These are a few of the pearls gleaned from Thomas Pazdernik, PhD of pharmacology, author of a fantastic book:
Pazdernik
Once you have identified where the drug belongs, you need to ask yourself, “what is the basic mechanism of the drugs within that class?” Usually that comes to you pretty easily. A lot of times, when you can put it in the right class you will know the mech. Then, don’t memorize all the pharmacokinetics, but memorize the UNIQUE pharmacokinetics. There are some drugs that can’t be given orally. Like Aminoglycosides. There are some drugs that rely primarily on renal mechanisms for elimination. So if you have renal dysfunction, you need to adjust the dose. There are other drugs that depend primarily on the liver.
We should know the difference between Neostigmine and Physostigmine. Neostigmine you would use if you wanted to treat Myasthenia Gravis. If you’re going to treat Atropine OD, then you need to use Physostigmine. Physostigmine crosses the Blood Brain Barrier.
What’s hit very hard on the boards is side effect profile. And many of the side effects you can figure out because they’re kind of an overextension of the pharmacological effect. So you should be understand, if you understand autonomic physiology, some of the side effects of some of the autonomic agents we’ve studied.
A lot of drugs have a signature side effect. It’s a side effect that’s kinda unique to that drug. This is particularly relevant in the anti-cancer drugs. Those are hit hard on board exams. You should know for example that Cyclophosphamide causes bladder cystitis. That Vincristine causes neurotoxicity. That Methotrexate causes Hepatotoxicity. That Cisplatin cause Nephro and Neurotoxicity. Duanorubicin and Doxirubicin causes Cardiac Toxicity. Bleomycin and Lung Toxicity. This is what I mean by signature side effects. These side effects are often kinda the rate limiting effect of the drug when it’s used clinically.
Then you should also have a good idea of some of the common uses of drugs. You don’t need to know all of the indications for a drug, but you should know how to treat Asthma. Know how to treat Arrhythmia and be able divide them into their classes.
Now what you uses to study for the boards and for your final depends a little bit by how you studied as you went through the course. Probably most of you are not going to have enough time to go back through all of your notes. If you made summary sheets or charts, you should use those.
Board Review books can also be very helpful at this point in time. There as helpful as how well you learned the material the first time you went through it. If you didn’t learn the material as you went through the course, then First Aid for the Boards is not going to be very meaningful to you at all.
I think maybe one of the best sources for the boards and maybe be more than what you can handle for the final, is the rapid review book that we’ve just came out with. It’s the Pharmacology Rapid Review Book by Mosely. This book is meant to be somewhere between what’s in First Aid and what’s in Baby Katzung. The strength of this is the disk in the back that has 500 questions that you can take in a tutorial mode or in an exam mode. If you take it in a Tutorial mode you can pull up the questions on Antibiotics. It will give you feedback as to whether it’s right or wrong. IF you take it in the exam mode it will give you 1 hour to do 50 questions. You can either do that within a subject area or a whole area of pharmacology. 100 of those questions are in here as a paper/pencil format. You can take it as an exam and go back and look at it.
One program on the web that is very high yield is under the General Principles Section. There’s a program that’s called MATCHING QUIZ. It kinda lists the hallmarks of some of the older classical drugs that are used to describe certain phenomena. Like Tetracycline causes discoloration of teeth. That Phenobarbital induces cytochrome P450. Phenoxybenzamine forms a covalent bond with the receptor.
On the board exams you’ll see a higher emphases on old classical drugs and prototypic drugs. It won’t necessarily look like the clinics are going to look. The drugs usually are chosen to illustrate a principle and if you’ve learned that principle, then it probably will be quite obvious why that drug is the right answer. So I think the matching thing is helpful.
Look at the clinical vignette-type questions presented in this course. We try to use questions that are very much like those that are on the board. A lot of those questions, you need to know 2 or 3 things to get them right. Q-bank from Kaplan is also very useful in preparing for the boards as well.
Look at table and figures when you look through your review books. Compare and contrast drugs. Many have done well on rote memorization from notes, but the boards will not be like that. You shouldn’t memorize verbiage, but you should understand the principles involved. A lot of the board questions are written so that most of the foils sound pretty good. If you really understand the basic principle, the right answer should be pretty obvious. Some situation that they’ve put the subject in may make one answer superior to the others.
Here’s an example:
Amiodarone has now become the recommended drug by ACLS for life threatening ventricular arrhythmias, but if you have a little clinical vignette with someone with severe COPD… then you’d go back to Lidocaine. The key here is that you have to recognize that Amiodarone has lung toxicity and should certainly be avoided.
You should have a good understanding of Absorbtion, Distribution, Metabolism and Excretion.
Some of the formulas that you might be seeing on the final or that you might be seeing on the boards… These are the ones you should probably know.
Vd = Amt. injected
--- ----------------
Amt. injected at time zero
Vd = Amt. IV
------------
C0
Kel = 0.7
-----
t ½
Cl = Kel x Vd
X = Css x Vd
Css = input = F x D/T
------ -----------
output Cl
IF you can work with these equations, you should be able to do any of the questions that you’ll be faced with.
Other important items you should know for boards:
- The difference between a Zero order and First order reaction, and how you would graph that
- Understand Half-life, 50% of the drug after one half life, 75% after two, 87% after three, etc.
- There’s a fair amount of questions that deal with Signaling Pathways, maybe more coming of Biochemistry than from Pharmacology
- You should know the kind of drugs that affect Gene Expression, like steroids for example. There’s multiple drugs (both endocrine and autonomic) that affect cAMP pathway. The PI pathway. You should know N.O. and EDRF. Also the various ionotropic mechanisms.
- Dose-Response curves—you should know the basic terminology like what is an agonist, what is potency, what is affinity.
- Understand graphically the difference between a full agonist and a partial agonist. Also an inverse agonist.
- Understand the various way for graphing a competitive antagonist vs. a non-competitive antagonist. Understand the various ways you can plot this, like Lineweaver-Burke, etc.
- Know the examples and definitions of Pharmacokinetic Tolerance, Pharmacodynamic Tolerance, the phenomena of Tachyphylaxis particularly with indirecting amines depleting the store of norepinephrine, Desensitization—usually due to a relatively rapid inactivation of a process (Ion channels can get trapped in an open or closed state—for example the nicotinic receptor), Down regulation—agonists down regulate receptor numbers per unit of tissue
- You should know terms like Therapeutic Index, Margin of Safety,
- You should know substances that are teratogenic
- Fetal toxicity
- Clozapine - Agranulocytosis (type II)
- Serum Sickness - Type III
- Contact Sensitivity - type IV, like poison ivy
- You should know and understand the abnormal responses that are influenced by Genetics
- Inducers and Inhibitors of P450, know that Valproic Acid inhibits Cytochrome P450 (it’s the one that’s different from some of the other drugs used like Primidone, etc.)
- ST. JOHN’S WART induces Cytochrome P450
- Inhibitors—particularly Macrolide Antibiotics and Azole Antifungals!
Chemotherapy will be the hardest section. Spend some time with it.
Buzzwords for Chemotherapy
| Drug that blocks excretion of penicillin and therefore can increase it’s half life | probenecid |
| Type of penicillin that has a half-life of more than 2 weeks and is considered a DEPOT form of penicillin | Benzathine Penicillin G |
| Which generation(s) of cephalosporins can enter the CNS | 3rd and 4th |
| This cell wall synthesis inhibitor is inactivated by renal dipeptidase | Carbapenem (imipenem) |
| What is cilastatin used for | Cilastatin blocks the metabolism of imipenem by renal dipeptidase and can therefore increase it’s half-life |
| This cell wall synthesis inhibitor is associated with Red Man Syndrome | Vancomycin |
| Don’t give this protein synthesis inhibitor to children because it can concentrate in their teeth and growing bones | Tetracycline |
| This protein synthesis inhibitor is associated with Gray Baby Syndrome | Chloramphenicol – babys are poor glucoronidators L |
| This protein synthesis inhibitor is a potent inhibitor of CYP3A4 and went through FDA accelerated approval | Streptogramins |
| This protein synthesis inhibitor follows “Once daily dosing” | aminoglycosides |
| This folic acid inhibitor is also used in Ulcerative Colitis as a topical anti-inflammatory | Sulfasalazine |
| This DNA gyrase inhibitor has been associated with spontaneous rupture of Achilles tendon in animal rats | Fluoroquinolones |
| This urinary tract antiseptic works best in acidic urine | Nitrofurantoin |
| Name three systemic antibiotics that are used to treat UTI because they are efficiently cleared in the urine | Penicillin Aminoglycoside Sulfas |
| This 1st line antimycobacterial drug is associated with resistance from deleting katG gene | Isoniazid (kat G gene is the gene that encodes a catalase that activates Isoniazid) |
| This 1st line antimycobacterial drug inhibits synthesis of arbinogalactan and is associated with visual disturbances(optic neuritis, low acuity, red-green problems) as it’s adverse effect | Ethambutol |
| This 1st line antimycobacterial drug is the only drug know to target RNA synthesis | Rifampin |
| This anti-parasitic drug is known to concentrate in the liver, spleen, and kidneys and is slowly released from those sites | Pentamidine |
| This alkylating agent is part of the MOPP regimen and is administered in arterial supply to the tumor | Mechlorethamine |
| This alkylating agent is associated with hemorrhagic cystitis which can be prevented with administration of mesna and adequate hydration | Cyclophosphamide |
| This alkylating agent is leukemogenic, teratogenic and is part of the MOPP regimen | Procarbazine |
| This anti-metabolite can be given in a high dose followed by “rescue with folinic acid (citrovorin, leucovorin)” | Methotrexate |
| Resistance to this group of anti-metabolite drugs is associated with a decrease in hprt activity | Purine Analogs: 6-Mercaptopurine 6-Thioguanine |
| These plant alkaloids are known as “spindle poisons” and stabilize microtubules so much so that they can’t be pulled apart | Taxol/Taxotere (used predominantly in breast and ovarian cancer) |
| This anti-tumor antibiotic is associated with cardiotoxicity | Daunorubicin/Doxorubicin |
| This anti-tumor antibiotic is associated with pulmonary fibrosis | Bleomycin |
| This anti-tumor antibiotic has mechanism of action that is favored by hypoxia | Mitomycin – this is also the most toxic of all anti-tumor antibiotics |
| This anti-tumor antibiotic can be administered by bladder instillation | Mitomycin |
| GnRH antagonists are used to treat this type of cancer | Leuprolide is used to treat Prostrate cancer |
| Name the aromatase inhibitor that blocks the conversion of androgen to estrogen and is used in breast cancer unresponsive to tamoxifen | Triazole |
| Which tyrosine kinase inhibitor inhibits bcr-abl and is a great drug for CML | Gleevec |
| Estrogens are used to treat what type of cancer | Prostrate |
| Androgens are used to treat what type of cancer | Breast |
CNS, and Autocoids, and Toxicity, should come back pretty easily.
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