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Pharm-Strathmann Exam 1 Who gives the ARNP authority to practice and prescribe medications? It's the state board of nursing in your respective state According to the WHO what is the first step in the prescribing process? Step 1: define the patient's problem to generate a clear indication for treatment. This step forms the basis for choosing and prescribing the correct treatment during the next steps. Summary of the diagnostic part of the consultation including
- Complaints
- Symptoms
- Diagnosis and relevant patient characteristics like co-morbidities,
- Co-medication
- Pregnancy
- Drug allergy Step 2 : Specify therapeutic objective, • Essentially not only for determining the right treatment but also for monitoring the effective treatment later on.
- Without clearly specified therapeutic objectives, preferably expressed in measurable parameters, o It is not possible to adequately monitor treatment which could result in incorrect conclusions and further actions.
Step 3: choose which drug or treatment is needed One of the key principles of the WHO approach is to divide step 3 into 2 parts. Step 3A: First, selection of the so-called p-drug or the prescribers personal drug of first choice for the indication. Step 3B: confirmation of its suitability for the patient in question ***Graduate nursing students should define their own p-drugs and are encouraged to develop a personal formulary on such drugs during their clinical attachments.
- These so-called standard treatments should be preferably evidence based.
- Verifying the suitability of a p-drug for individual patient requires thoroughly checking for potential contraindications and for interactions if the patient has co-morbidity, is taking other medications, is pregnant, or is allergic to certain drugs. Step 4: administered correctly this involves writing the prescription and starting treatment
How does hypoalbuminemia affect the process of prescribing?
- Many drugs that carry an electric charge are bound to albumin in the blood.
- The distribution of the drug target tissues may be affected if hypoalbuminemia is present.
- Most drugs are carried thru the body bound to protein.
- When albumin is low, instead of the drug getting to the target tissues, we have excess free drug floating around, which can lead to toxicity or different effects.
- Low albumin = more free drug = increased adverse effects
What is the drugs half-life?
- Half-life specifically means the amount of time it takes for an administered drug to be halfway cleared from the system
- It means that it takes about 4 to 5 times a half-life for a drug serum concentration to reach steady state after regular dosing is started, stopped, or the dose is changed.
- Example: Digoxin has a half-life of 24 to 36 hours o This means that a change in dose will have best part of a week to take effect. o For this reason, drugs with long half-life, like amiodarone, which has a half-life of 58 days are usually started with a loading dose to achieve their desired clinical effect more quickly. o You must use the drugs half-life to determine the length of time required between dosage administrations.
- How long it takes for the drug to be increased or decreased by 50%.
- Important b/c, especially with new meds, it takes 4 - 5 half-lives to reach a steady state. What is the steady-state? • In pharmacokinetics, steady-state refers to the situation where the overall intake of a drug is fairly in dynamic equilibrium with its elimination.
- In practice it is generally considered that steady state is reached when the time of 4 - 5 times the half-life for a drug after regular dosing is started. What is meant by the onset of action, peak of action, and duration of action of medications?
The length of time you have the drug in your system. On the drug concentration curve what is the first sign of a therapeutic effect? The onset of action What is the efficacy of a drug? • Efficacy is the maximum response achievable from a drug.
- Maximum effect a drug can produce.
- Ie drug for mild pain, no matter how high the dose is increased are ineffective in treating severe pain.
- Intrinsic activity is a relative term that describes a drug’s efficacy to a drug of the highest observed efficacy. The ability of a drug to produce a response once it has occupied specific receptors.
- Effectiveness refers to the ability of the drug to produce a beneficial effect. Explain first pass metabolism After a drug is swallowed, it is absorbed by the digestive system and enters the hepatic portal system, it is carried through to the portal vein into the liver before it reaches the rest of the body. The liver metabolizes many drugs, sometimes to such an extent that only a small amount of the active drug emerges from the liver to the rest of the circulatory system. This first pass through the liver, thus greatly reduces bioavailability of the drug. The first pass effect AKA pre-systemic metabolism- is a phenomenon of drug metabolism whereby the concentration of a drug is greatly reduced before it reaches the systemic circulation. It is the fraction of a drug lost during the process of absorption, which is generally related to the liver and the gut wall. Notable drugs that experience significant first pass affect: Imipramine Morphine Midazolam Demerol Cimetidine Lidocaine. Propranolol Diazepam
Sublingual administration can bypass this first pass metabolism, this route is also faster than oral and rectal administration. What factors affect the drugs absorption? Absorption involves several phases. First the drug needs to be introduced via some route of administration either
- Oral
- Topical
- Dermal
- However you want to get and its specific dosage forms such as a tablet, capsule, solution, etc. Other situations is even more straightforward and there's less variability in the absorption and bioavailability is often near 100%, such as: - Intravenous therapy - IM injection - Enteral nutrition - and others absorption Intravascular administration does not involve absorption there is no loss of drug. The fastest route of absorption is inhalation, and not as mistakenly considered the IV administration. The GI tract is lined with epithelial cells drugs must permeate through these cells in order to be absorbed into the circulatory system. One particular cellular barrier that may prevent absorption of a given drug is the cell membrane.
- Cell membranes are essentially lipid bilayers which form a semipermeable membrane.
- Pure lipid bilayers are generally permeable only to small and uncharged solutes, hence whether or not a molecule is ionized will affect its absorption, since ionic molecules are charged.
- Solubility favors charged species, permeability favors neutral species
- This aspect of absorption been targeted by medicinal chemistry, for example a suitable analog maybe chosen since the drug is more likely to be in a nonionic form. Also, prodrugs of a compound may be developed by medicinal chemists.
- These chemical variants may be more readily absorbed and then metabolized by the body into the active compound.
- However, changing the structure for molecule is less predictable than altering dissolution properties since changes in chemical structure may affect the pharmacodynamic properties of a drug. How will renal insufficiency effect drug elimination? The kidney is the primary organ of excretion for most drugs. General theme of metabolism is to produce drug metabolites that are more water soluble and more easily removed by the kidneys. The rate at which the drug is excreted by the kidneys depends on several factors. Renal blood flow influences the glomerular filtration rate (GFR) which is how much plasma is filtered per minute by the glomerulus. Renal excretion of drugs is typically well-characterized, what is variable is the level of renal function the patient. It is common to monitor renal function in patients by the clinical setting and to adjust dosages based on renal function. Typically assessed by the serum creatinine. Patients with poor renal function may have higher levels of drugs secondary to decreased excretion of metabolites. Identify drug metabolism and the role of isoenzymes in the p450 system
CYPs (Cytochrome P450)
- CYPs are the are the major enzymes involved in drug metabolism accounting for about 75% of the total metabolism.
- Most drugs that undergo deactivation by CYPs either directly or facilitated excretion from the body.
- Many substances are bio activated by CYPs to form their active compounds.
Naturally occurring compounds may induce or inhibit CYP activity For example:
- Bioactive compounds found in grapefruit juice
- Other fruit juices including
- Dihydroxy-Vit D
- Parasitin A- (natural ingredients and homeopathic compounds to destroy all known parasites in the digestive tract.) o have been found to inhibit CYP3a4 mediated metabolism of certain medications leading to increased bioavailability and the strong possibility of overdosing. ***Because of this risk avoiding grapefruit juice and fresh grapefruit entirely while on these drugs is usually advised. *** When 2 drugs are both metabolized by the p450 system the drug should be administered at separate times to prevent the metabolism of one drug resulting in toxic effects of the other drug.
CPY 450 is the reason behind drug interactions and the rationale of why drugs affect different people in different why; based on variation of that system. What is the purpose of a peak and trough level?
- To determine if the drug is in therapeutic range.
- Which refers to either the dosage range or blood plasma or serum concentration usually expected to achieve desired therapeutic effects.
- Some patients require doses or concentrations above or below this range.
- Some patients will experience drug toxicity within this range.
- Used for dosing purposes. Describe the purpose of blood brain barrier and the fetal placental barrier The BBB (Define) Is a highly selective permeability barrier that separates the circulating blood from the brain and extracellular fluid in the CNS. The BBB is formed by brain endothelial cells which are connected by tight junctions with an extremely high electrical resistivity of at least 0.1 micron. The BBB allows the passage of water, some gases, and lipid soluble molecules by passive diffusion as well as the selective transport molecules such as glucose and amino acids that are crucial to neuro function. The so-called placental barrier impedes certain chemicals although it allows most fat soluble chemicals to cross. Drugs that are more water soluble and that possess a higher molecular weight tend not to cross the placental barrier. In addition, if a drug binds to a large molecule, such as a blood-borne protein like albumin, it is even less likely to come into contact with fetus.
Both prescription drugs and over-the-counter drugs can be used in off-label ways, although most studies of off-label use focus on prescription drugs. Off-label use is generally legal unless it violates ethical guidelines for safety regulations. it is commonly used to good effect by physicians and nurse practitioners because we understand how to use it correctly. However, it can entail health risks and differences and legal liability. Insurance may not pay for off-label use. i.e. Wellbutrin for smoking cessation. What factors place an infant and child at risk when prescribing medication? In general, there is a lack of safety and efficacy studies in the pediatric population most medications are studied in adult populations which because of:
- age-related differences
- medication metabolism
- mechanisms of action don't necessarily apply to pediatric populations.
Children are not just small adults. Adverse drug reactions are most common in this age group. Meds are weight based. Kids do not have a fully mature liver and renal function, and are at higher risk for toxicity and adverse drug effects. What ADRs are the elderly at risk of developing? Physiologic changes In older adults increase the risk of harm for medication metabolized by the liver and kidneys.
Hepatic blood flow Decreases by nearly one-half or 40% in older adults. and some degree of chronic kidney disease is present in one-half of older adults. Furthermore, the median renal blood flow decreases by one-half by the time the patient reaches 80 years of age. Although, the normal individual rate of decline varies and one-third of older adults maintain normal
Common categories • genetics,
- age
- gender
- drug interactions
- medical Type 1 hypersensitivity or immediate hypersensitivity An allergic reaction provoked by re-exposure to a specific type of antigen Referred to as an allergen. Symptoms vary from:
- Mild irritation to sudden death from anaphylactic shock, called type 1 anaphylactic shock. Type 2 hypersensitivity or cytotoxic hypersensitivity In, the antibodies produced in the immune response bind to antigens of the patients on cell surfaces. The antigens recognized in the way may either be:
- intrinsic (a self-antigen, part of the patient’s cells)
- extrinsic (absorbed onto the cells during exposure to some foreign pathogens possibly as part of an infection with a pathogen). An example of type 2 hypersensitivity is the ABO blood incompatibility where the red blood cells have different antigens causing them to be recognized different. B-cell proliferation will take place in antibodies until foreign blood types are produced. IgG and IgM antibodies bind to these antigens to form complexes that activate the classical pathway of the complement activation to eliminate cells presenting foreign antigens. That is mediators of acute inflammation are generated at the site and the membrane attack of complexes cause cell lysis and death. This reaction takes between hours to a day. Type- 3 hypersensitivity occurs when there is:
- An accumulation of immune complexes
- Or A ntigen-antibody complexes that may not have been adequately cleared by innate immune cells o giving rise to an inflammatory response and attraction of leukocytes. Such reactions progress into the point of disease producing immune-complex diseases. The reaction can take hours, days, or even weeks to develop depending on whether or not there is immunologic memory of the precipitating antigen. Typically, clinical features emerged a week following initial antigen challenge from the deposited immune complexes that can precipitate the inflammatory response. Type 4 hypersensitivity is often called delayed-type hypersensitivity A reaction take 2 - 3 days to develop. Unlike other types it is not antibody-mediated but rather cell mediated response. Which medications interact with St. John's Wort?
