Chapter 12: Psycho pharmacology and other biologic treatments Flashcards
Overview
In the 1950s it was discovered that medication such as chlorpromazine relieved many of the symptoms of psychosis and medication for treating tuberculosis elevated mood. Lead to renewed interest in Nuro physiology and biologic treatments for treating mental disorders. The target for psychiatric medications are predominantly located in the central nervous system. The nurse excepts the rules and responsibilities of administering medications, proactively monitoring and treating side effects and educating the patient and family, which are all crucial to successful psychopharmacology therapy.
Psycho pharmacology is a sub speciality of pharmacology that studies medications that affect behaviour through their actions in the central nervous system and that are used to treat psychiatric and Nurodegenerative disorder’s. It is important to remember, however, that many drugs used to treat other conditions, such as pain syndrome, heart disease, an auto immune disease, they also have powerful effects on the brain
Targets of drug action: where drugs act
Most drugs act at receptor sites, binding sites on enzymes or transporters. Many psychopharmacologic drugs act at multiple receptors. Newer agents are more specific to one type of receptor but none act exclusively on one type. Example Benadryl an older drug interferes histamine receptors. It did this both in the body but also in the brain resulting in station. New generation Claritin H1 receptors in the body but not the brain. Receptors are proteins embedded in cell membrane that have binding sites for both naturally occurring chemicals and drugs. Endogenous brain chemicals involved in neural transmission such as dopamine and serotonin bind to specific groups of receptors administered drugs may compete with neurotransmitters for these receptors. Naturally occurring chemicals are called androgynous substances
Receptors
Drugs that act specifically at receptor sites went bound to the receptor causes the drug to act as an agonists (Chemicals producing the same biologic action as the neurotransmitter itself) Or antagonist (Chemicals blocking the biologic action of an agonist at a given receptor)
Selectivity
Selectivity is the ability of the drug to be specific for particular receptor. I selectivity results in a drug only interacting with a specific receptor in the area of the body where the receptors are car. Lock and key analogy. The more selective a drug the more likely it will affect only the specific receptors for which it is meant. Less selective drug will more likely bind to receptors intended for other neural chemicals and cause more unintended Effects. Example D2 receptors can treat positive symptoms of schizophrenia. Haloperidol does target the D2 receptors but will also interact with other receptors such as H one alpha one and two and serotonin receptors which accounts for many side effects with this drug
Affinity
Affinity is the degree of attraction or strength of the bond between the drug and its receptor. Bonds are produced by relatively weak electro chemical attractions. Their ability to bind to receptors, produce a response, move off the receptor, and continue to repeat this binding and binding process until the drug is cleared from the body.
Intrinsic activity
Intrinsic activity is the ability of the drug to produce a biologic response once it binds to receptors. A drug produces and ranges from maximum response full Agnost to partial response partial agonist to no response antagonist. Full agonist means the drug is the same as if it were stimulated by naturally occurring endogenous molecules. Drugs that act as agonists have all three properties selectivity, affinity and intrinsic activity. Antagonists only have selectivity and affinity because they produce no biologic response by attaching to the receptor.
Ion channels
Some drugs act directly on ion channels. Example local anaesthesia statics lock the entry of sodium into the cell. Benzodiazepine drugs affect a specific ion channels and help with anticonvulsants NT anxiety and sleep disturbances. It works by binding to a region of the GABA receptor chloride channel complex. When bound the drug increases the frequency and duration of chloride ion movement through GABA into the cell which causes a decrease in the ability of the cell to conduct nerve impulse
Enzymes
Enzymes are complex proteins that catalyze specific bio chemical reactions within cells know the target for some drugs used to treat mental disorders. Example monoamine oxidase is the enzyme required to break down monoamine neurotransmitters such as norepinephrine serotonin and dopamine and can be inhibited by medications from a group of antidepressants called monoamine oxidase inhibitor‘s. There are two types of MOA. MAOA is more specific to Norepinephrin and serotonin And is used to treat depression. MAOB is more specific to dopamine and is used to treat Parkinson’s. MAO inhibitor’s form a strong covalent bond with the enzyme which causes irreversible changes to the enzyme and more enzymes will need to be produced in order for further breakdown Neurotransmitters. This irreversibility may contribute to serious side effects and it’s a major reason these drugs are seldom used. Some MAO inhibitor’s do not use covalent bonds and are reversible and less flexibility significantly improves the drug safety.
Carrier proteins: uptake receptors
After a neurotransmitter has activated receptors in the sign-ups its actions are terminated by transporters that take serotonin back up into the presynaptic cell. These transporters have binding site specific for the type of molecule to be transported. Medications specific for this site may block or inhibit the transport and therefore increase the amount of no transmitter in the synaptic space available for action on the receptors. Most antidepressants increase the amount of neurotransmitters in the sign-ups by blocking the reuptake. Older antidepressants like Checklich antidepressant block the re-uptake of more than one neurotransmitter and have affinity for other receptors which produces increased side effects. Some such as Prozac or Zoloft are more selective for serotonin whereas reboxetine is more selective for norepinephrine. These medications are called selective serotonin reuptake inhibitor‘s and selective norepinephrine reuptake inhibitor‘s. Medications selective to both are called SNR eyes. These more selective medications have reduced the number of side effects experienced by patients
Efficacy and potency: how drugs act
Efficacy is the ability of a drug to produce a desired response. A drug may occupy a large number of receptors but not produce a response. Potency considers the amount of drug required to produce the desired biologic response. A drug may be able to achieve the same clinical affect as another drug but at a lower dose, making it more potent. Because both Drugs achieve similar effects they may be considered to have equal efficacy. Side effects are often related to dose so potential drug that can produce a therapeutic response at a lower dose may be preferable
Loss of affect: biologic adoption
Effects of medication may diminish with time especially if they are giving consistently. This can be a form of physiologic adoption as the cells attempt to regain homeostatic control. Progesterone combined to the same GABA receptors as benzodiazepine and can affect the efficacy Benzodiazepine at certain stages of the menstrual cycle. Tolerance is a gradual decrease in the action of a drug at a given dose or concentration in the blood. May take days or weeks to develop and results in the loss of therapeutic affect of a drug. The loss of affect is often called treatment refractories. Some psychologic adaption me result in gradual tolerance that can help the unpleasant side effects such as Drowsiness or nausea. This information is important for the nurse to convey to patients so that they know that the side effects will subside.
Target symptoms and side effects
Target symptoms are those measurable specific symptoms expected to improve with medication use. Side effects are the unwanted effects of medication. This includes drugs interacting with receptors not intended. Knowledge of medications affinity for receptors and subtypes of receptors give an indication of what target symptoms might improve and what side effects might be expected. Patients need to be encouraged to report side effects and be aware that suggestions and solutions may be available to address the side effects. Example changing from one truck to another within the same class of psychotropics can often decrease unwanted side effects
Drug toxicity
Toxicity refers to the point at which concentrations of the drug in the body have gone beyond the safe range and may become harmful or poisonous to the body. Side effects can be harmful but not toxic. Therapeutic index concepts used to discuss the toxicity of a drug is a ratio between median toxic dose and median effective dose. The dose at which 50% of the population will experience drug toxicity and drug effectiveness respectively. A high therapeutic index means there is a large range between the dose at which the drug begins to take affect end it does that would be toxic to the body. Both therapeutic index drugs have a narrow range and are often carefully monitored through blood levels. The therapeutic index of a medication may be greatly changed by the co-administration of other drugs. Example alcohol consumed with most CNS depressant drugs greatly increases the likelihood of toxicity or death.
Pharmacokinetics how drugs move through the body
The four processes of PKR absorption, distribution, metabolism and excretion A DME. The goal is to describe and predict the time course of drug concentrations throughout the body and factors that may interfere with these process.
Absorption And routes administration
Absorption is the movement of the drug from the state of Maine ministration into the plasma. Primary routes available include oral such as tablet and liquid, sublingual intramuscular and intravenous. Drugs taken orally are the most convenient for patients but absorption can be slowed or in Hanst by a number of factors. Taking drugs Orly with food or NTS it’s me slow the rate of absorption or change the amount of the drug absorbed. First pass metabolism is where the drug is an activated before it reaches the rest of the body due to passing from the Gastro intestinal track through the liver portal vein first. The problem is that the fraction of the drug reaching the systemic circulation is reduced. Bioavailability describes the amount of the drug that actually reaches systemic circulation. Liver disease and disfunction can decrease first pass metabolism and result in increased drug levels and increased risk for side effects. Increasing H, many disease states and concurrent medications can reduce gastrointestinal motility and slopes auction. In full strength many liquid preparations can irritate the mucosal lining of the mouth Oesophagus and stomach and must be adequately diluted. Some liquid concentrate preparations are incompatible with certain juices or liquids if a drug is mixed with an incompatible liquid it may become in active. A new drug form is the rapid dissolving oral pill. To take an orally disintegrating Tablet the nurse should dry hands to peel back the foil package immediately take out the tablet in place in mouth. No water is needed to swallow
Distribution
Distribution of a frug reflects how easily it is for a drug to pass out of the systemic circulation and move into other types of tissue such as brain, abdominal organs, skin or bone or target receptors are found. Factors that affect distribution include blood flow or perfusion within the tissue, how lipophilic the drug is, plasma protein binding and anatomic barriers such as blood brain barrier that the drug must cross. Almost all psychotropic drugs are lipophilic making it easy for the drug to passively cross blood Brain barrier.
Ionic characteristics of drugs
Drugs can be charged molecules or uncharged. Drugs that have an electrical charge cannot possibly cross the cell membrane and must be transported by carrier proteins. Uncharged drugs called lipophilic or fat loving drugs can move easily across cell membranes. Most psychiatric drugs are lipophilic which means that they can also cross the placenta. It also means that these agents can be taken into fat stores. Drugstore in fatty tissues are only slowly released back. This is why lipophilic drugs can be detected long after discontinuation in older women and overweight individuals
Protein binding
Mini drugs buying to large carrier proteins in the blood stream referred to as plasma protein binding. Only unbound refrigerators can move across membranes to the target. High protein binding prolongs the drugs duration of action allowing for less frequent dosing. Chronic disease and normal ageing can decrease the amount of plasma proteins shifting the ratio abound drug to free drug. For highly bound drugs like antipsychotics a decrease of only 10% pound drug would translate into a doubling a free drug and significantly increase the risk for side effects
Metabolism
Metabolism is the process by which the drug is altered, usually by adding to the drug molecule or breaking the drug molecules into smaller pieces both processes making the molecule or the piece more polar. Through this process lipid soluble drugs become more polar or hydrophilic so that they may be excreted more rapidly. Two types of metabolic transformation phase 1 reactions produce metabolites in phase 2 reactions produce conjugates. In phase 1 active inactive or toxic metabolites are produced. The cytochrome P – 450 super family of metabolic enzymes is responsible for most drug metabolism. Drugs that induce enzyme activity are known as CYP enzyme inducers. Substances such as tobacco smoke, alcohol, and coal tar in charcoal broiled foods can induce specific CYP 450 enzymes. Drugs can inhibit CYP 450 activity unless increase drug levels potentially pushing drug concentrations into toxic ranges. Grapefruit juice is an inhibitor of CYP3A enzymes. Differences in CYP enzyme activity are often caused by genetic variations. Example 3% of Caucasians and more than 20% of Japanese our poor metabolizers of CYP2C19. Pharmacogenomics blends pharmacology with genetic knowledge and is concerned with understanding and determining an individual’s specific CYP 450 make up and then individualizing medications to match the persons CYP 450 profile. Nurses should remain alert to the possibilities of drug drug interactions when patients are receiving more than one medication, especially in older adults. The widespread use of herbal products has introduced another potential source of drug drug interaction.
Excretion
Excretion refers to the illumination of drugs from the body either unchanged or asthma tablets. Clearance is the total volume of blood serum or plasma from which a drug S complete be removed from the bloodstream per unit of time. The elimination half-life refers to the time required for plasma concentrations of the drug to be reduced by 50%. It usually takes 4 to 7 1/2 life for a drug to be completely eliminated from the body. An exception is alcohol and assist to look acid which has specific enzymes responsible which limit the speed at which the illumination can occur. Please have a separate irrespective of concentration. Drugs that are in a more ionic form in the blood stream can be easily removed by the kidneys and excreted through urine. Many psychiatric medications Or large molecules and can be removed through bile and eliminated through feces. Any impairment in renal function or renal disease or even temporary dehydration may lead to severe toxic syndrome’s. Biliary illumination can lead to enteroportal recirculation process by which active drug metabolites We excreted in Bile into the small intestine are reabsorbed into the portal circulation. Example is oral contraceptives, oral antibiotics change the intestinal environment and decrease recirculation and efficacy. Dosing refers to the administration of medication overtime so that a consistent drug concentration may be achieved or maintained without reaching toxic levels. With repeating dosage a certain amount of the drug is accumulate in the body and reach a point where it’s a quantity of drug entering the body is equal to that leaving. This is called steady state plasma concentration.
Individual variations in drug effects
Age
Gastric absorption changes with H. In the newborn pH is 6 to 8 and decreases to 1 to 3 over the first 24 hours. There is an increase gastric pH seen an older Alex, decreased gastric emptying, slowed gastric motility and reduced spanchnic circulation. Addition of common conditions such as diarrhoea may significantly alter and reduce absorption combined with above. Renal function in the newborn is only about 20% of that I’ve been handled. In less than a week renal function develops to adult levels. Renal function also declines with H. The rate of creatinine clearance decreases by 10% per decade after the age of 40 with medical illnesses such as diabetes resulting in further loss. If it falls below 30 to 60 mL per minute the excretion of drugs is significantly impaired and potentially toxic. At birth many liver enzymes are not fully functional where is in early childhood there is evidence of increased activity compared to adult hood. Paediatric pharmacotherapeutic‘s cannot simply be based on relative dosing by weight. With age blood flow to the liver and the mass of liver tissue both decreased. Activities of hepatic enzymes slow with H as a result The ability of the liver to metabolize medications may slow as much as fourfold decrease between 20 and 70 years old. Most psychiatric medications are bound to P proteins such as albumin. Albumin production is lower in units, peaks in early childhood and declines with age. Medical conditions can change the ability of medications to bind with albumin. Malnutrition cancer and liver disease decreased production of albumin
Ethnicity and genetic make up
Individual variability in elimination half-life of a given drug is genetically determined. People of Asian dissent have decreased activities of enzymes involved stage of ethanol metabolism compared to Caucasians and produce higher concentrations of acetyl aldehyde resulting in adverse symptoms such as flushing palpitations and headaches. Asians are more susceptible to affect of drugs such as meohenytoin in then Caucasians where is Africans were less sensitive. Case reports indicate that Asians require 1/2 to 1/3 the dose of antipsychotic medications required by Caucasians and may be more sensitive to side effects because of higher blood levels. Lower doses of antidepressant meds are also required for individuals of Asian dissent.
Phases of drug treatment
Adherence is keeping with the therapeutic regimen. Considerations in terms of assessment, treatment and choose such as adherence, prevalence and severity of side effects and expected time limits for symptomless very across the phases of treatment.
Phases are initiation, stabilization, maintenance and discontinuation of the medication.
Initiation fees
Before taking medication patient undergo assessments. Psychiatric evaluation, an open discussion regarding adherence issues physical examination and indicated laboratory tests often including baseline tests Such as complete blood count and ECG, List of any other current medications including over-the-counter herbal remedies natural pathic or homeopathic alcohol tobacco weed illicit drugs.
Comparing future symptoms to patient’s baseline status may be useful in detecting improvement or worsening symptoms and potentially detect drug side effects. Nurses must keep their detailed drug knowledge current to answer clients questions and provide ongoing education. Nurses should treat the first dose S a test dose where they observe the patient closely for sensitivity to the medication such as changes in blood pressure pulse temperature mental status allergic reactions dizziness gastric distress.
Stabilization phase
Medication dosage is often adjusted to achieve the maximum amount of improvement with minimum number of side effects. Process is sometimes known as titration. Nurses must continue to assess target symptoms and look for change and provement and side effects. Outpatient basis should provide written and verbal materials about medication such as taken with food common interventions that might minimize side effects and what side effects require immediate attention. Therapeutic drug monitoring is important in the phase of treatment for drugs with a narrow therapeutic index such as lithium.The first medication shows and often does not adequately improve patient’s target symptoms. This possibility must be discussed before initiating antidepressant drug therapy. Medications may be changed when adverse reactions or serious uncomfortable side effects occur. An individual might show only partially improvement and the prescriber may try and argumentation strategy. Argumentation is the addition of another medication to enhance or potentially the effects of the first medication. Example adding a mood stabilizer such as lithium to an anti-depressant to improve the overall Efficavy. Treatment resistance is after several medication trials the individual has gained at best only partial improvement. Treatment resistant symptoms often require multiple medications which in combination provide overall additive pharmacological effects. Nurses must be familiar with potential FX side effects and drug interactions
Maintenance phase
Once the target symptoms have improved medication may be continued to prevent relapse or reoccurrence. Relapse is three emerging symptoms in response to premature discontinuation of treatment. Reoccurrence is an entirely new episode that occurs over time after full remission was achieved. Higher risk for relapse in depression is associated with people who are older, have chronic episodes, severe symptoms, psychotic symptoms, or three or more previous episodes. Re-emerging symptoms may also be due to the loss of drug FFSC, comorbid medical illness, psychosocial stressors and concurrent use of prescription or nonprescription medication.
Discontinuation phase
Mini psychiatric medications require a tapered discontinuation. Tapering involves slowly reducing dosage while monitoring closely for re-emergence of key symptoms such as drop in mood, increased anxiety, sleep disturbance, thought disorder or decreased level of self-care. Mild depression may respond to several months of treatment and not reoccur other disorders such as bipolar disorder MDD and schizophrenia require continued medication treatment for extended periods of time and me in fact never be discontinued. Withdrawal symptoms affects up to 25% of individuals after abrupt cessation ofSSR eyes and includes symptoms of dizziness, restlessness, increased anxiety, mood lability, G.I. upset and fatigue.
Antipsychotic medications
Antipsychotics among the very first drugs ever used to treat psychiatric disorders. Chloropromazine in 1950. It produced drowsiness and indifference to surgical procedures. Begin to administer to agitated psychotic patients. Especially effective in relieving hallucinations and delusions associated with schizophrenia. As more psychiatrists prescribed this the use of restraints and seclusions dropped.
Antipsychotics treat the symptoms of psychosis such as hallucinations, delusions, bizarre behavior, disorganized thinking and agitation.
Typical and atypical antipsychotics
Initially the term major tranquilizer was applied to this group of medications but later termed neuroleptics. Neuroleptic means to clasp the neuron and refers to the common and significant neurologic side effects produced by these drugs. Typical antipsychotic identifies the older antipsychotic drugs with greater risk for neurologic side effects. Atypical antipsychotic identifies the newer generation Of drugs with fewer adverse neurologic effects within the common dosing regimen’s. Older agents are used to secondary not first line drugs
Antipsychotics: indications and mechanisms of action
Indicated for treating acute psychosis or severe agitation. Target symptoms include hallucinations, delusions, paranoia, agitation, assaultive behavior, bizarre ID elation, disorientation, social withdrawal, catatonia, blurred affect, thought blocking, insomnia, anorexia, acute hypo mania. The older typical antipsychotics are equally effective in relieving hallucinations, delusions and bizarre I dilation termed positive symptoms in schizophrenia. The negative symptoms don’t respond well to typical antipsychotics and it may be worsened. Newer atypical antipsychotics are more effective at improving negative symptoms. Psychotic symptoms that occur during MDD episode anxiety or bipolar disorder can be treated with anti-psychotics primarily on a short-term basis. Off label uses of the drug have led to significant inappropriate prescribing of antipsychotic agents particularly in the treatment of anxiety dimension insomnia and PTSD. Typical and atypical antipsychotics have been used to treat delirium. Typical antipsychotic drugs are effective in decreasing positive target symptoms because they are potent post synaptic dopamine antagonist. Typical antipsychotics block serotonin receptors that reside on dopamine neurons and receptors.
Antipsychotics: pharmacokinetics
Antipsychotic medications administered orally have a variable rate of absorption. Clinical FX begin to appear in 30 to 60 minutes. Absorption after I am administration produces greater bio availability but increases risk for side effects. I am medications are absorbed more slowly when patients are on mobile. Plastic syringes me absorb some medications and should never remain in the syringe longer than 15 minutes. Metabolism of these drugs occur almost entirely in the liver. Excretion of the substances tends to be slow because the drugs can easily accumulate in fat stores. Most antipsychotics have a half life of 24 hours or longer. Some of these agents may be found in the year and months later. After discontinuation drug accumulated in body fat will diffuse back into plasma and the drug concentration in the plasma will move below the minimum concentration required to produce A drug affect over several days. Due to this the drug can be administered in once daily dosing increasing adherence.
