pharmreview

JAY DINOVITSER'S 14 PAGE PHARM REVIEW The most commonly prescribed drugs in the US and those I’ve seen prescribed a lot have a note next to them with their trade name as this is very useful in the wards. Otherwise, only generic names are given. Drugs in BOLD are the only ones you have to memorize for the USMLE. Information preceded by “Ward Tip”, “W.T.” or information listed in small font with a star * is extraneous information for the wards and should not be studied for the USMLE unless you already mastered the rest of the review by going over it 10 times. 5/09 Version 1.6 Beta
PARASYMPATHETIC Drugs

Muscarinic Agonists:

Bethanechol -for ileus, urinary retention
Pilocarpine - for dry mouth & glaucoma
Acetylcholinesterase Inhibitors: Don't let name fool you; they are muscarinic drugs. In overdose you get SLUDGE salivation, lacrimation, urination, diarrhea, gastric cramping, emesis. Also get miosis, bradycardia, bronchoconstriction and sweating. -also get muscle excitation that can paralyze the diaphragm. Can be fatal. Atropine doesn't reverse this.
Physostigmine -tertiary amide, enters CNS, antidote for atropine overdose, used in glaucoma
Neostigmine, Pyridostigmine -quaternary amide, used to treat myasthesia gravis, reversal of NM blockade
Edrophonium -to diagnose myasthesia
Donepezil [Aricept] -to treat Alzheimer's disease
Tacrine [Cognex] -also used to treat Alzheimer's disease
Organophsophates (pesticides malthion, parthion, sarin)-irrersible inhibitors -Pralidoxime is antidote, it regenerates acetylcholinesterase. In poisoning 1st give Atropine then Pralidoxime.
Muscarinic Blockers: "atropine makes you dry as a bone, red as a beet, hot as a hare, blind as a bat and mad as a hatter". Know hyperthermia. Know it dilates pupils.
Atropine -to treat ACh inhibitor OD, antidiarrheal, antispasmodic, anti secretary
Scopolamine - motion sickness
Benztropine [Cogentin], Trihexyphinidyl -CNS used for parkinsonism. Benztropine is also used used for extrapyrimidal effects from many PSYCHIATRY drugs, see that section.
Ipratropium [Atrovent] -asthma and COPD. WARD TIP: This drug is used a hell of a lot in the wards for asthma, ventillator patients with rhonchi and COPD. A similar drug Tiotropium [Spireva] also shows up a lot in the wards
Tolteridine [Detrol], Oxybutynin -urinary incontinence.

SYMPATHETIC Drugs WARD TIP: Know these three drugs as they are used a lot in the wards for shock
Epinephrine -acts on everything, good for anaphylaxis since it antagonizes histamine receptors. Epi reversal is unique to Epi, BP goes below normal after alpha blocker -at low doses similar to B agonist and at high doses it is similar to noronephrine (see below).
Noronephrine [Levophed] -acts on alpha1, alpha2, B1 USED FOR SEPTIC SHOCK -BP goes back to normal after give alpha blocker -BP increases. First HR incr. then it decreases (reflex)
Dopamine [Intropin]: D1>B1>alpha-1 -low does increases renal blood flow, mediium dose incr. CO, high doses cause vasoconstriction -USED FOR CARDIOGENIC SHOCK

Alpha1 Agonist: Phenylephrine     -nasal decongestant -increases BBP and lowers HR (reflex)
Alpha 2 Agonists:
Clonidine                                           W.T: Clonidine 0.1mg PO BID is starting dose for HTN
Alpha-methyldopa - lower BP
Beta Agonists:    -lowers BP and increases HR also widens pulse pressure -B1=heart
Isoproterenol -B1=B2
Dobutamine -B1>B2 USED FOR CARDIOGENIC SHOCK
       Selective B2 agonists: Albuterol [Proventil], Salmeterol, Metaproterenol, Terbutaline, Ritodrine USED FOR ASTHMA/COPD
-For wards only: Albuterol/Ipratropium=Combivent. Fluticasone/Salmeterol=Advair. These and Albuterol show up a lot in the wards.
Indirect Acting Adrenergic Agonists: Amphetamine, Methylphenidate [Ritalin], Ephedrine, Tyramine, Cocaine -some are addictive
Combined Alpha and B blockers: Letetalol & Carvdilol [Coreg] Used for hypertension    -WARD TIP: Coreg shows up a lot in the wards -Labetalol is safe to use during pregnancy.
Alpha Blockers:
General: Phenoxybenzamine, Phentolamine -S/E reflex tachycardia worse with phenoxybenzamine -for pheochromocytoma
Alpha-1 selective: Prazosin   -less reflex tachycardia, get first dose syncope and postural hypotension. -used for HTN and BPH
Note: special Alpha-2 agonists: Yohimbine, Mirtazapine [Remeron] -similar to alpha-1 blockers, used for BPHH
Beta Blockers: -mask signs of hypoglycemia so diabetics miss warning signs they are hypoglycemic like tachycardia. S/E include orthostatic hypotension, bradycardia. Rule: -olol is pure B blocker -ol is not pure B blocker -many uses like HTN, Heart Failure, post MI, angina, decr. aqueous humor formation so used in open angle glaucoma as well. Any drugs starting with letters BEAM=B1 selective
Propanolol [Inderal]
Metaprolol [Lopressor, Toprol-XL] Ward tip: Toprol-XL is one of the most prescribed drugs. Toprol-XL 25mg PO QD is starting dose for HTN. Starting dose of regular Lopressor for HTN is 50mg PO BID
Acebutolol, Pindolol    -partial agonist so they don't elevate lipids
Atenolol [Tenormin] etc.                     Ward tip: Starting dose of Atenolol for HTN is 50mg PO QD
Sotolol is a mixed B blocker and K channel blocker

Adrenergic Nerve Blockers: Guanethidine, Guanadrel, Bretyllium, Reserpine –Later one decr. NE by destruction of storage granules. Others lower norepinephrine release.
Ganglion blockers: Hexamethonium, Mecamylamine -blocks dominant input to organ (parasympathetic is dominant to everything except blood vessels)

Calcium Channel Blockers: -constipation thing calcium channel blockers, all cause gingival overgrowth -centrally acting agents contraindicated in CHF -used for angina and HTN
Verapamil & Diltiazem [Cardizem] -greater cardiac effects WARD TIP: Cardizem is a common ward drug especialy the cardizem drip
Amlodipine [Norvasc] and other drugs ending in _dipine -more vascular selective if primary agent. If secondary agent start at 2.5mg PO daily WARD TIP: Norvasc one of the most prescribed drugs in the US. Memorize 5mg PO daily [up to 10mg ]
ACE Inhibitors: Captopril, Lisinopril [Zestril], other prils -S/E dry cough, angioedema, teratogenic, hyperkalemia, renal toxicity -used for HTN, CHF, post MI   WARD TIP: Zestril is very commonly prescribed Memorize Zestril 10mg PO QD as starting dose 4 HTN
AngioTensin Blockers: Lorsartan, other sartans -teratogenic, also causes hyperkalemia and may cause renal toxicity.         WARD TIP: Valsartan [Diovan] is used a lot Memorize Diovan 80mg PO QD starting dose

Direct Acting Vasodilators -for severe HTN
Hydralazine -arteriolar vasodilater, can cause SLE like syndrome in slow acylators -safe in pregnancy.
Nitroprusside -dilates both arterioles and venules, cyanide toxicity
Minoxidil -arteriolar vasodilater, keeps potassium channels open, hyperpolarizing membrane, grow excess hair

Nitrates such as nitroglycerine used in angina. Mechanism is it incr. cGMP. Nitrates are venodilators only -S/E headache, reflex tachycardia, tolerance.
Extra Ward Info: Isosorbide Mononitrate [Imdur] is one of the m/c prescribed drugs and is used for angina. For angina prophylaxis use Imdur 30 or 60 mg PO QAM.

ANTIARRYTHMICS -Class 1 is sodium channel blockers, they all act to decr. phase 0. Class 1A also acts on phase 3 and it is proarrythmic. Proarrythmic=torsades possible
Class 1A: Quinidine, Procainamide    -Cinchonism with Quinidine (GI side effects, tinnitis, CNS excitation) -Quinidine weak base, antacids incr. abs., hemolytic anemia -Procainamide drug induced Systemic Lupus Erythematosis in 30% of people.
Class 1B: Lidocaine
Class 1C: Flecainide (and Encainide)
Class II is Beta blockers, they decr. phase 4 in pacemaker cells
Class II: Propanolol
Class III: Potassium Channel Blockers, they act at phase 3, they are proarrythmic
Sotalol -both classes 2 &3, it is a B blocker and K channel blocker
Amiodarone -really has features of every class -very long half life, S/E pulmonary fibrosis, blue pigmentation due to thyroid effects since the drug has tons of iodine, more side effects.
Class IV: Verapamil, Diltiazem    -can cause CHF especially verapamil. -calcium channel blockers act on phase 4
Unclassified: Adenosine -causes Gi coupled decr. in cAMP which increases K efflux and leads to membrane hyperpolarizing. -DOC for PSVT -S/E are flushing, seedation, dyspnea

Drugs for CHF
ACE Inhibitors, Angeotensin blockers, B blockers, already mentioned
Cardiac Glycosides: Digoxin -inhibits Na/K/ATPase pump which incr. calcium in the sarcoplasmic reticulum leading to increase in contractility. Used in HF and good for arrythmias as well because it somehow stimulates the vagus nerve. Long half life. Toxicity: A lot of EKG changes (first decr. QT interval, T wave inversion and PVC's) proarrythmic and tachycardiac effects. Give lidocaine and digibind for toxicity.    WARD TIP: Very popular drug for moderate to severe CHF. Memorize starting dose of 0.125 mg PO QD.

Bipyrides: Imamrinone, Milrinone -PDE inhibitor, increases cAMP, for short term use in Heart Failure

Nesiritide: B type naturinic peptide, incr. cGMP relaxing smooth muscle in the arteries and veins. Used in decompensated CHF pts.

               Diuretic Type                  Drug Mechanism    pH and Electrolytes _________
Carbonic Anhydride In.      Acetazolamide                                             inhibits carbonic anhidrase in PCT       Acidosis, hypokalemia
Loop Diuretics:              Furosemide, Torsemide, Bumetanide, Ethacrynic Acid inhibits Na/K/2Cl cotransporter in TAL Alkalosis, hypokalemia, hypocalcemia
Thiazide Diuretics:          Hydrochlorothiazide, Indapamide, Metolazone             inhibits Na/Cl cotransporter in DCT      Alkalosis, hypokalemia, hypercalcemia
Potassium Sparing::       Spirolactone, Epleronone, Amiloride, Triamterene        first 2 block aldosterone receptors           Hyperkalemia, Acidosis
                                                                                                              last 2 block sodium channels in CD       _________
"Loops lose calcium, thiazides save calcium" Carbonic anhydride inhibitors may cause hyperchloremic metabolic acidosis. Thiazide diuretics may cause hyperglycemia, hpertriglyceridemia. Loops may cause hypomagnesemia. Mannitol is an osmotic diuretic that is also used to decrease intracranial pressure. WARD TIP: HCTZ and Furosemide are very common Furosemide is known as Lasix. Memorize Furosemide 10mg PO BID starting dose for HTN. For edema start at 20-40 mg PO QD and increase dosage as necessary Memorize HCTZ starting dose for HTN 12.5mg PO QD

Related Drugs:
Pulmonary Hypertension Drugs:                                                                                                                                                                                            .
Sildenafil [Viagra] -PD V inhibitor
Bosentan -endothillin A receptor antagonist

Glycoprotein IIb/IIIa Receptor Inhibitor: Abciximab -used in unstable angia

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Lipid Lowering Drugs:
Bile acids sequesterants: Cholestyramine, Colestipol -The entire class decr. cholesterol, most decrease LDL, Cholestyramine decr TGs, S/E are bloating, constipation, decr. in GI abs. of lipid soluble vitamins & drugs
HMG-CoA reductace inhibitors: Lovastatin, Atorvastatin [Lipitor] Simvastatin [Zocor] other statins -inhibit rate limiting step in cholesterol synthesis, lower CHO, LDL and TGs. Raise HDL. S/E are myopathy, increased liver function tests -pregnancy category X.        WARD TIP: Lipitor is the number one most prescribed drug in the U.S. Memorize 10mg or 20mg PO daily
Nicotinic Acid/ Niacin: Inhibits synthesis of VLDL & appolippoproteins in hepatocytes & activates lipoprotein lipase. Incr. HDL, lowers LDL & TGs. S/E: Flushing, prurities (pretreat with aspirin & give @ PM)
Fenofibrate, Gemfibrozil -activates lipoprotein lipase -lowers CHO LDL and TGs. Raise HDL. S/E include myopathy and increased LFTs (similar profile to the statins)
Eztimbe -prevents intestinal abs. of cholesterol. Lowers LDL and TGs

ANESTHETICS
Inhaled Anesthetics: Nitrous Oxide -least potent, fastest onset Halothane -most potent, slowest onset, S/E are hyperthermia, hepatitis Notes: Lower blood gas ratio faster it is, lower MAC more potent
IV anesthetics:
Thiopental -short acting barbituate
Midasolam -short acting benzodiazepine
Propofol -short acting + antiemetic effects
Fentanyl - opiod analgesic
Ketamine -short acting, only anesthetic that causes CV stimulation, causes dissociative amnesia
Local anesthetics: Procaine, Cocaine, Benzocaine, Lidocaine, Bupivacaine, Mepivicain.    Rule is if it has only one I it is an ester. If it has greater than one I it is an amide. Mechanism: these bind the inactivated sodium channel . The drugs are active in their charged forum. First pain fibers get anesthetized and then motor neurons. Esters have possible allergic reactions due to PABA.

Skeletal Muscle Relaxants:
Pancuronium, Atacurium, Mivacurium -last two safe in hepatic or renal impairment - -all work at NM and are competitive nondepolarizing
Succinylcholine -noncompetitive depolarizing muscarinic agonist -phase 1 is depolarizing phase, phase 2 is desensitizing phase -S/E malignant hyperthermia
Benzodiazepines can also be used                ANTIDOTE in malignant hyperthermia is Dantroline. It blocks calcium release from the sarcoplasmic reticulum.
Beclofen -agonist on GABAB -much less sedation

OPIOD Analgesics:
Notes: -Cause analgesia, sedation, respiratory depression (major problem in OD).    They all can cause miosis, cough suppression, nausea, emesis, constipation. Tolerance develops but not to constipation. Morphine releases histamine which lowers BP.

Strong Opioids (the three M's): Morphine, Methadone, Meperidine -All are strong u agonists (full)
Weak Opiods: Buprenorphine, Codeine, Propoxyphene -first two are partial u agonists, last one full u agonist -first one strongest
Nalbuphine, Pentazocine are unique opiods since they are k agonists and weak u antagonists. The u antagonist effect will induce morphine withdrawal (can tell if they are an addict if they don't want these two)

Naloxone and Naltrexone are used in opiod overdose. They are strong u antagonists.

Drugs Used in Parkinsosnism: -parkinsonism has low DA/ACh ratio.   Drugs used either incr. DA or lower ACh. MAO A found everywhere. MAO B found in brain. -D2A receptor is important. -Parksinsons disease presents with slow movements, muscle rigidity and tremor.
Lovadopa -converted to Dopamine, given with carbidopa to inhibit its metabolism -can cause diskinesias, psycosis, on-off effects
Tolcapone, Entacapone -inhibit COMT-S/E of entacapone is hepatotoxicity
Bromocriptine & Pergolide -Dopamine agonists, lots of side effects like dyskinesias and CNS dysfunctions.
Selegiline -MAO type B inhibitor so it increases DA in the CNS -Bromocriptine has lots of side effects liike dyskinesias and CNS dyfunctions.
Muscarinic blockers like benzotropine & trihexyphenidy are used in parkinsonsm to lower ACh in the CNS.   Amantidine (anti viral) also has muscarinic blocking properties.

...........................................PSYCHIATRY DRUGS............................................

Sedatives & hypnotics: Benzodiazepines and Barbituates -Benzodiazepines increase the frequency off chloride influx in GABA and Barbituates lower the duration of chloride influx in GABA (mnemonic: "Ben is a guy and wants frequency, Barb is a girl and likes duration") -Barbituates are more dangerous in overdose and can cause respiratory dysfunction and coma. Benzodiazepines are safer in overdose and have an antidote (Flumazenil). All have a potential for tolerance and dependance.

Benzodiazepines: -used for sedation, anxiety, panic disorders, phobias, seizures and alcohol withdrawal -toxicity with other CNS depressing drugs - withdrawal symptoms are serious and can cause coma and death.
Alprazolam [Xanax]                          WARD TIP: Xanax is used a lot in the wards for anxiety. Usually give 0.25mg PO TID increased to 0.5mg TID if necessary
Diazepam [Valium] -longest acting
Lorazepam -no active metabolites                  3 Benzodiazepines are metabolized outside the liver "Outside The Liver" Oxazepam, Tamazepam, Lorazepam
Midazolam -shortest acting benzodiazepine            Note: Chlordiazepoxide (Librium) is the weird sounding BDZ that everyone forgets.

Barbituates: -all induce P450 -tolerance and dependence -barbiturates with CNS depressing drugs like alcohol can kill you due to additive CNS depression and respiratory depression. -Serious life threatening withdrawal symptoms such as seizures.
Phenobarbital -long acting, used for seizures
Thiopental -short acting, used for an anesthetic

Other sedatives and hipnotics:
Zolpidem [Ambien] & Zaleplon -activate BZ1 receptors, no withdrawal effects, little to no tolerance/dependance, used in sleep disorders WARD TIP: Ambien is prescribed a lot. 5-10mg PO QHS
Buspirone -partial agonist at 5HT1A receptors. Nonsedating, no CNS depression. The Nonsedating sedative for anxiety. Low potential for abuse.
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ANTICONVULSANTS: -partial list of most common drugs, also include Benzodiazepines and other drugs. Phenobarbital should be used during pregnancy as drugs below are teratogenic
Primary Anticonvulsants:
Phenytoin -blocks sodium channels in their inactivated state -also an antiarrythmic -induces P450, tight plasma protein binder -S/E is gingival overgrowth
Carbamazepine (Tegretol)-blocks Na channels. -induces P450 -S/E are hematotoxicity & hepatotoxicity. Causes aplastic anemia, agranulocytosis, leukopenia. DOC for trigeminal neuralgia
Valproic Acid (Depakote) -multiple mechanisms including Na and T type Ca channels, GABA inhibition. -Does not induce P450 S/E hepatotoxicity and thrombocytopenia.
Ethosuximide -blocks T-type Calcium channels -only used for absence seizures
Rules for anticonvulsants: 1- When in doubt, pick Valproic acid. 2- If your patient is experiences multiple types of seizures give Valproic acid. 3-Phenytoin and Carbamezepine go together so if you see both of them on your answer choices then rule them both out and pick something else. 4- Ethosuximide is used for absence seizures.
New anticonvulsants:
Felbamate -blocks sodium and calcium channels -S/E include aplastic anemia
Lamotrigine -blocks sodium channels and glutamate receptors -S/E include Steven-Johnson syndrome
Gabapentin -increases GABA -many extra uses like migraines, neuropathic pain
Tiagabine -GABA drug
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Antipsycotics -The D2A receptor is blocked in the typical antipsycotics, in atypicals the serotonin receptor is also blocked. MOST HIGH YEILD DRUG CLASS
1. These have anti-HAM effects: anti-Histaminic (sedation), anti-Adrenergic (alpha blocking effects like orthostatic hypotension, sexual dysfunction, tachycardia and arrythmias) & anti Muscarinic side effects (dry mouth, constipation, urinary retention, blurred vision, tachycardia)
2. Extrapyrimidal Symptoms (EPS) is a possible side effect with the D2A blockers. EPS includes pseudoparkinsonism effects like cogwheel rigidity and tremor (recall Parksinsonism results from low dopamine to acetylcholine ratio). EPS also includes dystonic reactions which are sustained contraction of muscles of the eyes, neck or tongue. EPS includes akathisia which as a feeling of restlessness that makes the patient always want to walk around, shuffle or move. EPS is treated by adding a Muscarinic blocker to decrease ACh like Benztropine (Cogentin). 3. Tardive Dyskinesia is chorea like movements that may occur with DA blockers. Unlike EPS, this may not be reversible and M blockers are not effective. They usually start with the mouth and the tounge. The worst side effect is Neuroleptic Malignant Syndrome includes fever, autonomic instability, leukocytosis, tremor, hyperthermia, muscle rigidity, elevated CPK. It is treated with a DA agonist such as bromocriptine and dantroline (for hyperthermia).
4. Antipsycotics also may cause hyperprolactinemia which includes impotence, amenorrhea, galactorrhea, gynecomastia.
5. Weight gain is a major side effect. Typicals all cause weight gain and most Atypicals do as well.
6. Other important side effects include hepatotoxicity, dermatologic problems and seizures (high potency antipsycotics and Clozapine).

Typicals: Chlorpromazine, Thioridazine, Fluphenazine, Haloperidol (Haldol) -First 2 have worst autonomic blocking symptoms and worst sedation. Last 2 have most EPS, low sedation. Thioridazine can cause cardiotoxicity and Torsades.   Chlorpromazine causes deposits in the eye, Thioridazide can cause irreversible retinal pigmentation at high doses leading to blindness
Atypicals: Clozapine (Clozaril), Olansapine (Zyprexa) Rispidone (Risperdal), Quetiapine (Seroquel), Ariprazole (Abilify), Molindone (Moban) -blocks dopamine receptor and also the serotonin 5HT2 receptor -have least EPS, low sedation. -Clozapine may cause agranulocytosis so it required weekly blood tests. Clozapine also has seizure risk. The last two (aripiprazole and molindone) have no weight gain.

Selective serotonin Reuptake Inhibitors (SSRIs)- as name implies blocks serotonin pumps leading to incr. serotonin. The most commonly prescribed anti-depressant.
Fluoxetine (Prozac), Paroxetine (Paxil), Sertaline (Zoloft), Citalopram (Celexa), Escitalopram (Lexapro) -The most common side effects are GI disturbance, headache and sexual dysfunction. Also anxiety, agitation, weight loss, serotonin syndrome when used with SSRIs.   WARD TIP: Zoloft and Lexapro are one of the most prescribed US drugs. Memorize Zoloft 50mg PO QD
Tricyclic Antidepressants (TCAs) -block reuptake of both NE and serotonin. -S/E are anti-HAM: anti-Histaminic (sedation), anti-Adrenergic (alpha blocking effects like orthostatic hypotension, tachycardia and arrythmias) & anti Muscarinic side effects (dry mouth, constipation, urinary retention, blurred vision, tachycardia), lower seizure threshold, cardiotoxicity. 3C's coma, convulsions, cardiotoxicity. Also causes weight gain, lethal in overdose.
Amitryptyline, Nortriptyline, Imipramine, Clomipramine, Desipramine, Doxepin -used for migranes, neuropathic pain, enuresis (bed wetting, works bec. of M blocking effects) 2nd choice for many other disorders after SSRIs. Nortriptyline cuases little to no orthostatic hypotension. Desipramine is least sedating & less anticholinergic effects. "Desipramine will keep you awake during the Day."

Monoamine Oxidase Inhibitors (MAOIs) -rarely used because of side effect profile, only used as last resort
Phenelzine, Tranylcypromine -inhibit MAO type A and MAO type B so it inhibits the breakdown of NE, serotonin, tyramine and dopamine. -S/E are anti-HAM like TCAs, malignant hypertension occurs with tyramine products (found in cheese and red wine), or sympathetic drugs like phenylephrine in cold medicine. Serotonin syndrome occurs when taken with SSRIs (diaphoresis, tremor, hyperthermia, muscle rigidity, progressing to rhabdomyolysis, renal failure, convulsions, coma and death) must wait 2 wks to switch from MAOI to SSRI.

Atypical antidepressants: It is NOT high yield to remember the classes of these drugs, just remember the names of the drug and the underlined stuff.
Venlafaxine (Effexor) is a serotinin/norepineprhine reuptake inhibitor. Similar to SSRIs.
Bupropion (Wellbutrin) is used to quit smoking and is also used as a substitute for SSRIs since it lacks sexual side effects. It is a norepinephrine/dopamine reuptake inhibitor.
Nefazodone and Transodone- causes sedation and priaprism ("Nefazodone raises the bone"). Also has TCA like effects including anti-HAM and arrythmias. They are serotonin antagonist and reuptake inhibitors.
Mirtazapine (Remeron)- the only thing you got to remember about this is that it causes weight gain. It also causes sedation. Class is norepinephrine and serotonin antagonists.

Lithium: DOC for Bipolar Disorder -mechanism is it inhibits the inositol pathways (IP2 pathway) and affects sodium transport -S/E are tremor, sedation, ataxia, polyuria & polydipsia (nephrogenic diabetes insipidus), hypothyroidism, goiter, bad acne. Must monitor lithium levels due to narrow therapuitic index (between 0.7-1.2) and also monitor kidney function & thyroid fx. Amiloride is used to treat nephrogenic diabetes insipidus due to Lithium. Valproic acid is also commonly used for Bipolar Disorder and Carbamazepine is also used.

The drug Sumatripton [Imitrex] is used for migrane headaches and cluster headaches. Mechanism: Activates serotonin 5-HT1 receptors causing vasoconstriction. In the wards they tend to use this instead of TCAs for migrane headaches S/E: Mostly from vasoconstriction: Severe HTN, coronary vasospasm, MI, arrythmias, stroke, bowel ischemia.

*Extra info for psyc. boards: Valproic Acid and Carbamazepine are good for mixed episodes and for raipid cycling bipolar disorder while lithium is better for acute mania and for manic and depressive episodes. Atypical antipsycotics also have mood stabilizing effects and since these 3 drugs take up to 2 wks to work, pts can be started on a short course of atypical antipsycotics for quick results. Lamotrigine can also be used for bipolar disorder.
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Miscellaneous Drugs:
Fumethazole is used as an antidote for toxic alcohol ingestion (like methanol) . It inhibits alcohol dehydrogenase.

DOC for Tourettes is Pimozide. Pimozide is actually a typical antipsychotic not listed above.

Amitryptiline & Gabapentin DOC for neuropathic pain

Verenicline -new drug used for quitting smoking. It is an N partial agonist and it also blocks dopamine release in the mesolimbic tract. Newer and better.

Atomoxetine is a selective NE reuptake blocker used for attention deficit hyperactivity disorder. As you recall, sympathomimetics are also used for ADHD like methylphenidate (Ritalin).

1 Minute Review of Psychiatry: Rule is for bipolar disorder you give usually Lithium or Valproic Acid. For enuresis (bed wetting) give TCAs. For Neuropathic pain and migranes you give TCAs. For anxiety initially you use benzodiazepines then discontinue and use SSRIs. For psychotic disorders like schitzophrenia give atypical antipsycotics. For everything else you give SSRIs! Ex. OCD, Panic disorder, eating disorders, PTST, social phobia, depression.
----------------------------------------------------------END PSYCHIATRY DRUGS-----------
High Yield Pharm Facts Part ONE:
IV drugs have 100% bioavailability. If a large percentage of a drug is bound to plasma proteins, there is a low volume of distribution

Warfarin and sulfonamides are strongest binders to plasma proteins.
General Inducers: Anticonvulsants (Phenobarbital, phenytoin, carbamazepine), rifampin, glucocorticoids, chronic alcohol, cigarettes
General Inhibitors: Cimetidine, Macrolides, grape fruit juice, INH, Azoles

Thiazides, Aspirin and Penicillins are weak acids
Morphine, local anesthetics, methamphetamines, PCP are weak bases

Drug induced lupus occurs most often in hydralazine and procainamide. Slow acylators tend to get drug induced lupus.

Zero order drugs are high doses of Ethanol, Phenytoin and Aspirin

Zero order drugs have constant amount of drug eliminated, variable half life, first order has constant fraction, constant half life) -half life and clearance are inversely related.
If CL>GFR you are secreting the drug, if CL<GFR you are absorbing the drug. -about 4 half lives to reach steady state
Affinity is the ability of the drug to bind the receptor. The greater proximity to the Y axis the greater the affinity. Curves must be parallel (otherwise different receptor).
Potency: The closer the curve is to the Y axis the more potent it is. Lines must not cross.
Efficacy: Shown by maximum height of curve

Drugs with low therapeutic index: Warfarin, Lithium, Digoxin, Theophyline

Gs stimulates adenylate cylcase- Receptors: All Beta and D1
Gi inhibits adenylate cyclase- Receptors: Everything with a two
Gq activates phospholipase C- Receptors: Everything with a 1 (except D1) and M3

ANS rules: 1st neurotransmitter is always acetylcholine. First receptor is always Nicotinic. Parasympathetic nerves always act on Muscarinic receptors and release acetylcholine.Sympathetic neurons always act on alpha or beta receptors release NE except for the sweat glands where they have a Muscarinic receptor and release ACh.

Epinephrine will act with or without innervation. MAO type A is found Anywhere. MAO type B is found in the Brain.

Alzheimer's- decreased ACh in meymert's nucleus
Huntington's -increased DA to ACh ratio
Parkinson's -low DA to ACh ratio
Psychosis -increased DA in mesolimbic and mesocortical tract
Depression -decreased Noronephrine & Acetylcholine

PCP gives you horizontal and vertical nystagmus, paranoia, rhabdomyalysis, OD leads to convulsions and death. It is a weak base so by acidify urine in OD

Marijuana acts on CB1 and CB2 cannabinoid receptors. Hallucinogenic properties, causes sedation, euphoria, increases heart rate. Dronabinol is a drug derived from this.

Monoamine oxidase type A breaks down noronephrine, serotonin, and tyramine. Monoamine oxidase type B breaks down dopamine.
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Antibiotics Inhibiting Cell Wall Synthesis

Penicillins: Inhibit bacterial cell wall synthesis by inhibiting the transpeptidase reactions involved in cross linking. Beta Lactimases break the Beta Lactam ring structure of the drug and this is how resistance is acquired. -Work well against most gram positive organisms and Nisseria. Most won't work against Staph since these make Beta Lactamase. Synergy with the aminoglycosides.
Side Effects are hypersensitivity (types 1-4), GI side effects of N/V/D

Very Narrow Spectrum Beta Lactamase Resistant -basically used for Staph but not MRSA
Methicillin, Nafcillin, Oxacillin         "MNO"

Narrow Spectrum Beta Lactamase Susceptible -for gram positive cocci and Neisseria -DOC for trepenoma pallidum (syphillis) is penicillin G
Penicillin G and Penicillin V

Wide Spectrum Beta Lactamase Susceptible -most gram positives (except Staph since it makes Beta Lactamase) and some gram negative rods [E. coli, Salmonella, Shigella, Proteus, H. influenzae]. -Amoxicillin is first line for otitis media in kids
Ampicillin, Amoxicillin -activity enhanced with clavulanic acid or sulbactam, or tazobactam which are inhibitors of penicillinase   WARD TIP: Amoxicillin is one of the most prescribed drugs

Very Wide Spectrum: -Also covers more gram negative rods and Pseudomonus. Beta Lactamase susceptible.
Piperacillin, Ticarcillin, Azlocillin -In wards, only available with penicillinase inhibitor like Piperacillin-tazobactam, Piperacillin-sulbactam or Ticarcillin-clavulanate

Cephalosporins: Same mechanism as Penicillins, also contain a beta lactam ring. S/E are Hypersensitivity reactions. Assume someone allergic to Penicillins will be allergic to Cepalosporins only though this only occurs 5% of the time. All start with Ceph or Cef. Ceftriaxone is unique since it eliminated in the bile.
"Organisms not covered by the Cephalosporins are LAME" L=Listeria A=Atypicals (Chlamydia Mycoplasma) M= MRSA E=Enterococci

First Generation: Narrow Spectrum Beta Lactamase Susceptible. Ex: Cefazolin. Covers gram + cocci and PEK (Proteous, E coli, Klebsiella). Trick: Anything that has a ph in its name is first generation (but there are first generations w/o a ph in their name). Used a lot for community acquired UTIs and during abdominal surgeries.
Second Generation: Medium Spectrum Beta Lactamase Susceptible. Ex: Cefuroxime, Cefoxitin, Cefotetan. Covers more gram negatives but are less effective against gram positives with the exception of Cefuroxime which retains the first generation coverage of gram positive organisms.
Third Generation: Wide Spectrum Beta Lactamase Resistant. Most ENTER CNS so they are good for meningitis. Ceftriaxone is example, it is the DOC to treat gonorrhea and has very wide coverage. Other examples: Cefotaxime, Ceftazidime, Cefepime. If the 4th letter is a consonant it will be in the third generation. Ceftriaxone can cause gallbladder sludging since a lot of this drug is released into the bile. *Extra Ward Info: They are not as good as the first generation for staph although Cefepime has the best staph coverage in the 3^rd generation. Ceftazidime stands out as being the least active against staph and streptococci (remember the one with the Z in its name holding a dime is the odd one). Cefepime and Ceftazidime have anti pseudomonal coverage.

Imipenem and Meropenem   -Beta Lactamase Resistant Very Wide Spectrum -Same mechanism as Penicillin -Broadest spectrum antibiotic available so it is good for empiric therapy. They cover all bacteria in existence except for MRSA, E. faecium and Stenotrophomonas. Imipenem must be given together with Cilastatin to inhibit its metabolism in the body. S/E: Cross allergy with penicllins, CNS effects

Aztreonam: -Covers only gram negative rods. Same mechanism as penicillin but no cross allergenicity seen with penicillins or cephalosporins. Mneumonic: If you chop down a tree, the chopped down tree will look like a negative sign. It is also not effective against any anaerobic organism. Covers pseudomonas.

Vancomycin: -Only cell wall targeting antibiotic that doesn't have a Beta Lactam ring. Mechanism is it inhibits cell wall synthesis by binding to some D-ala-D-ala peptide that stops the elongation of peptidoglycan chains. Only works on gram positive organisms. DOC for MRSA. If you see any serious life threatening gram positive infection, give Vancomycin.
S/E are permanent ototoxicity, diffuse hyperemia (red man syndrome) if given too rapidly since it releases histamine, hypotension, nephrotoxicity. *So give slowly over an hour & never give Vanco IV push since someone in a Hospital actually died from this due to sudden hypotension. Red man syndrome is not considered an allergic reaction to the drug.
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Antibiotics that Inhibit Protein Synthesis Most protein inhibitors are bacteriostaic, but aminoglycosides are bactericidal. There are four steps in protein synthesis:
1-the tRNA at the A site goes to the vacant P site (initiation complex) <Inhibited by Aminoglycosides (hint: A is the first letter of the alphabet, the initiation complex is the first thing)
2-new tRNA enters at the now empty A site <Inhibited by Tetracyclins (block tRNA from binding)
3-the tRNA at the A site is added to the growing peptide chain at the P site by peptidyl transferase <Inhibited by chloramphenicol (inhibits peptide bond formation)
4-the thing translocates <Inhibited by macrolides (Hint: all end in thromycin so the T is for translocation)

Most work at the 50S subunit except for aminoglycosides and tetracylins which work at the 30S subunit

Macrolides:   Broad spectrum, great alternative to penicllins. Covers gram positives and atypicals. The m/c adverse rxns are GI related.
Erythromycin -used for gram positive cocci except MRSA, atypicals such as Chlamydia, Mycoplasma, Legionella, Campylobacter, and Ureaplasma. -mainly cleared in bile
Azithromycin -DOC for chylamydia -safe to use in pregnancy
Clarithromycin -very good against MAC

Clindamycin is similar to the macrolides. Used for anaerobes. S/E include pseudomembranous colitis. It covers MRSA and is frequently used for outpatient treatment of minor MRSA infections

Aminoglycosides: Need oxygen to be transported inside the bacteria, therefore they can't kill anaerobes. But if you mix them with something that destroys the cell wall like penicllins then they can get inside. They cover only gram negative rods and staph. S/E includes serious nephrotoxicity (6-8%) and permanent Ototoxicity.
Gentamicin, Tobramycin, Streptomycin, Neomycin, Amikacin Ward Tip: Tobramycin has the greatest activity against pseudomonas. Amikacin tends to work if the organism is resistant to Gentamicin or Torbramycin.

Tetracyclins: Broad spectrum antibiotics plus they cover a lot of atypicals. Backup for Penicillin G in treating syphilis. Antacids and milk chelate the Tetracyclins. S/E Phototoxicity, GI effects, avoid in children since it causes tooth enamel dysplasia and inhibits bone growth.
Tetracycline –not to be used with renal insufficiency
Doxycycline -half eliminated in feces so good for renal failure patients. Used to treat lyme disease.
Demeclocycline -also used for SIADH since it blocks ADH receptors in the collecting ducts (can cause nephrogenic DI) -*Minocycline causes vertigo in 70% of women.

Chloramphenicol: -Back up drug due to toxicity. Common to cause bone marrow suppression. Gray baby syndrome in babies due to low glucuronysyl transferase.

Quinupristin-Dalfopristin: -used for vancomycin resistant organisms -block tRNA from binding –*S/E include severe venous irritation when give through peripheral IV line, arthralgias and myalgias, rash, hepatoxicity.
Linezolid: -only used for vancomycin resistant gram positive organisms -blocks formation of initiation complex &##8211;S/E: hematotoxicity -It is also a MAOI inhibitor & can cause seratonin syndrome with cheese or red wine.

* = indicates extra information for wards probably not in USMLE
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Inhibitors of Folic Acid Synthesis or Folic Acid Metabolism:

Sulfonamides: -Complexes with PABA which inhibits dihydropteroate synthetase -All start with Sulf -very tight binder to albumin, can displace drugs from plasma proteins and can even displace bilirubin causing kernicterus in newborns. S/E include all types of hypersensitivity that can progress to Stevens-Johnson syndrome, rashes, phototoxicity, hematotoxicity, hemolysis especially in G6PDH deficiency -Examples:
Sulfaslazine (for ulcerative colitis) Silver Sulfadiazine (topical for burns)

Trimethoprim-Sulfamethoxazone[Bactrim] -inhibit dihydrofoliate synthetase and reductase -Cover Staph and faculative gram negative organisms. Used for UTIs (E. coli) -DOC for Pneumocystis carinii pneumonia, S/E include those listed above for sulfonamides and a unique side effect of hyperkalemia.
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Other Antiobiotics:

Fluoroquinolones -inhibit topisomerase II (DNA gyrase) and topoisomerase IV -very broad spectrum that cover a variablee amount of gram positive organisms and most faculative gram negative rods. All end in floxacin like Ciprofloxacin, Levofloxacin [Levaquin], Moxifloxacin etc. Side Effects: Don't give during pregnancy or to children since it effects cartilage development. Tendonitis and tendon rupture may occur in adults, for this reason contraindicated if pt is under 18. May incr. the QT interval, cause phototoxicity, are chelated when taken with milk and antacids like the tetracyclines. WARD TIP: Used a lot. Memorize dose of 750 mg PO/IV QD Levofloxacin for nosocomial pneumonia or acute pyelonephritis, double frequency to q12hr in sepsis. Ciprofloxacin has limited gram positive coverage while all of the later quinolones have excellent gram positive coverage. They do cover pseudomonas.
Metronidazole [Flagyl]: -mechanism unclear, has something to do with free radicals. DOC for protozoa ("GET") and anaerobes. G=Giardia E=Entamoeba T=Trichomonas. Anaerobes include B. fragilis and Clostridium difficle. S/E include metallic taste, disulfiram like reaction with ethanol.

Ampicillin/Sulbactam [Unasyn] is a common antibiotic used in the Hospital especially for cellulitis. Usual dose is 1.5-3 grams IM/IV Q6 hrs.

Anti Tuberculosis Drugs:

Isoniazid [INH] -inhibits mycolic acid synthesis -S/E include hepatitis, peripheral neuritis that can be reversed by B6, hemolysis in G6PD deficiency -P450 inhibitor
Rifampin -inhibits RNA polymerase. P450 inducer. Urine, tears and sweat turn red/orange.
Ethambutol -inhibits cell wall synthesis -toxicity: red/green color blindness
Pyrazinamide -S/E hyperuricemia
Streptomycin -S/E include deafness, nephrotoxicity

Polymyxin B: All you have to know is the mechanism which pokes holes in the cell wall of the bacteria. Has a lot of side effects (especially renal toxicity) so used as a last resort.
Nitrofurantoin only gets to the lower urinary tract and covers gram negative enteric bacteria. Used a lot for UTIs.

How to be the antibiotic KING of the wards: The following is a list of the common “high doses” of the most frequently encountered antibiotics used in sepsis and serious infections. Memorize it and you will be king. Piperacillin-tazobactam 3.375g q4 hrs, Ticarcillin-clavulanate 3.1g q4 hrs, Ceftriaxone 1 gram q12 hrs, Cefepime 2g q12hrs, Gentamicin or Tobramycin 5-7mg/kg q24hrs, Clindamycin 600mg q8hrs, Vancomycin 15mg/kg q12hrs, Ciprofloxacin 400mg q12hrs, Levofloxacin 750mg q12hrs, Imipenem-cilastatin 0.5g q6hrs, Meropenem 1g q8hrs.
Antifungal Drugs:

Amphotericin B: -reacts with ergosterol in the fungal membrane and makes pores in it. Broad spectrum anti fungal agent that is very toxic. The oral form is called nystatin and it is used for oral candidiasis and topical fungal infections.     S/E: Fever, chills, muscle rigors, hypotension due to histamine release, nephrotoxic. Also causes nephrogenic diabetis insipidus.

Azoles: Ketoconazole, Fluconazole, Itraconazole -block synthesis of ergosterol -only fluconazole enters the CNS and is used in meningitis and invasive diseases -P450 inhibitor. S?E include disulfiram like reactions with alcohol, rash.

Low Yield- Grisefulvin, Terbinafine work against dermatophytes
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Antiviral Agents   GUIDE: If it ends in AVIR it is an Aids drug. If it ends in IVIR it is an Influenza drug. If it ends in OVIR it is a herpes drug. Many of these drugs can cause seizures, can be hematotoxic, hepatoxic and nephrotoxic. Some also may cause pancreatitis. You just have to know the underlined side effects of these drugs for the boards, which are the most tested ones.

Anti Herpes Drugs: Acyclovir is the prototype it is an antimetabolite that gets incorporated into the DNA molecule and terminates the growing chain inhibiting viral DNA polymerase. It is first activated by the virus specific viral thymidylate kinase and then activated by host cell kinases. Resistance develops if the virus lacks thymidylate kinase.
Acyclovir [Zovirax] -S/E include seizures, hematotoxicity. Used for HSV and varicella zoster virus.
Ganciclovir -very similar mechanism but doesn't terminate the chain. S/E include seizures, hematotoxicity, pancreatitis, nephrotoxicity.

Foscarnet -not an antimetabolite -it inhibits viral DNA and RNA polymerase -good for acyclovir resistant HSV -S/E include seizures, hematotoxicity, pancreatitis, nephrotoxicity.

Reverse Transcriptase Inhibitors: -antimetabolites that inhibit reverse transcriptase and they don't require metabolic activation -plasma lvls of zidovudine are decreased by rifampin. All RTIs are used in AIDS. Resistance occurs by mutation in reverse transcriptase.
Zidovudine [Retrovir] -seizures, hematotoxicity and hepatotoxicity are major side effects.
Didanosine -pancreatitis is the major side effect that is tested. It also can cause hematotoxicity and hepatoxicity.
Lamivudine -supposidly least toxic. Can also cause pancreatitis, hematotoxicity and hepatotoxicity.

Protease Inhibitors: -used in HIV/AIDS -The viral protease is encoded by the pol gene. The protease inhibitors prevent the virus from maturing. All protease inhibitors inhibit p450
Indinavir -Most common tested side effect is nephrolithiasis (kidney stones), which is common. Also causes nephrotoxicity, pancreatitis, hepatitis.
Ritonavir -toxicity is insulin resistance, seizures, hepatotoxicity, hematotoxicity.

Fusion Inhibitors: Enfurvitide -binds to gp41 so it inhibits the fusion of HIV to CD4+ cells.

Prophylaxis for needle stick is zidovudine + lamivudine for one month. In high risk add indinavir

Zanamiver, Oseltamiver -inhibit neuraminidases which prevents the virus from penetrating normal cells. -used for influenza

Ribavirin -inhibits RNA polymerase. -used for RSV
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Antimalarial Drugs: Chloroquine +/- Primaquine. For Plasmodium malariae use only Chloroquine, for P. vivax and P. ovale use both.

Drugs for Helmith Infections:
For most intestinal nematodes (round worms) use Mebenadazole or Pyrantel pamoate
For most cestodes (tapeworms) and trematodes (flukes) use Praziquantel
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Histamines and Antihistamines:   H1 activation cause capillary dilation (lowers BP), increases capillary permeability (edema), causes bronchiolar smooth muscle contraction, activates peripheral nociceptive receptors which increase pain and pruritus. H2 activation activates the parietal cells of the stomach which increases gastric acid secretion, leading to ulcers.

H1 Antagonists: -used for allergies, motion sickness, nausea and vomiting of pregnancy. -side effects are muscarinic block, sedation, GI and allergic reactions.
Diphenhydramine, Meclizine -First Generation.       Most M block, most sedation, only class with antimotion effects.
Loratadine [Claritin], Fexofenadine, Cetirizine [Zyrtec] -Second Generation   Very little M block, does not enter CNS so no sedation. WARD TIP: Claritin [OTC] and Zyrtec are very commonly used. Memorize Claritin 10mg PO QD for allergy. Zyrtec is 5-10mg PO QD

H2 antagonists: Cimetidine -used for peptic acid disease, GERD, zolliger-ellinson syndrome, major inhibitor of P450, S/E include gynecomastia

Other GI drugs:
Proton Pump Inhibitors: Omeprazole [Prilosec], Pantoprazole [Protonix], Lansoprazole [Prevacid], Esomeprazole [Nexium], other prazoles -irreversible inhibitors of proton pump, more effective than H2 blockers in GERD and ZE syndrome.    WARD TIP: These are among the most commonly prescribed US drugs, especially Protonix, Prevacid and Nexium. Protnix is used on almost every adult patient in the hospital for GI prophylaxis 40mg PO or IV daily.   Prilosec is over the counter and is usually prescribed at 20mg PO daily.

Misoprostol: PGE1 analog which increases mucus and bicarbonate secretion. Used only in NSAID induced ulcers. Abortifactant

Sucralfate: Polymerizes on the GI surface and coats it. Requires low pH to function so PPIs and antacids will decrease its activity.
Bismuth is also a protective agent that coats the GI surface.

Antacids: Ca, Mg, and Al hydroxides. Aluminum causes constipation, magnesium causes diarrhea.

Laxatives: Mild: Docusate (detergent) Strong: Bisacodyl which increases peristalsis.
Anti Diarrheal: Loperamide, Diphenoxylate

For constipation in the hospital, give Docusate Sodium [Colace] 100mg PO QD. Increase to BID up to 500mg if necessary. It's a liquid that you mix with fruit juice or milk. You can also give Bisacodyl [Dulcolax] for constipation 5-15mg PO QD
GoLytely is powerful cathartic given for bowel preperation.
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Serotonin Receptor Drugs All work through second messengers except 5HT3. The serotonin 1 receptors are found in the CNS and are usually inhibitory.
Buspirone is a partial agonist on 5HT1D receptors. Used for anxiety disorders. The nonsedating sedative (above)
Sumatriptan is an agonist at 5HT1D receptors, used for migraine pain.
The serotonin 2 receptors when found in the CNS are excitatory, in periphery stimulate GI system.
Clozapine & Olanzapine is an antagonist at 5HT2A receptors in CNS, atypical antidepressant
Cyproheptadine is a 5HT2 antagonist used in carcinoid
The serotonin 3 receptor stimulate vomiting.
Ondansetron is 5HT3 antagonist, antiemetic
The serotonin 4 receptor is inhibitory to the GI system.
Tegaserod is a 5HT4 agonist used in irritable bowel syndrome
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Ergot Alkaloids: All are potent vasocontritors, may cause ischemia and gangrene.
Ergonovine, Ergotamine, Methylsergide. First one used to stimulate uterine contraction after placental delivery. Last two are used for migraines.

NSAIDs: Most NSAIDs cause bronchoconstriction. Mild pain treated with NSAIDS while severe pain treated with opiods.
Aspirin:   Low dose inhibits TxA2 (inhibits platelets). Moderate dosage inhibits the formation of prostaglandins which provides analgesia. Moderate doses also act as an antipyretic. High doses have anti-inflammatory effects by inhibiting COX 1 &2. Only NSAID that causes irreversible inhibition of COX.   Only NSAID that interferes with uric acid elimination. Can cause hyper uricemia and uricosuria. It is also the only NSAID that causes acid base disturbances. At toxic doses, it causes respiratory alkalosis and metabolic acidosis. S/E are gastritis, ulcers, tinnitis, bronchoconstriction, Reye's syndrome (encephalopathy in children), renal dysfunction with chronic use, increased GI bleeding with ethanol. It is a weak acid so alkalization of urine will increase its elimination.    WARD TIP: Ecotrin 81 mg is prescribed a lot for cardioprotection of elderly patients. It is actually aspirin.
Ibuprofen, Naproxen, Indomethacin, Ketorolac, Sulindac.   -inhibit COX 1 and COX 2 -Indomethacin cann cause agranulocytosis and thrombocytopenia.
Selective COX 2 inhibitors: Celecoxib [celebrex] -less GI toxicity, cross allergenic with sulfonamides, potential cardiotoxicity and death.
Acetaminophen: Inhibits COX only in the CNS but not in periphery so lacks anti inflammatory effects but has similar analgesic and antipyretic effects to aspirin.   Also has no antiplatelet action, no effects on uric acid, no bronchoconstriction, little GI distress, no Reye syndrome. -S/E include hepatotoxicity. Minor ppathway via P450 forms something toxic that is inactivated by glutathione. In overdose, glutathione is depleted and the metabolite destroys the liver. P450 inducers like ethanol will increase toxicity. Antidote is N-acetylcysteine which replenishes glutathione.

Disease Modifying Anti Rheumatoid Arthritis Drugs: -for RA use NSAIDs combined with these druugs
Hydroxychloroquine -for mild RA
Methotrexate               -for severe RA
Etanercept                    -binds TNF
Infliximab                     -antibody to TNF

Drugs for Gout:
For acute inflammatory episodes give Colchicine and NSAIDs. Colchicine binds to tubulin inhibiting microtubular polymerization. S/E is bone marrow suppression.
For chronic gout, use Allopuriniol. It inhibits xanthine oxidase which decreases uric acid in blood and urine. Also can use Probenecid which inhibits proximinal tubular reabsorption of ureate. Increases urine levels of uric acid and decreases the blood levels of uric acid.

Steroids: Dexamethasone, Triamcinolone, Prednisone, Cortisol.   Listed from long acting to short acting. -cortisol has aldosterone like effect. deccrease PGs, LTs, COX2, platelet activating factor, interleukins. S/E are suppression of ACTH that can cause adrenal atrophy, cushing syndrome, hyperglycemia, osteoporosis, ulcers, sodium/water retention, decreased skeletal growth in children, decreased wound healing, immune suppression, glaucoma, cataracts etc. Must taper off.   -used for adrenal insufficiency, addson's disease, premature delivery to prevent respiratory distress syndrome. WARD TIP: Methylpregnisolone is another popular IV or IM steroid, it's trade name is Solu-Medrol. Used a lot for COPD and asthma or for autoimmune conditions.

Drugs for Asthma:   Introduction: Acetylcholine, Adenosine and Leukotrienes cause bronchoconstriction. Drugs that increase cAMP cause vasodilatation (B2 agonist incr cAMP)).
Beta 2 agonists like Albuterol, M blockers like Ipratropium are used.
Theophylline -bronchodilator that inhibits phosphdiesterase (phosphodiesterase breaks down cAMP so this drug increases cAMP).
Cromolyn and Nedocromil prevent degranulation of pulmonary mast cells which lowers the release of histamine from the inflammatory cells.
Inhaled steroids Beclomethasone, Flunisolide, Butesonide. S/E is oropharyngeal candidiasis.
Antileukotrienes: Monetelukast, Zileuton.   -first one acts only on LTD4 and last one inhibits all leukotrienes by inhibiting 5-lipooxygenase.
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Anticoagulants:               WARD TIP: Know these three drugs well as they are very frequently used.
Heparin is a large molecule, water soluble given usually SQ. Rapid onset. Short half life, does not cross placenta. Monitor PTT. Give protamine sulfate in overdose. Toxicity is thrombocytopenia, hypersensitivity.
Warfarin is a small molecule, lipid soluble, orally given, highly protein bound, long half life, slow onset, crosses placenta, lowers hepatic synthesis of vitamin K dependent factors 2,7,9,10. Incr. PT. Antidote is vitamin K. Toxicity is drug interactions (especially with P450 inhibitors), teratogenic.
Enoxaparin [Lovenox] is a low molecular weight heparin given subcutaneously.
WARD TIP: Memorize Deep Vein Thrombosis prophylaxis is Lovenox 40mg SC daily or Heparin SC 5000 Units Q8-12 hours.

Thrombolytics:
Streptokinase -acts on both bound and free plasminogen (not clot specific) -is antigenic
Alteplase (tPA) -acts only on fibrin bound plasminogen (clot specific). -is not antigenic

Antiplatelet Drugs: Aspirin
Clopidogrel [Plavix] -It blocks ADP receptors on platelets inhibiting their activation. WARD TIP: Plavix is among the m/c prescribed medications in the US. Memorize 75mg PO QD
Abciximab (binds glycoprotein IIb/IIIA receptors inhibiting platelet aggregation by cross linking). Used in pts w/ past MI or for acute coronary syndrome (In ACS it is given with ASA)
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Endocrine:
For GH tumors (acromegally) or carcinoid syndrome give Octreotide
For hyperprolactinemia, give Bromocriptine or Pergolide (DA agonists, see above)
Antithyroid Agents: Propylthiouracil, Methimazole. PTU safer in pregnancy     More drugs: I-131 can be used -KI may be used in thyrotoxicosis but only short term since thyroid escapes
Levothyroxin [Synthroid] used in hypothyroidism. WARD TIP: Synthroid is one of the m/c drugs in the US.
Steroids: See above. Endocrine uses for adrenal insufficiency, addson's disease.
Mineralicoids: Fludrocortasone is used if you want to replace aldosterone.
Adrenal Steroid Antagonists: Spirolactone is a diuretic that also blocks aldosterone and androgen receptors. Mefepristone blocks glucocorticoid and progestin receptors (aborfactant).

Estrogens: Ethinyl Estradiol (steroidal), Diethylstilbestrol (DES nonsteroidal) -S/E are increased blood coagulation, if DES is given during breast feeding or pregnancy it increases vaginal clear cell carcinoma in offspring.

Anti Estrogen Drugs:
Anastozole: -aromatase inhibitor (decreases estrogen synthesis) used in breast cancer
Tomoxifin: -estrogen antagonist in breast, estrogen agonist in bone, partial agonist in endometrium -used for breast cancer, increased risk of endometrial carcinoma
Raloxifen: -antagonist in breast and uterus agonist in bone. -better than Tamoxifin since no risk of enndometrial carcinoma when used in menopause.

Other Drugs:
Danazol: -inhibits FSH/LH -used in endometriosis and fibrocystic breast disease
Clomiphene -fertility pill -decreases feedback inhibition so it increases FSH and LH stimulating ovulation

Progestins: Medroxyprogesterone, Norethindrone, Norgestrel etc. If starts with Nor it is derived from testosterone so has androgen side effects -S/E is the decrease HDL and incr. LDL
>
Androgens: Methyltestosterone, Oxandrolone, Nandrolone

Androgen antagonists:
Flutamide -androgen blocker used in prostate cancer
Finasteride -5 alpha reductase inhibitor (converts testosterone to DHT), used in BPH and baldness

Drugs used to stop nausia and vomiting:
Meclopropramide [Reglan]: Give 5-10 mg PO or IM TID-QID. S/E include EPS, dystonia, Parkinsonian syndrome, tardive dyskinesia, rare neuroleptic malignant syndrome, rare seizures, CHF, hematotoxicity, a lot of other side effects.
Trimethobenzamide [Tigan]: Give 200 mg IM TID-QID, also has PO route where you give 300mg instead S/E include seizures, allergic rxn, cholestasis, hypotension for IM form, rare EPS, hematotoxicity. This one is newer and isn't tested on the boards yet.
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Diabetes Drugs: For type 1 diabetes give insulin. For type 2 diabetes, diet and exercise then oral hypoglycemics, them possibly insulin. WARD TIP: These show up over and over again

Insulins:   Ward Tip: M/C dosage for all insulins is 0.5-1 unit per killogram total requirement per day. You need to divide this dosage over 24 hours to figure out how much to give after every meal. Gets complicated when several are used.
Ultra-Short Acting: Aspart and Lispro - Duration is about 4 hours. Half life is about half of the duration for all the insulins. These are given right before meals
Short Acting: Regular Insulin -Duration is about 6 hours. Given a half hour to an hour before meals.
Long Acting: NPH, Lente - Duration is about 12 hours. Really the duration is about 16 hours but it is easier to remember 4,6,12,24 for the insulins.
Ultra Long Acting: Ultralente, Glargine -last for about 24 hours -glargine has no peak

Oral Hypoglycemics: Know the following in order of importance: 1. The mechanism of the class 2. Which 2 classes cause hypoglycemia (Sulfonureas, Repaglinide) 2. Which ones cause weight gain (Thialidinediones & the S.U. Glyburide ) 3. The first three side effects listed 4. Only after you know these perfectly then glance over everything else
Sulfonylureas -increase insulin release by blocking K channels -S/E for the entire class are hypoglycemia, hematotoxicity and cross allergy with sulfonamides
Chlorpropamide, Glipizide [Glucotrol], Glyburide, Glimepiride [amaryl]   -glyburide can cause weight gain
Metformin [Glucophage]-lowers postprandial glucose levels but does not cause hypoglycemia or weight gain -mechanism: it somehow lowers hepatic gluconeogenesis. Memorize for DM2 Glocophage 500-1000mg PO BID
Thiazolidinediones: Pioglitazone [Actos] & Rosiglitazone [Avandia] -increases insulin receptors, if used alone doesn't cause hypglycemia but may to so in combination with other hypoglycemics -S/E include edema, weight gain, CHF, hepatotoxicity, fractures in females ("Glitazones will break your bones"), URI.
Acarbose: -inhibits alpha-glucosidase in the brush border of the small intestine, lowers postprandial glucose. -S/E mostly GI effects such as flatulance, bloating
Repaglinide [Prandin] -stimulates insulin release from pancreatic beta cells -"repairs insulin". -Can cause hypoglycemia, hypersensitivity, upper respiratory infections, arthralgias.
Dipeptidyl peptidase-4 (DPP-4) inhibitors: Januvia [sitagliptin] -inhibits insulin sythesis and release, also decreases glucogon levels. Does not induce hypoglycemia. S/E include angioedema, hypersensitivity (that could progress to Steven-Johonson syndrome), upper respiratory infections, arthralgias.
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Biphosphonates: Alendronate [Fosamax]-stimulates osteoblasts to secret osteoclast inhibitors decreasing bone resorption. For osteoporosis use estrogens, calcitonin, alendronate, vitamin D, Calcium. WARD TIP: Fosamax is one of the m/c prescribed medications. Memorize 70mg PO every week for postmenopausal osteoparosis.

Anticancer Drugs: G1-S-G2-M -Antimetabolites are S phase specific. Bleomycin is the only one that is G2 specific. M phase specific ones are vinblastine, vincristine and paclitaxel. Everything else G0. Alkylating agents act in G0. Most anticancer drugs cause bone marrow suppression.
Methotrexate -antimetabolite that inhibits DHF reductase. -antidote is leucovorin
Cyclophosphamide -alkylating agent -S/E are hemorrhagic cystitis, use mesna with it to prevent this
Doxorubicin -intercales in DNA, forms free radicals -antidote is dexrazoxane -toxicity is dilated cardiomyopathy
Vincristine and Vinblastine -stops microtubular polymerization -vincristine is neurotoxic
Cisplatin: -Alkylating agent -renal toxicity, neuro toxicity
Bleomycin -S/E pulmonary fibrosis              Notes: Vincristine & Bleomycin don't cause bone marrow supression.
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Immunosuppressive Agents:
Cyclosporin is DOC for organ transplantation. Mechanism: Binds to cyclophilin lowering calcineurin.
Tacrolimus -binds to Fk binding protein inhibiting cytokine secretion

Monoclonal Antibodies:
Abciximab -antiplatelet drug -antagonist of IIb/IIIa receptors
Infliximab -binds TNF -used for RA and chron's   [related drug is Ethanercept which is a recombanent form of TNF receptor that binds TNF]
Trastuzumab -used for breast cancer

Most Important Cytokine: Erythropoietin which is used for anemias.
Toxicology:

Miosis, Decreased HR, Low Respirations                      Mydriasis, Increased HR
Acetylcholinesterase inhibitors -diarrhea     &nbbsp;             Muscarinic blockers and TCAs - hot dry skin
Opiods    -constipation     p;         Stimulants                                      -warm, sweaty skin

Iron Poisoning get hematemisis, bloody diarrhea. Antidote is Deferoxamine.
Lead poisoning get GI distress and pain, neuropathy (wrist drop), mental retardation. Antidote is Dimercaperol, EDTA. Succimer in children.
Basically Dimercaperol works for everything except for iron.

Important Herbals: Saw Palmetto is a 5 alpha reductase inhibitor used for BPH
St. John's Wort may enhance serotonin. Used for depression.
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High Yield Facts #2:
Treat Listeria with ampicillin or gentimycin. Treat Atypicals (Chlamydia, Mycoplasma) with macrolide or tetracyclin. Treat Enterococci if serious with vancomycin and if not serious with gentimycin.

Antibiotics that safe to use in pregnancy: Penicillins, Cephalosporins, Azithromycin/Erythromycin and Nitrofurantoin.

Drugs commonly causing hemolytic anemia:
Penicillin and Sulfonamides can cause autoimmune hemolytic anemia. Remember Methyldopa causes anti RBC antibodies and hemolysis.
Chloroquine and the Sulfonamides are infamous for causing hemolysis in G6PD deficiency.

Top three Histamine releasing drugs: Amphotericin B, Vancomycin, Morphine

Most Nephrotoxic Drugs: Amphotericin B, Aminoglycosides, Cisplatin

Treatment for H. pylori: "MCAT gave you ulcers" Metronidazole, Clarithromycin, Amoxicillin, Tetracyclin.

Treatment for Pseudomonas: Ceftazidime + Tobramycin.

Vancomycin + Aminoglycoside = high incidence of ototoxicity and renal toxicity

Antibiotics not renally eliminated: Ceftriaxone, Doxycycline, Nafcillin, Erythronycin (No Can Do)

Drugs that cause Phototoxicity: Tetracyclins, Sulfonamides, Fluroquinolones

Drugs to treat MAC: Azithromycin or Clarithromycin

Microtubule Inhibitors (work during M phase): Colchicine, vincristine, Vinblastine, Paclitaxel

Amiodarone and Lithium have thyroid effects

Alprostadil is a PGE1 analog is an alternative drug to the PDE-5 inhibitors so if the guy has angina and erectile dysfunction, give this. It is injectable only.

Ammonium Chloride acidifies urine, Sodium Bicarbonate alkalizes urine

First pass effect: orally given drug enters portal circulation and undergoes hepatic metabolism
Biotransformation: Phase 1: P450 (oxidation, reduction, hydrolytic rxns)
Phase 2: Conjugation (Glucoronidation, Acetylation, Sulfonation, Glutathione)

Loading dose = steady state conc. X volume of distribution
Maintenance dose = steady state conc X clearance X dosing
Half Life = (0.7Vd)/CL

Drugs safe to use in pregnancy: Acetaminophen, penicillin, cephalosporins, erythromycin, nitrofurantion, H2 blockers, heparin, hydralazine, methyldopa, lebetalol, insulin, docusate sodium (see below).

For iron deficiency anemia, give Ferrous Sulfate [Ferratab] 300mg BID

Drugs that patients with Sulfa allergy can not take: Sulfonamides, Sulfonureas, Sulfasalasine, Thiazides, Loop Diuretics (except Ethacrynic Acid), Celecoxib, and Sumatriptan.

Drugs that can cause syndrome of inappropriate antidiuretic hormone secretion: Sulfonureas and Morphine (although both are rare).

Drugs that cause diabetes insipidus: Lithium, Demeclocycline, Methoxyflurane (an inhaled anesthetic not listed earlier).