Pharmacology Past Paper PDF

Like the picture…this was a picture one of my face-to-face students gave me – she said it described how she felt when reviewing pharmacokinetics/dynamics….that she was diving into the deep end of the pool and was afraid she wouldn’t resurface after reading the material. Happy to say she “survived” a...

Like the picture…this was a picture one of my face-to-face students gave me – she said it described how she felt when reviewing pharmacokinetics/dynamics….that she was diving into the deep end of the pool and was afraid she wouldn’t resurface after reading the material. Happy to say she “survived” and re-surfaced very nicely. 1 Last module we looked at what the body did to the drug, now we’re going to look at what the drug does to the body. How the drug molecule interact with cell receptors – the binding and affinity of the drug to the receptor – so that a physiologic reaction occurs (which we hope is a therapeutic response). 2 Read slide 3 Not all drugs are equally effective at treating a disorder – some antihypertensives are better than others at lowering blood pressure; some analgesics are better than others at relieving severe pain. The efficacy and potency of a drug relates to what is known as a dose response. It gives a way to compare medications within the same classification. Efficacy relates to the magnitude of maximal response that can be produced. While potency – a drug that is more potent will produce a therapeutic effect at a lower dose compared to a drug with the higher dose. For example, drugs X and Y both lower the systolic BP by 20 (so they have the same efficacy – they’re able to exert the same effect). Drug X can do this at 10 mg while Drug Y does this at 60 mg  so drug X is more potent than Y (because it takes a lower dose to achieve the same effect). Despite what intuition may tell us – a drug with a very high maximal efficacy does not mean it is always more desirable than one with a lower efficacy. You want to match the intensity of the response to the client’s needs for example diuretics – lasix has such high maximal efficacy that it can cause dehydration. If you only want to mobilize a modest volume of water then a diuretic with lower efficacy (like diuril) would be preferred. While potency – relates to the amount of drug that has to be given to elicit an effect. A drug that is more potent will produce a therapeutic effect at a lower dose compared to a drug with the higher dose. Need to be aware that the public (mainly because of direct-to-consumer advertising) have a misconception about potency – they want the most “potent” drug when really it’s the results you want. If you had cancer –do you really care if the one drug is 2 mg and the other is 200 mg? You would want the one that kills the most cancer cells. Here’s another headache example – the dose of aspirin (ASA) is 650 mg and the dose of Advil (ibuprofen) is 200 mg. Which is more potent  Advil. Their ability to relieve headache at recommended doses is the same so their efficacy is the same. Drugs act through receptors by binding to the receptors. Most receptors are proteins found on the cell membranes. By binding to the receptor the drug can do two things: 1. initiate (produce) a response 2. block (prevent) a response The degree to which a drug molecule binds to a receptor and elicits a response if known as affinity. They form a chemical bond with a specific receptor (fit like a key into a lock) – the better the fit – the better the response. 4 Drug binding site are primarily on proteins (transmembrane), glycoproteins and enzymes 1. Kinase-linked receptors  drug activated an enzyme on the protein and a response is initiated 2. Ligand-gated ion channels  transmembrane proteins and with this receptor the channel opens allowing for flow of ions in & out of cell (neurotransmitters and catecholamines). 3. G-protein coupled receptor systems  this has three components: a. Drug activates receptor  activated G protein (guanosine triphosphate) which  activates effect. 4. Nuclear receptors  found in cell nucleus (not cell membrane) 5 Drug molecules that “fit” that specific receptor and produce a response is known as an agonist. For example, a drug that is said to be a epinephrine agonist is a drug whose effects mimic those of the body’s on epinephrine A drug that is said to be a cholinergic agonist is a drug whose effects would mimic those of the cholinergic system Antagonists are drug molecules that attach to a receptor (but not quite fit) and so do not elicit a response. They actually block a response. Partial agonists (also referred to as agonist-antagonists) have characteristics of both – they produce a weaker response. 6 One of the important aspects of the NP prescriber is monitoring the effectiveness of the drug and monitoring for the development of adverse effects. 7 I did a short audio on the ED50 = click or cut and paste the following site to access it: https://www.educreations.com/lesson/view/ed50/31392665/?ref=link&s=jPWMCm One of the important aspects of the NP prescriber is monitoring the effectiveness of the drug and monitoring for the development of adverse effects. Have to be able to predict whether a drug will produce a significant change in a client Responses to drugs is best understood by frequency distribution curve (bell curve) Drug guides sometimes report the ED 50 as the “average or standard dose”. So, clinically important to realize that this predicts therapeutic dose for ½ population  may need to adjust dose up/down ED50 – it’s the dose required to produce a response in 50% of the clients 8 The safety of drugs is a major concern and the therapeutic index (TI) estimates the margin of safety of the drug. In your drug formulary book it will tell you what the TI of the drug is. TI = LD50/ED50 Drugs with a low therapeutic range have narrow margin of safety and often require monitoring of drug levels to ensure that the client is not in a toxic range. In those drugs that have a low therapeutic index the dose that is considered effective is also very close to the dose that is toxic. Those with a wide margin of safety often do not require monitoring (which is the majority of drugs typically used in primary care practice). 9 Another short audio on the Therapeutic Index is at: https://www.educreations.com/lesson/view/therapeutic- index/31392703/?ref=link&s=IKws0W 10 These three drugs – have a very narrow therapeutic index (and these are drugs you may be prescribing or monitoring for your clients). These three drugs and their toxic levels – you will need to memorize … and rest assured - we’ll be seeing these drugs later in the semester  11 Drugs can interact with other drugs, with foods, with herbs – knowledge of these interactions is an essential part of monitoring for safety. Alteration of the action of one drug by another drug is referred to as drug interaction. Many terms are used to categorize drug interactions. Additive effect is when two drugs with similar action are given together they have an increased effect than either of them alone. For example giving the combination of aspirin with codeine has more of a pain relieving effect than either of these drugs alone Synergistic effect  the effects (results) of two combined drugs are better than what can be achieved by either alone For example the combination of two different classifications of antibiotics is better at killing bacteria than one Antagonistic effect  effects of two drugs are less than the sum of the effects for each drug given separately – at times, the drugs can cancel each other out. For example  when certain antibiotics are given to a woman on oral contraceptives  the antibiotics decrease the effectiveness of the OCP significantly Incompatibility refers to the physical interaction of 2 drugs interferes with the effects of at least one of the drugs. Usually it results in the chemical deterioration of one or both drugs. Typically this is seen with parenteral drugs. 12 Always need to consider the above concept whenever your patient is on more than one drug – and this also includes OTC (over-the-counter) medications they may take. 13 Please read slide above – note the difference between inducers and inhibitors. 14 15 Adverse drug events (ADE) is term that describes the potential unwanted effects that may be experienced while taking the medication: it may occur within minutes, days, or weeks after taking the medication. Side effects (sometimes referred to as Type A reaction) – read slide – are basically the result from unwanted but normal pharmacologic action (they are predictable). For example – hair loss is an expected side effect of taking antineoplastic drugs. Side effects typically resolve with the discontinuation of the drug. Idiosyncratic and allergic reactions are unpredictable ADE’s (these are referred to as Type B reactions). An allergic reaction involves the person’s immune system which recognized the drug molecule as a dangerous foreign substance. The body will produce antibodies (IgE) against these molecules and cause the release of histamine which can result in various reactions from mild skin rash to severe, life-threatening reaction known as anaphylactic shock. Idiosyncratic reaction occurs unexpectedly as a result of a genetic abnormal response to normal doses of a drug (usually due to a genetic polymorphism). Many times you don’t known that the patient will have this until the drug is given. It can happen with the first dose. 16 Poor lady (remember from patho  this is a hypersensitivity type I reaction resulting from “sensitized IgE” causing mast cell degranulation and histamine release. See I told you those patho concepts will come back to haunt you. 17 Remember from patho (NU 608) –hypersensitivity type II reactions in which you have sensitized IgE which upon exposure to the antigen will cause mast cell degranulation and release of histamine which can lead to allergic reaction of which anaphylaxis is worse-case scenario (see…I told you those patho concepts will come back to haunt you). 18 These ADE are sometimes referred to as Delayed reactions: Carcinogenic effects are the cancer-causing effects of certain drugs. Tetratogenic effects are drugs or chemicals that result in structural damage to the fetus. It is always important in doing a drug history of a female to ask if they are or think they may be pregnant. The period of greatest danger for tetratogenic effects is the embryonic period (14days to 8 weeks) as this is the period when organ development is occurring.  important, hint! Hint! Also, be aware that in the last trimester due to increased placental blood flow and thinning of the placental membranes there can be increased transfer of substances from the maternal to fetal circulation. The fetus may lack or have decreased hepatic enzymes to metabolize these medications so drugs may accumulate and have prolonged action and/or toxic effects.  important, hint! Hint! FDA safety classification for drugs used by pregnant women. The drug formulary’s will list the classification of the drugs (most of the drugs are “C”  adverse effects seen in animals; no information in humans available). Drugs in category D such as… ace inhibitors and tetracyclines – show that possible risk in humans has been reported  need to consider potential benefit to mother vs risk before placing a pregnant woman on these medications. Drugs known to be in the X category are contraindicated for pregnant women: thalidomide (known to cause limb hypoplasia) cocaine – causes fetal vasoconstriction, renal & GU abnormalities. Vitamin A (accutane) No prescription or OTC, herbal product or dietary supplement should be taken by pregnant women unless her health care provider verifies that the benefit to the mother outweighs the risk to the unborn child.*** 19 Need we say more? 20