Psychopharmatology (3) Flashcards
Drugs
Chemical compound administered to bring about some desired change in the body and brain.
Psychoactive drugs
Substances that alter mood, thought, or behavior; are used to manage neuropsychological illness and may be abused.
Route of administration
The way a drug enters and passes through the body to reach its target.
Orally, inhaled into the lungs, administered rectally in a suppository, absorbed from patches applied to the skin or mucous membranes, or injected into the bloodstream, into a muscle, or even into the brain.
Drugs dosage
With each obstacle eliminated en route to the brain, a drugs dosage can be reduced by a factor of 10.
1000 mg = 1 ug
Orally = 1000 ug
Inhaled/injected blood = 100 ug
Cerebrospinal fluid = 10 ug
Neurons = 1 ug
Barriers internal movement drugs
Cell membranes, capillary walls, placenta.
The passage of drugs across capillaries in the brain is made difficult by the blood-brain barrier, the tight junctions between the cells of blood vessels in the brain that block passage of most substances. It protects the brains ionic balance and denies neurochemicals from the rest of the body passage into the brain, where they can disrupt communication between neurons.
The brain has a rich capillary network; none of its neurons is farther than about 1 um away from a capillary. They are composed of a single layer of endothelial cells; in the brain the endothelial cell walls are fused to form tight junctions, so molecules of most substances cannot squeeze between them. They are surrounded by the end feet of astrocytes attached to the capillary wall. The glial cells provide a route for the exchange of food and waste between capillaries and the brains extracellular fluid and from there to other cells.
The cells of capillary walls in three brain regions lack a blood brain barrier.
- Pituitary = source of many hormones secreted into the blood and their release is triggered in part by other hormones carried to the pituitary by the blood.
- Lower brainstem area postrema = allows toxic substances in the blood to trigger vomiting.
- Pineal gland = enabling hormones to reach it and modulate the day-night cycles it controls.
Cross blood-brain barrier
Few psychoactive drug molecules are sufficiently small or have the correct chemical structure to gain access to the CNS. An important property possessed by those few drugs that have CNS effects, then, is an ability to cross the blood-brain barrier.
How the body eliminates drugs
After a drug is administered, the body soon begins to break it down (catabolize) and remove it. Drugs are diluted throughout the body and are sequestered in many regions, including fat cells. They are catabolized throughout the body, including in the kidneys and liver, and in the intestine by bile. They are excreted in urine, feces, sweat, breast milk and exhaled air. Drugs developed for therapeutic purposes are usually designed not only to increase their chances of reaching their targets but also to enhance their survival time in the body. The liver is especially active in catabolizing drugs, owing a family of enzymes involved in drug catabolism (cytochrome P450 enzyme family), the liver is capable of breaking down many different drugs into forms more easily excreted from the body.
Substances that cannot be catabolized or excreted can be build up in the body and become toxic.
Drug action at synapses
Most drugs that produce psychoactive effects work by influencing chemical reactions at synapses.
7 steps in neurotransmission at a synapse:
1. Synthesis of the neurotransmitter in the cell body, axon or terminal.
2. Storage of the neurotransmitter in granules or vesicles.
3. Release from the terminals presynaptic membrane into the synapse.
4. Receptor interaction in the postsynaptic membrane as the neurotransmitter acts on an embedded receptor.
5. Inactivation of excessive neurotransmitter at the synapse.
6. Reuptake into the presynaptic terminal for reuse.
7. Degradation of excess neurotransmitter by synaptic mechanisms and removal of unneeded by-products from the synapse.
Drug that affects synaptic functions
Either increases r diminishes neurotransmission.
Drugs that increase neurotransmission = agonists.
Drugs that decrease neurotransmission = antagonists.
Agonists
Black widow spider venom promotes release of ACh.
Nicotine stimulates receptors (passes bbb).
Physostigmine (passes bbb) and organophosphates block inactivation.
Amphetamine
Antagonists
Botulin toxin blocks release of ACh.
Curare blocks receptors (cannot pass bbb).
Flupentixol
Tolerance
A decreased response to a drug with repeated exposure.
Metabolic tolerance = the number of enzymes needed to break down alcohol in the liver, blood and brain increases. As a result, any alcohol consumed is metabolized more quickly, so blood alcohol levels fall.
Cellular tolerance = brain cells activities adjust to minimize the effects of alcohol in the blood. Cellular tolerance can help explain why the behavioral signs of intoxication may be so low despite a relatively high blood alcohol level.
Learned tolerance = explains a drop in outward signs of intoxication.
Sensitization
Drug tolerance is much more likely to develop with repeated use than with periodic use, but tolerance does not always follow repeated exposure to a drug. Tolerance resembles habituation in that the response to the drug weakens with repeated presentations. The drug uses may have the opposite reaction, sensitization, increased responsiveness to successive equal doses. Whereas tolerance generally develops with repeated rug use, sensitization is much more likely to develop with periodic use.
= Amphetamine; dopamine synapse.
Sensitization is not always characterized by an increase in elicited behavior but may also manifest as a progressive decrease in behavior.
= Flupentixol
Neural basis of sensitization lies in part in changes at the synapse, changes in receptor numbers on the postsynaptic membrane, in the rate of transmitter metabolism in the synaptic space, in transmitter reuptake by the presynaptic membrane, and in the number and size of synapses.
Another basis of sensitization is learned; animals show a change in learned responses to environmental cues as sensitization progresses.
Psychoactive drugs names
Three:
Chemical: describes a drugs structure
Generic: nonpropriety and spelled lowercase.
Propriety: brand, name, given by the pharmaceutical company that sells it, is capitalized
Group I
Anxiety agents and sedative-hypnotics: low doses: reduce anxiety, medium doses: sedate, and high does: they anesthetize or induce coma, very high doses: kill.
Benzodiazepines: diazepam (Valium), alprazolam (Xanax, clonazepam (Klonopin); aid sleep and and are also used as presurgical relaxation agents.
Sedative hypnotics: barbiturates and alcohol; induce sleep, anesthesia, and coma at doses only slightly higher than those that sedate; someone who takes repeated doses develops a tolerance for them.
Other: GHB, ketamine, phencyclidine (PCP, angel dust).
Group II Antipsychotic agents
First generation: phenothiazines, chlorpromazine (Thorazine), butyrophenones, haloperidol (Haldol); mainly block the dopamine D2-receptor.
Second generation: clozapine (Clozaril), aripiprazole (Abilify, Aripiprex); weakly block the dopamine D2-receptor, but also block serotonin 5-HT2-receptors.
Dopamine hypothesis of schizophrenia holds that some forms of the disease may be related to excessive dopamine activity, especially in the frontal lobes. Other support for the dopamine hypothesis comes from the schizophrenia-like symptoms of chronic uses of amphetamine, a stimulant. Amphetamine is a dopamine agonist; it fosters dopamine release from the presynaptic membrane of D2 synapses and block dopamine re-uptake from the synaptic cleft. The logic is that if amphetamine cause schizophrenia-like symptoms by increasing dopamine activity, perhaps naturally occurring schizophrenia is related to excessive dopamine action too.
Group III Antidepressants and mood stabilizers
Three types of drugs have antidepressant effects:
- Monoamine oxidase (MAO) inhibitors
- Tricyclic antidepressants
- Second generation antidepressants.
They act by improving chemical neurotransmission at serotonin, noradrenaline, histamine, and acetylcholine synapses, and perhaps at dopamine synapses.
MAO inhibitors, tricyclic and second generation depressants all act as agonists but have different mechanisms for increasing serotonin availability.
MAO inhibitors: provide more serotonin release with each action potential by inhibiting monoamine oxidase, an enzyme that breaks down serotonin in the axon terminal.
Triglycerides and second generation antidepressants block the re-uptake transporter that takes serotonin back into the axon terminal; second generation specifically effective therefore called selective serotonin re-uptake inhibitors (SSRIs). Because the transporter is blocked serotonin remains in the synaptic cleft, prolonging its action on postsynaptic receptors.
Antidepressants: MAO inhibiters, Tricyclic antidepressants: imipramine (Tofranil), SSRIs: fluoxetine (Prozac), sertraline (Zoloft), paroxetine (Paxil, Seroxat).
Mood stabilizers mute the intensity of one pole of the disorder, thus making the other less likely to occur. A variety of drugs for epilepsy have positive effects; perhaps they mute the excitability of neurons during the mania phase. And antipsychotic drugs that block D2-receptors effectively control the hallucinations and delusions associated with mania.
Mood stabilizers: lithium, sodium valproate, carbamazepine (Tegretol)
Group IV Opiod analgesics
A opioid is any compound that binds to a group of morphine-sensitive brain receptors. The term narcotic analgesic was first used to describe these drugs because opioid analgesics have sleep inducing (narcotic) and pain-relieving (analgesic) properties.
The peptides in our body that have opioid-like effects are collectively called endorphins (endogenous morphines)
Opium derivatives: morphine (most closely mimics the endomorphins and binds most selectively to the mu receptors), codeine, heroin (affect mu receptors).
Endogenous opioid neuropeptides: endorphins (relatively specific on the receptors mu, kappa and delta), enkephalins, dynorphins, endorphins.
Many drugs including nalorphine and naloxone act as antagonists at opioid receptors. Many people addicted to opioids carry a competitive inhibitor as a treatment for overdosing. They can be used to treat opioid addiction after the addicted person has recovered from withdrawal symptoms.
Morphine does not readily cross the blood-brain barrier but heroin does.
Opioids create tolerance; morphine also creates sensitization.
Group V Psychotropics
Psychotropic drugs are stimulants that mainly affect mental activity, motor activity, arousal perception, and mood. Behavioral stimulants affect motor activity and mood. Psychedelic and hallucinogenic stimulants affect perception and produce hallucinations. General stimulants mainly affect mood.
Behavioral stimulants: amphetamine, heroin; both dopamine agonists that act first by blocking the dopamine re-uptake transporter. Interfering with the re-uptake mechanism leaves more dopamine available in the synaptic cleft. Amphetamine also stimulates dopamine release from synaptic membranes Both mechanisms increase the amount of dopamine available in synapses to stimulate dopamine receptors. Amphetamine bases drugs are widely described to treat ADHD.
Psychedelic drugs alter sensory perception and cognitive processes and can produce hallucinations.
Psychedelic and hallucinogenic stimulants:
- Acetylcholine psychedelics: atropine (block), nicotine (facilitate); block or facilitate transmission at ACh synapses.
- Anandamide psychedelics: tetrahydrocannabinol (THC); enhances forgetting; positive effect on mental overload; interacts with anandamide CBI receptor (neurons) and anandamide CB2 receptors (glial cells).
- Glutamate psychedelics: phencyclidine (PCP), ketamine; hallucinations and out of body experiences; blocking glutamate NMDA receptors involved in learning.
- Norepinephrine psychedelics: mescaline; sense of spatial boundlessness and visual hallucinations.
- Serotonin psychedelics: Lysergic acid diethylamide (LSD), psilocybin MDMA (Ecstasy); stimulate some 5-HT autoreceptors.
General stimulants: caffeine; cause an overall increase in cells metabolic activity; inhibits an enzume that ordinarily breaks down the second messenger cyclic adenosine monophosphate (cAMP), which leads to increased glucose production, making more energy available and allowing higher rates of cellular activity.
Cross-tolerance
Results when the tolerance for one drug is carried over to a different member of the drug group. For example anti-anxiety and sedative-hypnotic drugs, which suggests that they act on the nervous system in similar ways. One target is common to both alcohol and barbiturate drugs; the receptor for GABA, the inhibitory neurotransmitter that is widely distributed in the CNS. Zie p. 6. Sedative-hypnotics drugs increase GABA binding thereby maximizing the time the pore it open, anti-anxiety drugs influence the frequency of pore opening; because their different actions summate, these drugs should not be taken together.
Alcohol effects explanation
Disinhibition theory: holds that alcohol has a selective depressant effect on the cortical brain region that controls judgement while sparing subcortical structures, those responsible for more instinctual behaviors, such as desire.
A variation of disinhibition theory argues that the frontal lobes check impulsive behavior; according to this idea impulse control is impaired after drinking alcohol because of a higher relative sensitivity of the frontal lobes to alcohol. A person may then engage in risky behavior.
None of the theories explains why the behavior is different on different occasions; if alcohol is a disinhibitor why is it not always so.
