IMPORTANT DRUGS AND THEIR MECHANISM OF ACTIONS

ZALJALAALE WAL IKRAM US/CANADIAN PHARMACY EXAM EDNAN

IMPORTANT DRUGS AND THEIR MECHANISM OF ACTIONSNoDrugs and Therapeutic ClassMechanism of Action

1Antiepileptic: Seizures: Anticonvulsants

Carbamazepine (drug of choice in Parial and tonic cloinc seizures)Oxcarbamazepine

Clonazepam

Ethosuximide (drug of choice in absence seizures)Felbamate

Phosphenytoin

Gabapentin

Lamotrigine

Phenobarbital (drug of choice of febrile seizures and grand mal seizures in children)Phenytoin

Primidone

Tiagabine

Tpoimarate

Valproate

Sodium divalproex

Vigabatrin

Levetiractem

Many typical anticonvulsants work by blocking voltage-sensitive sodium channels in the brain.

Phenobarbital potentiates synaptic inhibition through an action on GABA receptor.Ethosuximide inhibits calcium ion influx through T type channels in the thalmic neurons.

Gabapentin promotes the release of GABA.

Absence seizures (sometimes referred to as petit mal seizures) involve an interruption to consciousness where the person experiencing the seizure seems to become vacant and unresponsive for a short period of time (usually up to 30 seconds). Slight muscle twitching may occur.

Tonic-clonic seizures (sometimes referred to as grand mal seizures), involve an initial contraction of the muscles (tonic phase) which may involve tongue biting, urinary incontinence and the absence of breathing.

Myoclonic seizures involve sporadic muscle contraction and can result in jerky movements of muscles or muscle groups.

Atonic seizures involve the loss of muscle tone, causing the person to fall to the ground. These are sometimes called 'drop attacks' but should be distinguished from similar looking attacks that may occur in narcolepsy or cataplexy.

2Antidepressants: SSRIsFluoxetine (Prozac; Sarafem)

Sertraline (Zoloft)

Escitalopram: (Lexapro:Cipralex)

Citalopram(Celexa)

Fluvoxamine (Luvox)

Paroxetine (Paxil)They act within the brain to increase the amount of the neurotransmitter, serotonin (5-hydroxytryptamine or 5-HT), in the synaptic gap by inhibiting its reuptake (Reuptake is the reabsorption of a neurotransmitter by the molecular transporter of a pre-synaptic neuron after it has performed its function of transmitting a neural impulse).

3Selective Norepinehprine Reuptake Inhibitor (SNRI)Venlafaxine (effexor)Venlafaxine is chemically unrelated to other antidepressants, and is categorized as a serotonin-norepinephrine reuptake inhibitor (SNRI). It works by blocking the transporter "reuptake" proteins for key neurotransmitters affecting mood, thereby leaving more active in the synapse.

4TCAs; Antidepressantsamitriptyline (Elavil)

amoxapine (Asendin)

clomipramine (Anafranil)

desipramine (Norpramin)

doxepin (Adapin, Sinequan)

imipramine (Tofranil)

nortriptyline (Pamelor)

trimipramine (Surmontil)It was thought that tricylic antidepressants work by inhibiting the re-uptake of the neurotransmitters norepinephrine and serotonin by nerve cells. However, this response occurs immediately, however mood does not lift for around two weeks. It is now thought that changes occur in receptor sensitivity in the cerebral cortex and hippocampus.

5Tetracyclic AntidepressantRemeron (Mirtazipine)Mirtazapine is chemically unrelated to other antidepressants. It is thought to work by blocking presynaptic alpha-2 adrenergic receptors that normally inhibit the release of the neurotransmitters norepinephrine and serotonin, thereby increasing active levels in the synapse. Mirtazapine also blocks post-synaptic 5-HT2 and 5-HT3 receptorsan action which is thought to enhance serotonergic neurotransmission while causing a low incidence of side effects.

6Antipsychotic: SchizophreniaTypical AntipsychoticsChlorpromazine

Fluphenazine

Haloperidol

Thiothixene

Thioridazine

Trifluoperazine

LoxapineAtypical Antipsychotics

Clozapine (Clozaril)Olanzapine (Zyprexa)

Quetiapine (Seroquel)

Risperidone (Risperidal)

DA SchizophreniaDA PDThese drugs are also referred to as neuroleptic drugs, or simply neuroleptics. Typical antipsychotics are sometimes referred to as major tranquilizers because some of them can tranquilize and sedate when taken in large doses. All antipsychotic drugs tend to block the D2 neuroreceptors in the dopamine pathways in the brain, so the normal effect of dopamine release in the relevant synapses is reduced.

It is the blockade of D2 receptors in the mesolimbic pathway of the brain which is thought to produce the intended antipsychotic effect.

All atypical antipsychotics are FDA approved for use in the treatment of schizophrenia. Some carry FDA approved indications for acute mania, bipolar mania, psychotic agitation, bipolar maintenance, and other indications.

Modulation of the dopamine neurotransmitter system is necessary for antipsychotic activity while D2 receptor antagonism coupled with 5 HT2A receptor antagonism is responsible for the atypicality of atypical antipsychotics.

7Mood Stabilizers

Lithium carbonate - Valproic acid, divalproex sodium and sodium valproate.

Carbamazepine (Tegretol) - CBC should be monitored; can lower white blood cell count. Therapeutic drug monitoring is required.

Oxcarbazepine (Trileptal)

Gabapentin (Neurontin)

Lamotrigine (Lamictal)

Topiramate (Topamax)Mania describes a medical condition characterised by severely elevated mood. Lithium blocks the enzyme inositol 1 phosphatase which affects neurotransmitters.Most mood stabilizers are anticonvulsants.

Other manic symptoms include irritability, reduced need of sleep, hypersexuality, religiosity, hyperactivity, talkativeness, flight-of-ideas, and grandiose plans.

8Alzheimers Disease; Dementia

donepezil (Aricept)

galantamine (Reminyl)

rivastigmine (Exelon)

Mematine (NMDA receptor Antagonist) A novel drug

Acetylcholinesterase (AChE) inhibition was thought to be important because there is selective loss of forebrain cholinergic neurons as a result of Alzheimer's. AChE-inhibitors reduce the rate at which acetylcholine (ACh) is broken down and hence increase the concentration of ACh in the brain Acetylcholinesterase-inhibitors seemed to modestly moderate symptoms but do not prevent disease progression including cell death.

The NMDA receptor (NMDAR) is an ionotropic receptor for glutamate (NMDA is a name of its selective specific agonist). NMDARs play a critical role in synaptic plasticity mechanisms and thus are necessary for several types of learning and memory.

95 HT3 Antagonists; Antiemetic

Granisetron

Ondansetron (zofran)

Dolasetron (anzemet)

Metoclopramide (GIT motility inhibitor; Prokinetic)Ondansetron is a 5-HT3 receptor antagonist principally used as an antiemetic (cancer). The 5-HT3 receptor is a ligand-gated Na+ and K+ cation channel, resulting in a direct plasma membrane depolarization.

Metoclopramide is a parasympathomimetic, and is also a potent dopamine antagonist that enters the central nervous system. It is used for gastric emptying in patients with gastric motor failure (gastroparesis).It is also useful for facilitating small bowel intubation and as an antiemetic. Metoclopramide is indicated for the prevention of nausea and vomiting associated with emetogenic cancer chemotherapy and surgery. In addition, metoclopramide is indicated for the treatment of gastroesophageal reflux disease and gastroparesis as well as to aid in intubation of the small intestine and in radiologic examination of the upper gastrointestinal tract.

10Anti Migraine; 5 HT Receptors Agonists (Triptans)

Sumatriptan (Imitrex) 5HTD1Rizatriptan (Maxalt)

Naratriptan (Amerge)

Zolmitriptan (Zomig) 5HTB1/D1Triptans are a family of tryptamine drugs used in the treatment of migraine and cluster headaches. Their action is attributed to their binding to serotonin 5-HT1B and 5-HT1D receptors in cranial blood vessels (causing their constriction) and subsequent inhibition of pro-inflammatory neuropeptide release.

11Antiarrrhythmics

Class Ia agents include quinidine, procainamide and disopyramide.

Class Ib agents include lidocaine, mexiletine, tocainide, and phenytoin.

Class Ic agents include encainide, flecainide, moricizine, and propafenone.

Class II agents include esmolol, propranolol, and metoprolol.

Class III agents include amiodarone, azimilide, bretylium, clofilium, dofetilide, ibutilide, sematilide, and sotalol.

Class IV agents include verapamil and diltiazem.

Class V agents include adenosine and digoxin.

Antiarrhythmic agents are a group of drugs that are used to suppress fast rhythms of the heart (cardiac arrhythmias), such as atrial fibrillation, atrial flutter, ventricular tachycardia, and ventricular fibrillation.

Class I agents interfere with the sodium (Na+) channel, which prolongs the action potential duration by slowing conduction

Class II agents are anti-sympathetic nervous system agents. All agents in this class are beta blockers. They act by slowing conduction through the AV node.

Class III agents affect potassium (K+) influx. They prolong repolarization.

Class IV agents affect the AV node. They decrease conduction through the AV node.Class V agents work by other or unknown mechanisms.

12Calcium Channel Blockers

Dihydropyridine calcium channel blockers

Amlodipine besylate (Norvasc)

Nicardipine (Cardene, Carden SR)

Nifedipine (Procardia, Adalat)

Nitrendipine (Cardif, Nitrepin)

Nimodipine (Nimotop)

Phenylalkylamine calcium channel blockers

Verapamil hydrochloride (Calan)

Diltiazem hydrochloride (Cardizem)Calcium channel blockers work by blocking voltage-sensitive calcium channels in the heart and in the blood vessels. This prevents calcium levels from increasing as much in the cells when stimulated, leading to less contraction. This decreases total peripheral resistance by dilating the blood vessels, and decreases cardiac output by lowering the force of contraction. Because resistance and output drop, so does blood pressure.

Unlike with beta-blockers, the heart is still responsive to sympathetic nervous system stimulation, so blood pressure can be maintained more effectively

13Fibrates;Hypercholesterolemia

Clofibrate (largely obsolete due to side-effect profile, e.g. gallstones)

Gemfibrozil (e.g. Lopid)

Fenofibrate

Bezafibrate (e.g. Bezalip)

Statins

atorvastatin (Lipitor)

fluvastatin (Lescol)

lovastatin (Mevacor, Altocor, not marketed in the UK)

pravastatin (Pravachol, rosuvastatin (Crestor)

simvastatin (Zocor)

The fibrates are a class of amphipathic carboxylic acids. Fibrates increase the activity of lipoprotein lipase, a plasma enzyme that degrades chylomicrons and VLDL.Fibrates are structurally and pharmacologically related to the thiazolidinediones, a novel class of anti-diabetic drugs that also act on PPARs .Although less effective in lowering LDL, fibrates improve HDL and triglyceride levels, and seem to improve insulin resistance when the dyslipidemia is associated with other features of Syndrome X (hypertension and diabetes mellitus type 2).

Statins are the most potent cholesterol-lowering agents, lowering LDL-cholesterol (so-called "bad cholesterol") by 3050%. However, they are less effective than the fibrates in reducing triglycerides and raising HDL-cholesterol. Statins act by competitively inhibiting 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase, an enzyme of the HMG-CoA reductase pathway, the body's metabolic pathway for the synthesis of cholesterol.

14Diuretics

Osmotic diuretics (e.g., mannitol)

Carbonic anhydrase inhibitors (e.g., acetazolamide, dorzolamide)

Thiazides (e.g., hydrochlorothiazide, bendroflumethiazide)

Loop diuretics (e.g., furosemide, bumetanide, ethacrynic acid)

Potassium-sparing diuretics (e.g., spironolactone, amiloride, triamtrene)Diuretic is any drug that tends to increase the flow of urine from the body (diuresis). They also decrease the extracellular fluid volume, and are primarily used to produce a negative extracellular fluid balance. Diuretics are used to treat heart failure, liver cirrhosis, hypertension and certain kidney diseases. Some common diuretics are caffeine, cranberry juice and alcohol.

Thiazides are a class of drug that promote water loss from the body ((diuretics)). They inhibit Na+/Cl- reabsorption from the distal convoluted tubules in the kidneys. Thiazides also cause loss of potassium and an increase in serum uric acid.

Loop diuretics act on the Na+/K+/Cl- cotransporter in the ascending loop of Henle to inhibit sodium and chloride reabsorption. Because magnesium and calcium reabsorption in the thick ascending loop is dependent on sodium and chloride concentrations, loop diuretics also inhibit their reabsorption. This raises the osmotic pressure inside the loop, driving more water into the filtrate causing increased urine volume.

Potassium sparing diuretics work by inhibiting sodium reabsorption in the distal convoluted tubules and collecting ducts in the kidneys. This promotes the loss of sodium and water from the body, but without depleting potassium.

15Alpha Adrenergic Receptor Blockers

Alfuzosin

Doxazosin

Terazosin

Prazosin

Tamsulosin

In BPH, the prostate grows larger and presses against the urethra and bladder, interfering with the normal flow of urine. It leads to symptoms of urinary hesitancy, frequent urination, increased risk of urinary tract infections and urinary retention. Alpha blockers are used to block alpha 1 receptors that mediate muscular activity in the bladder neck, prostate and prostatic capsule.

16Anti Diabetic, Type 2

Thiazolidinediones

Rosiglitazone (Avandia)

Pioglitazone (Actos)

Thiazolidinediones are selective agonists for nuclear peroxisome proliferator-activated receptor-gamma (PPAR). These drugs bind to PPAR, which activates insulin-responsive genes that regulate carbohydrate and lipid metabolism. Thiazolidinediones require insulin to be present for their action. Thiazolidinediones exert their principal effects by increasing insulin sensitivity in peripheral tissue but also may lower glucose production by the liver.

17Sulfonylurea; Antidiabetic

First generation:

Chlorpropamide

Tolbutamide

Tolazamide

Second generation:

Glipizide , Gliclazide

Glibenclamide , Glimepiride

GlyburideSulfonylureas bind to an ATP-dependent K+ channel on the cell membrane of pancreatic beta cells. This inhibits a tonic, hyperpolarizing outflux of potassium, which causes the electric potential over the membrane to become more positive. This depolarization opens voltage-gated Ca2+ channels. The rise in intracellular calcium leads to increased fusion of insulin granulae with the cell membrane, and therefore increased secretion of proinsulin.

18Cancer

Alkylating Agents

Cisplatin, Carboplatin, Ifosfamide, Chlorambucil, Busulfan, Thiotepa. Cyclophosphamide

Cancer; Antimetabolites

5 Fluoro Uracil (5 FU)

Methotrexate,

Fludarabine

Caner; Plant alkaloids

Vincristine

Vinblastine

Cancer; Anti tumor Antibiotics

Doxorubicin

Daunorubicin

Bleomycin

Actinomycin

plicamycinAlkylating agents are so named because of their ability to add alkyl groups to many electronegative groups under conditions present in cells. They stop tumor growth by cross-linking guanine nucleobases in DNA double-helix strands - directly attacking DNA. This makes the strands unable to uncoil and separate.

Anti-metabolites masquerade as purine or pyrimidine - which become the building blocks of DNA. They prevent these substances becoming incorporated in to DNA during the "S" phase (of the cell cycle), stopping normal development and division. An important example is 5-Fluoro Uracil (5FU), which inhibits thymidylate synthase. Fludarabine inhibits function of multiple DNA polymerases, DNA primase, DNA ligase I and is S phase-specific. Methotrexate (being folate antagosnist) inhibits dihidrofolate reductase, enzyme essential for purines and pyrimidines synthesis.

These alkaloids are derived from plants and block cell division by preventing microtubule synthesis and mitotic spindle formation. These are vital for cell division and without them it can not occur. The main examples are vinca alkaloids such as vincristine, and vinblastine which bind to specific sites on tubulin, inhibiting the assembly of tubulin into microtubules

They prevent cell division by several ways: (1) binding to DNA through intercalation between two adjacent nucleotide bases and making it unable to separate, (2) inhibiting ribonucleic acid (RNA), preventing enzyme synthesis, (3) interfering with cell replication. Bleomycin acts in unique way through oxidation of a DNA-bleomycin-Fe(II) complex and forming free radicals, which induce damage and chromosomal aberrations.

19Immunosuppressant, Eczema

Organ Transplant

Tacrolimus (Prograf, Protopic)

Mycophenolate mofetil (Cellcept)

CyclosporineTacrolimus is a macrolide antibiotic. It acts by reducing peptidyl-prolyl isomerase activity by binding to the immunophilin FKBP-12, creating a new complex. This inhibits both T-lymphocyte signal transduction and IL-2 transcription.

Cellcept is metabolised in the liver to mycophenolic acid which inhibits inosine mononophosphate dehydrogenase, the enzyme which controls the rate of synthesis of guanine monophosphate in the de novo pathway of purine synthesis used in the proliferation of lymphocytes.

Cyclocporine has same action as Tacrolimus.

20Immunosuppressive

AzathioprineAzathioprine is used for immunosuppression in organ transplantation and autoimmune disease such as rheumatoid arthritis or Crohn's disease. It is converted in the body to 6-mercaptopurine. Azathioprine acts to inhibit purine synthesis necessary for the proliferation of cells, especially leukocytes and lymphocytes.

21DMARD

gold salts (sodium aurothiomalate, auranofin)

D-penicillamine

chloroquine and hydroxychloroquine (antimalarials)

sulfasalazine (SSZ)

methotrexate (MTX)

azathioprine

cyclosporin A

Leflunomide (Arava)Disease-modifying antirheumatic drugs (DMARDs) are a category of drugs used in many autoimmune disorders to slow down disease progression. They are used in diseases such as Crohn's disease and ulcerative colitis, lupus erythematosus (SLE), idiopathic thrombocytopenic purpura (ITP), myasthenia gravis and various others.

Methotrexate inhibits dihydrofolate reductase, an enzyme that is part of the folate synthesis metabolic pathway. Dihydrofolate reductase catalyses the conversion of dihydrofolate to the active tetrahydrofolate. Methotrexate, therefore, inhibits the synthesis of DNA, RNA, thymidylates, and proteins. Methotrexate is cell cycle S-phase selective, and has a greater negative effect on rapidly dividing cells, which are replicating their DNA, and thus inhibits the growth and proliferation of these cells.

Arava inhibits pyrimide sysnthesis.

22Proton Pump Inhibitors (PPIs)

Omeprazole, Lansoprazole,

Esomeprazole, Pantoprazole, Rabeprazole

PPIs act by irreversibly blocking the K/H ATPase or more commonly just proton pump of the gastric parietal cell. The proton pump is the terminal stage in gastric acid secretion, being directly responsible for secreting H+ ions into the gastric lumen, making it an ideal target for inhibiting acid secretion.

23Antithyroids

PTU (propylthyouracil)

Tepazole (methimazole)

Both agents inhibit iodide oxidation and iodorhiouracil coupling but PTU only diminishes peripheral deiodonation of T4 to T3.

24Corticosteroids

Prednisone

Methylprednisone

Dexamethasone

Corticosteroids have potent anti-inflammatory and immunosuppressive properties.They bind to glucocorticoid receptors altering DNA and RNA translation causing drop in circulating T lymphocytes. As a consequence, corticosteroids are widely used as drugs to treat inflammatory conditions such as arthritis or dermatitis, and as adjunction therapy for conditions such as autoimmune diseases.

25Anti obesity

Orlistat (Xenical)

It works by inhibiting pancreatic lipase, an enzyme that breaks down fat in the intestine. Without this enzyme, fat from the diet is excreted undigested, and not absorbed by the body.

26OCPs

Birth Control PillsThe Pill works by preventing ovulation, as well as making the uterus less likely to accept implantation of an embryo if one is created, and thickens the mucus in the cervix making it more difficult for sperm to reach any egg. Taken correctly, it is the single most reliable form of reversible contraception. Most brands use 20 to 40 micrograms of ethinyloestradiol as the estrogen component and either a fixed or varying (the bi and triphasic pills) amount of progestogen as the progesterone analogue. Most progestagens are used for their antiestrogenic properties in oral contraceptives to avoid over stimulation of the endometrium which could lead to endometriosis.

27Inflammatory Bowel Disease (IBD)

Ulcerative Colitis and Crohns Disease

Mesalamine (5 ASA) (Pentasa, Asacol)

Sulfasalazine

Olsalazine

Ulcerative colitis is an inflammatory disease of the bowel, that usually affects the distal end of the large intestine and rectum.. The main difference between the two is the location and nature of the inflammatory changes in the gut. Crohn's can affect any part of the gastrointestinal tract, from mouth to anus. Ulcerative colitis, in contrast, is restricted to the colon, and spares the anus.

Mesalamine, also known as 5-aminosalicylic acid (5-ASA), is an anti-inflammatory drug used to treat inflammation of the rectum, mild to moderate ulcerative colitis and inflammation of the lower colon.

Sulfasalazine is a sulfa drug used primarily in the treatment of inflammatory bowel disease. It is a 5-acetylsalicyclic acid derivative. It is also used for rheumatoid arthritis.

28Leukotriene receptors antagonists (LTRA); Asthma

Zafirlukast (Accolade)

Montelukast (Singulair)Leukotrienes are autocrine and paracrine eicosanoid lipid mediators derived from arachidonic acid by 5-lipoxygenase.

Zafirlukast is an oral leukotriene receptor antagonist (LTRA) for the maintenance treatment of asthma. Available as a tablet, it blocks the action of leukotriene C4 on its receptors, thus reducing constriction of the airways, build-up of mucus in the lungs and inflammation of the breathing passages.

Montelukast blocks the action of leukotriene D4 on the cysteinyl leukotriene receptor CysLT1, thus inhibiting bronchoconstriction.

29Bisphosphonates

Alendronate

Risedidronte

etidronateBisphosphonates inhibit osteoclastic activity. They reduce both the resorption and formation of hydroxyapetite crystals.

30Influenza A and B

Tamiflu (Oseltamivir)Oseltamivir is a neuraminidase inhibitor used in the treatment of and prophylaxis of both influenza A and influenza B. Oseltamivir is a prodrug, usually administered as oseltamivir phosphate, with the drug being converted heptically to the active metabolite.

31Influenza A (Flu)

Amantadine

Influenza (or as it is commonly known, the flu or the grippe) is a contagious disease caused by an RNA virus of the orthomyxoviridae family. Amantadine inhibits replication of the influenza A virus by interfering with viral attachment and uncoating.

32Anticoagulants

Warfarin

Phenindione

HeparinThe oral anticoagulants are a class of pharmaceuticals that 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.

Vitamin K is converted to vitamin K epoxide in the liver. This epoxide is then reduced by the enzyme epoxide reductase. The reduced form of vitamin K epoxide is necessary for the synthesis of many coagulation factors (II, VII, IX and X, as well as protein C and protein S). Warfarin inhibits the enzyme epoxide reductase in the liver, thereby inhibiting coagulation.

Common indications for warfarin use are atrial fibrillation, artificial heart valves, deep venous thrombosis and pulmonary embolism.

Heparin works by potentiating the action of antithrombin III, as it is similar to the heparan sulfate proteoglycans which are naturally present on the cell membrane of the endothelium. Because antithrombin III inactivates many coagulation proteins, the process of coagulation will slow down.

33Beta Blockers

Cardioselective

Acebutolol, Atenolol, Betaxolol Bisoprolol, Esmolol, Metoprolol Nebivolol

Nonselective

Nadolol, propanolol, Sotalol, Pindolol, Beta blockers or beta-adrenergic blocking agents are a class of drugs used to treat a variety of cardiovascular conditions and some other diseases.

Beta blockers block the action of epinephrine and norepinephrine on the -adrenergic receptors in the body (primarily in the heart, peripheral blood vessels, bronchi, pancreas, and liver). The hormones and neurotransmitters stimulate the sympathetic nervous system by acting on these receptors.

Propanolol is used for social phobia.

34Biguanide; GlucophageMetformin is antihyperglycemic, not hypoglycemic. It does not cause insulin release from the pancreas and generally does not cause hypoglycemia, even in large doses. Metformin has no significant effects on the secretion of glucagon, cortisol, growth hormone, or somatostatin. Metformin reduces glucose levels primarily by decreasing hepatic glucose production and by increasing insulin action in muscle and fat.

35Digitalis: Cardiac Glycoside

Digoxin

Digoxin inhibits the Na+-K+ ATPase pump in the membranes of the heart cells (myocytes). This causes an increase in the level of sodium ions in the myocytes, which then leads to a rise in the level of calcium ions. This increased level of calcium increases the contractility of the myocardium (muscle of the heart). Digoxin also decreases the conduction of electrical impulses through the AV node, making it a commonly used drug in controlling the heart rate during atrial fibrillation or atrial flutter.

36Selective Estrogen Receptor Modulator (SERM)

clomifene (an ovulation)

raloxifene (osteoporosis)

tamoxifen (breast cancer)

toremifine (breast cancer)Selective estrogen receptor modulator (SERMs) is a class of medication that acts on the estrogen receptor. A characteristic that distinguishes these substances from receptor agonists and antagonists is that their action is different for various tissues, thereby granting the possibility to selectively inhibit or stimulate estrogen-like action in various tissues.

There are three types of estrogen receptors, which are intracellular: ( homodimer), ( homodimer) and (- and -receptor heterodimer). The -receptor is generally stimulatory, but the -receptor may inhibit the -isoform as well as suppressing transcription independently

37Antiretroviral Drugs; HIV

Protease inhibitors (PIs); HIV

Saquinavir, Ritonavir, Indinavir, Nelfinavir

Reverse Transcriptase Inhibitors (RTIs)

Nucleoside Analog Reverse Transcriptase Inhibitors (NARTIs) or (NRTIs).

(Zidovudine, didanosine, Zalcitabine, Stavudine, Lamivudine, Abacavir)Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs)

(nevirapine: Viramune, efavirenz: Sustiva, delavirdine: Rescriptor)Protease inhibitors are a class of medication used in viral infections. They act by inhibiting specific viral enzymes that are essential to the viral life cycle by cleaving viral proteins. Protease inhibitors are molecules that inhibit the function of peptidases and In medicine, protease inhibitor is often used interchangeably with alpha 1-antitrypsin.

Reverse Transcriptase Inhibitors inhibit activity of reverse transcriptase, a viral enzyme HIV needs to reproduce. Lack of this enzyme prevents HIV from building DNA based on its RNA.

38Antituberculosis

Rifampin

Isoniazid

Rifampicin inhibits DNA-dependent RNA polymerase in bacterial cells by binding its beta subunit, thus preventing transcription of messenger RNA (mRNA) and subsequent translation to proteins.

Isoniazid inhibits the mycolic acid cell wall synthesis via oxygen-dependent pathways, such as the catalase-peroxidase reaction.

39Vancomycin (Vancocin)

The drug of choice and last resort where other antibiotics are not effective.Vancomycin is an antibiotic used in the prophylaxis and treatment of infections caused by Gram-positive bacteria. Vancomycin acts by inhibiting proper cell wall synthesis in Gram-positive bacteria. Vancomycin needs to be given intravenously (IV) for systemic therapy since it does not cross through the intestinal lining. It is a large hydrophilic molecule which partitions poorly across the gastrointestinal mucosa. The only indication for oral vancomycin therapy is in the treatment of pseudomembranous colitis, where it must be given orally to get to reach the site of infection in the colon.

40Metronidazole (Flagyl)Metronidazole is an antibiotic and antiparasitic drug classified as a nitroimidazole. It inhibits nucleic acid synthesis and is used for the treatment of infections involving anaerobic bacteria as well as protozoal infections.

Conditions it is useful in include: giardiasis, amoebiasis, Trichomonas vaginalis infections, bacterial vaginosis, pseudomembranous colitis, Helicobacter pylori infections, and acne rosacea.

41Polyene Antibiotics

Imidazole (Miconazole,Ketoconazole

Clotrimazole ,Econazole, Mebendazole ,Oxiconazole

Thiabendazole ,Tiaconazole)

Triazole (Fluconazole ,Itraconazole)

Allyalamine (Terbinafine; Lamisil)

The polyenes bind with sterols in the fungal cell wall, principally ergosterol. This causes the cell's contents to leak out and the cell dies. Human (and other animal) cells contain cholesterol rather than ergosterol so are much less susceptible.

The imidazole and triazole groups of antifungal drugs inhibit the enzyme cytochrome P450 14-demethylase. This enzyme converts lanosterol to ergosterol, and is required in fungal cell wall synthesis. These drugs also block steroid synthesis in humans.

Allylamines inhibit the enzyme squalene epoxidase, another enzyme required for ergosterol synthesis

42Quniolones and Fluoroquinolones Antibiotics

Ciprofloxacin (Cipro)

Levofloxacin (Levaquin)

Norfloxacin (Noroxin)

Ofloxacin (Floxin)

Moxifloxacin (Avelox)

Gatifloxacin (tequin)Quinolones and fluoroquinolones form a group of broad-spectrum antibiotics. They are derived from nalidixic acid. Quinolones act by inhibiting the bacterial DNA gyrase enzyme. This way they inhibit nucleic acid synthesis and act bacteriocidically.

43Macrolides Antibiotics

(erythromycin ,clarithromycin azithromycin roxithromycin)

The macrolides are a group of drugs (typically antibiotics) whose activity stems from the presence of a macrolide ring, a large lactone ring to which one or more deoxy sugars, usually cladinose and desosamine, are attached. The lactone ring can be either 14, 15 or 16-membered. Macrolides belong to the polyketide class of natural products.

The mechanism of action of the macrolides is inhibition of bacterial protein synthesis by binding reversibly to the subunit 50S of the bacterial ribosome, thereby inhibiting translocation of peptidyl-tRNA. This action is mainly bacteriostatic, but can also be bactericidal in high concentrations. Macrolides tend to accumulate within leukocytes, and are therefore actually transported into the site of infection.

Macrolides are used to treat infections such as respiratory tract infections and soft tissue infections. Beta-hemolytic streptococci, pneumococci, staphylococci and enterococci are usually susceptible to macrolides. Unlike penicillin, macrolides have shown effective against mycoplasma, mycobacteria, some rickettsia and chlamydia.

44

Aminoglycosides

Amikacin, gentamicin, kanamycin, neomycin, streptomycin, and tobramycin.

Aminoglycosides are a group of antibiotics that are effective against certain types of bacteria. Aminoglycosides work by binding to the bacterial 30S ribosomal subunit, causing misreading of t-RNA, leaving the bacterium unable to synthesize proteins vital to its growth. Aminoglycosides are useful primarily in infections involving aerobic, Gram-negative bacteria, such as Pseudomonas, Acinetobacter, and Enterobacter.

45Finasteride (Propecia): Antiandrogen

5 alpha reductase inhibitor

Flutamide

Bicalutamide (Casodex)

Nilutamide (Anandron)

Finasteride acts by inhibiting 5-alpha reductase, the enzyme the converts testosterone to dihydrotestosterone. It is used in benign prostate hyperplasia (BPH) in low doses, and in prostate cancer in higher doses. It is registered in many countries for male-pattern baldness.

46Tetracyclines

Doxycylcine

Demeclomycin

MinocyclineTetracyclines bind to 30S subunit of bacterial ribosome, blocking aminosyl transfer RNA on the receptor site on the m RNA ribosomal complex

47eta Lactam Antibiotics

Penicillins

Cephalosporins

First generation cephalosporins

cephalexin ,cephalothin

cephazolin

Second generation cephalosporins

cefaclor ,cefuroxime

cefamandole

Second generation cephamycins

Moderate spectrum with anti-anaerobic activity.

cefotetan , cefoxitin

Third generation cephalosporins

Broad spectrum.

ceftriaxone , cefotaxime

Broad spectrum with anti-Pseudomonas activity.

ceftazidime

Fourth generation cephalosporins

cefepime

Carbapenems-lactam antibiotics are a broad class of antibiotics including penicillin derivatives, cephalosporins, monobactams, carbapenems and -lactamase inhibitors; basically any antibiotic agent which contains a -lactam nucleus in its molecular structure. -lactam antibiotics were mainly active only against Gram-positive bacteria, the development of broad-spectrum -lactam antibiotics active against various Gram-negative organisms has increased the usefulness of the -lactam antibiotics. All -lactam antibiotics are bactericidal, and act by inhibiting the synthesis of the peptidoglycan layer of bacterial cell walls. The peptidoglycan layer is important for cell wall structural integrity, especially in Gram-positive organisms. The final transpeptidation step in the synthesis of the peptidoglycan is facilitated by transpeptidases known as penicillin binding proteins (PBPs). Inhibition of PBPs may also lead to the activation of autolytic enzymes in the bacterial cell wall. -lactam antibiotics are indicated for the prophylaxis and treatment of bacterial infections caused by susceptible organisms.

48Analgesics: Narcotics

Endogenous opioids

Opioid-peptides that are produced in the body:endorphins ,dynorphins

enkephalins

Opium alkaloids

Phenanthrenes naturally occurring in opium:morphine ,codeine

thebaine

Semisynthetic derivatives

diamorphine (heroin) , oxycodone

hydrocodone ,dihydrocodeine

hydromorphone ,oxymorphone

Synthetic opioids

Phenylheptylamines

methadone

levomethadyl acetate hydrochloride

Phenylpiperidines

pethidine (meperidine)

fentanyl , alfentanil

sufentanil

Diphenylpropylamine derivatives

propoxyphene

dextropropoxyphene

Benzomorphan derivatives

pentazocine , phenazocine

Oripavine derivatives

buprenorphine

Morphinan derivatives

butorphanol, nalbufine

tramadol, loperamide

diphenoxylate Opioid antagonists

naloxone , naltrexoneAn opioid is any agent that binds to opioid receptors found principally in the central nervous system and gastrointestinal tract. There are four broad classes of opioids: endogenous opioid peptides, produced in the body; opium alkaloids, such as morphine (the prototypical opioid) and codeine; semi-synthetic opioids such as heroin and oxycodone; and fully synthetic opioids such as pethidine and methadone that have structures unrelated to the opium alkaloids.

There are at least three major classes of opioid receptors: , and . These are all G-protein coupled receptors acting on GABAergic neurotransmission. The receptor (the represents morphine) is perhaps the most important - being responsible for most of the analgesic and other major pharmacological effects as well as many of the adverse effects of opioids.

Opioid overdose can be rapidly reversed with any of several opioid antagonists such as naloxone. These competitive antagonists are drugs that bind to the -opioid receptors with higher affinity than agonists but do not activate them.

Common ADRs include: nausea and vomiting, drowsiness, dry mouth, miosis, orthostatic hypotension, urinary retention, and constipationThe main clinical indications of opioids include;

moderate-to-severe acute pain and chronic pain

cough (mainly codeine)

diarrhea (mainly loperamide and diphenoxylate used therapeutically)

relief of severe dyspnoea (e.g. lung cancer, terminal COPD)

49Gout

Colchicine

AllopurinolColchicine inhibits the cytoskeleton by binding to tubulin, one of the main constituents of microtubules. Allopurinol is used for long term treatment. Allopurinol treatment should not be initiated during an attack of gout, as it can then worsen the attack. In humans, xanthine oxidase is normally found in the liver and not free in the blood. Because xanthine oxidase is a metabolic pathway for uric acid formation, the xanthine oxidase inhibitor allopurinol is used in the treatment of gout.

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