Some ANS pharm review

You can view it here in a better format!
http://docs.google.com/View?id=ddb246wq_9f8qm94

Parasympathetic Nervous System

Cholinoreceptor:

G protein-linked (Muscarinic): CNS, PNS-targeted tissues, vascular endothelium (not innervated by CNS)

- seven transmembrane domains (third cytoplasmic loop is coupled to G proteins)

M1 & M3: Gq everything except heart → activates the IP3, DAG cascade = ↑ Ca2+

M2 & M4: Giα → heart, inhibits adenylyl cyclase activity (inhibit cAMP & Giβ = ↑K+ flux)

Ion channel (nicotinic): “Neuronal” - ANS postganglions, some CNS neurons; “NMJ” - somatic motor fibers innervating muscles

- 4 subunits form cation-selective ion channels→ electrical and ionic changes→ depolarization

*Prolonged agonist occupancy→ "depolarizing blockade" abolishes the effector response→ can produce muscle paralysis


Direct Muscarinic Agonists:

CV: Direct effect = vasoconstriction; masked by NO-mediated vasodilation (requires intact endothelium) → reflex tachycardia

Pulm: Bronchoconstriction, ↑mucus secretion, *exacerbates asthma

GIT: ↑secretions (salivary, gastric, pancreatic & intestinal) & ↑peristalsis (contract longitudinal muscle while relaxing sphincters)

GUT: Promotes voiding: Detrusor contraction, relax trigone & sphincters

Eye: Miosis (iris contraction), Accommodation (ciliary contraction - facilitates aqueous humor outflow)

Secretory: ↑ secretion by thermoregulatory sweat glands (anomalous Muscarinic receptors of SNS)

Choline Esters - poorly absorbed & poorly distributed into CNS

Acetylcholine [Endogenous transmitter] – rapidly hydrolyzed - Affects both Muscarinic & nicotinic receptors

Low Dose: mostly vascular Muscarinic receptors→ NO→ vasodilation→ reflex tachycardia; cardiac effects hidden by baroreceptor response

High Dose: vascular + direct bradycardia (potential atrial flutter) * Can evoke SNS response thru ganglia (see when using Muscarinic antag)

Methacholine - Slightly resistant to AChE - Specific to Muscarinic (methyl group reduces potency @ nicotinic)

Bethanechol - Resistant to degradation by AChE - Specific to Muscarinic (methyl group reduces potency @ nicotinic)

Carbachol - Resistant to degradation by AChE

- Affects both Muscarinic & nicotinic receptors (i.e. can cause endogenous ACh release through ganglionic nicotinic receptors)

Alkaloids

Muscarine - Fungal (4° amine) alkaloid ACh mimetic

- Activates Muscarinic receptors, CNS activity

- Resistant to AChE

- No therapeutic use

Pilocarpine (ophthalmic) – (natural 3° amine) alkaloid ACh mimetic

- Used to treat glaucoma by allowing for fluid drainage from eye & atropine poisoning

- Resistant to AChE


Muscarinic Receptor Antagonists: Block action of ACh/agonists at Muscarinic receptors;

CNS: Minimal effects – Toxic doses→ agitation, hallucinations & coma; often used w/ dopamine precursor in Parkinson’s, also relieves vagal syncope

CV: Tachycardia (blocks PNS tone @ SA node), few hemodynamic effects

Pulm: Bronchodilation & ↓mucus secretion (not as useful as B2 agonists in asthma)

GIT: ↓motility & secretions – useful for mild GI hypermotility, excessive salivation, or as pre-op adjuvant before abdominal surgery

GUT: can cause urinary retention, especially w/ BPH

Eye: Mydriasis (dilated pupils); Cycloplegia (paralyzed ciliary muscle) – good for ophthalmic exam; Acute glaucoma (narrow anterior chamber angle)

Secretory: “atropine fever” - ↓ thermoregulatory sweating (anomalous Muscarinic receptors of SNS); helpful in hyperhidrosis

Contraindications: Glaucoma (especially closed angle), Prostatic hyperplasia, may ↑ gastric ulcer symptoms

3° Amine – Used for effects in eye or CNS

Atropine [Prototype] – reversible (competitive) blockade with relatively long duration of action; non-selective between M1, 2 & 3

- classic antidote to organophosphate poisoning

- “Atropine Poisoning”: dry (as a bone) mouth, mydriasis (blind as a bat), tachycardia, flushed skin (red as a beet), delirium (mad as a hatter)

Treat with Physostigmine or symptom management

Scopolamine - has a relatively long duration of action, better CNS, motion sickness

Homatropine

Pirenzepine - M1-selective (nerves)

Tropicamide

Tolterodine - M3-selective (urinary urgency, frequency & incontinence)

4° Amine – Only peripheral effects, cannot penetrate CNS (due to charge) – NOT used to reverse cholinergic poisoning

Atropine Methyl Nitrate

Methscopolamine

Ipratropium - asthma

Propantheline

Glycopyrrolate

Indirect Cholinomimetics: ACh-esterase inhibitors (also inhibit ButyrylCh-esterase) → amplify effect of endogenous ACh (modifies PNS tone)

Prominent effects on CV, GIT, eye & skeletal muscle; but NO effect on peripheral vasculature

@ NMJ: low conc. → ↑force of contraction; high conc. →depolarizing neuromuscular blockade

Clinical Uses: Atropine or TCA (tricyclic antidepressant) intoxication/overdose

CNS: Mild to moderate Alzheimer’s disease

GIT & GUT: ↑smooth muscle activity – postop ileus, congenital megacolon, reflux esophagitis, neurogenic bladder, urinary retention

Eye: Glaucoma (closed angle) - ciliary contraction →↑ aqueous humor outflow→ ↓intraocular pressure

NMJ: Myasthenia Gravis

Toxicity: SLUDGE = Salivation, Lactation, Urinary incontinence, Diarrhea, Gastrointestinal cramps & Emesis – reversed by atropine (& 2-PAM)

Simple Alcohol Esters (simple alcohols bearing a 4° ammonium group)

Edrophonium – [very short half-life] - Diagnostic Test for myasthenia gravis

Carbamates (carbamic acid esters of alcohols bearing 3° or 4° ammonium group)

* Undergo 2-step hydrolysis (covalent bond formed w/ enzyme is resistant to hydration; inhibition is longer (30 minutes - 6 hours)

Ambenonium (Mestinon)

Carbaryl – high lipid solubility (rapid CNS effects)

Demecarium- Used to treat glaucoma

Neostigmine – (4° amine - permanent charge renders them relatively insoluble in lipids – poor absorption/CNS distribution)

* Used to treat myasthenia gravis, ileus (severe abdominal cramping due to obstruction)

* Has both indirect & direct effects in PNS (inhibits AChE & stimulated Muscarinic receptors)

Physostigmine – (3° amine - well absorbed, CNS distribution); duration of effect is determined by stability of inhibitor-enzyme complex

- Used to treat glaucoma, myasthenia gravis & atropine overdose

Pyridostigmine - Used to treat myasthenia gravis

Organophosphates - well absorbed topically w/ good CNS distribution (except Echo); * Before aging, pralidoxime (2-PAM) can restore enzyme fxn

bind→ hydrolyzed/phosphorylated AChe active site – extreme stability (strengthened by “Aging”) → lifetime inhibition

Diisoprophylfluorophosphate (DFP) - Can cause cumulative overdose due to extremely long duration of action

Donepezil

Echothiophate – poorly absorbed, very long half-life (~100 minutes) - Used to treat glaucoma

Isoflurophate (ophthalmic) - Used to treat glaucoma

Malathion – [irreversible] - converted to phosphate derivative, used as insecticide

Parathion – [irreversible] – converted to phosphate derivative (Active only after biotransformation), used as insecticide

Sarin

Soman - Immediately & completely binds AChE (no aging) - Potential biological weapon

Tacrine - anticholinesterase and cholinomimetic actions – used for mild/moderate Alzheimer’s disease


Cholinesterase Regenerator

Pralidoxime (2-PAM)

Direct Nicotinic Agonist: Mostly targets ganglia; ↑SNS & PSNS: predominant tone determines effect (SNS = vasculature, PSNS = everything else)

Toxicity: CNS stimulation→ convulsion, coma, resp arrest (NMJ depolarization block); HTN & arrhythmias – Tx w/ Muscarinic Antag. & mech. resp

Nicotine – (natural 3° amine)

Lobeline – (natural 3° amine) a plant derivative similar to nicotine


Ganglion-Blockers (Nicotinic Antagonists): Block action of ACh/agonists at nicotinic receptors in SNS & PSNS ganglia; All are synthetic amines

Blocks homeostatic reflexes (e.g. baro & sweating), but effector cell receptors are NOT blocked; End-Organ effects depend on predominant ANS tone

CV: ↓SNS tone→↓BP & orthostatic hypotension (no baro); ↓PSNS tone @ SA node→ mild tachycardia

GIT: ↓PSNS tone→↓secretions & motility→ constipation & xerostomia (dry mouth)

GUT: Hesitancy or urinary retention (esp. with Prostatic hyperplasia); Impaired sexual function (requires both SNS & PSNS)

Eye: ↓PSNS tone→ cycloplegia (paralyzed ciliary muscle) & moderate pupil dilation (Normal Input: PSNS>SNS)

Tetraethylammonium (TEA) [prototype] - short half-life; used to manage HTN

Hexamethonium

- No therapeutic use currently

Mecamylamine – readily enters CNS→ sedation, tremor, choreiform movements, mental aberrations

Trimethaphan (IV) – 4° Amine →lacks CNS effects

- Extremely short acting

- Can be used to treat acute dissecting aneurysm or autonomic hyperreflexia

Sympathetic Nervous System

Adrenergic Neuron Blockers:

Reserpine - non-selective blocker of uptake & storage of amines

Guanadrel - similar to reserpine


Adrenoreceptor Agonists:

A1- forms IP3, DAG & activates phospholipase C; A2 - presynaptic autoregulation of SNS outflow, inhibits cAMP formation

B1 & B2 - activates adenyl cyclase;


CV: A1→ vasoconstriction, ↓renin secretion; B1 – Ca++ influx into cells (↑ino & chronotropic), ↑renin secretion

Pulm: A1in vessels of URT mucosa→ contraction→decongestion

GIT: A2→↓PNS tone on enteric system; Beta on smooth muscle mediates relaxation

GUT: A1→contract bladder base & urethral sphincter; B2→relax bladder wall smooth muscles – both actions promote urinary retention

Eye: Alpha→ radial dilator contraction→ mydriasis (dilated pupil); Beta→↑aqueous humor production by ciliary epithelium→ ↑intraocular pressure

Exocrine: A1 on aprocrine (stress) sweat glands→ sweating on palms, brow & upper lip

Metabolic: A2→↓ insulin release; Beta→ ↑lipolysis, ↑glycogenolysis, ↑glucose release, ↑insulin secretion

Toxicity: Extended effects – hypertension, tachycardia, CNS – restless, tremor, insomnia, anxiety, paranoia


Catecholamines:

Epinephrine – A1, A2; B1, B2: skeletal muscle arteriodilation & ↑venous capacity (mixed TPR effects)

Norepinephrine - A1: ↑TPR, A2; B1: Heart effects overcome by vagal reflex; = ↑Sys, Dias; High doses = ↑HR

Isoproterenol - B1= ↑CO; B2: skeletal muscle arteriodilation & ↑venous capacity = ↓Dias & MAP

Dolbutamine (B1; A1 @ high doses) - Uses: Heart failure/cardiac decompensation (short-term) – limited by tolerance/desensitization

Dopamine - D1 stimulates adenyl cyclase in renal vasculature→ renal vasodilation→ ↑GFR; A1; B1 @ high doses


Alpha-1 Specific – mydriasis (fundoscopic exam) & decongestant, can ↑BP;

Uses: nasal congestion, hypotension, paroxysmal atrial tachycardia

Phenylephrine [prototype] – not a catechol derivative, thus not inactivated by MAO/COMT; longer duration of action

Methoxamine

Oxymetazoline & Xylometazoline – used as topical decongestants


Alpha-2 Specific – Use as anti-HTN

Clonidine

Methyldopa

Guanfacine

Guanabenz


Beta-1 Specific – ↑CO w/ less reflex tachycardia;

Dolbutamine

Prenalterol (partial)


Beta-2 Specific – bronchodilation; Uses: Asthma & bronchial constriction

Albuterol

Salmeterol

Terbutaline

Ritodrine - uterine relaxation in premature labor


Indirect Sympathomimetics:

Ephedrine – first orally active

Pseudoephedrine [also direct] – cause release of endogenous NE; widely available OTC decongestant

Cocaine - block uptake1 (potentiates effects of NE) - Used as local anesthetic

Tyramine – enter thru uptake1, displace stored catecholamines→ hypertensive crisis; potentiated by MAO inhibitors * fermented foods (cheese)

Amphetamine (NOT a catecholamine) – mech=same as tyramine; ↑mood & alertness; ↓appetite *Common Drug of Abuse – Used for narcolepsy

Methamphetamine – similar, but w/ ↑ratio of central to peripheral effects

Methylphenidate - used to treat ADHD

Adrenoreceptor Blockers:

Alpha Receptor Antagonists - * Nitrates are preferred in hypertensive crises

Non-selective Alpha Antagonists

Phentolamine [prototype] – reversible, competitive; ↓TPR & MAP→reflex tachycardia

Tolazoline – similar to phentolamine;

Phenoxybenzamine – irreversible, slightly alpha-1 selective; Uses: Pheochromocytoma, limited by postural hypotension & reflex tachycardia

*Excessive release of NE & Epi from adrenal medulla

Alpha-1 Selective Antagonists: Uses: HTN & BPH - ↓TPR & BP, May cause postural hypotension & reflex tachycardia

Prazosin

Terazosin

Trimazosin

Doxazosin – longer half-life

Tamsulosin & Alfuzosin – competitive; Uses: BPH (prostate subtype selectivity)

Labetalol - also non-specific beta blocker


Alpha-2 Selective Antagonists

Yohimbine - no established clinical role, has been used in ED


Beta Receptor Antagonists – well absorbed orally

CV: ↓SNS tone to heart → slower AV conduction & ↓BP, but NOT hypotension; ↓SNS tone to kidney→ ↓renin secretion

Pulm: B2 block→ ↑airway resistance

Eye: ↓aqueous humor production by ciliary epithelium→ ↓intraocular pressure

Metabolic/Endocrine: ↓SNS stimulation of lipolysis & glycogenolysis; Use with caution in IDDM patients; Chronic use→ ↑VLDL & ↓HDL

Clinical Uses: HTN (w/ diuretic or vasodilator);

Ischemic Heart Disease - ↓angina frequency, cardiac work/oxygen demand; improves exercise tolerance; prolongs post-MI survival

Cardiac Arrhythmias (atrial & ventricular) - ↑AV refractory period, ↓ventricular response in A-fib, ↓ventricular ectopic beats

Glaucoma – refer to Eye above, better tolerated than Epi or Pilocarpine in open-angle glaucoma

Hyperthyroidism – limits excessive catecholamine activity

Toxicity: Minor= F, rash, depression, sedation; Major= exacerbates asthma, cardiac decompensation, supersensitivity (taper), hypoglycemia in IDDM

Non-selective Beta Antagonists - used to treat: HTN, angina, arrhythmias, glaucoma, and migraine; do NOT use in asthmatics

Propranolol [prototype] – extensive hepatic (first-pass) metabolism, low bioavailability

Nadolol – very long duration of action

Timolol – very long duration of action

Partial Agonists – may prevent bradycardia, changes in lipid profile & precipitation of asthma

Dichloroisoproterenol – first beta-blocking drug

Pindolol

Cartelolol

Penbutolol

Labetalol – reversible alpha-1 antagonist; → hypotension w/ less tachycardia than alpha-blockers


Beta-1 Selective Antagonists - treat HTN; Can also ↑airway resistance when used in asthmatics

Metoprolol

Esmolol – rapid hydrolysis by esterases in RBCs: half-life = 10 min.

Atenolol

Acebutolol – intrinsic sympathomimetic effects

Betaxolol

Bisoprolol


Beta-2 Selective Antagonists

Butoxamine - no clinical use

Pharmacology Review

These are a few of the pearls gleaned from Thomas Pazdernik, PhD of pharmacology, author of a fantastic book:

•Mosby’s Rapid Review:Pharmacology;

Pazdernik

This book is money in the bank. I have no monetary interest in promoting this book. Only my admiration for a truly student committed professor!

Dr. Paz not only outlines the majors and some of the minors needed for the USMLE, he highlights the must knows. I am somewhat biased, he did teach our course at the University of Kansas School of Medicine. However, our Pharmacology course consistently scored above the 90th percentile on the national shelf exams, so the praise is warranted. And if there is one course that pulled together the 1st two years of medical school, it is pharm. You must know Pharm to score well on the USMLE Step 1 and 2 (Esp. Step 1)

Now how do you go back and pull out all of this information? First thing you have to be able to do is put the drug in the right class. Usually if you can put the drug in the right class and you’ve learned the material reasonably well, it will come back to you fairly quickly. In some cases this is pretty easy because they have common endings. This is quite true for the second block. You have -quils and -olols and -sartans. But, as you saw in chemotherapy and in CNS, those drug names didn’t match so well within a given class.

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.

V_d = Amt. injected

--- ----------------

Amt. injected at time zero

V_d = Amt. IV

------------

C₀

K_el = 0.7

-----

t ½

Cl = K_el x V_d

X = Css x V_d

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

You should understand the four types of Hypersensitivity Reactions For example:

1. Clozapine - Agranulocytosis (type II)
2. Serum Sickness - Type III
3. 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.

Here is a sample of what to know:

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.