Barbiturate

Uses: induce anesthesia, anticonvulsant, head trauma, GI antisposmotic

Mechanism: Binds GABA receptor, increases Cl influx causing inhibition independent of GABA; enters CNS quickly and easily

Toxicity: Cleared by alkalinization of urine (barbiturates are acids) low margin of safety, CNS depression; effects are supra-additive i.e. EtOH combo; metabolized by liver

Side effects: contraindicated in porphyria, contraindicated in pulmonary insufficiency, physical dependance, mainly drugs of abuse now, SEVERE WITHDRAWAL THAT IS LIFE THREATENING! Induce liver enzymes

Other drugs: Phenobarbital (Luminal Sodium^®)- long acting, anticonvulsant

Thiopental (Pentothal^®)- super short acting, used for anesthesia

Secobarbital (Seconal^®)

Benzodiazapine

Mechanism: Binds GABA receptor and intensifies its effect, enhances binding of GABA, doesn't work in absence of GABA: "ceiling effect" where GABA release is inhibited with higher benzo concentrations

Uses: Status epilepticus, Anxiety, Insomnia, epilepsy and seizures, sedation, amnesia and anesthesia, EtOH withdrawal, anticonvulsant, Muscle relaxation, pre-anesthesia

Side effects: CNS depression; Do not induce liver enzymes

Other drugs: Chlordiazepoxide (Librium^®)- long acting; EtOH; barbituate withdrawal

Chlorazepate (Tranxene^®)- long acting

Flurazepam (Dalmane^®)- long acting, insomnia where pt wakes in early morning

Lorazepam (Ativan^®, Alpazam^®) - intermediate length, status epilepticus, EtOH, not converted to active metabolite

Oxazepam (Serax^®)- intermediate length

Triazolam (Halcion^®)- short acting, insomnia, pt can't fall asleep but stays asleep

Alprazolam (Xanax^®)- short acting, depression/anxiety

Estazolam (Prosom^®)

Temazepam (Restoril^®)- insomnia

Benzodiazepine antagonist

Mechanism: competes for benzo receptor, separate from barbiturate and EtOH receptors

Use: reverse CNS depressant effects of benzos (Z drugs also), including midazolam (versed) during Sx (resp dep)

Must be given IV, may need to be readministered (very short acting)

Side effects: Triggers withdrawals and seizure in EtOH and Benzo dependent pts; can cause seizure in pts with barbiturate and TCA OD

Mechanism+difference from benzo: partial serotonin agonist, NOT GABA receptor; decreases 5-HT release from dorsal raphe neurons, increaseing NE and DA pathways

Disadvantage+not used for EtOH: great for recovering alcoholics but won't prevent benzo and etoh withdrawal symptoms!

Use: relieves anxiety w/o sedation in about 2 weeks; anxiety, antidepressants, pain, PMS, autism, 

Mood stabilizers

Pharmacokinetics: excreted by kidneys, competes with sodium for reabsorption; low sodium diet = increased Li concentration; thiazide diuretics and NSAIDs decrease Li clearance

Dx interactions: Antidepressants = increase mania; 

Diseases that alter the effects or interact with Li: 

Side effects: tremor, nausea, headache, renal effects, decreased thyroid function, edema, weight gain; safe for pregnancy

Tox. Signs: mild tox = nausea, vomit, diarrhea, muscle weakness, fasciculation, hyperreflexia, memory/concentration impaired, slurred speech, sedation, fine tremor, Rash.

 Severe tox = same as above but add clonic-tonic twitch, rep complications, cardiac arrhythmias, renal failure, coma death; Treated with discontinue drug, dialysis/gastric lavage, saline, antiepileptic meds.; increased thirst and urine output, treat with amiloride (prevent Li from getting to collecting duct, prevents ability to block ADH).

Anticonvulsant

Mechanism: Block thalamic, low-threshold (T-type) Ca+2 current; "pacemaker" of thalamic neurons in abscence seirzure; 

Uses: DOC FOR ABSENCE SEIZURES

Tox: GI irritant, Preg. cat. C

Anticonvulsant

Mechanism: Blocks Na+ Channel, holds channel in inactive state longer; inhibits rapidly firing neurons, little effect on normal neurons

Use: Partial seizures, generalized tonic-clonic seizures, trigeminal neuralgia, bipolar

Tox: GI upset, idiosyncratic blood dyscrasias (AGRANULOCYTOSIS), HLA-B*1502

MAOI: Antidepressant

Mechanism: MAOIs irreversibly inhibit MAO which breaks down circulating catecholamines; MAO-A breaks down NE and 5-HT, MAO-B breaks down DA;

Pharmacokinetics: effect lasts 1-3 weeks since MAO inhibition is irreversible

Drug of last choice; question will say "pt has been treated for depression for a long time and is given this now"

Foods to avoid: red wine, beer, aged cheese and prepared meats; alcohol, bean curd, aged cheese, smoked, fermented picled herring, spoiled meat and fish, ginseng, protein extract, sausage, bologna, pepperoni and salami sauerkraut, soups, yeat, brewere's or extracts; 

Other drugs: Tranylcypromine (Parnate^®)

Side effects: HTN crisis

Antidepressant

Uses: antidepressant, childhood ADHD, recovery from drug of EtOH abuse or weight loss (decreases cravings)

Mechanism: inhibits reuptake of DA and NE

Side effects: CNS stim, psychois, headache, nausea, weight loss, NOT sexual dysfunction, seizures at high doses

Contraindications: pts with seizures or on drugs that lower seizure threshold (TCAs or antipsychotics)

Other Drugs: Mirtazapine (Remeron^®)

Atomoxetine (Strattera)- Inhibit NE reuptake only; ADHD (non-stimulant)

Maprotiline (Ludiomil^®)

Amoxapine (Asendin^®)- depression, schizophrenia, DA antagnist, may cause parkinson syndrom

Antidepressant

Uses: Depression, sleep aid, pain management

Side effects: sedation, dizziness, hypotension, nausea, priapism (rare, but you see priapism, ALWAYS TRAZADONE)

Mechanism: partial 5-HT1A agonist and may block 5-HT2A receptor

Anticonvulsant

Mechanism: Prob block Na channels, may enhance GABA, blocks high freuency repetitive firing; prob wont be asked about mechanism

Uses: 1st choice for mixed seizure disorders; 1st choice for complicated tonic-clonic seizures, 2nd choice for absence, myoclonic seizures, migraine prophylaxis, bipolar (works for alot of things)

Tox: weight gain, hepatotoxicity, Preg cat D

Interactions: other anti-seizure meds

Anticonvulsant

Mechanism: Blocks Na+ Channel, holds channel in inactive state longer; inhibits rapidly firing neurons, little effect on normal neurons

Pharmacokinetics: 1st order at low dose, zero order at high; doesn't take much to get out of therapeutic range

Use: Partial seizures, generalized tonic-clonic seizures (primary and secondary); NOT effective for absence

Interactions: Metab by liver, warfarin competes, will increase significantly if combined with phenytoin (starts bleeding in hospital in question)

Tox:Gingival hyperplasia, pregnancy category D

Other Drugs: Fosphenytoin (Cerebyx) = soluble prodrug for injection

Muscle relaxant (no CNS, at the muscle)

Uses: neuroleptic malignant syndrom, malignant hyperthermia (caused by general anesthesia of NMJ blocking agents)

Mechanism: interferes with excitation-contraction coupling in muscle fiber; decreases Ca release from SR; SM more than smooth M; DOES NOT WORK THROUGH CNS, works at the muscle

Side effect: weakness, sedation

Centrally acting muscle relaxant; Sedative

Mechanism: antimuscarinic effect, acts as sedative at the level of the brain stem; 

Uses: acute muscle spasms caused by trauma or sprain

Side effects: causes sedation, confusion is common

Others: Chlorzoxazone (Paraflex^®) 

Metaxalone (Skelaxin^®); Methacarbamol (Robaxin); Orphenadrine (Norflex)

Muscle relaxant (no CNS, at the muscle)

Uses: neuroleptic malignant syndrom, malignant hyperthermia (caused by general anesthesia of NMJ blocking agents)

Mechanism: interferes with excitation-contraction coupling in muscle fiber; decreases Ca release from SR; SM more than smooth M; DOES NOT WORK THROUGH CNS, works at the muscle

Side effect: weakness, sedation

Mechanism: inhibits aldehyde dehydrogenase, making pt sick when they drink from acetaldehyde buildup, could be dangerous

Long duration, don't drink for 3-4 days following administration

Dangerous and not recommended

Alcohol dehydrogenase inhibitor

Uses: Ethylene glycol (antifreeze) and methanol poinsoning

Administration of fomepizole or ethanol are given in both cases

Centrally acting muscle relaxant

Mechanism: Alpha 2 receptor agonist; inhibits pain transmission in dorsal horn; reinforces pre adn post synaptic inhibition in the psinal cord

Uses: reduce chronic muscle spasticity due to spinal cord injury; acute muscle spasms

Major Side effects: sedation, hyptension, dry mouth, muscle weakness (elderly)

Centrally acting muscle relaxant; Sedative

Mechanism: antimuscarinic effect, acts as sedative at the level of the brain stem; 

Uses: acute muscle spasms caused by trauma or sprain

Side effects: causes sedation, confusion is common (hallucinations!)

Others: Chlorzoxazone (Paraflex^®) 

Metaxalone (Skelaxin^®); Methacarbamol (Robaxin); Orphenadrine (Norflex)

MAOI

Uses: Parkinsons disease (early to decrease ROS damage); 

Mechanism: inhibits MAO-B (CNS only); MAI-B is predominant form in the striatum and thus reduces striatal metabolism DA; Reversible MAOI

Effects: Increases effect of DA in the brain, relieving parkinson's symptoms

Advantages: Decrease free radical production from MAO-B oxidation of DA, so may slow progression of disease!

Adverse effect: DO NOT combine with meperidine (seretonin syndrome)

Others: Rasagiline (Azilect®)

COMT inhibitor

Use: Parkinson's (adjunct to l-dopa

Mechanism: Inhibits CNS and peripheryl Catechol-O-methyltransferase (COMT) which metabolizes DA; Tolcapone (Tasmar) penetrates CNS

Effect: Prolongs duration of action of dopamine in the synaptic cleft and prolong l-dopa action

Adverse effects: dyskinesias, confusion, nausea

Tolcapone has been associated with death from liver disease, requires pt consent

Side effect: orange urine! Liver failure

Others: Entacapone (Comtan®) - Inhibits peripheral COMT (no BBB cross)

Adverse: Tolcapone has been associaed with death from liver disease, require pt consent

Dopamine agonist (KNOW all 4)

Uses: Parkinsons disease

Mechanism: acts directly on DA receptors, primarily DA D2

Advantages:  *continue to be effective as the disease progresses*

Side effect: Bromocriptine is an ergot derivative -> erythromelalgia (red, swollen feet, intense burning pain); anorexia, nausea, vomiting, postural hypotension, cardiac arrhythmias for all agonists

Others: Pramipexole (Mirapex®) - NOT ergot (no erythromelalgia); sudden sleep during day (rare) D2, D3 agonist

Ropinirole (Requip®) - transdermal patch for Restless leg syndrome; D2

Apomorphine (Apokyn®) - rescue of off periods in PD! potent DA agonist; take antiemetic, causes bad nausea

Classic Antipsychotic: Phenothiazine

Mechanism: Blocks D2 receptor, also a-adrenergic and histamine receptors. 

Uses: schizophrenia, relieves "positive"symptoms; pre-anesthetic, sedative, premature ejaculation, severe itching; also manic episodes, EtOH hallucinations, psychosis and hallucinations in drugs of abuse; can be given in ER

Side effects: anticholinergic (blurred vision, constipation, urnary retention, decreased GI motility); Alphar block (postural hypotenstion, inhibits ejactulation); Jaundice necessitates drug change; decreased seizure threshold; retinal deposites; extrapyramidal effects, endocrine effects, tardive dyskinesia, neuroleptic malignant syndrome. 

Dx interactions: increase sedation with sedative hypnotics, increase anticholinergic effects with anticholinergics,

Other drugs: Thioridazine (Mellaril^â)- high antichoinergic acitvity, more sedation+hypotension, less extrapyramidal symptoms

Fluphenazine (Prolixin^â) - "high potency", more selective for DA receptors, less anti-cholinergic activity. more likely to cause extrapyramidal (parkinsons) symptoms

Prochlorperazine (Compazine^â) - for nausea and vomiting

            Trifluoperazine (Stelazine^â) - low anticholinergic activity, high incidence of extrapyramidal effects, less sedation and hypotension

Typical Antipsychotic

Mechanism: Selective D2 blockade, some effect at a1 and 5HT2r, no anticholinergic effects.

Uses: Injected in acute psychotic situations i.e. drug or alcohol abuse; Tourrett's

Dx interactions: increase sedation with sedative hypnotics, increase anticholinergic effects with anticholinergics,

Other drugs: Thiothixene (Navane)- similar to pheonthiazines

Pimozide (Orap)- binds only D2; motor and phonic tics in tourette's; +extrapyramidal +sedation +anticholinergic     

Molindone (Moban) - high extrapyramidal symptoms

Loxapine (Loxitane) - lowers seizure threshold

New gen "Atypical" Antipsychotics

Drug of last choice (agranulocytosis)

Advantages: has greater mesocortical and limbic system specificity -> very low extrapyramidal side effects; no tardive dyskinesia; 

Limiting Side effects: agranulocytosis in 1% of pts; sedation, seizure threshold lower, hypotension, tachy, increased saliva, dizziness, weight gain

Dx interactions: increase sedation with sedative hypnotics, increase anticholinergic effects with anticholinergics,

"Dopamine system stabilizer"

Use: first line schizophrenia, Tx resistant depression,

Unique mechanism of action: Activates dopamine receptors when dopaminergic tone is low, blocks them if dopaminergic tone is high; partial D2 adn 5-HT1A agonist

Uses: drug-resistant depression; antipsychotic

Side effects: hyperglycemia, esophageal motility problem (no elderly); ortho hypo, seizures, sedation, inability to regulate body temp;