NSG 552 Psychopharmacology Exam 1 Study Guide Complete Updated 2024/2025

NSG 552 Psychopharmacology Exam 1 Study Guide Complete Updated 2024/2025. Phenylalanine (amino acid from diet) -> phenyalanine hydroxylase -> Tyrosine -> Tyrosine hydroxylase -> DOPA -> Dopa decarboxylase -> Dopamine KEY POINT: Dopamine is synthesized directly from tyrosine or indirectly from phenylalanine • Dopamine is packed and stored into synaptic vesicles via the vesicular monoamine transporter (VMAT2) and stored until its release into the synapse. • When dopamine is released during neurotransmission, it acts on 5 types of postsynaptic receptors (D1-D5). • A negative feedback mechanism exists through the presynaptic D2 receptor which regulates the release of dopamine from the presynaptic neuron. • Any excess dopamine is cleared out o Presynaptically by Dopamine transporter (DAT) o VMAT2 will take excess DA and store it in the synaptic vesicles for future neurotransmission • Excess dopamine is broken down within the presynaptic neuron by monoamine oxidase A (MAO-A), MAOB and extracellularly (outside the neuron) by catechol-o methyltransferase (COMT). • All antipsychotic drugs can reduce dopaminergic neurotransmission. DOPAMINE RECEPTORS • Dopamine neurotransmission is perpetuated via G protein-coupled receptors categorized into two broader subtypes • D1 – like family: o Includes subtypes D 1 and D 5 o Activation is coupled to Gs ; activates adenylyl cylcase which leads to increase in concentration of cAMP • D2 – like family: o Includes D 2, D3 and D4 o Activation is coupled to Gi ; inhibits adenylyl cyclase leading to decrease in concentration of cAMP o Also open K channels & closes Ca influx • DAT (dopamine transporter) and VMAT2 are DA receptors that also regulate DA neurotransmission • Presynaptic D2 autoreceptors are “gatekeepers” and provide negative feedback input. When D2 receptors are NOT bound to DA DA release. When D2 receptors bind to DA inhibit DA release o Location: Striatum, substantia nigra, pituitary o Located presynaptic and postsynaptic FGAs and Neurotransmitters • Mesolimbic pathway: involved in pleasure and reward. Blocking D2 in this pathway by FGA’s not only treats positive symptoms, but it blocks the reward mechanism and can cause apathy, lack of motivation, lack of interest and the ability to feel joyful • Negative symptoms of psychosis are due to low dopamine in the mesocortical pathway. When FGA’s block D2 receptors here, negative symptoms such as blunted affect, lack of pleasure, reduced social interaction can worse • Dopamine inhibits prolactin release in the tuberoinfundibular pathway. When FGA’s bind to D2 in this pathway, there is an increase in serum prolactin levels leading to galactorrhea, infertility or low sex drive. 2 • The degree of D2 receptor binding in the mesolimbic pathway needed for antipsychotic effects is close to 80% , while D2 receptor occupancy greater than 80% in the dorsal striatum is associated with EPS and in the pituitary is associated with hyperprolactinemia. This creates a very narrow therapeutic window Between the threshold for antipsychotic efficacy and that for side effects in terms of a D2 binding. • If D2 receptors in the nigrostriatal DA pathway are blocked chronically, it can cause TD. D2 receptors are hypothesized to become super sensitive or to upregulate (ase in number) perhaps in an attempt to overcome drug induced blockade of D2 receptors in the striatum. After long term treatment the D2 receptors apparently cannot or do not reset back to normal even when conventional antipsychotics are discontinued. This leads to tardive dyskinesia that is irreversible, continuing whether conventional antipsychotic drugs are administered or not • In addition to binding to D2 in all pathways, FGA’s also block muscarinic M1 cholinergic receptors, leading to blurry vision, dry mouth, constipation and cognitive blunting (Stahl, p.138). FGAs that caused more EPS are the agents that have weak anti cholinergic properties, whereas those FGAs that cause fewer EPS are the agents that have stronger anti cholinergic properties. Dopamine normally inhibits acetylcholine. If dopamine can no longer suppress acetylcholine release then acetylcholine becomes overly active. Therefore, EPS is a result of dopamine deficiency and excess acetylcholine. Drugs with anticholinergic actions will diminish the excess acetylcholine activity caused by removal of dopamine inhibition when dopamine receptors are blocked by FGAs. Thus, EPS is reduced. This occurs in the nigrostriatal dopamine pathway. • The use of anticholinergic drugs with an FGA does not lessen the ability of the FGA to cause tardive dyskinesia. • Other properties of FGA’s is the blockade of histamine receptors which leads to weight gain and drowsiness (Stahl, 2013). Blockade of alpha1 receptors can have cardiovascular effects, such as hypotension and drowsiness. • An old-fashioned way to sub classify FGAs is low potency versus high potency. Low potency agents tend to have more of the additional properties such as blockade of muscarinic M1-cholinergic receptor, blockade of histamine and alpha1-adrenergic receptors. SEROTONIN SYNTHESIS AND TERMINATION OF ACTION • Serotonin also known as 5- hydroxytryptamine (5HT) is produced from enzymes after the amino acid precursor tryptophan is transported into the serotonin neuron. Tryptophan is converted by the enzyme tryptophan hydroxylase (TRY-OH) into 5-hydroxytryptophan, which is then converted into 5HT by the enzyme, aromatic amino acid decarboxylase (AAADC). • Serotonin is then taken up into synaptic vesicles via the vesicular monoamine transporter (VMAT2), where it stays until released by a neuron impulse. The 5HT neuron also has a presynaptic transport pump for serotonin called the serotonin transporter (SERT) that terminates serotonin's actions by pumping it out of the synapse and back into the presynaptic nerve terminal where it can be restored in synaptic vesicles for subsequent use.