia (inhalant anesthetic, succinycholine toxicity)
• -neuroleptic malignant syndrome (antipsychotic toxicity)

• centrally acting SKM relaxant
• GABA-b agonist
• GPCR--> K+ efflux (just like M2 in SA and AV node!)

USE- Spasticity

• 3 receptors: Mu, Kappa, Delta--> Gi--> open K+, close Ca channels--> decrease synaptic transmission
• -decrease release of ACh, NE, 5-HT, Glutamate, Substance-P

• 3 endogenous opioids:
• -Endorphins -->mu
• -Dynorphins--> kappa
• -Enkephalins--> delta

• Pain
• Cough suppression (dextromethorphan)
• Diarrhea (Loperamide, Diphenoxylate)
• Acute pulm. edema
• Maintenance programs (Methadone)

SE- Addiction, Resp depression, constipation, miosis, additive CNS depression with other drugs

• Opioid (central analgesic)
• Prototype mu-agonist --> decr NE release

• ACTIONS-analgesia (dissociative)
• -CNS sedation
• -Resp. sedation (block brain response to high CO2)-->pt breathes under hypoxic drive only
• -NO effect on heart
• -Histamine release--> vasodilate
• -GI- relax longitudinal, constrict circular--> constipation, urinary retention, constrict all sphincters (biliary)--> GI/gallbladder spasm
• -Miosis
• -NOT mu-mediated: Suppress cough, Nausea/vomit (CTZ D2 receptors)

KINETICS: glucuronidated to a more potent metabolite (Morphine6glucuronide), be careful with renal disease pts!!

DO NOT give O2 to pts on Opioids unless they're on a ventilator!!! may stop breathing

• Head injuries (increase ICP)
• Pulm disease (except Pulm edema)
• Liver/Kidney disease (accumulate metaboite)
• Adrenal/ Thyroid deficiencies (exaggerated response)
• Pregnancy (neonatal depression/dependence)- except Meperidine

• Opioid
• Full-mu agonist
• anti-muscarinic!

• USE- central analgesic
• -NO miosis, NO GI/gallbladder spasm

• SE-tachycardia
• -metabolized by Cyp450--> Normeperidine (SSRI) can cause Serotonin syndrome + seizures!

• Opioid
• Full mu-agonist
• -slower kinetic, long half-life (1-3 days)

• USE- maintenance of opioid addict
• -slower, tapers off--> prevents opioid withdrawal.

SE- takes long time to reach steady state (b/c long half-life)--> pt may overdose

• Opioid
• Full mu-agonist
• morphine-like, but much much weaker!

• USE- Cough suppressant, Analgesia
• (used in combo w/ NSAIDS)

SE-Addiction, Resp depression, constipation, miosis, additive CNS depression with other drugs

• Opioid
• Partial mu-agonist

USE- IV mild/moderate pain (safer)

• SE- b/c partial agonist (blocker in presence of a full agonist), may ppt withdrawal on some already on a full opioid!!!
• Addiction, Resp depression, constipation, miosis, additive CNS depression with other drugs

• Opioid
• Mixed- partial mu-agonist, kappa-agonist

USE- analgesia (less resp. depression than full agonists), dysphoria

SE- ppt withdrawal if pt is on full opioid!

• Very weak opioid agonist +inhibits 5-HT, NE reuptake!
• -works on multiple NT "tram it all"in

USE- chronic pain

SE-Lower seizure threshold, Addiction, Resp depression, constipation, miosis, additive CNS depression with other drugs

• Opioid
• Mixed agonist (kappa) + antagonist (mu)

• USE- Kappa-> spinal analgesia (decr subP), dysphoria (NOT euphoria)
• Mu block--> may ppt withdrawal!

• Opioid
• Mixed agonist (kappa) + antagonist (mu)

• USE- Kappa-> spinal analgesia (decr subP), dysphoria (NOT euphoria)
• Mu block--> may ppt withdrawal!

• Opioid receptor antagonist
• IV only

USE- IV reversal of opioid-induced respiratory depression

• Opioid receptor antagonist
• PO

USE- decrease craving for Alcohol and Opioid addiction (nothing to do w/reversal!)

• Opioid receptor antagonist
• -does NOT cross BBB

USE- opioid-induced constipation! (often used in end-stage cancer pts on heavy opioid analgesics)

• Acute opioid toxicity:
• -Pinpoint pupils (except Meperidine)
• -Resp depression
• -Coma

Rx- Supportive, give Naloxone (IV)

Dependence: Physical + Psychologic

• Unique pharmacodynamic tolerance!
• -NOT receptor downregulation/desensitization
• -at level of Gi signal transduction-- increased cAMP cancels effects of Gi-> decr cAMP
• -tolerance occurs to all effects except miosis, constipation.

• -Sympathetic surge! (upregulated alpha-1, beta-1 receptors due to decrease NE release with an opioid is now overstimulated)
• -Reverse effects of Opioids

• -Yawning
• -lacrimate, salivate, rhinorrhea (from anxiety, agitation)
• -Anxiety, sweating, goose bumps
• -Diarrhea, incontinence
• -muscle cramps, spasm, CNS-ongoing pain

• Rx-Clonidine (alpha-2 agonist--> decr NE release)
• -Methadone maintenance.

• Opioid related
• OCT as Imodium

USE- diarrhea

• Opioid related
• OTC
• similar to Ketamine

USE- cough suppressant

SE- high abuse potential, high dose--> status epilepticus

• Nigrostriatal path (D 2A-->Gi) - SN-->Striatum (DA inhibit GABA-ergic neruons)
• -DA initiate movement
• DA agonist--> diskinesia (hyperkinetic)
• DA antagonist--> bradykinesia (extrapyramidal dysfunction)

• Mesolimbic-mesocortical (D 2C--> Gi)
• - midbrain-->cortex, limbic sys.
• -affect, reward, cog fxn, sensory.
• -increased in psychosis.
• DA-agonist-->reward, high dose-->psychosis
• DA-blocker-->decr cog fxn, Rx. psychosis

• Tuberoinfundibular
• -hypothalamus-->ant pituitary-->DA--> decr Prolactin, GH
• -DA controls temp, cause anorexia (w/ NE)
• DA-agonist--> Rx hyperprolactinemia
• DA-antagonist-->gynecomastia, amennorrhea/galactorrhea, hyperthermia, weight gain

• Chemoreceptor trigger zone
• DA--> emesis
• DA-agonist-->emetic (Apomorphine)

5 subtypes, divided into 2 families

• D1--> Gs
• D2--> Gi

• D2A- nigrostriatal (movement)
• D2C- mesolimbic (mood)

Subtype specificity important! ex. Clozapine

• 2% pop (70's)
• oxidative damage to SN-->degeneration of DA-->imbalance, low DA, high Ach

• -bradykinesia (dec DA)-shuffling gate
• -Muscle rigidity (incr Ach, cogwheel rigidity)
• -Resting tremor (incr Ach, NOT intention tremor as in cerebellar damage or alcoholics)

• Direct/Excitatory pathway:
• SN-->DA-->D1 (caudate/putamen)-->Gs-->stimulate excitatory pathway-->incr motion.
• (loss of DA decrease excitatory pathway!)

• Indirect/Inhibitory pathway:
• SN-->DA-->D2 (caudate/putamen)-->Gi-->block GABAergic neuron-->inhibit inhibitory pathway-->incr motion
• (loss of DA activates inhibitory pathway!)

• Levodopa- prodrug-->AAAD--> DA
• -DA cannot cross BBB, Levodopa can.
• -converted to DA by brain AAAD
• -AAAD exists in both brain and CNS

• Carbidopa irreversibly inhibits peripheral AAAD
• -Carbidopa should NOT cross BBB (we need CNS AAAD!)
• -noncompetative-->decr Vmax
• -maximize amount of Levodopa to go into brain

USE- Parkinson's disease

• SE- Dyskinesia (DA there all the time), On-Off effects, Psychosis
• -Hypotention (D1 on BV-->vasodilate). Arrythmia
• -Vomit (D2 on CTZ)
• -decrease prolactin

• COMT inhibitor
• -COMT in both periphery and CNS convert DA, Levodopa-->3-O-methyldopa (partial agonist of D receptors-->compete w/ DA!)
• Entacapone (peripheral COMP)
• Tolcapone(central)!!

• USE-Parkinson's disease, adjunct to Levodopa
• -inhibit COMT--> increase Levodopa, DA available.
• -Tolcapone, Entacapone must cross BBB to inhibit all COMPT!

SE- hepatotoxic

• Selevtive MAOb inhibitor
• -MAOb breakdown DA (not NE, 5-HT) and Levodopa
• -so NO tyramine interactions (NO HTN crisis!)
• (MAOa inhibitors-->Tyramine worry)

• USE- Parkinson's disease, Adjunct to Levodopa
• -allow Levodopa, DA to last longer

• SE- dyskinesia, psychosis
• -metabolized to amphetamine!!! (hyper, insomnia, agitation)

Full DA receptor agonist (ergot)

• USE-hyperprolactinemia, acromegaly
• (b/c DA--> inhibit Prolactin, GH release from ant. pituitary)
• -NOT used in Parkinson's b/c too much SE

SE- Dyskinesia, Psychosis

• non-ergot DA receptor agonist
• weaker than ergots
• -also antioxidants!!!

USE- Parkinson's disease

• non-ergot DA receptor agonist
• weaker than ergots
• -also antioxidants!!!

USE- Parkinson's disease

antimuscarinic

• USE- Parkinson's disease, improves tremor, rigidity
• NO effect on Bradykinesia (must incr DA)

• SE-atropine-like! (dry, mydriasis, constipated, blurred vision, mad)
• -do NOT use in glaucom, BPH!
• -3C's of antimuscarinic toxicity: cardiotoxicity (torsades), Convulsions, Coma

antimuscarinic

• USE- Parkinson's disease, improves tremor, rigidity
• NO effect on Bradykinesia (must incr DA)

• SE-atropine-like! (dry, mydriasis, constipated, blurred vision, mad)
• -do NOT use in glaucom, BPH!
• -3C's of antimuscarinic toxicity: cardiotoxicity (torsades), Convulsions, Coma

• antihistamine
• (all antihistamines are strong antimuscarinics too!)

USE- Parkinson's disease, IV to decrease tremor, rigidity (incr Ach effects)

• Antiviral
• -also blocks M receptors, increase DA release, decrease DA reuptake!

• USE- Parkinson's disease
• -antiviral against Influenza A, Rubella

SE- atropine-like, Livedo reticularis !! (pale skin rash,with purple dilated BVs)

Propranolol

• + symptoms: due to stimulation (too much DA)
• - symptoms: due to 5-HT

• block DA and/or 5-HT2 receptors
• atypicals- block both DA, 5-HT2 receptors

D2- in mesolimbic sys--> decrease excess DA in psychosis (Gi)-->improve positive symptoms

• 5-HT2 (presynaptic receptor in mesolimbic) like
• alpha-2-->block-->decr neg feeback--> increase 5-HT in synapse--> improve negative symptoms

USE- Schizophrenia, Schizoaffective, Bipolar, Tourette syndrome (Pimozide), Huntington's disease, anti-emetic!

• highly lipid soluble, goes to fat, slow clearance
• 1. Extrapyramidal symptoms (EPS, dyskinesia)
• acute EPS- blocking DA in nigrostriatal
• Hrs~days: pseudoparkinsonism, dystonia (ex. torticolis)
• weeks: sensitization of D2 (incr affinity, lower Km)--> akathisia (compelling need to move!)
• Rx- antimuscarinics (Benztropine, Diphenhydramine)

• Chronic EPS: irreversible, chronic adaptation
• months: D-receptors upregulate (incr #, Vmax)--> Tardive dyskinesia (Chorea, oral-facial, Hungtinton-like signs)-irreversible...
• Rx- switch to atypical

• 2. Dysphoria (decr DA)-worsen neg symptoms
• 3. increase Prolactin (galactorrhea, gynecomastia, amenorrhea)
• 4. eat more, weight gain
• 5. neuroleptic malignant syndrome! (central thermostat screwed->hyperthermia) -Rx w/ Bromocriptine (D-agonist)
• 6. histamine blockade, Sedation
• 7. muscarinic blockade (3 Cs)
• 8. alpha-blockade (hypotension)
• - like Quinidine!

4 hrs- acute dystonia (muscle spasm, stiffness, oculogyric crisis)

4 days- akinesia, parkinsonian symptoms

4 weeks- akathisia (restlessness- D2receptor sensitization)

4 months- Tardive dyskinesia (D2 receptor upregulation)

• Fever
• Encephalopathy
• Vials unstable
• Elevated enzymes
• Rigidity

Rx- Dantrolene + Bromocriptine

• Phenothiazines..
• Block D2 (Gi)--> increase cAMP in mesolimbic system

• -treat positive symptoms of psychosis
• -acute mania, tourette's syndrome

must worry about EPS, high Muscarinic block, Alpha block, Sedation...

Block 5-HT2, DA, alpha, H1 receptors

-treat both positive + negative symptoms

• -fewer EPS and antimuscarinic effects that typicals
• more weight gain?

• prototype traditional antipsychotic
• -Block D2 (Gi)--> increase cAMP in mesolimbic
• -low potency
• -high M, alpha, Histamine blockade, sedation

USE- + symptom psychosis

SE- orthostatic hypotension, blue skin, photosenstivity, lower EPS, high M, Alpha, Histamine block! high sedation. corneal deposits

• traditional antipyschotic
• -Block D2 (Gi)--> increase cAMP in mesolimbic
• -low potency
• -strongest M, alpha blockade of all!!
• -most Quinidine like!
• -LOW EPS! (b/c antimuscarinic, autotreat its EPS)

USE- + symptom psychosis

SE- high antimuscarinic effect (3C's- cardiotoxic, convulsion, coma), Retinal deposits (Retinitis pigmentosa)

• Traditional antipsychotic
• -block D2 (Gi)--> incr cAMP in mesolimbic
• -mid potency
• -metabolite is an antidepressant!

USE- + symptom psychosis

SE- higher risk for seizure

• traditional antipsychotic
• -Block D2 (Gi)--> incr cAMP in mesolimbic
• -mid potency

USE- + symptom psychosis

• SE- ocular pigment changes
• EPS, anti-His, adr, musc effects

• traditional antipsychotic
• mid potency

USE- +symptom psychosis, anxiety

SE- EPS, anti-His,Adr, Musc effects

• traditional antipsychotic
• -Block D2 (Gi)-->incr cAMP in mesolimbic
• -mid potency

USE- +symptom psychosis

SE- EPS, anti-His, Adr, Musc effects

• traditional antipyschotic
• -Block D2 (Gi)--> increase cAMP in mesolimbic
• -high potency
• -HIGH EPS!! (b/c vey potent D2 blocker)

• USE-+ symptom psychosis
• (has parenteral formulations)

SE- HIGH EPS! less M, Alpha, His block, sedation than Chlorpromazine, Thioridazine

• traditional antipyschotic
• -Block D2 (Gi)--> increase cAMP in mesolimbic
• -high potency
• -HIGH EPS!! (b/c very potent D2 blocker)
• -MOST likely to cause TD and neuroleptic malignant syndrome

• USE- + symptom psychosis
• (has parenteral formulations)

SE- HIGHest EPS! less M, Alpha, His block, sedation than Chlorpromazine, Thioridazine

• traditional antipsychotic
• high potency

USE- + symptom psychosis

SE- high EPS, less seation,hypotension, anticholinergic effects, heart block, v-tach!

• Prototype Atypical antipsychotic
• UNIQUE:
• -block D2C (NOT D2A- in nigrostrital)- NO EPS!
• -block D-HT2 (presynaptic)-->incr 5-HT

USE-both + and - schizophrenia

• SE- NO EPS!!
• - Agranulocytosis! (hypersensitivity against WBCs, do weekly WBC count)
• -salivation! (from 5-HT) 'wet pillow syndrome'
• -weigh gain, seizures

• Atypical antipsychotic
• -block D-HT2 (presynaptic)-->incr 5-HT

• USE- both + and - schizophrenia
• -OCD, anxiety disorder, depression, mania, Tourettes'

SE- weight gain!! less EPS, M, alpha, histamine block than traditionals.

• Atypical antipsychotic
• -block D-HT2 (presynaptic)-->incr 5-HT

USE- both + and - schizophrenia

SE- less EPS, M, alpha, histamine block than traditionals.

• Atypical antipsychotic
• -partial agonits of D2 (won't be as potent for + signs)
• -block 5-HT2 (presynaptic)-->incr 5-HT
• -LEAST weigh gain!

USE- both + and - schizophrenia

SE- less EPS, M, alpha, histamine block than traditionals. LEAST weight gain!!

• Atypical antipsychotic
• -block 5-HT2 (presynaptic)-->incr 5-HT

USE- both + and - schizophrenia (good for young pts?)

SE- less EPS, M, alpha, histamine block than traditionals.

• Atypical antipsychotic
• -block 5-HT2 (presynaptic)-->incr 5-HT

USE- both + and - schizophrenia

SE- less EPS, M, alpha, histamine block than traditionals.

• alzheimer's drug
• NMDA-blocker
• -decrease excitotoxicity (med by Ca)

USE- Alzheimer's disease

SE-dizziness, confusion, hallucinations

AchE-inhibitor

USE- alzheimer's disease

SE- nausea, dizziness, insomnia

AchE-inhibitor

USE- alzheimer's disease

SE- nausea, dizziness, insomnia

AchE-inhibitor

USE- alzheimer's disease

SE- nausea, dizziness, insomnia

disease- high DA, low GABA + Ach

Rx- Reserpine + tetrabenzine (deplete amine)

Haloperidol- DA-blocker

• 5-HT1B/1D- agonist
• -vasoconstrict
• -inhibit trigeminal activation + vasoactive peptide release
• -short half life

USE- acute migraine, cluster headache attacks

• SE- coronary vasospasm, fatigue, chest pain, mild tingling
• do NOT use in CAD or Prinzmetal angina!!

• mood stabilizer
• -unknown mech (inhibit PIP cascade?)
• -also block ADH receptor
• -narrow T.I
• - req close monitoring of serum levels
• -almost exclusive excretion by kidney
• -most reabsorbed at PCT like Na!
• -TZD (not loops), ACE inhibitors, NSAIDs, volume depleteion (cirhhosis, heart failure)->reabsorb more Lithium at PCT-->toxicity!

• USE- mood stabilizer for bipolar
• -block relapse and acute manic events
• -SIADH

• SE- tremor, sedation, edema, heart block, ataxia, chorea!
• -hypothyroidism, polyuria
• -ADH antagonist--> nephrogenic DI!!
• -teratogenesis! fetal cardia defects- Ebstein anomaly, malform great vessels

• dizziness
• headaches
• nausea
• insomnia
• malaise

Increase NE and 5-HT

• but, it takes several weeks to take effect!!
• (changes in gene expression)

• MAO-inhibitors (nonselective)
• block MAOa-->incr NE, 5-HT
• block MAOb-->incr DA

USE- atypical depression (refractory to SSRI), anxiety, hypochondriasis

• SE- drug interactions!
• NE-> Hypertensive crisis (HTN, arrhythmia, hyperthermia)
• -w/ Tyramine (releaser), TCA (block NE reuptake), amphetamines, ephedrine (releasers), alpha1-agonist (vasoconstrict), Levodopa (alpha)

• 5-HT--> serotonin syndrome
• (sweating, rigidity, myoclonus, hyperthermia, seizures)
• -w/ SSRIs, TCAs, Dextromethorphan, St. John's wart (SSRI effect), Meperidine (opiate+antimuscarinic, but metabolite is SSRI-Normeperidine)

• TCA
• -nonspecific blocker of 5-HT and NE reuptake

• USE- major depression (old)
• -neuropathic pain! (Trigeminal, shingles)
• -migrainesm, insomnia

• SE-sedation
• muscarinic and alpha blockade! (more than nortriptyline)
• 3C's- coma, convulsions, cardiotoxicity
• confusion, hallucination
• -Hypertensive crisis w/ MAO-inhibitors
• -Serotonin syndrome w/ SSRIs, Meperidine, MAO inhibitors, Dextromethorphan, St. John's wort
• -cancel anti-HTN drugs Alpha2-agonists and Guanethidine

• TCA
• -nonspecific blocker of 5-HT and NE reuptake

• USE- major depression (old)
• -Enuresis! (decrease phase4 sleep before REM when kids wet bed)
• -Panic DO

• SE-sedation
• muscarinic and alpha blockade!
• 3C's- coma, convulsions, cardiotoxicity
• confusion, hallucination
• -Hypertensive crisis w/ MAO-inhibitors
• -Serotonin syndrome w/ SSRIs, Meperidine, MAO inhibitors, Dextromethorphan, St. John's wort
• -cancel anti-HTN drugs Alpha2-agonists and Guanethidine

• TCA
• -nonspecific blocker of 5-HT and NE reuptake
• -most serotonin specific!

• USE- major depression (old)
• -OCD !

• SE-sedation
• muscarinic and alpha blockade!
• 3C's- coma, convulsions, cardiotoxicity
• confusion, hallucination
• -Hypertensive crisis w/ MAO-inhibitors
• -Serotonin syndrome w/ SSRIs, Meperidine, MAO inhibitors, Dextromethorphan, St. John's wort
• -cancel anti-HTN drugs Alpha2-agonists and Guanethidine

TCA (tertiary amine)

USE- chronic pain, sleep aid (low dose)

• TCA
• -nonspecific blocker of 5-HT and NE reuptake
• -no muscarinic blockade!
• -least likely to cause ortho hypotension

• USE- major depression (old)
• -good for elderly b/c no anticholinergic effects
• -chronic pain!

• SE-sedation
• alpha blockade! (more than nortriptyline)
• -Hypertensive crisis w/ MAO-inhibitors
• -Serotonin syndrome w/ SSRIs, Meperidine, MAO inhibitors, Dextromethorphan, St. John's wort
• -cancel anti-HTN drugs Alpha2-agonists and Guanethidine

• TCA
• -nonspecific blocker of 5-HT and NE reuptake
• -least sedation, but lowest seizure threshold!
• -least anticholinergic!

USE- major depression (old)

• SE-muscarinic and alpha blockade!
• 3C's- coma, convulsions, cardiotoxicity (lowest seizure threshold!)
• confusion, hallucination
• -Hypertensive crisis w/ MAO-inhibitors
• -Serotonin syndrome w/ SSRIs, Meperidine, MAO inhibitors, Dextromethorphan, St. John's wort
• -cancel anti-HTN drugs Alpha2-agonists and Guanethidine

• TCA
• -nonspecific blocker of 5-HT and NE reuptake

USE- major depression (old)

• SE-sedation
• muscarinic and alpha blockade!
• 3C's- coma, convulsions, cardiotoxicity
• confusion, hallucination
• -Hypertensive crisis w/ MAO-inhibitors
• -Serotonin syndrome w/ SSRIs, Meperidine, MAO inhibitors, Dextromethorphan, St. John's wort
• -cancel anti-HTN drugs Alpha2-agonists and Guanethidine

• highly protein bound, lipid soluble
• -antihistamine- sedation, wt gain
• -antiadrenergic- hypotension, reflex tachy, arrhythmias, widening QRS, QT, PR, dizzy
• -antimuscarinic- dry mouth, constipation, urinary retention, blurred vision, tachy, exacerbate narrow-angle glaucoma

Overdose: agitation, tremor, ataxia, delirum, hyperreflexia, seizures, coma, seizures, myoclonus

• 3 C's
• Convulsions
• Coma
• Cardiotoxicity (torsades)

• resp depression
• hyperpyrexia
• confusion + hallucinations from anticholinergic (use nortriptyline)

Rx- NaHCO3 (for cardiotoxicity)

• SSRI
• -selective 5-HT reuptake inhibitor
• -less toxic than TCAs!
• -longest half-life w/active metabolites; no need to taper
• -safe in pregnancy, approved for kids

• USE- major depression (1st line), OCD
• Bulimia, Anxiety disorder
• PMS (takes few weeks to work)

• SE- anxiety, agitation initially! (give with Alprazolam initially)
• -can elevated levels of neuroleptics-->incr SE
• -Bruxism (teeth grinding), sexual dysfunction (anorgasmia), weight loss
• -Serotonin syndrome (w/ MAO inhibitors, Meperidine, TCAs)

• SSRI
• -selective 5-HT reuptake inhibitor
• -less toxic than TCAs!
• -high protein bound!
• -shoter half-life-->withdrawal if not taken consistently

• USE- major depression (1st line),OCD
• Bulimia, Anxiety disorder
• PMS (takes few weeks to work)

• SE-more anticholinergic SE (sedation, constipation, wt gain)
• -anxiety, agitation initially! (give with Alprazolam initially)
• -Bruxism (teeth grinding), sexual dysfunction (anorgasmia), weight loss
• -Serotonin syndrome (w/ MAO inhibitors, Meperidine, TCAs)

• SSRI
• -selective 5-HT reuptake inhibitor
• -less toxic than TCAs!
• -highest risk for GI SE!!
• -more common sleep changes

• USE- major depression (1st line), OCD
• Bulimia, Anxiety disorder
• PMS (takes few weeks to work)

• SE- anxiety, agitation initially! (give with Alprazolam initially)
• -Bruxism (teeth grinding), sexual dysfunction (anorgasmia), weight loss
• -Serotonin syndrome (w/ MAO inhibitors, Meperidine, TCAs)

• SSRI
• -selective 5-HT reuptake inhibitor
• -fewest drug interactions
• -fewer sexual SE?

• USE- major depression (1st line), OCD
• Bulimia, Anxiety disorder
• PMS (takes few weeks to work)

• SE- anxiety, agitation initially! (give with Alprazolam initially)
• -Bruxism (teeth grinding), sexual dysfunction (anorgasmia), weight loss
• -Serotonin syndrome (w/ MAO inhibitors, Meperidine, TCAs)

• -SSRI
• -levo-enantiomer of citalopram (similar efficacy, possibly fewer SE)
• -more expensive than citalopram

• -fewer SE than TCAs and MAOIs b/c serotonin selective
• -much safer in overdose
• -SEs mostly resolve within few weeks

• -GI: nausea, diarrhea (food helps)
• -Sexual dysfunction (25-30%, usu doesn't resolve)
• -Insomnia, vivid dreams
• -headaches
• -anorexia, weight loss
• -restlessness (akathisia-like state)
• -seizures (0.2%)
• -can increase levels of Warfarin (monitor when starting/stopping)

• hyperthermia
• tremor, myoclonic jerks ,hyperreflexia
• hypertonicity, rhabdomyolysis
• CV collapse, tachycardia
• flushing, diarrhea
• delirium
• seizures
• renal failure--> death

RX- Cyproheptadine (5-HT2 receptor blocker)

• SNRI
• -nonselective reuptake blocker of NE, 5-HT
• -less autonomic SE! (NO antimuscarinic, alpha-1 blockade)
• -has XR form

USE- depression, generalized anxiety disorder

• SE-HTN, sedation, nausea, stimulant effects
• do NOT use in BP-labile pts!!

• SNRI
• -nonselective reuptake blocker of NE, 5-HT
• -expensive!

USE- Depression + neuropathic pain/ fibromyalgia

• SE- more dry mouth, constipation!
• HTN, sedation, nausea, stimulant effects
• more liver SE!

• atypical antidepressant
• - NE, DA-reuptake blocker

• USE- atypical antidepressant
• - Smoking cessation, adult ADHD

• SE- no sexual SE!!
• stimulant effects (tachycardia, insomnia)
• -seizures!
• -psychosis (at high doses)
• do NOT give to pt w/seizure, eating DO, taking MAOI

• atypical antidepressant
• -alpha-2 blocker
• potent 5-HT2, 5-HT3 agonist!
• increase NE

• USE- atypical antidepressant, refractory major depression
• -good for anorexic pts! (cause weigh gain)

• SE- sedation, increase appetite, weight gain, dry mouth,constipation
• rarely agranulocytosis
• (unusual b/c SSRIs cause weight loss..)

• tetracyclic antidepressant
• NE-reuptake inhibitor

USE- atypical antidepressant

• SE- seizure, arrhythmia, sedation, orthostatic hypotension
• fatal in overdose!

• tetracyclic antidepressant
• -metabolite of antipsychotic loxapine

SE- EPS, similar SE as typical antipsychotics.

• atypical antidepressant
• 5-HT receptor agonist
• -has strong alpha-1 blockade (vasodilate)
• USE- insomnia, refractory depression
• -high doses req for antidepressant effects

SE- arrhythmia, priapism (bc vasodilate), hypotension, sedation!

• -increase catecholamines in synaptic cleft
• -increase esp NE, DA

USE- ADHD, narcolepsy, appetite control

Hallucinogens

hallucinogen

• effects
• - Belligerence, impulsiveness, psychomotor agitation
• -fever
• -vertical, horizontal nystagmus
• -tachycardia
• -homicidality, psychosis, delirium
• -depression, anxiety, restlessness, anergia
• -disturbed sleep

hallucinogen

• effecs:
• -makred anxiety or depression
• -delusions
• -visual hallucinations
• -flashbacks
• -mydriasis

Hallucinogen

• effects:
• -Euphoria
• -anxiety, paranoid delusions
• -perception of slowed time
• -impaired judgement
• -social withdrawl
• -increased appetite, dry mouth
• -hallucinations

• longterm effects:
• -irritability, depression, insomnia, nausea
• -anorexia
• -most sympootms peak in 48 hrs, last upto 5~7 days

-can be detected in urine upto 1 month after last use

• users at risk for hepatitis, abseceses, overdose
• hemorroids, AIDS, R-side endocarditis
• (look for track marks)

• Methadone - long acting oral opiate
• - used for heroin detox or long-term maintenance

• Suboxone- Naloxone + Buprenorphine (partial agonist)
• -long acting w/ fewer withdrawl symptoms than methadone.
• -Naloxone NOT ative when taken orally, so withdrawal symptoms only if injected (less abuse potential)

physiologic tolerance, dependence w/ symptoms of withdrawal if stopped

Withdrawal: tremor, tachycardia, HTN, malaise, nausea, DTs

Complications- Alcoholic cirrhosis, hepatitis, pancreatitis, peripheral neuropathy, testicular atrophy

Wernicke- confusion, opthalmoplegia, ataxia

Korsakoff- irreversible memory loss, confabulation, personlaity change (psychosis)

• -caused by Thimine deficiency
• -assoc w/ periventricular hemorrhage/ necrosis of Mammillary bodies

• Rx- IV vit B1 (thiamine)
• -give thiamine w/ glucose when giving glucose!!

• life-threatening alcohol withdrawal syndrome
• -peak 3-5 days after last drink

• symptoms in order of appearance:
• -autonomic systemic hyperacticity
• (tachycardia, tremors, anxiety, seizures)
• -psychotic symptoms (hallucinations, delusion)
• -confusion

RX- benzodiazepines!

Benzodiazepines

-SSRIs

• Benzodiazepines
• Buspirone
• SSRIs

• Methylphenidate (Ritalin)
• Amphetamine (Dexedrine)

• MAO inhibitors
• SSRIs

• Mood stabilizers:
• Lithium
• Valproic acid
• Carbamazepine

Atypical antipsychotics

• SSRIs
• SNRIs
• TCAs

Mirtazapine

• SSRIs
• Clomipramine

• SSRIs
• TCAs
• Benzodiazepines

SSRIs

Antipsychotics

Antisychotics (haloperidol)

SSRIs

overdose: mood elevation, decreased anxiety, sedation, behavioral disinhibition, resp depression

withdrawal: anxiety, tremor, seizures, insomnia

• overdose: emotional lability, slurred speech, ataxia, coma, blackouts. GGT, AST> ALT
• Rx- Naltrexone

• withdrawal: anxiety, tremor, seizures, insomnia, delirium tremens
• Rx- BDZ

• overdose: CNS depression, nausea, vomiting, constipation, miosis, seizures (overdose lifethreatening)
• Rx- Naloxone, Naltrexone

withdrawal: sweating, mydriasis, piloerection, fever, rhinorrhea, nausea, stomach cramps, diarrhea (flu-like) Rx- Methadone, Naltrexone, Buprenorphene

• overdose: low safety margin. Marked respiratory depression
• Rx- assist resp, pressors

withdrawal: delirium, life-threatening CV collapse!

• Overdose: greater safety margin. Ataxia, minor resp depression
• Rx- Flumazenil

overdose: mood elevation, psychomotor agitation, insomnia, cardia arrhythmias, tachycardia, anxiety

withdrawal: post-use crash- depression, lethargy, weight gain, headache

overdose: impaired judgement, mydriasis, prolonged wakefulness, attention, delusions, hallucinations, fever

withdrawal: stomach cramps, hunger, hypersomlemnence

• overdose: impaired judgement, mydriasis, hallucinations, paranoia, angina, sudden cardiac death
• Rx- BDZ

withdrawal: suicidality, hypersomnolence, malaise, severe craving

overdose: restlessness, increase diuresis, muscle twitch

overdose: restlessness

• withdrawal: irritability, anxiety, craving
• Rx- nicotine patch, gum, lozenges, bupropion, varenicline