pharmacology

1

NBDE IIPHARMACOLOGY

EXAM SECTION[34 Questions]

Dr. Glenn Clark

Pharmacology Exam Components:1.0. General Principles [5 Qs]2.0. Central Nervous System [4 Qs]3.0. Autonomic [3 Qs]4.0. Cardiovascular [4 Qs]5.0. Local anesthetics [4 Qs]6.0. Chemotherapy [5 Qs]7.0. Endocrines/Immunosuppressants [ 2 Qs]8.0. Analgesics [5 Qs]9.0. Antihistamines and Autocoids [2 Qs]

Total = 34 questions

1.0. General Principles [5 Qs]1.1. Rx writing, drug laws, and drug abuse1.2. Toxicity and drug interaction1.3. Dose response1.4. Mechanism of action1.5. Biotransformation1.6. Absorption, distribution, excretion1.7. Alternative (herbal) medications

Pharmacology is the study of how substances interact with living organisms to produce a change in function.[1] To protect the consumer and prevent abuse, many governments regulate the manufacture, sale, and administration of medication. In the United States , the main body that regulates pharmaceuticals is the Food and Drug Administration and they enforce standards set by the United States Pharmacopoeia. The FDA categorizes drugs into six schedules (I to VI). The safety and effectiveness of prescription drugs in the U.S. is regulated by the federal Prescription Drug Marketing Act of 1987 .

All drugs have two properties that govern their efficacy. First,Pharmacokinetics describes the effect of the body on the chemical (e.g. half-lifeand volume of distribution), and second pharmacodynamics describes the chemical's effect (desired or toxic). The pharmacokinetic properties have 4 properties or characteristics (ADME):Absorption - How is the drug absorbed (skin, the intestine, the oral mucosa)? Distribution - How does it spread through the organism? Metabolism - Is the drug converted chemically inside the body, and into whic h substances. Are these active? Could they be toxic? Excretion - How is drug eliminated (through bile, urine, breath, skin)?

Finally drugs have a therapeutic index or therapeutic window which is the ratio of desired effect to toxic effect. A drug with a narrow therapeutic index (close to one) exerts its desired effect at a dose close to its toxic dose.

Schedule I: [Use illegal/restricted to research; high abuse potential; no accepted medicinal use in US]. Examples: hallucinogens, heroin, marijuana Schedule II: [Requires prescription; high abuse potential; no refills or verbal orders allowed; some states require triplicate Rx]. Examples: amphetamines, barbiturates, opiates (single entity, some combos) Schedule III: [Requires prescription; moderate abuse potential; max 5 refills/6mo; verbal orders allowed]. Examples: anabolic steroids, dronabinol, ketamine, opiates. Schedule IV: [Requires prescription; low/moderate abuse potential; max 5 refills/6mo; verbal orders allowed]. Examples: appetite suppressants, benzodiazepines, sedative/hypnotics. Schedule V: [Requires prescription or may be OTC with restrictions in some states; limited abuse potential; max 5 refills/6mo; verbal orders allowed]. Examples: opiate or opiate-derivative antidiarrheals and antitussives.

A medical prescription (? ) is an order (often in written form) by a qualified health care professional to a pharmacist or other therapist for a treatment to be provided to their patient. Usually on the prescription is text that identifies the document as a prescription, the name and address of the prescribing provider and any other legal requirement such as a registration number (e.g. DEA #).The symbol "Rx" meaning "prescription" is a transliteration of a symbol resembling a capital R with a cross on the diagonal (? ). Many brand name drugs have less expensive generic drug substitutes that are chemically equivalent. Prescriptions will also contain instructions on whether the prescriber will allow the pharmacist to substitute a generic version of the drug (e.g. substitution permitted). Some prescriptions will specify whether and how many "repeats" or "refills" are allowed; that is whether the patient may obtain more of the same medication without getting a new prescription from the doctor. In the USA, physicians, veterinarians, dentists, and podiatrists have full prescribing power. Each state regulates what (if any) prescription powers members o f the above group are allowed.There are always 3 elements to a prescription (in addition to patient info, doctor info and dsignature):1. Rx: medication (including dosage)2. Disp.: dispensing instructions (number of pills) 3. Sig.: patient instructions (how to take)

2

Toxicity is a measure to the degree to which something is toxic or poisonous. The study of poisons is known as toxicology. Toxicity can refer to the effect on a whole organism, such as a human or a bacterium or a plant, or to a substructure, such as a cell (cytotoxicity) or the liver. In the science of toxicology, the subject of such study is the effect of an external substance or condition and its deleterious effects on living things: organisms, organ systems, individual organs, tissues, cells, subcellular units. A central concept of toxicology is that effects are dose-dependent; even water – by itself not toxic – can lead to water intoxication when taken by a human in large enough doses, whereas for even a very toxic substance such as snake venom there is a dose for which there is no toxic effect detectable.Drug interaction is a situation in which a substance e.g. another drug, affects the activity of a drug, i.e. the effects are increased or decreased. Typically, interaction between drugs come to mind (drug-drug interaction). However, interactions may also exist between drugs & foods (drug-food interactions), as well as drugs & herbs (drug-herb interactions). Drug interactions may be the result of various processes that alter the the pharmacokinetics of the drug (ADME). Alternatively, drug interactions may be the result of the pharmacodynamic properties of the drug, e.g. via the co -administration of a receptor antagonist and an agonist for the same receptor.

Metabolism based drug interactions: One notable system involved in metabolic drug interactions is the enzyme system comprising the cytochrome P450 oxidases. This system may be affected by either enzyme induction or enzyme inhibition, as discussed in the examples below.Enzyme induction - drug A induces the body to produce more of an enzyme which metabolises drug B. This reduces the effective concentration of drug B, which may lead to loss of effectiveness of drug B. Drug A effectiveness is not altered. Enzyme inhibition - drug A inhibits the production of the enzyme metabolisingdrug B, thus an elevation of drug B occurs possibly leading to an overdose.

Bioavailability - drug A influences the absorption of drug B. The examples described above may have different outcomes depending on the nature of the drugs. For example, if Drug B is a prodrug, then enzyme activation is required for the drug to reach its active form. Hence, enzyme induction by Drug A would increase the effectiveness of the drug B by increasing its metab olism to its active form. Enzyme inhibition by Drug A would decrease the effectiveness of Drug B.

Drug- Route of AdministrationEnteral : GI vs Parenteral : Non-GI

Enteral: Oral = stomach = intestines = liver (portal circulation) = heart = general circulation = target tissues. Sublingual or Rectal = straight into general circulation and bypasses first-pass liver metabolism.

Parenteral: Intravascular, intramuscular, subcutaneous goes straight into general circulation and bypasses first -pass liver metabolism.

Other: - Inhalation [i.e. anesthetics, steroids for asthma] - Intra-nasal [i.e. calcitonin for osteoporosis, cocaine] - Intrathecal [i.e. analgesics, anti-neoplastics]- Topical [i.e. anesthetics, antibiotics, antifungals]

Key Concepts of Drug Activity1. Pharmacokinetics: the body’s effect on a drug.2. Pharmacodynamics: the drug’s effect on the body.

Pharmacokinetics (ADME)1. Absorption: The onset of action of a drug is primarily determined by the rate of absorption

Absorption (continued): 4 factors that affect the absorption of drugs into the bloodstream: (1) Bioavailability: The amount (quantity %) that reaches the blood or plasma. Usually, a drug’s major effect is produced by the amount of drug that is free in plasma. (2) Stability: Insulin is unstable in the GI tract, hence the injections for Diabetics to bypass the enteral route. (3) Permeability: this is determined by pH (acid-base interactions, protonation, pKa, Hendersson-Hasselbach) Coated tabs (buffered) Gastric Emptying, Parasympathetic vs. Sympathetic co-activity, Food in the stomach (delays gastric emptying and increases acid production to allow for proper digestion); NOTE: drugs destroyed by acid should be taken without food when possible. Lipid solubility of drug (hydrophobic, non-ionized, i.e. sterols); Water solubility of drug (hydrophilic, ionized or charged). Transport mechanisms (passive, active, or facilitated)Contacttime, surface area, blood supply. (4) First-pass hepatic metabolism: For enteral drugs, some are inactivated by the liver before reaching systemic circulation, thus decreasing bioavailability; others drugs are activated by the liver, increasing bioavailabilityIV (intravenous) route of administration bypasses first-pass liver metabolism, also increasing bioavailability.

3

-When using this product: increased dryness or irritation of the skin may occur immediate ly following use of this product or if you are using other topical acne drugs at the same time. If this occurs, only one drug should be used unless directed by your doctor

Topical Acne Drugs

-When using this product: limit the use of foods, beverages, and other drugs that have caffeine. Too much caffeine can cause nervousness, irritability, sleeplessness, and occasional rapid heart beat; be aware that the recommended dose of this product contains about as much caffeine as a cup of coffee

Stimulants

-Ask a doctor before taking if you: consume three or more alcohol-containing drinks per day. (The following ingredients are found in different OTC pain relievers: acetaminophen, aspirin, ibuprofen, ketoprofen, magnesium salicylate , and naproxen. Important to read the label of these products to learn about various drug interaction warnings for each ingredient.)

Pain Relievers

-Ask a doctor or pharmacist before use if you are: taking sedatives or tranquilizers-Ask a doctor before use if you have: a breathing problem such as emphysema or chronic bronchitis; glaucoma; difficulty in urination due to an enlarged prostate gland-When using this product: avoid alcoholicbeverages

Nighttime Sleep Aids

-Ask a doctor before use if you: have high blood pressurenot controlled by medication; have heart disease or have had a recent heart attack or irregular heartbeat, since nicotine can increase your heart rate-Ask a doctor or pharmacist before use if you are: taking a prescription drug for depression or asthma (your dose may need adjustment); -Do not use: if you continue to smoke, chew tobacco, use snuff, or use other nicotine-containing products

Nicotine Replacement Products

-Ask a doctor before use if you: have heart disease, high blood pressure, thyroid disease, diabetes, or difficulty in urination due to an enlarged prostate gland

Nasal Decongestants

Sample Drug Interaction InformationCategory

-Ask a doctor before use if you have: kidney disease and the laxative contains phosphates, potassium, or magnesium; stomach pain, nausea, or vomiting

Laxatives

-Ask a doctor before use if you: have heart disease, high blood pressure, thyroid disease, diabetes, or difficulty in urination due to an enlarged prostate gland;

Bronchodilators

-Ask a doctor or pharmacist before use if you are: taking sedatives or tranquilizers-Ask a doctor before use if you have: glaucoma or difficulty in urination due to an enlarged prostate gland

Antitussives(Cough Medicine)

-Ask a doctor or pharmacist before use if you are taking: sedatives or tranquilizers ; a prescription drug for high blood pressure or depression-Ask a doctor before use if you have: glaucoma or difficulty in urination due to an enlarged prostate; breathing problems, such as emphysema, chronic bronchitis, or asthma-When using this product: alcohol, sedatives, and tranquilizers may increase drowsiness; avoid alcoholic beverages

Antihistamines

-Ask a doctor or pharmacist before use if you are: taking sedatives or tranquilizers-Ask a doctor before use if you have: a breathing problem, such as emphysema or chronic bronchitis; glaucoma; difficulty in urination due to an enlarged prostate gland-When using this product: avoid alcoholicbeverages

Antiemetics

-Ask a doctor or pharmacist before use if you are: allergic to milk or milk products if the product contains more than 5 grams lactose in a maximum daily dose; -Ask a doctor before use if you have: kidney disease

Antacids

-For products containing cimetidine, ask a doctor or pharmacist before use if you are : taking theophylline(oral asthma drug), warfarin (blood thinning drug), or phenytoin(seizure drug)

Acid Reducers ( H2 Receptor Antagonists)

Sample Drug Interaction InformationCategory

A dose-response curve is a simple X-Y graph relating the amount of a drug or toxin given to the response of the organism to that drug. The curves are usually qualitative , though they can use quantitative information.The measured dose (usually in [[milligrams, micrograms, or grams per kilogram of body-weight) is generally plotted on the X axis and the response is plotted on the Y axis. Commonly, it is the logarithm of the dose that is plotted on the X axis, and in such cases the curve is typically sigmoidal , with the steepest portion in the middle. The first point along the graph where a response above zero is reached is usually referred to as a threshold-dose. For most beneficial or recreational drugs, the desired effects are found at doses slightly greater than the threshold dose. At higher doses still, undesired side effects appear and grow stronger as the dose increases. The stronger a particular substance is, the steeper this curve will be. In quantitative situations, the Y-axis usually is designated by percentages, which refer to the percentage of users registering a standard response (which is often death, when the 50% mark refers to LD50).

Phase I and Phase II reactions are biotransformations of chemicals that occur during drug metabolism.Phase I metabolism usually precedes Phase II, though not necessarily. During these reactions, polar bodies are either introduced or unmasked, which results in (more) polar metabolites of the original chemicals. Phase I reactions may occur by oxidation, reduction or hydrolysis reactions. If the metabolites of phase I reactions are sufficiently polar, they may be readily excreted at this point. However, many phase I products are not eliminated rapidly and undergo a subsequent reaction in which an endogenoussubstrate combines with the newly incorporated functional group to form a highly polar conjugate.Phase II reactions — usually known as conjugation reactions (e.g., with glucuronic acid, sulfonates (commonly known as sulfation) , glutathione or amino acids ) — are usually detoxication in nature, and involve the interactions of the polar functional groups of phase I metabolites.

Examples of some commonly used herbal medicines:Artichoke and several other plants reduced total serum cholesterol levels.[9]Black cohosh and other plants that contain phytoestrogens have some benefits for treatment of symptoms resulting from menopause.[10]Echinacea extracts limit the length of colds in some clinical trials, although some studies have found it to have no effect.[11]Garlic lowers total cholesterol levels, mildly reduces blood pressure, reduces platelet aggregation, and has antibacterial properties.[12]Grapefruit seed extract as a natural antimicrobial has minimal effectiveness as an anti-bacterial, anti-parasitic, and anti -fungal herb.[13][14][15][16][17]Nigella sativa (Black cumin) is a general medicinal plant used for cough, pulmonary infections, asthma, influenza, allergy, hypertension and stomach ache. The seeds are considered carminative, stimulant, diuretic and galactogogue. Seed powder or oil is externally applied for eruptions of skin. Peppermint tea for problems with the digestive tract , including irritable bowel syndrome and nausea. Rauvolfia Serpentina, used extensively in India for sleeplessness, anxiety, and high blood pressure. St John's wort, has yielded positive results, proving more effective than a placebo for the treatment of mild to moderate depression.[18]Valerian root can be used to treat insomnia .

2.0. Central Nervous System [4 Qs]2.1. Sedatives - hypnotics & alcohols2.2. Antianxiety & conscious sedation drugs2.3. Anticonvulsants & anti-Parkinson2.4. Psychotropics (antipsychotic &

antidepressant )

4

A sedative is a substance that depresses the central nervous system (CNS), resulting in calmness, relaxation, reduction of anxiety, sleepiness, slowed breathing, slurred speech, staggering gait , poor judgment, and slow, uncertain reflexes. Sedatives may be referred to as tranquilizers, depressants, anxiolytics, soporifics, sleeping pills, downers, or sedative-hypnotics. At high doses or when they are abused, many of these drugs can cause unconsciousness (see hypnotic) and death.

Examples of sedativesAntidepressants

mirtazapine (Remeron®) trazodone (Desyrel®)

Barbituratessecobarbital (Seconal®) pentobarbital (Nembutal ®) amobarbital (Amytal ®)

Benzodiazepines ("minor tranquilizers") alprazolam (Xanax®) diazepam (Valium®) lorazepam (Atavan ®)

Herbal sedativescatnipValerian (plant)MandrakeKava Kava

Uncategorized sedativeseszopiclone (Lunesta®) ramelteon (Rozerem®) methaqualone (Sopor®, Quaalude®) ethchlorvynol (Placidyl®) chloral hydrate (Noctec ®) meprobamate (Miltown ®) glutethimide ( Doriden ®) methyprylon (Noludar ®) gamma-hydroxybutyrate (GHB) ethyl alcohol (alcoholic beverage) diethyl ether (Ether) methyl trichloride (Chloroform) zopiclone (Imovane®, Zimovane ®) chloral hydrate (Noctec ®) zaleplon (Sonata®) zolpidem (Ambien®)

Hypnotic drugs are a class of drugs that induce sleep (which differentiates them from the sedative category), used in the treatment of severe insomniaand in surgical anesthesia. Often the treatment of insomnia will not begin with drugs at all, however, as many (not all) hypnotic drugs are habit forming. A physician will usually recommend alternative sleeping patterns and exercise before prescribing medication for sleep. These drugs include:BarbituratesBenzodiazepinesZolpidemZaleplonZopicloneEszopiclonechloral hydrateChlormethiazoleAntihistaminesDoxylaminePromethazinediphenhydramine.

Alcohol is often tried as a hypnotic drug but it is not particularly effective.

Anti-Convulsants1 Aldehydes2 Aromatic allylic alcohols3 Barbiturates4 Benzodiazepines5 Bromides6 Carbamates7 Carboxamides8 Fatty acids9 Fructose derivatives10 Gaba analogs11 Hydantoins12 Oxazolidinediones13 Propionates14 Pyrimidinediones15 Pyrrolidines16 Succinimides17 Sulfonamides18 Triazines19 Ureas20 Valproylamides (amide derivatives of valproate)

The anticonvulsants, sometimes also called antiepileptics, belong to a diverse group of pharmaceuticals used in prevention of the occurrence of epileptic seizures. The goal of an anticonvulsant is to suppress the rapid and excessive firing of neurons that start a seizure. Failing this, a good anticonvulsant would prevent the spread of the seizure within the brain and offer protection against possible excitotoxic effects that may result in brain damage. An excellent anticonvulsant would have few serious side effects. However, no such drug exists.

Many anticonvulsants block Sodium (Na+) channels , Calcium (Ca2+) channels, AMPA receptors or NMDA receptors . Some anticonvulsants inhibit the metabolism of GABA or increase its release.

Antipsychotics are drugs used to treat psychosis (e.g. schizophrenia, maniaand delusional disorder. Antipsychotics also have some effects as mood stabilizers , leading to their frequent use in treating mood disorder (particularly bipolar disorder) even when no signs of psychosis are present. Antipsychoticsare also referred to as neuroleptic drugs. The word neuroleptic is derievedfrom Greek. 'Neuro ' refers to the nerves and 'lept' means 'to take hold of'. Thus the word means 'taking hold of one's nerves' which implies their role in mood stabilization. There are currently two main types:1. Typical antipsychotics ("major tranquilizers")

fluphenazine (Prolixin®) haloperidol (Haldol®) thiothixene (Navane®) trifluoperazine (Stelazine®, Trifluoperaz®) loxapine succinate (Loxitane®) perphenazine (Etrafon®, Trilafon®) prochlorperazine (Compazine®)

2. Atypical antipsychoticsclozapine (Clozaril®) quetiapine (Seroquel®) risperidone (Risperdal®) ziprasidone (Geodon®) (some become tired, some get insomnia) olanzapine (Zyprexa®)

An antidepressant is a medication designed to treat or alleviate the symptoms of clinical depression. Some antidepressants, notably the tricyclics , are commonly used off-label in the treatment of neuropathic pain, whether or not the patient is depressed. Smaller doses are generally used for this purpose, and they often take effect more quickly. Many antidepressants also are used for the treatment of anxiety disorders , and tricyclicantidepressants are used in the treatment of chronic pain disorders such as chronic functional abdominal pain (CFAP), myofascial pain syndrome, and post-herpetic neuralgia.The main classes of antidepressants have similar efficacy, but the newer types are generally regarded to have a more benign side -effect profile and less risk of lethality if taken in overdose.Mechanism of action: The therapeutic effects of antidepressants are believed to be related to an effect on neurotransmitters , particularly by inhibiting the monoamine transporter proteins of serotonin and norepinephrine. SSRI’s specifically prevent the reuptake of serotonin (thereby increasing the level of serotonin in synapses of the brain), whereas earlier monoamine oxidase inhibitors (MAOIs) blocked the destruction of neurotransmitters by enzymes which normally break them down. Tricyclicantidepressants (TCAs) prevent the reuptake of various neurotransmitters , including serotonin, norepinephrine, and dopamine.

Anti-depressants

MirtazapineNoradrenergic and specific serotonergicantidepressant (NaSSA)

Maprotiline, Mianserin , Nefazodone, TrazodoneTetracyclic antidepressants

Amitriptyline, Amoxapine, Butriptyline, Clomipramine, Desipramine, Dibenzepin , Dothiepin , Doxepin , Imipramine, Iprindole, Lofepramine, Melitracen , Nortriptyline, Opipramol, Protriptyline, Trimipramine

Tricyclicantidepressants (TCA)

TianeptineSelective serotonin reuptake enhancer (SSRE)

Alaproclate , Etoperidone, Citalopram, Escitalopram, Fluoxetine, Fluvoxamine, Paroxetine, Sertraline, Zimelidine

Selective serotonin reuptake inhibitor(SSRI)

Duloxetine, Milnacipran , VenlafaxineSerotonin -norepinephrine reuptake inhibitor(SNRI)

Atomoxetine, Maprotiline, Reboxetine, ViloxazineNorepinephrine reuptake inhibitor(NRI) or (NARI)

BupropionNorepinephrine-dopamine reuptake inhibitors

Amineptine, Phenmetrazine, Vanoxerine, ModafinilDopamine reuptake inhibitor(DARI)

Brofaromine, MoclobemideReversibleinhibitor of monoamineoxidase A(RIMA)

Harmaline, Iproclozide, Iproniazid , Isocarboxazid , Nialamide, Phenelzine, Selegiline, Toloxatone, Tranylcypromine

Monoamine oxidase inhibitors (MAOI)

5

3.0. Autonomic [3 Qs]3.1. Adrenergics3.2. Cholinergics3.3. Blocking agents

(adrenergic, cholinergic, etc)

EphedrineMixed Action:

Amphetamine – TyramineIndirect Acting

Albuterol – Clonidine –Dobutamine –Dopamine - Epinepherine- Formoterol - Isoproterenol - Metaproterenol - Methoxamine -Norepinephrine - Phenylephrine - Piruterol - Salmeterol -Tamsulosine - Tamsulosine – Terbutaline

Direct Acting:

Adrenergic Agents bind with adrenergic receptors (or adrenoceptors), which are a class of G protein-coupled receptors that are targets of the catecholamines. Adrenergic receptors specifically bind their endogenousligands , the catecholamines adrenaline and noradrenaline (also called epinephrine and norepinephrine in the USA), and are activated by these. Many cells possess these receptors, and the binding of an agonist will generally cause the cell to respond in a fight-or-flight manner. For instance, the heart ratewill increase and the pupils will dilate, energy will be mobilized, and blood flow diverted from other organs to skeletal muscle.

A synapse is cholinergic if it uses acetylcholine as its neurotransmitter.Cholinergic means "related to the neurotransmitter acetylcholine". The parasympathetic nervous system is entirely cholinergic. A substance is cholinergic if it is capable of producing, altering, or releasing acetylcholine.A cholinergic, also known as a cholinergic agent or a parasympathomimetic , is any chemical which functions to enhance the effects mediated by acetylcholine in the central nervous system, the peripheral nervous system, or both. These include acetylcholine's precursorsand cofactors , acetylcholine receptor agonists (such as muscarine and nicotine), as well as cholinergic enzymes such as the anticholinesterases.-----------------------------An anticholinergic agent is a member of a class of pharmaceuticalcompounds which serve to reduce the effects mediated by acetylcholine in the central nervous system and peripheral nervous system.Anticholinergics are typically reversible competitive inhibitors of one of the two types of acetylcholine receptors , and are classified according to the receptors that are affected: antimuscarinic agents operate on the muscarinic acetylcholine receptors , and antinicotinic agents operate on the nicotinic acetylcholine receptors . The majority of anticholinergics are antimuscarinics .

Anticholinergic Drugs

Darifenacin (Enablex®)

Solifenacin (Vesicare®)

Tropicamide

Tolterodine (Detrusitol®)

Tiotropium

Pirenzepine

Oxybutynin

Ipratropium

Flavoxate

DicyclomineSynthetic and Semisynthetic

Atropine (D/L-Hyoscyamine)

Scopolamine (L-Hyoscine)Belladonna alkaloids

Muscarinic receptor antagonists

benztropine (Cogentin®)`Unclassified

Suxamethonium chlorideDepolarizing neuromuscular blocking agents

Vecuronium

Tubocurarine

Pancuronium

Mivacurium

Doxacurium

AtracuriumNondepolarizingneuromuscular blocking agents

TrimethaphanGanglionicblocking agents

Nicotinic receptor antagonists

Alpha blockers (also called alpha-adrenergic blocking agents) constitute a variety of drugs which block a1-adrenergic receptors in arteries and smooth muscles.

Indications: These drugs may be used to treat:•benign prostatic hyperplasia (BPH) •high blood pressure (hypertension). This is not typically the drug of choice unless the patient also has BPH. •symptoms of non inflammatory chronic pelvic pain syndrome, a type of prostatitis. As a side effect they may reduce blood pressure and result in lightheadedness.

Examples of alpha blockers: Alpha blockers include:•Doxazosin (Cardura) •Prazosin (Minipress ) •Phenoxybenzamine•Phentolamine (Rogitine) •Tamsulosin (Flomaxtra/Flomax) •Alfuzosin (Uroxatral) •Terazosin (Hytrin)

Beta blockers are a class of drugs used for various indications, but particularly for the management of cardiac arrhythmias and cardioprotectionafter myocardial infarction. Beta blockers block the action of endogenous catecholamines, epinephrine(adrenaline) and norepinephrine (noradrenaline) in particular, on ß-adrenergic receptors , part of the sympathetic nervous system which mediates the "fight or flight" response. There are three known types of beta receptor, designated ß1, ß2 and ß3. ß1-Adrenergic receptors are located mainly in the heart, kidney, and adipose tissue. ß2-Adrenergic receptors are located mainly in the heart, lung, GI tract, liver, pancreas, and skeletal muscle. The role and location of ß3-receptors is less well-defined.

Indications for beta blockers include:HypertensionAnginaCardiac arrhythmiaCongestive heart failureMyocardial infarctionGlaucomaMigraine prophylaxisSymptomatic control (tachycardia , tremor) in anxiety and hyperthyroidismEssential tremorPhaeochromocytoma, in conjunction with a-blocker

6

Non-selective agentsAlprenololCarteololLevobunololMepindololMetipranololNadololOxprenololPenbutololPindololPropranololSotalolTimolol

ß1-Selective agentsAcebutololAtenololBetaxololBisoprololEsmololMetoprololNebivololMixed a1/ß-adrenergic antagonistsCarvedilolCeliprololLabetalolß2-Selective agentsButoxamine (weak a-adrenergic agonist activity)

Beta-Blocking Drugs

4.0. Cardiovascular [4 Qs]4.1. Cardiac glycosides4.2. Antiarrhythmics4.3. Antihypertensives - diuretics4.4. Anti-anginal agents4.5. Anticoagulants, coagulants &

antihyperlipidemics

Cardiac glycosides are drugs used in the treatment of congestive heart failureand cardiac arrhythmia. These glycosides are found as secondary metabolitesin several plants, but also in some animals. Some of these compounds (ouabain and some frog poisons) are used in Africa as arrow-poisons for hunting. Cardiac glycosides work by inhibiting the Na+/K+ pump. They do this by stabilizing the E2-P transition state of the Na+/K+ pump. This inhibition increases the amount of Ca++ ions available for contraction of the heart muscle, improves cardiac output and reduces distention of the heart. T hey have an antiarrhythmic effect by prolonging the refractory period of the AV node (Atrioventricular node), reducing the number of impulses reaching the ventricles. Cardiac output is restored but atrial fibrillation or atrial flutter are not abolished. Examples of plants producing cardiac glycosides:- Strophanthus - ouabain g/k/e-strophanthin- Digitalis lanata and Digitalis purpurea - digoxin, digitoxin---------------------------------------------------------------- ----------------------------------------Digoxin is a cardiac glycoside extracted from the foxglove plant, digitalis. Its corresponding aglycone is digoxigenin. Digoxin is widely used in the treatment of various heart conditions, namely atrial fibrillation, atrial flutter and congestive heart failure that cannot be controlled by other medication. Digoxinpreparations are commonly marketed under the trade name Lanoxin.

Antiarrhythmic agents are used to suppress fast rhythms of the heart (cardiac arrhythmias), such as atrial fibrillation, atrial flutter, ventricular tachycardia, and ventricular fibrillation. Suppression is often done to relieve the symptoms that may be associated with the loss of the atrial component to ventricular filling (atrial kick ) that is due to atrial fibrillation or flutter. In individuals with ventricular arrhythmias, antiarrhythmic agents are often still in use to suppress arrhythmias. If these drugs fail it may lead to implantation of an implantable cardioverter-defibrillator (ICD). ---------------------------------------------------------------- --------------------------------------------5 main classes in the Vaughan Williams system of antiarrhythmic agents:Class I agents interfere with the sodium (Na+) channel. Class II agents are anti-sympathetic nervous system agents (all: beta blockers ). Class III agents affect potassium (K+) efflux. Class IV agents affect the AV node. Class V agents work by other or unknown mechanisms. ---------------------------------------------------------------- --------------------------------------------class Ia:Ajmaline , Disopyramide, Prajmaline, Procainamide, Quinidine, Sparteineclass Ib:Aprindine, Lidocaine , Mexiletine, Tocainideclass Ic:Encainide, Flecainide, Lorcainide, Moricizine, Propafenoneclass II: various Beta blockersclass III:Amiodarone, Bretylium tosilate, Bunaftine, Dofetilide, Ibutilideclass IV: various Calcium channel blockersclass V:Adenosine, Digoxin

Antihypertensives:1.1 Diuretics1.2 Anti-adrenergics1.3 Calcium channel blockers1.4 ACE inhibitors1.5 Angiotensin II receptor antagonists1.6 Aldosterone antagonists1.7 Vasodilators1.8 Centrally acting adrenergic drugs

1.8.1 Adrenergic neuron blockers1.9 Herbals provoking hypotension

1. Diuretics: help the kidneys eliminate excess salt and water from the body'stissues and blood. There are several types including:-Loop diuretics: (bumetanide, ethacrynic acid, furosemide, torsemide) -Thiazides: (chlortalidone, epitizide, hydrochlorothiazide & chlorothiazide) -Thiazide-like diuretics: (indapamide, metolazone)-Potassium-sparing diuretics : (amiloride; triamterene)

(NOTE: evidence suggest that by lowering blood pressure. Evidenc e suggests that reduction of the blood pressure by 5-6 mmHg can decrease the risk of stroke by 40%, of coronary heart disease by 15-20%, and reduces the likelihood of dementia, heart failure, and mortality from cardiovascular disease.)

Anti-anginal agents: for treatment of angina pectoris, a symptom of ischaemicheart disease. Drugs used are:1. nitrates such as nitroglycerin (glyceryl trinitrate) or pentaerythritol tetranitrateThese drugs cause vasodilation of the venous capacitance vessels by simulating the endothelium-derived relaxing factor (EDRF). Used to relieve both exertional and vasospastic angina by allowing venous pooling, reducing the pressure in theventricles and so reducing wall tension and oxygen requirements in the heart. Short-acting nitrates are used to abort angina attacks that have occurred, while longer-acting nitrates are used in the prophylactic management of the condition.---------------------2. beta blockers , either cardioselectives such as acebutolol or metoprolol , or non-cardioselectives such as oxprenolol or sotalolThese drugs are used in the prophylaxis of exertional angina by reducing the work the heart is allowed to perform below the level that would provo ke an angina attack. They cannot be used in vasospastic angina and can precipitate heart failure.----------------------3. calcium channel blockers , either Class I agents (e.g., verapamil), Class II agents (e.g., amlodipine, nifedipine), or the Class III agent diltiazem.These drugs are Calcium ion antagonists and are used for treatment of exertional & vasospastic angina. In vitro, they dilate coronary & peripheral arteries. T hey have negative inotropic & chronotropic effects, decreasing afterload, improving myocardial efficiency, reducing heart rate & improving coronary blood flow.

7

An anticoagulant is a substance that prevents coagulation; that is, it stops blood from clotting. Anticoagulants are given to people to stop thrombosis (blood clotting inappropriately in the blood vessels). This is useful in primary and secondary prevention of deep vein thrombosis , pulmonary embolism, myocardial infarctions and strokes in those who are predisposed.1. Vitamin K antagonists: Oral anticoagulants are a class of pharmaceuticalsthat act by antagonizing the effects of vitamin K. It is important to note that they take at least 48 to 72 hours for the anticoagulant effect to develop fully. In cases when an immediate effect is required, heparin must be given concomitantly. The most important oral anticoagulants are Warfarin (Coumadin). Heparin and derivative substances: Heparin is a biological substance, usually made from pig intestines. It works by activating antithrombin III, which blocks thrombin from clotting blood. 2. Direct thrombin inhibitors: Another type of anticoagulant is the direct thrombin inhibitors . Current members of this class include argatroban, lepirudin, and bivalirudin.

Citrate, EDTA, OxalateNon-medicinal:

Dabigatran, Defibrotide, Dermatan sulfate, Fondaparinux, Rivaroxaban

Other antithrombotics:

Argatroban, Bivalirudin, Dabigatran, Desirudin, Hirudin, Lepirudin, Melagatran, Ximelagatran

Direct thrombin inhibitors:

Alteplase, Ancrod, Anistreplase, Brinase, Drotrecoginalfa, Fibrinolysin, Protein C, Reteplase, Saruplase, Streptokinase, Tenecteplase, Urokinase

Enzymes:

Abciximab, Acetylsalicylic acid (Aspirin), Aloxiprin, Beraprost, Ditazole, Carbasalate calcium, Cloricromen, Clopidogrel, Dipyridamole, Epoprostenol , Eptifibatide, Indobufen, Iloprost, Picotamide, Prasugrel , Ticlopidine, Tirofiban, Treprostinil, Triflusal

Other plateletaggregationinhibitors:

Antithrombin III, Bemiparin , Dalteparin, Danaparoid, Enoxaparin, Heparin, Nadroparin, Parnaparin , Reviparin, Sulodexide, Tinzaparin

Heparin group(Platelet aggregationinhibitors):

Acenocoumarol, Clorindione, Dicumarol(Dicoumarol}, Diphenadione, Ethyl biscoumacetate, Phenprocoumon, Phenindione, Tioclomarol, Warfarin

Vitamin K antagonists:

The coagulation of blood is a complex process during which blood forms solid clots. It is an important part of hemostasis (the cessation of blood loss from a damaged vessel) whereby a damaged blood vessel wall is covered by a fibrinclot to stop hemorrhage and aid repair of the damaged vessel. Disorders in coagulation can lead to increased hemorrhage and/or thrombosis and embolism. In a normal individual, coagulation is initiated within 20 seconds after an injury occurs to the blood vessel damaging the endothelial cells. Plateletsimmediately form a haemostatic plug at the site of injury. This is called primary haemostasis . Secondary haemostasis then follows—plasma components called coagulation factors respond (in a complex cascade) to form fibrinstrands which strengthen the platelet plug. Contrary to popular belief, coagulation from a cut on the skin is not initiated by air or drying out, but by platelets adhering to and activated by collagen in the blood vessel endothelium. The activated platelets then release the contents of their granules, these contain a variety of substances that stimulate further platelet activation and enhance the haemostatic process.

Many different hemostatic agents!!!! (need table)

Not available in the United States at this time.Fibrin/tissue glue.Beriplast

Useful in short term (2-8 d) for preventing hemorrhage following dental extractions.

Tranexamic acid. Works as a competitive inhibitor of plasminogen activation. Used as a rinse.

Cyklokapron

One 5000 -unit vial dissolved in 5 mL of saline solution can clot equal amount of blood in less than 1 sec. For severe bleeding.

Topical thrombin. Directly converts fibrinogen to fibrin. Derived from bovine sources.

Thrombostat, Thrombinar , Thrombogen

Shaped according to intended use; Cote 3 /4 in × 1.5 in, Tape 1 in × 3 in, Plug 3/8 in × 3/4 in. All are superior hemostats for moderate-to-severe bleeding.

Absorbable dressings from bovine collagen. Can be sutured into place, used under stents, dentures, or alone. Fully resorbed in 10-14 days.

Colla-Cote,, Tape, Plug

Thrombin ineffective with these agents due to inactivation as a result of pH factors. Moderate-to-severe bleeding.

Microfibrillar collagen hemostat (MCH). Dry, sterile, fibrous, water insoluble, HCl acid salt purified bovine corium collagen. MCH attracts platelets and triggers aggregation in fibrous mass.

Avitene, Helistat

After 24-48 h, it becomes gelatinous. Can be left in place or removed. Useful to control bleeding when other agents ineffective.

Oxidized regenerated cellulose. Exerts physical effect rather than physiologic. Swells upon contact with blood, with resulting pressure adding to hemostasis. Thrombin ineffective with these agents because of inactivation as a result of pH factors.

Surgicel, Oxycel

Mild-to-moderate bleeding is usually controlled in 2 -5 min. More expensive than Gelfoam .

Absorbable collagen made from purified and lyophilized bovine dermal collagen. Can be cut or shaped. Adheres to bleeding surfaces when wet, but does not stick to instruments, gloves, or gauze sponges.

Instat

Useful for most patients taking an antithrombotic agent. Helpful to place topical Thrombin on Gelfoam . For extensive or invasive surgery, one should consider placing inside a splint.

Absorbable gelatin sponge made from purified gelatin solution. Absorbs in 3 -5 days.

Gelfoam

Indications and featuresDescriptionProduct

There are several classes of hypolipidemic drugs (a.k.a. anti-hyperlipidemics ). Some lower lower bad cholesterol (low density lipoproteins) and others may increase high density lipoprotein (HDL), "the good cholesterol". 1. statins are good at lowering LDL, which is strongly linked to cardiovascular diseases. The studies show they lower LDL-C by 18% to 55%, depending on the specific statin being used. Risk of severe muscle damage (myopathy & rhabdomyolysis) with statins. 2. fibrates are indicated for hypertriglyceridemia . Fibrates typically lower triglycerides by 20% to 50%. Level of the good cholesterol HDL i s also increased. Fibrates may decrease LDL, though generally less than statins. Risk of severe muscle damage (myopathy & rhabdomyolysis) with fibrates. 3. nicotinic acid, like fibrates , is also well-suited for lowering triglycerides by 20-50%. It may also lower LDL by 5-25% and increase HDL by 15-35%. Nicotinic acid may cause hyperglycemia, and may also cause liver damage. 4. bile acid sequestrants (resins) are particularly effective for lowering LDL -C by sequestering the cholesterol-containing bile acids released into the gut and preventing their reabsorption. This decreases LDL by 15-30% and raises HDL by 3-5%. It has little effect on triglycerides. Risk with resins is G.I. problems, and may also reduce the absorption of other drugs and vitamins from the gut. 5. ezetimibe (Zetia) is a selective inhibitor of dietary cholesterol absorption. 6. phytosterols may be found naturally in plants. Similar to ezetimibe, phytosterols reduce the absorption of cholesterol in the gut. Hence, they are most effective when consumed with meals.

5.0. Local anesthetics [4 Qs]5.1. Basic pharmacology5.2. Vasoconstrictors

8

A local anesthetic is a drug that reversibly inhibits the propagation of signals along nerves. When it is used on specific nerve pathways, effects such as analgesia (loss of pain sensation) and paralysis (loss of musclepower) can be achieved. Clinical local anesthetics belong to one of two classes: aminoamide and aminoester local anesthetics. These so-called synthetic local anesthetics are structurally related to cocaine . Local anesthetic drugs act mainly by inhibiting sodium influx through sodium-specific ion channels in the neuronal cell membrane, in particular the voltage-gated sodium channels. When the influx of sodium is interrupted, an action potential cannot arise and signal conduction is inhibited. Local anesthetics are weak bases and are usually formulated as the hydrochloride salt to render them water-soluble. Acidosis such as caused by wound infection partly reduces the action of local anesthetics because of reduced ability to cross the cell membrane.

Amino esters BenzocaineChloroprocaineCocaineProcaine

Amino amides BupivacaineLevobupivacaineLidocaineMepivacainePrilocaineRopivacaineSeptocaine

Combinations Lidocaine/prilocaine (EMLA)

Adverse reactions to local anesthetics are not infrequent, but true allergyis very rare. Non-allergic reactions may resemble allergy in their manifestations. In some cases, skin tests and provocative challenge may be necessary to establish a diagnosis of allergy. There are also cases of allergy to paraben derivatives, which are often added as preservatives to local anesthetic solutions.---------------------------Methemoglobinemia: The systemic toxicity of prilocaine is comparatively low, however its metabolite, o-toluidine, is known to cause methemoglobinemia. As methemoglobinemiareduces the amount of hemoglobin that is available for oxygen transport, this side effect is potentially life-threatening. Therefore dose limits for prilocaineshould be strictly observed. Prilocaine is not recommended for use in infants.

A vasoconstrictor , also vasopressorand simply pressor , is any substance or that acts to cause vasoconstriction (narrowing of the lumena of blood vessels) and usually results in an increase of the blood pressure. The opposite process, vasodilation, is the opening of blood vessels. Many vasoconstrictors act on specific receptors, such as vasopressinreceptors or adrenoreceptors . Vasoconstrictors are also used clinically to increase blood pressure or to reduce local blood flow. Exposure to moderately high levels of stress also induces vasoconstriction. Vasoconstriction also occurs in superficial blood vessels of warm-blooded animals when their ambient environment is cold; this process diverts the flow of heated blood to the center of the animal, preventing the loss of heat.

VasoconstrictorsAntihistaminesAdrenalineAsymmetric dimethylarginineATPCannabisCatecholaminesCocaineDecongestantsEndothelinPhenylephrinePseudoephedrineNeuropeptideYNorepinephrineTetrahydrozoline hydrochlorideThromboxane

6.0. Chemotherapy [5 Qs]6.1. Antibacterials6.2. Antifungals6.3. Antivirals6.4. Antineoplastics

An antibiotic is a drug that kills or slows the growth of bacteria . They have no effect against viruses, fungi, or parasites. Antibiotics are generally small molecules with a molecular weight less than 2000 kd. They are not enzymes. Some antibiotics have been derived from mold, for example the penicillin class. Antibiotics can be categorized based on their target specificity: 'narrow-spectrum' antibiotics target particular types of bacteria, such as Gram-negative or Gram-positive bacteria, while 'wide -spectrum' antibiotics affect a larger range of bacteria. The effectiveness of individual antibiotics varies with the location of the infection, the ability of the antibiotic to reach the site of infection, and the ability of the bacteria to resist or inactiva te the antibiotic. Some antibiotics actually kill the bacteria (bactericidal), whereas others merely prevent the bacteria from multiplying (bacteriostatic ). Antibiotics can also be classified by the organisms against which they are effec tive, and by the type of infection in which they are useful, which depends on the sensitivities of the organisms that most commonly cause the infection and the concentration of antibiotic obtainable in the affected tissue.

Meropenem

PrimaxinImipenem/ Cilastatin

ErtapenemCarbapenems

LorabidLoracarbefCarbacephem

NebcinTobramycin

Streptomycin

Netilmicin

Neomycin

Kanamycin

GaramycinGentamicin

Hearing lossVertigoKidney damage

Infections caused by Gram-negative bacteria, such as Escherichia coliand Klebsiella

AmikinAmikacinAminoglycosides

Side EffectsCommon UsesBrand Names

Generic NameClass

Antibiotics Antibiotics Antibiotics Antibiotics Antibiotics

9

Gastrointestinal upset and diarrheaNausea (if alcohol taken concurrently)Allergic reactions

MaxipimeCefepimeCephalosporins(Fourth generation)

RocephinCeftriaxone

Ceftizoxime

Ceftibuten

FortumCeftazidime

Cefpodoxime

ClaforanCefotaxime

CefobidCefoperazone

Cefditoren

OmnicefCefdinir

Gastrointestinal upset and diarrheaNausea (if alcohol taken concurrently)Allergic reactions

CefiximeCephalosporins(Third generation)

CeftinCefuroxime

CefzilCefprozil

Cefoxitin

MandoleCefamandole Gastrointestinal upset and diarrheaNausea (if alcohol taken concurrently)Allergic reactions

CeclorCefaclorCephalosporins(Second generation )

KeflexCephalexin

AncefCefazolinGastrointestinal upset and diarrheaNausea (if alcohol taken concurrently)Allergic reactions

DuricefCefadroxilCephalosporins(First generation)

Side EffectsCommon UsesBrand NamesGeneric NameClass


AztreonamMonobactam

Troleandomycin

Roxithromycin

Erythromycin

Dirithromycin

BiaxinClarithromycin

Nausea, vomiting, and diarrhea (especially at higher doses)Jaundice

Streptococcal infections, syphilis, respiratory infections , mycoplasmalinfections , Lyme disease

Zithromax , SumamedAzithromycinMacrolides

VancocinVancomycin

TeicoplaninGlycopeptides



Ticarcillin

Piperacillin

Penicillin

Nafcillin

Mezlocillin

Flucloxacillin

Dicloxacillin

Cloxacillin

Carbenicillin

Azlocillin

Ampicillin

Gastrointestinal upset and diarrheaAllergy with serious anaphylactic reactionsBrain and kidney damage (rare)

Wide range of infections; penicillin used for streptococcal infections, syphilis, and Lyme disease

NovamoxAmoxicillin

Penicillins


Generic NameClass


TrovanTrovafloxacin

OcufloxOfloxacin

Norfloxacin

AveloxMoxifloxacin

Lomefloxacin

LevaquinLevofloxacin

TequinGatifloxacin

Enoxacin

Nausea (rare)Urinary tract infections, bacterial prostatitis, bacterial diarrhea, gonorrhea

Ciproxin, Ciplox

CiprofloxacinQuinolones

Polymyxin B

ColistinKidney and nerve damage (when given by injection)

Eye, ear or bladder infections; usually applied directly to the eye or inhaled into the lungs; rarely given by injection

MupirocinBacitracin

Polypeptides


Generic NameClass


SumycinTetracycline

Oxytetracycline

Minocycline

VibramycinDoxycyclineGastrointestinal upsetSensitivity to sunlightStaining of teethPotential toxicity to mother and fetus during pregnancy

Syphilis, chlamydialinfections, Lyme disease, mycoplasmalinfections, acne rickettsial infections

DemeclocyclineTetracyclines

BactrimTrimethoprim-Sulfamethoxazole(Co-trimoxazole )

Trimethoprim

Sulfisoxazole

Sulfasalazine

Sulfanilimide (archaic)

Sulfamethizole

Sulfacetamide

Prontosil (archaic)

Nausea, vomiting, and diarrheaAllergy (including skin rashes)Crystals in urineKidney failureDecrease in white blood cell countSensitivity to sunlight

Urinary tract infections(except sulfacetamideand mafenide); mafenide is used topically for burns

MafenideSulfonamides


Generic NameClass


Spectinomycin

Rifampin

SyncercideQuinupristin/ Dalfopristin

Pyrazinamide

Platensimycin

MacrodantinNitrofurantoin

FlagylMetronidazole

ZyvoxLinezolid

Isoniazid

Furazolidone

Fosfomycin

Ethambutol

CleocinClindamycin

ChloromycetinChloramphenicolOthers



10

Use or misuse of antibiotics may result in the development of antibiotic resistance by the infecting organisms, similar to the development of pesticide resistance in insects. Evolutionary theory of genetic selection requires that as close as possible to 100% of the infecting organisms be killed off to avoid selection of resistance; if a small subset of the population survives the treatment and is allowed to multiply, the average susceptibility of this new population to the compound will be much less than that of the original population, since they have descended from those few organisms which survived the original treatment. This survival often results from an inheritable resistance to the compound which was infrequent in the original population but is now much more frequent in the descendants thus selected entirely from those originally infrequent resistant organisms.An abscess caused by methicillin-resistant Staphylococcus aureus bacteria (MRSA). By 1984 half of the people with active tuberculosis in the United States had a strain that resisted at least one antibiotic. In certain settings, such as hospitals and some child-care locations, the rate of antibiotic resistance is so high that the normal, low cost antibiotics are virtually useless for treatment of frequently seen infections. The situation is worsened by the fact that genes coding for antibiotic resistance can be transferred between bacteria, making it possible for bacteria never exposed to an an tibiotic to acquire resistance from those which have.

Antifungals work by exploiting differences between mammalian and fungal cel ls to kill off the fungal organism without significantly harming the host. Unlike bacteria, both fungi and humans are eukaryotes. The basic structure of fungal cells and human cells is nearly identical. This means it is more difficult to find a target for an antifungal medication to attack that does not also exist in the infected organism. Consequently, some of the side-effects of systemic anti -fungals can be life -threatening. Classes include:1. Polyene antibiotics: bind with sterols in the fungal cell wall, principally ergosterol and this causes the cell's contents to leak out and the cell di es. Animal cells have cholesterol instead of ergosterol and are less susceptible: Nystatin ; Amphotericin B; Natamycin ; Rimocidin; Filipin; Pimaricin. 2. Imidazoles and triazoles: inhibit the enzyme cytochrome P450 14a-demethylase. This enzyme converts lanosterol to ergosterol, and is required in fungal cell wall synthesis and block steroid synthesis in humans. Imidazoles:Miconazole; Ketoconazole; Clotrimazole ; Econazole; Mebendazole; Bifonazole ; Butoconazole ; Fenticonazole; Isoconazole; Oxiconazole ; Sertaconazole; Sulconazole; Thiabendazole; Tiaconazole. Triazoles: Fluconazole; Itraconazole; Ravuconazole; Posaconazole; Voriconazole. 3. Allylamines: inhibit enzyme squalene epoxidase, an enzyme required for ergosterol synthesis: Terbinafine (Lamisil ); Amorolfine; Naftifine ; Butenafine. 4. Echinocandin: inhibit the synthesis of glucan in the cell wall, probably via the enzyme 1,3-ß glucan synthase: Anidulafungin; Caspofungin ; Micafungin5. Others: Flucytosine is an antimetabolite; Griseofulvin binds to polymerizedmicrotubules and inhibits fungal mitosis; Fluocinonide; Gentian Violet

Antiviral drugsare a class of medication used specifically for treating viral infections. Most of the antivirals now available are designed to help deal with HIV, herpesvirus, which is best known for causing cold sores but actually covers a wide range of diseases, and the hepatitis B and C viruses, which can cause liver cancer. Researchers are now working to extend the range of antivirals to other families of pathogens.The emergence of antivirals is the product of a greatly expanded knowledge of the genetic and molecular function of organisms, al lowing biomedical researchers to understand the structure and function of viruses, major advances in the techniques for finding new drugs, and the intense pressure placed on the medical profession to deal with the human immunodeficiency virus (HIV), the cause of the deadly acquired immunodeficiency syndrome (AIDS) epidemic. Though no one could sensibly claim that AIDS has been a benefit to humankind, it has certainly done much to advance the state of antiviral technology.

Adefovir, Fomivirsen, Imiquimod, Inosine,Interferon, Podophyllotoxin, Ribavirin, Viramidine

Other antiviral agents

EnfuvirtideFusion inhibitors

Amprenavir, Atazanavir, Darunavir, Fosamprenavir, Indinavir, Lopinavir, Nelfinavir, Ritonavir, Saquinavir, TipranavirPIs

Efavirenz, Delavirdine, NevirapineNNRTIs

TenofovirNtRTIs

Abacavir, Didanosine, Emtricitabine , Lamivudine, Stavudine, Zalcitabine, ZidovudineNRTIs

Anti-retroviraldrugs

Amantadine, Oseltamivir, Peramivir, Rimantadine, ZanamivirAnti-influenza agents

Aciclovir, Cidofovir, Docosanol, Famciclovir, Fomivirsen, Foscarnet, Ganciclovir, Idoxuridine, Penciclovir, Trifluridine, Tromantadine, Valaciclovir, Valganciclovir, Vidarabine

Anti-herpesvirusagents

Antineoplastics (or "antitumor antibiotics", or "noncovalent DNA-binding drugs", or "cytotoxic antibiotics", see also neoplastics) are drugs that inhibit and combat the development of tumors.Modes of action: antineoplastics work by inhibiting topoisomerase IIwhich stops DNA being unwound, which is required for both DNA replication and RNA/protein synthesis. Examplesactinomycin. dactinomycinanthracyclines

doxorubicindaunorubicinepirubicinwhich also inhibit topoisomerase II)

other cytotoxic antibiotics Bleomycin. This agent forms free radicals, which induce damage and chromosomal aberrations. plicamycinmitomycin

Chemotherapeutic agents/Antineoplastic agents

Alitretinoin, Altretamine, Amsacrine, Anagrelide, Arsenic trioxide, Asparaginase , Bexarotene, Bortezomib, Celecoxib, Dasatinib, Denileukindiftitox, Erlotinib, Estramustine , Gefitinib, Hydroxycarbamide, Imatinib, Pentostatin, Masoprocol, Mitotane, Pegaspargase , Tretinoin

Other:

Aminolevulinic acid, Methyl aminolevulinate, Porfimer sodium, VerteporfinPhotosensitizers:

Alemtuzumab, Bevacizumab, Cetuximab, Gemtuzumab, Panitumumab, Rituximab, Trastuzumab

Monoclonal antibodies:

Topotecan, Irinotecan, Podophyllum: ( Etoposide, Teniposide).Topoisomeraseinhibitors:

Anthracycline family: (Daunorubicin, Doxorubicin, Epirubicin, Idarubicin, Mitoxantrone, Valrubicin). Bleomycin, Hydroxyurea, Mitomycin

Cytotoxic/antitumor antibiotics:

Taxane: ( Docetaxel, Paclitaxel). Vinca: ( Vinblastine , Vincristine, Vindesine, Vinorelbine).

Plant alkaloids:

Folic acid: ( Methotrexate, Pemetrexed, Raltitrexed). Purine: ( Cladribine, Clofarabine, Fludarabine, Mercaptopurine, Tioguanine). Pyrimidine: ( Capecitabine). Cytarabine, Fluorouracil, Gemcitabine

Antimetabolites:

Nitrogen mustards: ( Chlorambucil, Chlormethine, Cyclophosphamide, Ifosfamide, Melphalan). Nitrosoureas: ( Carmustine, Fotemustine, Lomustine, Streptozocin). Platinum: ( Carboplatin, Cisplatin, Oxaliplatin, BBR3464). Busulfan, Dacarbazine, Mechlorethamine, Procarbazine, Temozolomide, ThioTEPA, Uramustine

Alkylatingagents:

11

7.0. Endocrines and Immunosuppressants [2 Qs]

The endocrine system consists of several glands, that secrete hormones directly into the blood rather than into a duct system. To be classified as a hormone, a chemical must be produced by an organ, be released (in small amo unts) into the blood, and be transported by the blood to a distant organ to exe rt its specific function. This definition holds for most ‘classical ’ hormones, but there are also paracrine mechanisms (chemical communication between cells within a tissue or organ), autocrine signals (a chemical that acts on the same cell), and intracrinesignals (a chemical that acts within the same cell). Three class es of hormone: 1. Amines: such as norepinephrine, epinephrine, and dopamine, are derived from single amino acids, in this case tyrosine. Thyroid hormones such as 3,5,3’-triiodothyronine (T3) and 3,5,3’,5’-tetraiodothyronine (thyroxine, T4) make up a subset of this class because they derive from the combination of two iodinated tyrosine amino acid residues.2. Peptides and Proteins: consist of three (in the case of thyrotropin-releasing hormone) to more than 200 (in the case of follicle-stimulating hormone) amino acid residues and can have molecular weights as large as 30,000. All hormones secreted by the pituitary gland are peptide hormones, as are leptin from adipocytes , ghrelin from the stomach, and insulin from the pancreas.3. Steroids: are derivatived from cholesterol and are subdivided into those with an intact steroid nucleus (gonadal and adrenal steroids) and those with a broken steroid nucleus (vitamin D). Steroid horomones include estrogen and progesterone from the ovary, testosterone from the testes, and cortisol and aldosterone from the adrenal gland.

Immunosuppressive drugs or immunosuppressants are drugs that are used in immunosuppressive therapy to inhibit or prevent activity of the immune system. Clinically they are used to:prevent the rejection of transplanted organs and tissues (e.g. bone marrow, heart, kidney, liver) treatment of autoimmune diseases or diseases that are most likely of autoimmune origin (e.g. rheumatoid arthritis , myasthenia gravis, systemic lupus erythematosus, Crohn's disease, and ulcerative colitis). These drugs are not without side effects and risks. Because the majority of them act non-selectively, the immune system loses its ability to successfully resist infections and spreading of malignant cells. There are also other side effects, like hypertension, dyslipidemia, hyperglycemia, peptic ulcers , liver and kidney injury. The immunosuppressive drugs also interact with other medicines and affect their metabolism and action.

Immunosuppressive drugs can be classified into four groups and others:glucocorticoidscytostaticsantibodiesdrugs acting on immunophilinsother drugs

Glucocorticoids: glucocorticoids are used to suppress various allergic, inflammatory, and autoimmune disorders. They are also administered as posttransplantory immunosuppressants to prevent the acute transplant rejectionand graft-versus-host disease. Nevertheless, they do not prevent an infection and also inhibit later reparative processes. These drugs suppress the cell-mediated immunity. They act by inhibiting genes that code for the cytokines IL-1, IL-2, IL-3, IL-4, IL-5, IL-6, IL-8 and TNF-?, the most important of which is the IL-2. Smaller cytokine production reduces the T cell proliferation. Glucocorticoids also suppress the humoral immunity, causing B cells to express smaller amounts of IL-2 and of IL-2 receptors . This diminishes both B cell clone expansion and antibody synthesis.AntiinflammatoryeffectsGlucocorticoids influence all types of inflammatory events, no matter what thei r cause. They induce the lipocortin-1 (annexin-1) synthesis, which then binds to cell membranes preventing the phospholipase A2 from coming into contact with its substrate arachidonic acid. This leads to diminished eicosanoid production. The cyclooxygenase (both COX-1 and COX-2) expression is also suppressed, potentiating the effect.Glucocorticoids also stimulate the lipocortin-1 escaping to the extracellular space, where it binds to the leukocyte membrane receptors and inhibits various inflammatory events: epithelial adhesion, emigration, chemotaxis , phagocytosis , respiratory burst and the release of various inflammatory mediators (lysosomalenzymes, cytokines, tissue plasminogen activator, chemokines etc.) from neutrophils , macrophages and mastocytes .

Cytostatics: inhibit cell division. And include the alkylating agents and antimetabolites. In immunotherapy, they are used in smaller doses than in the treatment of malignant diseases. They affect the proliferation of both T cells and B cells. 1. Alkylating agents: are used in immunotherapy are nitrogen mustards(cyclophosphamide), nitrosoureas, platinum compounds and others. Cyclophosphamide is probably the most potent immunosuppressive compound. In small doses, it is very efficient in the therapy of systemic lupus erythematosus, autoimmune hemolytic anemias, Wegener's granulomatosis and other immune diseases. High doses cause pancytopenia and hemorrhagic cystitis.2. Antimetabolites: interfere with the synthesis of nucleic acids. These include:folic acid analogues, such as methotrexate; purine analogues such as azathioprine and mercaptopurine; pyrimidine analogues and protein synthesis inhibitors. (1) Methotrexate: is a folic acid analogue. It binds dihydrofolate reductase and prevents synthesis of tetrahydrofolate. It is used in the treatment of autoimmune diseases (for exampl e rheumatoid arthritis) and in transplantations.(2) Azathioprine and Mercaptopurine: are is extensively used to control transplant rejection reactions. It is nonenzymatically cleaved to mercaptopurine, that acts as a purine analogue and an inhibitor of DNA synthesis. Mercaptopurine itself can also be administered directly.By preventing the clonal expansion of lymphocytes in the induction phase of the immune response, it affects both the cell and the humoral immunity.(3) Cytotoxic antibioticsAmong these, dactinomycin is the most important. It is used in kidney transplantations. Other cytotoxic antibiotics are anthracyclines, mitomycin C, bleomycin, mitramycin.

Antibodies: are used as a quick and potent immunosuppression method to prevent the acute rejection reaction.1. Polyclonal antibodies: Heterologous polyclonal antibodies are obtained from the serum of animals (e.g. rabbit , horse) and injected with the patient's thymocytes or lymphocytes. The antilymphocyte (ALG) and antithymocyte antigens (ATG) are being used. They are part of the steroid-resistant acute rejection reaction and grave aplastic anemia treatment. However, they are primarily added to other immunosuppressives to diminish their dosage and toxicity. They also allow transition to cyclosporine therapy. These agents inhibit T lymphocytes and cause their lysis, which is both complement mediated cytolysis and cell-mediated opsonization followed by removal of reticuloendothelial cells from the circulation in the spleen and liver]]. In this way, polyclonal antibodies inhibit cell-mediated immune reactions, including graft rejection, delayed hypersensitivity (i.e. tuberculin skin reaction), and the graft-versus-host disease (GVHD), but influence thymus-dependent antibody production. Because of a high immunogenicity of polyclonal antibodies, almost all patients have an acute reaction to the treatment. It is characterized by fever, rigor episodes and even anaphylaxis. Later during the treatment, some patients develop serum sickness or immune complex glomerulonephritis. Serum sickness arises 7-14 days after the therapy has begun. The patient suffers from fever, joint pain and erythema that can be soothed with the use of steroids and analgesics. Urticaria (hives) can also be present. It is possible to diminish their toxicity by using highly purified serum fractions and intravenous administration in the combination with other immunosuppressants, for example calcineurin inhibitors, cytostaticsand cortisteroids. The most frequent combination is to simultaneously use antibodies and cyclosporine. Patients gradually develop a strong immune response to these drugs, reducing or eliminating their effectiveness.2. Monoclonal antibodies: are directed towards exactly defined antigens. Therefore, they cause fewer side effects. Especially significant are the IL-2 receptor (CD25) and CD3 directed antibodies. They are used to prevent the rejection of transplant ed organs, but also to track changes in the lymphocyte subpopulations. It is reasonable to expect similar new drugs in the future.

12

3. T-cell receptor directed antibodiesOKT3 (R) is presently the only approved anti-CD3 antibody. It is a mouse anti-CD3 monoclonal antibody of the IgG2a type that prevents T-cell activation and proliferation by binding the T-cell receptor complex present on all differentiated T cells. As such, it is one of the most potent immunosuppressive substances and is clinically used to control the steroid and/or polyclonal antibodies resistant acute rejection episodes. For acting more specifically than polyclonal antibodies, it is also used preventively in transplantations. Presently, the OKT3's action mechanism is not yet sufficiently understood. It is known that the molecule binds TCR/CD3, the T-cell receptor complex. During the first few administrations, this binding non-specifically activates T cells, leading to a serious syndrome 30 to 60 minutes later. It is characterized by fever, myalgia, headache and artralgia. In some cases, it progresses to a life-threatening reaction of the cardiovascular system and the central nervous system needing a lengthy therapy. Past this period, CD3 (R) blocks the TCR - antigen binding and causes conformation change or the removal of the entire TCR3/CD3 from the T-cell surface. This lowers the number of T cells, perhaps by sensitising them for the uptake by the reticular epithelial cells. The cross-binding of CD3 molecules also activates an intracellular signal, causing the T cells' anergy or apoptosis, unless they receive another signal through a costimulatory molecule. CD3 antibodies also shift the balance from Th1 to Th2 cells.IL-2 receptor directed antibodies: is an important immune system regulator necessary for the clone expansion and survival of activated lymphocytes T. Its eff ects are mediated by the trimercell surface receptor IL-2a, consisting of the a, ß and ? chains. The IL-2a (CD25, T-cell activation antigen, TAC) is expressed only by the already activated T lymphocytes. Therefore, it is of special significance to the selective immunosuppressive treatment and the research has been focused on the development of effective and safe anti-IL-2 antibodies. By the use of the recombinant gene technology, the mouse anti-Tac antibodies have been modified leading to the presentation of two himeric mouse/human anti-Tac antibodies in the year 1998: basiliximab (Simulect (R)) and daclizumab (Zenapax (R)). These drugs act by binding the IL-2a receptor's a chain, preventing the IL-2 induced clonal expansion of activated lymphocytes and shortening their survival. They are used in the profilaxis of the acute organ rejection after the bilateral kidney transplantation,

Drugs acting on immunophilinsCyclosporin: Together with tacrolimus, cyclosporin is a calcineurin inhibitor. It has been in use since 1983 and is one of the most widely used immunosuppressive drugs. It is a fungal peptide, composed of 11 amino acids. Cyclosporin is thought to bind to the cytosolic protein cyclophilin (an immunophilin) of immunocompetent lymphocytes, especially T-lymphocytes. This complex of ciclosporin and cyclophilin inhibits calcineurin, which under normal circumstances induces the transcription of interleukin-2. The drug also inhibits lymphokine production and interleukin release, leading to a reduced function of effector T-cells.Cyclosporin is used in the treatment of acute rejection reactions, but has been increasingly substituted with newer immunosuppressants, as it is nephrotoxic.Tacrolimus (Prograf(TM): is a bacterial product (Streptomyces tsukubaensis). It is a macrolidelactone and acts by inhibiting calcineurin. The drug is used particularly in the liver and kidney transplantations, although in some clinics it is used in heart, lung and heart/lung transplants. It binds to an immunophilin, followed by the binding of the complex to calcineurin and the inhibition of its phosphatase activity. In this way, it prevents the passage of G0 into G1 phase. Tacrolimus is more potent than cyclosporin and has less pronounced side effects.Sirolimus (Rapamune(Tm), Rapamicin): Sirolimus is a macrolide lactone, produced by the actinomycetes Streptomyces hygroscopicus. It is used to prevent rejection reactions. Although it is a structural analogue of tacrolimus, it acts somewhat differently and has different side effects. Contrary to cyclosporine and tacrolimus that affect the first phase of the T lymphocyte activation, sirolimusaffects the second one, namely the signal transduction and their clonal proliferation. It binds to the same receptor (immunophilin) as tacrolimus, however the produced complex does not inhibit calcineurin, but another protein. Therefore, sirolimus acts synergistically with cyclosporine and, in combination with other immunosuppressants, has few side effects. Indirectly it inhibits several T lympohocyte kinases and phosphatases, preventing the transmission of signal into their activity and the transition of the cell cycle from G1 to S phase. Similarly, it prevents the B cell differentiation to the plasma cells, which lowers the quantity of IgM, IgG and IgA antibodies produced. It acts immunoregulatory.

Other drugsInterferons: IFN-ß suppresses the production of Th1 cytokines and the activation of monocytes. It is used to slow down the progression of multiple sclerosis. IFN-? is able to trigger lymphocytic apoptosis.Opioids: Prolonged use of opioids may cause immunosuppression by inhibiting the migration of leukocytes.TNF binding proteins: A TNF-a (tumor necrosis factor alpha) binding protein is a monoclonal antibody or a circulating receptor such as infliximab (Remicade®), etanercept (Enbrel ®), or adalimumab (Humira®) that binds to TNF- a and prevent it from inducing the synthesis of IL- 1 and IL- 6 and the adhesion of lymphocyte activating molecules. They are used in the treatment of rheumatoid arthritis, ankylosing spondylitis, Crohn's disease and psoriasis.TNF or the effects of TNF are also suppressed by various natural compounds, including curcumin (an ingredient in turmeric) and catechins (in green tea).These drugs may raise the risk of contracting tuberculosis or inducing a latent infection to become active. Infliximab and adalimumab have label warnings stating that patients should be evaluated for latent TB infection and treatment should be initiated prior to starting therapy with them.Mycophenolate: Mycophenolic acid acts as a non-competitive, selective and reversible inhibitor of inosine monophosphate dehydrogenase (IMPDH), which is a key enzyme in the de novo guanosine nucleotide synthesis. In contrast to other human cell types, ly mphocytes B and T are very dependent on this process.[edit] Small biological agentsFTY720 is a new synthetic immunosuppressant, currently in phase 3 of clinical trials. It increases the expression or changes the function of certain adhesion molecules ( a4/ß7 integrin) in lymphocytes, so they accumulate in the lymphatic tissue (lymphatic nodes) and their number in the circulation is diminished. In this respect, it dif fers from all other known immunosuppressants.

8.0. Analgesics [5 Qs]8.1. Opioids8.2. Non-opioids, NSAIDs

Morphine is an extremely powerful opiate analgesic drug and is the principal active agent in opium. Like other opioids, e.g. heroin, morphine acts directly on the central nervous system(CNS) to relieve pain. Side effects include impairment of mental performance, euphoria, drowsiness, lethargy, and blurred vision. It also decreases hunger, inhibits the cough reflex, and produces constipation. Morphine is highly addictive when compared to other substances, and tolerance and physical and psychological dependence develop quickly. Morphine is an opioid receptoragonist – its main effect is binding to and activating the µ-opioid receptors in the central nervous system. Activation of these receptors is associated with analgesia, sedation, euphoria, physical dependence and respiratory depression. Morphine is also a ?-opioid receptor agonist, with this action associated with spinal analgesia and miosis. The effects of morphine can be countered with naloxone or naltrexone.Morphine is primarily metabolized into morphine-3-glucuronide and morphine-6-glucuronide. High doses of morphine may be fatal due to respiratory depression.

Non-steroidal anti-inflammatory drugs

NimesulideSulphonanilides

Celecoxib , Etoricoxib , Parecoxib, Rofecoxib, ValdecoxibCoxibs

Meloxicam, PiroxicamOxicams

PhenylbutazonePyrazolidinederivatives

Mefenamic acidN-Arylanthranilicacids (fenamicacids)

Carprofen , Flurbiprofen , Ibuprofen , Ketoprofen , Ketorolac, Loxoprofen , Naproxen , Tiaprofenic acid,

2-Arylpropionic acids (profens)

Diclofenac, Indometacin, SulindacArylalkanoic acids

13

Ziconotide, TetrahydrocannabinolOthers:

Paracetamol (acetaminophen), PhenacetinAnilides:

Aminophenazone, Metamizole, PhenazonePyrazolones:

Aspirin (Acetylsalicylic Acid), Diflunisal, Ethenzamide

Salicylic acidand derivatives:

Buprenorphine, Butorphanol , Codeine, Dextropropoxyphene, Dihydrocodeine, Fentanyl , Diamorphine (Heroin), Hydrocodone, Hydromorphone, Ketobemidone, Morphine, Nalbuphine, Oxycodone, Oxymorphone, Pentazocine, Pethidine (Meperidine), Tramadol

Opioids :

Analgesics

9.0. Antihistamines and Autocoids [2 Qs]

Autocoids and AntihistaminesAutocoid agonists or antagonists include:

-H1 and H2 receptor antagonists -Eicosanoids (prostaglandins)-Thromboxanes-Leukotensin-Serotonin agonists-Angiotensin inhibitors-Cytokinins-Histamine

NOTE: Histamine is released during allergic reactions, immune reactions, or after admin. of certain drugs and amount released determines effects.

Pharmacologic effects: H1-agonists produce vasodilation, increased capillary permeability, bronchoconstriction, pain or itching. H2-agonist effect includes increased gastric acid secretion.

Adverse effects includes: Anaphylaxis – serious and sometimes fatal, difficulty breathing, convulsions, lapses into unconsciousness, vasodilation and increased capillary permeability, if high levels of histamine released, this will decrease BP severely causing shock and CV collapse.

Uses include: diagnosis of achlorhydria and pheochromocytoma. Drug of choice to counteract histamine rxn is epinephrine.

Antihistamines (H1 receptor antagonists): Widely used for hay fever, mild allergic reactions and additive with other CNS depressantsFour common: Dipheniramine (Benedryl ); Chlorphenhydramine (ClorTrimeton); Promethazine (Phenegan); Loratidine (Claritin)Pharmacologic effects: H1 blocking effects include: Capillary permeability is blocked producing reduced edema; Blocks dilation of vascular smooth muscle; Blocks some bronchoconstriction; Suppresses the itching and painOther effects: CNS depression (Sominex, Nytol); Anticholinergic ; Antiemetic(Dramamine, Bonine); Adverse reactions: Undesirable CNS depression. Sedative effect cancelled out when combined with decongestant (adrenergic agonist). CNS stimul ation can occur in a few cases. More common in children, elderly with larger doses. Newer nonsedating H1 blockers (Clariton) produce less sedation. XerostomiaToxicity: More common due to easy accessibility in OTC preparationsDeath can result.Uses: Control seasonal hay fever; Relieve itching, edema and erythemaSome topical anesthetic effect; To prevent and treat motion sicknessPreop sedation and antiemetic effects; OTC sleep aids.

The End &

Good Luck

14

The conjugation of glucuronic acid to a drug by the liver is an example of a:A. Cytochrome P450 reactionB. Transformation reactionC. Phase I activation reactionD. Phase II inactivation reaction

Drugs showing zero-order kinetics of elimination:A. Are more common than those showing first-order kineticsB. Decrease in concentration exponentially in timeC. Have a half-life that is independent of doseD. Show a plot of drug concentration versus time that is linear

Question: Why or When do we use drugs (clinically)?

Answer: To control, cure, or prevent disease

Question: Who can prescribe drugs, and

Where?Answer: Licensed doctors, requires DEA registration

and is state specific.

Question: What can you Rx? Answer: Drugs within the scope of your

practiceAnswer: Drugs within

the scope of your practice

pharmacology

Documents

systemic lupus erythematosus

central nervous system

peripheral nervous system

enlarged prostate gland

high abuse potential

platelet aggregation inhibitors

verbal orders allowed

direct thrombin inhibitors