Drug Action Exam 3

Types of depression

Reactive (external/exogenous), Major Depressive Disorder, Post-partum, Maniac-depressive or bipolar

Cause of depression

Deficiencies of NE and 5-HT

Monoamine Theory of Mental Depression

NE/Serotonin levels could explain bipolar episodes where low=depression, high=mania

5-HT, NE, and DA Degradation

Caused by MAO-A and sometimes MAO-B

Limits to the Monoamine THeory

Chemicals show unexplained delay like reserpine so clearly people respond different to increases

Antidepressant drug classes

Selective Serotonin reuptake inhibitors, Serotonin-NE reuptake inhibitors, Tricyclic Antidepressants, MAO inhibitors

MAO inhibitors 

Increases 5-HT and NE by limiting their degradation

MAOI examples

Iproniazid, Phenelzine (Irreversible)
Moclobemide, Befloxatone, and brofaromine (Reversible)

Adverse effects of MAOIs

Dry mouth, Urinary retention, constipation, blurred vision, hypotension, weight gain, Sexual dysfunctionM

MAOIs Dietary restrictions

Foods containing Tyramine

Tricyclic Antidepressants (TCAs)

Blocks the reuptake of NE and Serotonin with Secondary Amines affect NE and Tertiary Amines affect the Serotonin (5-HT)`

TCA Sample frugs

Imipramine, Amitriptyline, Clomipramine, Desipramine, Nortriptyline

Effects of TCAs

Produces sedeation, anticholinergic (Dry mouth, constipation, urinary retention), and Alpha-andrenergic blockage (Postural hypotension, blurred vision, drowsiness)

TCA interactions

Alcohol, Amphetamines, Anticholinergics, Anticonvulsants, Barbiturates, MAOIs, Phenothiazines, SSRIs, SNRIs

Selective Serotonin Reuptake Inhibitors (SSRIs)

Disrupts MOA and selectively blocks the reuptake of 5-HT. Drugs vary in degree of CNS activation (not fluvoxamine) and widespread anxiety disorder

Effects of SSRIs

GI disturbance, Sexual dysfunction, CNS effects

Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs)

Blocks the reuptake of 5-HT and NE. General anciety, Chronic Pain Disorder, Fibromyalgia

SSRI examples

Fluoxetine (Prozac), Fluvoxamine, Paroxetine, Sertraline, Citalopram, Escitalopram

SNRI Examples

Venlafaxine (moderate), Desvenlafaxine (active metabolite of previous drug), Duloxetine (Low CNS activation)

Effects of SNRIs

Increased blood pressure, heart rate, CNS stimulation

Norepinephrine Reuptake Inhibitors (NRIs)

Selectively block NE uptake transporters for ADHD

NRI Examples

REBOXETINE, Atomoxetine, Maprotiline

NRI Effects

Cardiovascular strain, liver injury, seizure, suicidal thoughts, weight loss, GI discomfort, headache, urinary retention

All Antidepressant drugs are

Hydrophobic and cross the BBB

Reserpine

Can induce depression and blocks uptake of monoamines into vesicles, destroying the vesicles in the process

Buspirone

Serotonin1A selective agonist treatment

Serotonin Receptor agonists

SUMATRIPTAN, rizatriptan, almotriptan, frovatriptan, eletriptan, zolmitriptan, ergotamine

Effects of Serotonin Receptor Agonists

Myocardial ischemia/infarcation, stroke, dizziness, confusion, headache

Nefazodone and Trazodone

Antidepressants that are ineffective at stopping 5HT and NE reuptake, but antagonize 5HT2A receptors

Bupropion

Helpful for Bipolar and reduces CNS effects of nicotine withdrawl

Mirtazapine

Antidepressants that antagonizes serotonin 5HT2 and 3 receptors to act as a sedative

Brexanolone/Zuranolone

Antidepressant in the form of a Neuroactive steriod that positively modulates GABAA receptors

Psychomotor stimulates

Amphetamines treat narcolepsy or hyperkinesis to calm down or stimulate by increase NE and Dopamine

Psychomotor Stimulant Effects

Dry mouth, Rapid heartbeat, increase BP, restlessness

Lithium

Used to treat mania and bipolar disorder, reduces hyperactivity and excitement by replicating Na to block signaling cascase

Lithium Effects

Nausea, Tremors, disturbances of the thyroid

Mood stabilizers

Lithium, Carbamazepine (inhibits electrical neurotransmission of sodium channels, VALPROIC ACID (effects the low-threshold T-type calcium channels of MOA)

Depolarization vs Hyperpolarization

Membrane become more + versus more -

GABA (Y-amino Butyric acid) Major inhibitory neurotansmission

Opens K channels to induce efflux, loss of cation, membrane hyperpolarization
Opens Cl channels to induce influx, gain anions, decreased membrane resistance. Decreased neuron firing

Glutamate primary excitatory neurotransmission

Opens channels to gain Na ions, membrane depolarization
Close potassium channels to reduce flow of K, Membrane depolarization. (Increased neurons)

GABA Receptors affect

Arousal, Attention, Memory formation, Anxiety, Sleep, Muscle tone

Gaba synthesis step 1

GAD decarboxylates glutamate to produce GABA in presense of vitamin B6

GABA synthesis step 2

Vesicular GABA transporter does what its name suggests

GABA Metabolism Step 1

GABA-Transaminase (GABA-T) convert GABA to succinic semialdehyde which is oxidized by SSA dehydrogenase to go into kerb cycle

GABA metabolism Step 2

SSA dehydro make SSA go into kerbs which makes it into A-ketoglutarate which GABA-T regenerates into glutamate

Vigabatrin

Irreversibly inhibits GABA-T to increase GABA

Glial cells and glutamine sythetase

transforms glutamate into glutamine (Gln)

Two types of GABA

Ionotropic and Metabotropic

Ionotropic GABA Receptor

binds to Cl por of pentameric transmembrane glycoprotein. A and C. 

GABAa

Activation requires a and b subunits. Each suunit has 4 membrane spanning and a cysteine loop on the N terminal. Inhibitory postsynaptic cyrrents activated from release. penicillian is antagonist

Benzodiazepine

binds to allosteric site between a/y subunits of GABAa and increases Cl channel openings

Barbiturate

Binds adjects to a/b subunits to increase the duration of Cl channel opening, with or without GABAa

Mutation in GABAa

Inherited human epilepsy