Routes of Drug Administration



| | |

| |Oral |

| |Topical (Percutaneous) |

|Routes of Drug Administration |Rectal or Vaginal |

| |Pulmonal |

| |Parenteral |

| |Pills (single dose) |

| |Tablets |

| |Coated Tablets (shell) |

|Types of Orally Administered Drugs |Matrix Tablets (carrier meshwork) |

| |Capsules (gelatin shell) |

| |Troches/Lozenges |

| |Solutions |

| |Ointment + Lipophilic cream |

| |Paste |

| |Lotion |

|Percutaneous Drug Administration |Gels |

| |Can be single or multilayer, or contained in a reservoir |

| | |

| |Eye Drops |

| |Nose Drops |

|Other Topicals |Pulmonary Formulations |

| |Suppositories |

| |Ampules |

| |Vials |

| |Cartridge Ampules |

|Parenteral Drug Administration |Infusions |

| |Advantage: 100% Absorption, enters circulation without hepatic elim, better |

| |bioavailability of hydrophilic drugs |

| |External Absorption Barriers: (epithelial layer on skin, lung, intestine—Lipophilic |

| |barrier) |

|Types of Barriers for Drug Distribution/Absorption |Internal Blood-Tissue Barriers: Cardiac muscle, endocrine glands, gut, liver, CNS |

| |Passive Diffusion |

| |Active Transport |

|Drug Distribution |Receptor-mediated Endocytosis |

| |[DRUG] IS A FUNCTION OF ABSORBTION AND ELIMINATION! |

| | |

| |The AUC of the administered drug divided by the AUC of the intraveneously administered |

| |drug |

|Bioavailability |IV>TD>IM=SC>Rectal>Oral=Inhal |

| | |

| |Vd=Amt of drug in the mody/[drug] |

| |R of E: Via kidney (filtration) or liver (metabolism) |

|Volume of Distribution |Usually first order kinetics |

|Rate of Elimination |3 drugs have zero-order kinetics |

| |Rate of Elim/[Drug] |

| | |

| |Rate of Elim= k*Cp*Vd |

|Clearance |K= ln2/T ½ |

| | |

| |CL= K*Vd |

| |Convert parent compound into more polar metabolite |

|Phase I Reactions |Add/unmask functional group: |

| |OH, SH, NH2, COOH, etc |

| |Oxidation, Reduction, hydrolytic cleavage, Alkylation, Dealkylation, etc… |

| | |

| |Conjugation with endogenous substrate (increase aq solubility) |

| |Conjugation with gucoronide, sulfate, acetate, amino acid |

|Phase II Reactions | |

| |Require reducing agent and molecular oxygen |

| |Two enzymes: 1) Flavoprotein, NADPH-cytochrome c reductase |

| |2) Cytochrome P450 (electron acceptor); CYP |

|MFO | |

|Mixed Function Oxidases | |

| |PPAR ligands, CYP1, CYP2E, CYP2B |

| |Polymorphisms cause changes in drug metab: CYP2C19, CYP2B, CYP2D6 |

|P450 Enzymes |Induction of P450 enzymes=metabolize drug |

| |Glucoronidation |

| |Sulfation |

|Conjugation Reactions |Acetylation |

| |Amino acid Conj |

| |Glutathione Conj |

| |Fatty acid Conj |

| |Condensation Reaction |

| |Catalyze oxidative deamination of endogenous catecholamines (epinephrine) |

| |Lacated in never terminals and peripheral tissues |

| |Many drug/food interactions! (cheese, wine) |

|Monoamine Oxidases (MAO) |Inhib by MAO inhib |

| |Maximum non-toxic dose/Min effective dose |

| |Doesn’t take into account variability btw indivs |

|Therapeutic Index |LD50/ED50 |

| |Can be drugs or endogenous ligands for the receptor |

| |Increasing [agonist] will produce increase in biological response |

| |Full:evokes 100% max possible effect |

|Agonist |Partial: not 100% |

| |Block or reverse effect of agonist |

| |No effect on their own |

|Antagonist |Competitive, Non-competitive, inverse agonist (triggers neg response) |

| | |

| | |

| |Receptor |

|Four major drug targets |Enzyme |

| |Ion Channel |

| |Transporter |

| |Regulates many cellular and phys. Responses |

| |Gradient btw extracellular and intracellular (high:low) creates many opportunities for |

| |regulation |

|Ca++ as a Second Messenger |Stored in ER and other |

| |Voltage mediated: L, N, T |

| |Ligand gated |

| |Store operated |

|Ca Channels |Sesnsors: Annexins, EF-hand proteins, Calmodulin, ProponinC |

| |Target of many drugs! |

| |GPCR: transmembrane |

| |Bind GTP and GDP |

| |GAPS, GEFS, RGSs important in this regulation |

|G-Protein-coupled Receptors |Main Targets: Phospholipase C, Adenylate cyclase |

| |G-Proteins: Guanine nucleotide binding proteins |

| |2 groups: |

| |Small GTP binding |

|G-Proteins |Heterotrimeric G proteins |

| | |

| |Target of cAMP |

| |Four subunits (2 reg, 2 catalytic) |

|PKA |Phosphorylates transcription factors ex: CREB |

| |Heterologous desensitization (Incoming signal from different receptor) |

| |Homologous desensitization (only occurs on receptor which has already been stimulated) |

|Regulation of Receptors | |

| |Lipid soluble ligands that penetrate cell membrane, Receptors contain DNA-binding |

| |domains (transcriptional activators/suppressors) |

|Nuclear Receptors |Takes longer to act—requires penetration and protein synth first |

|GC, Mineralcorticoids, Retinoids PPARs | |

| |Common fatty acid chain+glycerol backbone+phosphor-residue |

| |PLA2 (reg through Ca++ and phos), PLC (Beta: Reg through GPCR, Gamma: EGFR or TCR, |

| |activated through tyrosine phosphorylation |

|Phospholipids | |

|Phospholipases | |

| |DAG: membrane bound, acts as a substrate for PLA2 |

|Phospholipases… |IP3: Ca++ regulated |

| | |

| | |

| |Eicosanoids: derivative of arachadonice acid |

| |Rapidly metab by COX into PG and LTs |

| |1st reaction: cyclic ring structure (COX), 2nd reaction: oxidation (Peroxidase) |

|Arachidonic Acid Metabolism | |

| |Vascular tone (relaxation, constriction) |

| |Platelet agg (Inc and Dec) |

|Function of PGs |Uterus tone (Inc) |

| |Bronchial Muscle (Contriction, relaxation) |

| |Gastric secretion (Inib), temp/pain |

| |LTC4, D4 and E4 mediate allergic rxn (SRS-A) |

| |Mediate anaphylactic shock, 10,000 more postent than histamine |

|Leukotrienes |Constricts bronchi, dilates bv |

| |LTB4 strong chemattractant for macrophage |

| |Divided into CNS and PNS |

| |PNS div into Somatic and Autonomous |

|Nervous System |Auto: Sypmathetic and Parasympathetic |

| |Muscarinic Receptors: Heterotrimeric G protein coupled, CNS, gastric mucosa M1 |

| |Cardiac=M2, Glandular=M3 |

|Cholinergic Receptors |Nicotinic Receptors: Ion channel coupled Muscle type, Ganglion type, CNS type |

| |Direct Parasympathomimetics: Affinity for M or N receptors (mimic Ach) |

| |Inderect Parasympathometics: Inhibit activity of Achesterase (Ach increased) |

| | |

|Cholinomimetics= | |

|Parasympathomimetics | |

| |Mimic Input |

| |Block Input |

|To affect Paraympathetic… | |

| | |

|To Treat associated diseases…. |Promote Parasymp |

| |Block Symp |

|Pilocarpine |Muscarinic Parasymp, does not activate N rec, treates glaucoma (local! Eyedrops) |

| | |

| |Muscarine has no therapeutic application! |

| | |

|Muscarine | |

| |Achestease Inhibitors, raise Ach |

|Carbamate |Physiostigmine (topical only) |

| |Neostigmine |

| | |

|Quaternary Alcohols |Edrophonium (diagnose Myasthenia Gravis) |

| |AcCh-ase inhib |

| |Acts as AcCh-ase inhib but active ingredient unkown |

| |Indirect stimulation of M3 receptor (vascular), triggers NO production=vasodilation |

|Horny Goat Weed |Action similar to Viagra (dangerous) |

| | |

| | |

|Ogranophosphates |AcCh-ase inhibitors (irreversible) |

| |No medical application |

|Nerve Gasses | |

| |Muscarinic Parasympathomimetic |

| |Atropine (antagonist of cholinergic system): CNS stimulant, before anesth. Prevent |

|Atropine |hypersecretion of bronchial mucus, treats bradycardy.. |

| |Hyoscine=CNS depressant, antiemetic, |

|Hyoscine | |

| |Competitive Antagonists: Compete with AcCh for N rec, prevent depolarization, |

| |reversible |

| |Agonists: Depolarizing blockers, AcCh mimetics not hydrolyzed by AcCh-ase, trigger a |

|Nicotinic Parasympatholytics |sustained depolarization, irreversible |

| |Dimeric AcCh, Acts as agonist like AcCh, not hydrolyzed by AcCh-ase (only plasma |

| |esterase) |

|Succinocholine/Suxamethonium |Depolarization triggers muscle twitching initially, |

| |Used for brief procedures |

| |AcCh: Preganglionic, parasyathetic post ganglionic neurons |

| |Norepinephrine: Most symp. Post ganglionic neurons (except sweat glands and renal |

|Transmitters in the Autonomic Nervous System |arteries) |

| |Epinephrine (adrenalin): Adrenal medulla--symp impulses (no gang) |

| | |

| |Reuptake into presynaptic nerve ending |

|Termination of (Nor)epinephrine action |Catechol-O-methyltransferase |

| |MAO |

| |Presynaptic alpha 2 receptors |

| |Alpha1 (vasc smooth muscle) |

| |Alpha 2 (presynaptic) |

|Adrenergic Receptors |Beta 1 (Heart) |

| |Beta 2 (repiratory, uterine SM cells) |

| |Beta 3 (Adipocytes) |

| |MAO-Inhibitors |

| |Indirect Sympathicomimetics |

| |Inhib of MAO causes increase in free Nor-Ep, in CNS NAO metab dopamine and serotonin |

|Tranylcypromine |(inhib=increase in happy hormones) |

|Moclobemide | |

| | |

| |Indirect Sympathicomimetics |

| |Displace nor-E in storage vesicles=forced release of NorE |

|Ephedrine |Dietary Supplements |

| |Indirect Sympathomimetics |

|Amphetamines |Displace norE in storage vesicles, forced release, inhib NorE re-uptake and deg by MAO |

|Methylphenidate |(TRIPPLE ACTION), Meth=ADD, Fen=Appetite suppressant, Meta=more lipophilic, depletes |

|Fenfluramine |NorE |

|Metamphetamine | |

| | |

| |Non-selective Agonists |

|Epinephrine |Sympathomimetics |

| |Ep: Activates alpha and beta rec |

|Norepinephrine |Blood pressure increase, dilates bronchii, vasopressor, Treat anaphylactic shock |

| |NorE: alph receptors, increase BP, potent vasopressor |

| |Alpha1 selective agonist |

|Methoxamine |Sympathomimetics |

|Phenylephrine |Methoxamine: treatment of hypotensive state |

|Naphazoline |Phen: Local vasoconstrictor, nasal decongestant |

|Oxymetazoline |Zoline=alpha 1 |

|Xylometazoline | |

| |Alpha 2 selective agonist |

| |Produce sympatholytic effect, but sympathomimetics! Actviate presynaptic a-2 rec in |

| |cardiovascular control in the CNS |

|Clonidine |BP decrease |

|Guanfacine | |

| | |

| |B1-selective agonist, stimulate heart |

| |Strgon inotropic effect, little chronotropic effect, short term treatment of impaired |

|Dobutamine |cardiac function |

| |B2 selective agonist |

|Metaproterenol |Treat asthma, non-selective sympathomimetics |

|Albuterol |Differ in speed and onset, duration of action |

|Formoterol | |

| |Indicated for pheocromocytoma. |

| |Blocking α1 causes vasodilation; reducing BP |

|Non-selective Blockers |Blocking α2 removes inhibition, increasing NE action on β receptors ( increasing HR and |

|Phentolamine |cardiac output |

| | |

| |Selective α1 Blocker |

|Prazosin, Terazosin, etc |Indicated for hypertension and urinary retention. |

| |Side effects: Reflex tachycardia and postural hypotension |

| | |

| |Selective α2 Blocker (sympathomimetic!) |

|Yohimibine |Increases sympathetic outpout. Used for male sexual dysfunction and as a weight loss |

| |drug |

| |Noncardioselective β blockers |

| |1st gen. drug, cross reaction w/ β2 causes bronchoconstriction |

|Propranolol |Labetalol also blocks α1 receptors (strong antihypertensive drug) |

| |same indications as cardioselective blockers |

| |Cardioselective β blockers |

| |Newer drugs are more β1 selective. |

|Metoprolol, Atenolol… |Indicated for angina pectoris, hypertension, cardiac dysrhythmias, myocardial |

| |infarction, heart failure, and stage fright (anxiolytic). |

| | |

| |CNS/ANS (decrease symp. tone) |

|Potential targets of Antihypertensive drugs |Heart: decrease cardiac output |

| |Veins: Dilate, decrease preload |

| |Arterioles: dilate, decrease afterload |

| |Kidneys: increase diuresis |

| |Calcium channel blockers (antagonist) |

|Dihydropyridines: |Inhibit Ca entry into cells of arteries |

|Nifedipine, Nicardipine, Nimodipine… |Targets specifically L-type channels on VSMC, no cardiac effect |

| |Can cause peripheral edema |

|Minoxidil |Potassium Channel Agonists |

| |Increases membrane permeability to K+, K+ efflux causes membrane hyperpolarization, |

| |inhibiting voltage gated Ca2+ channels ( relaxation of smooth muscles ( vasodilation ( |

| |reduces BP |

| |Side effect: hair growth (Rogaine) |

|Nitroprusside |Vasodilator |

| |Delivered thru iv only and is metabolized into NO which directly activates cGMP |

| |production ( vasodilation, Rapid action! |

| |(Caffeine & Viagra) |

| |Hypertensive Emergencies! |

| |ACE-Inhibitors, angiotensin I not converted into the active peptide (ATII), no |

|Captopril |aldosterone & ADH release ( no fluid retention |

|Enalapril |-no sympathomimetic effects |

|Benazepril |-no vasoconstriction |

|Lisinopril |Side effect – causes coughing |

| |Angiotensin II (ATII) Receptor Blocker |

| |Inhibits the effect of AT II by blocking the receptor |

|Losartan |usually used if patient cannot tolerate the cough caused by ACE inhibitors |

|Candesartan | |

|etc… | |

|Stable Angina |Predictable episodes; usually during/after physical exertion or stress. Treatment: |

| |Nitrates & β-Blockers (Propranolol, etc.) |

| | |

|Unstable Angina |Chest pain unexpected and usually occurs at rest |

| |Treatment: Nitrates |

| | |

|Variant Angina |Chest pain almost always occurs at rest. Due to coronary artery spasm. Treatment: |

| |Calcium channel blockers (Nifedipine, etc…) |

| |Treats angina pectoris. Reduces cardiac workload (and its oxygen demand) by reducing |

| |venous return. Causes vasodilation primarily in veins. Oral, sublingual, IV, Buccal |

| |and Transdermal ROA |

|Nitroglycerine |Do not combine w/ other vasodilators (Viagra) |

|Isosorbide-dinitrate |More stable than nitroglycerine |

|(ISDN) |Tolerance can occur, give lowest dose |

| |Do NOT combine w/ other vasodilators |

| | |

| |Promotes peripheral vasodilation. |

|Nitroprusside |IV only; rapid onset and short duration – allows for titration |

| |Sodium Channel Blockers |

| |Slows depolarization phase of AP. |

|Arrythmia Treatment |Procainamide – used for atrial & ventricular arrhythmias |

|Class I |Lidocaine – used for acute ventricular arrhythmias |

| |Flecainide – used for chronic treatment of ventricular arrhythmias |

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|Arrythmia Treatment |β-Blockers |

|Class II |Propranolol |

| |used for tachycardia |

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| | |

|Arrythmia Treatment |Potassium Channel Blockers |

|Class III: |Prolongs repolarization by blocking potassium efflux. |

| |Bretylium & Amiodarone |

| |used for intractable ventricular arrhythmias |

|Class IV: |Prolongs repolarization by blocking calcium influx |

|Calcium Channel Blockers |Verapamil – blocks both L & T Type calcium channels! |

| |Blocking T Type channels ( slows conduction |

| |(Blocking L Type channels ( coronary + arterial vasodilation) |

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| | |

| |Adenosine – for paroxysmal supraventricular tachycardia |

| |Digoxin – atrial fibrillation |

|Other Cardiac Arrythmia Drugs |Epinephrine - bradycardia |

| |Inadequate contractility; ventricles unable to expel blood ( rise in venous blood |

| |pressure. Caused by blocked coronary arteries, viral infections, hypertension, leaky |

| |heart vavles, myocardial infarction |

|Congestive Heart Failure |Right sided failure – lower limb edema, Left sided failure – pulmonary edema & |

| |respiratory distress |

|Cardiac Glycosides |Slows heart rate and increases contractility. |

|(Digoxin) |Inhibits Na/K ATPase, leading to an increase intracellular Na+, Increased Na+ slows |

| |Na/Ca exchanger, leading to an increase intracellular Ca++. Low therapeutic index. |

| |Potassium competes with digoxin in binding to Na/K ATPase |

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| |Reduces cardiac workload, inhibits vasoconstriction, inhibits sodium/fluid retention, |

|ACE inhibitors & |inhibits NE release |

|ATII antagonists | |

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|Captopril & Losartan | |

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|Vasodilators |Nitrates: Nitroglycerine, etc. (review Nitrates notes) |

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|Carbonic Anhydrase Inhibitors |Inhibits conversion of CO2 ( (H+) + (HCO3-), blocking reabsorption of Na+ |

|Azetazolamide |-Usually indicated for Glaucoma |

|Dorzolamide |Causes metabolic acidosis (lower HCO3-) |

| |Inhibits Na+/K+/2Cl- symporter at ascending limb in the Loop of Henle; blocking Na, K, |

| |Cl reabsorption |

|Loop Diuretics (high ceiling) |most potent diuretic |

|Furosemide |for severe/moderate hypertension & edema |

|Torasemide |Causes hypokalemia |

| |Inhibits Na+/Cl- symporter at distal convoluted tube |

| |Used for moderate hypertension & heart failure (edema) |

|Thiazide Diuretics |Causes hypokalemia |

|Hydrochlorothiazide | |

|Benzthiazide | |

| |Acts as distal portion of distal tube; enhances Na excretion & reduces K excretion |

| |Spironolactone – aldosterone receptor antagonist (slow) |

|Potassium-Sparring Diuretics |Amiloride – directly blocks Na/K channel (fast) |

|Spironolactone |Used in combo w/ other diurectics |

|Amiloride | |

| |Non-reabsorbable molecules that inhibit passive reabsorption of water (promoting water |

| |excretion w/ little Na excretion), does not cross blood-brain barrier, so water goes |

|Osmotic Diuretics |from brain to blood, Used to reduce intracranial pressure, IV only |

|Mannitol | |

| |Indicated for kidney stones and gouts. |

| |Therapeutic dose: promotes excretion and inhibits reabsorption of uric acid |

|Uricosuric Agents |Sub-therapeutic dose: inhibits both excretion and reabsorption |

|Probenecid |Strongly inhibits penicillin excretion which is good if need long lasting penicillin |

| |performance |

| |Neutralizes stomach acid. |

|Weak Bases: |Magnesium Hydroxide – causes diarrhea |

|Aluminum Hydroxide |Aluminum hydroxide – causes constipation |

|Magnesium Hydroxide |Often combined to reduce side effects of each |

|PeptoBismol, Tums | |

| |Competitively inhibits binding of histamine to H2 receptors on parietal cells; reduces |

| |histamine stimulated gastric acid production |

|H2 Receptor Blockers: | |

|Cimetidine | |

|Ranitidine | |

| |Irreversible inhibition of H+/K+ ATPase in parietal cells |

|Proton Pump Inhibitors: |Only active at low pH (activity restricted to stomach) |

|Omeprazole |Inhibits acid production for 1-2days |

|Lansoprazole |Does not neutralize acid in stomach, only prevents production |

|Esomeprazole | |

|Rabeprazole | |

| | |

|Mucosal Protective Agents: |Misoprostol: PGE analog; stimulates mucus and HCO3 production |

|Misoprostol |Combined w/ NSAIDS |

|Sucralfate |Sucralfate: stabilizes mucus to inhibit H+ diffusion, not absorbed |

| | |

| |H1 Antagonists |

| |Muscarinic receptor antagonists |

|Antiemetic Drugs: |Benzodiazepines |

|Potential Treatment Options |D2 antagonists |

| |Cannabinoids |

| | |

|H1 Antagonists |Diphenhydramine, Meclizine, etc |

| |Blocks H1 (histamine) receptors competitively |

| | |

| |Scopolamine (anticholernergic) |

|Muscarinic Receptor Antagonists | |

| |Lorazempam; potentiates effects of GABA in CNS |

|Benzodiazepines | |

| | |

| | |

|D2 (dopamine) Antagonists: |Competitively blocks C2 receptors in the CTZ |

|Metoclopramide |Increases gastric emptying |

|Domperidone |Contraindicated in patients w/ Parkinson’s disease |

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| | |

| |Synthetic cannabinoids: Nabilone, Dronabinol |

|Cannabinoids | |

| |Acts as agonist at cannabinoid receptors in the CNS |

|Bulk Laxatives |Increases bowel content volume triggering stretch receptors |

| | |

| |Insoluble, expands with water |

|Carbohydrate Based |May cause constipation if not enough water |

|Vegetable Fibers, Bran | |

| |partially soluble/non-absrobable |

|Osmotically Active |potent and fast acting |

|Epsom salt | |

|Glauber’s salt | |

|Irritants: | |

|Ricinoleic acid (Castor Oil) |Castor oil converted to ricinoleic acid |

| |works in the small intestine |

| | |

|Anthraquinones | |

|Diphenolmethanes |Works in the large intestine |

|Bisacodyl | |

|Sodium picosulfate | |

| | |

| |Longer interval needed to refill colon, most common cause of constipation |

| |Loss of water/salt in gut leads to aldosterone release |

| |Causes excretion of K+ |

|Laxative Abuse | |

| |Opiod derivative that selectively acts in the GI tract (w/no CNS activity) |

| |Acts on the intestinal muscles reducing motility=increase in water and electrolyte |

|Antidiarrheal: |reabsorption |

|Loperamide |Dimethicone: anti-gas agent that is often combined with anti-diarrheal drugs |

|(Imodium) | |

|Insulin (unmodified) |short acting |

| |only insulin that can be administered thru iv |

| | |

| |rapid onset and short acting |

|Insulin Lispro (Humalog) | |

| |SC injection only, insulin + zinc ( micro-precipitates delayed absorption |

| |long lasting, UltraLente = longest lasting |

|Insulin Lente | |

| |SC injection only, insulin + zinc ( micro-precipitates delayed absorption |

|Insulin Lente |long lasting, UltraLente = longest lasting |

| | |

| | |

| |insulin + protamine (delayed absorption |

|NPH Insulin |long lasting |

| | |

| |Synthetic insulin that is soluble at low pH, but becomes insoluble and forms |

| |precipitates at neutral pH after SC administration |

|Insulin Glargine |long lasting (similar to Lente) |

|Lantus | |

| | |

|Sulfonylureas |Stimulates insulin release; useful for diabetes caused by low insulin levels where β- |

|Tolbutamide (1st gen.) |pancreatic cells are still present |

|Glimepiridide | |

|Glipizide | |

| | |

|Glitazones |Increases insulin sensitivity at target cells |

|Rosiglitazone |Acts as a nuclear hormone receptor (PPARγ agonist) increasing transcription of insulin |

|Pioglitazone |receptor signaling components and glucose transporters |

| | |

| |Unknown mechanism |

| |Increases glucose uptake & inhibits gluconeogenesis |

|Biguanides |Lowers LDL and VLDL |

|Metformin |Suppresses appetite |

| |No hypoglycemic effects |

| |Reversible HMG-CoA Reductase inhibitors. HMG-CoA reductase is the rate-limiting enzyme |

| |in the production of cholesterol. Inhibition effectively reduces de novo synthesis of |

|Statins |cholesterol precursors. |

|Lovastatin |Lower cholesterol levels upregulates LDL receptors in liver removing LDL from the |

|Atorvastatin (Lipitor) |bloodstream |

| |PPARα agonists – stimulates β-oxidation of fatty acids |

| |Promotes lipoprotein lipase activity |

|Fibrates |Lowers VLDL (minor effect on LDL) |

|Clofibrate |Increases HDL levels |

|Benzafibrate | |

| |Bile acid binding resins prevent reabsorption of bile acids in enterohepatic |

| |circulation, Increases cholesterol synthesis to make more bile acid-plasma cholesterol |

|Resins |levels remain unchanged. The liver also upregulates LDL receptors to increase hepatic |

|Cholestyramine |uptake of LDL (reducing plasma LDL) |

|Colestipol | |

| | |

| |Inhibit all phases of inflammation, inhibits NFκB, upregulates lipocortin (lipocortin |

| |inhibits PLA2, =no PT or LT synthesis, promotes fetal lung development by increasing |

|Glucorticoids (GCs) |surfactant |

|Addison’s Disease |Adrenal cortex failure, Lack of GC production |

| | |

| |Adrenal cortex tumors, GC overproduction |

|Cushing Syndrome | |

| | |

| |=Cortisol, main GC in humans |

| |Used for adrenal insufficiency (Addison’s Disease) |

|Hydrocortison |mostly topical application |

| |Binds with mineralcorticoid receptors |

| |Have Na retaining effects |

|Prednisone |Pro-drug; converted to active form (prednisolone) |

| | |

|Prednisolone |Drug of choice for systemic administration |

| |Lower Na retaining effects |

| |Stronger anti-inflammatory than cortisol |

|Triamcinoline |No Na retaining effect |

| | |

| |Betamethasone, Dexamethasone: 30x more potent than cortisol, no water or Na retaining |

|Halogenated GC |effects |

|Estrogens: |Produced from andgrogen precursors |

| |Estradiol=primary estrogen in human, breast devel, bone density, growth of uterus, |

|Estradiol |increase HDL, etc., no oral admin (1st pass hepatic elim) |

| | |

|Estrone |Estriol only during pregnancy |

| | |

|Estriol | |

|Ethinylestradiol |Most widely used |

| |Induce expression of progesterone receptors, Progesterone inhib expression of estrogen |

| |receptors |

| | |

| |Oral contraceptive |

|Diethyl-Stilbestrol | |

|Raloxifene |Indicated for postmenopausal osteoporosis, Selective estrogen receptor modifier (SERM), |

| |Anti-estrogenic effect on breast and endometrium, Estrogenic effect on bone and lipid |

| |metabolism |

| | |

| |Oral contraceptives, prodrug |

| | |

|Mestranol | |

| | |

|Tamoxifene | |

|(antiestrogen) |Indicated for breast cancer |

| |anti-estrogenic effect on breast tissue |

| |weak effect on bone and lipid metabolism |

|Progesterones: |Inhibits rhythmic contractions of myometrium, not for oral admin (1st pass elim) |

| | |

|Progesterone | |

| |Stable derivatives |

|Hydroxyprogesterone | |

| | |

|Medroxyprogesterone | |

| | |

|Progesterone | |

| |Testosterone derivatives with progesterone activity |

|Norethindrone | |

|Norgestrel | |

|Desogestrel | |

| |1980s French company, found that it blocks progesterone receptors, induces abortion |

|Anti-Progesterones |Addition of small doses of prostaglandin analogue few days later stimulates uterine |

|Mifepristone |contractions=very efficacious for termination of pregnancy |

|Testosterone |Responsible for both anabolic and androgenic effects |

| |Rapidly metabolized by the liver. |

| |-ester derivatives increases its half-life |

| | |

|Nandrolone |Strong anabolic effects, Injection only |

|(banned) | |

| | |

| | |

|Stanozolol |Strong anabolic effects (Not a β blocker!) |

|(banned) |Oral admin |

| |Dehydroepiandrosterone. Marketed as an anabolic steroid |

| |Misleading b/c it’s a precursor for both testosterone and estrogen. |

|DHEA |High levels of DHEA may lead to elevated levels of testosterone and estrogen. |

| | |

| | |

|Flutamide |Used to treat prostate cancer |

| |Competitive androgen receptor antagonist |

| |Blocks testosterone stimulating effects |

| | |

| |Treats prostate gland enlargement and baldness, blocks the conversion of testosterone to|

|Finasteride |DHT (testosterone metabolite that is much more potent) |

| |Bald men have elevated levels of DHT |

| | |

| |Treats endometriosis (growth of endometrium outside of the uterus) |

|Danazol |Inhibits GnRH release, no LH/FSH production=no steroid production |

|Synthetic GnRH |Given in pulses (s.c.), induced ovulation (stimulates LH/FSH) |

|-Gonadorelin |Given continuously, medical castration (desensitize GnRH receptors) |

|-Buserelin | |

| |Bile acid binding resins prevent reabsorption of bile acids in enterohepatic |

| |circulation, Increases cholesterol synthesis to make more bile acid-plasma cholesterol |

|Resins |levels remain unchanged. The liver also upregulates LDL receptors to increase hepatic |

|Cholestyramine |uptake of LDL (reducing plasma LDL) |

|Colestipol | |

| | |

| |Inhibit all phases of inflammation, inhibits NFκB, upregulates lipocortin (lipocortin |

| |inhibits PLA2, =no PT or LT synthesis, promotes fetal lung development by increasing |

|Glucorticoids (GCs) |surfactant |

|Addison’s Disease |Adrenal cortex failure, Lack of GC production |

| | |

| |Adrenal cortex tumors, GC overproduction |

|Cushing Syndrome | |

| | |

| |=Cortisol, main GC in humans |

| |Used for adrenal insufficiency (Addison’s Disease) |

|Hydrocortison |mostly topical application |

| |Binds with mineralcorticoid receptors |

| |Have Na retaining effects |

|Prednisone |Pro-drug; converted to active form (prednisolone) |

| | |

|Prednisolone |Drug of choice for systemic administration |

| |Lower Na retaining effects |

| |Stronger anti-inflammatory than cortisol |

|Triamcinoline |No Na retaining effect |

| | |

| |Betamethasone, Dexamethasone: 30x more potent than cortisol, no water or Na retaining |

|Halogenated GC |effects |

|Estrogens: |Produced from andgrogen precursors |

| |Estradiol=primary estrogen in human, breast devel, bone density, growth of uterus, |

|Estradiol |increase HDL, etc., no oral admin (1st pass hepatic elim) |

| | |

|Estrone |Estriol only during pregnancy |

| | |

|Estriol | |

|Ethinylestradiol |Most widely used |

| |Induce expression of progesterone receptors, Progesterone inhib expression of estrogen |

| |receptors |

| | |

| |Oral contraceptive |

|Diethyl-Stilbestrol | |

|Raloxifene |Indicated for postmenopausal osteoporosis, Selective estrogen receptor modifier (SERM), |

| |Anti-estrogenic effect on breast and endometrium, Estrogenic effect on bone and lipid |

| |metabolism |

| | |

| |Oral contraceptives, prodrug |

| | |

|Mestranol | |

| | |

|Tamoxifene | |

|(antiestrogen) |Indicated for breast cancer |

| |anti-estrogenic effect on breast tissue |

| |weak effect on bone and lipid metabolism |

|Progesterones: |Inhibits rhythmic contractions of myometrium, not for oral admin (1st pass elim) |

| | |

|Progesterone | |

| |Stable derivatives |

|Hydroxyprogesterone | |

| | |

|Medroxyprogesterone | |

| | |

|Progesterone | |

| |Testosterone derivatives with progesterone activity |

|Norethindrone | |

|Norgestrel | |

|Desogestrel | |

| |1980s French company, found that it blocks progesterone receptors, induces abortion |

|Anti-Progesterones |Addition of small doses of prostaglandin analogue few days later stimulates uterine |

|Mifepristone |contractions=very efficacious for termination of pregnancy |

|Testosterone |Responsible for both anabolic and androgenic effects |

| |Rapidly metabolized by the liver. |

| |-ester derivatives increases its half-life |

| | |

|Nandrolone |Strong anabolic effects, Injection only |

|(banned) | |

| | |

| | |

|Stanozolol |Strong anabolic effects (Not a β blocker!) |

|(banned) |Oral admin |

|Combination Pills |Highly effective, Estrogen component: Ethinylestradiol, Progesterone component varies |

| |Biphasic preparation – includes progesterone break after 7 day break |

| |Monophasic preparation – no progesterone break (but [progesterone] varies throughout |

| |cycle) |

|Mini Pill |Less reliable than combination pills |

| |Contains only progesterone, used when estrogen is contraindicated |

| |Contraception mechanism relies mainly on increased mucus viscosity. |

| |-mucolytic agents (cough medications) may cause contraception failure |

| | |

| | |

|Morning After Pill |High dose of progesterone |

|Levonorgestrel |Must be taken within 72 hours of sexual intercourse |

|Dephenhydramine |H1 antagonists (antihistamine), 1st generation |

|(Benadryl) |Indicated for seasonal and skin allergies |

| | |

| |Anti-emetic |

|Dimenhydrinate |Also blocks mAChRs |

|(Dramamine) | |

|Doxyamine |H1 antagonist, 1st generation |

|(Nyquil) |Most potent OTC sedative (better than barbiturates) |

| |Same efficacy as diphenhydramine in terms of anti-allergies |

| | |

| | |

|Clemastine | |

| |1st generation H1 antagonist |

|Chlorpheniramine |Also anti-depressant (inhib serotonin uptake) |

| | |

| |Antiemetic (less drowsiness) |

|Meclizine | |

| |Antihistamine due to metabolite |

|Hydroxyzine | |

|Cetrizine |2nd generation H1 antagonist |

| | |

|Loratadine |No entry to CNS, no drowsiness T ½=8 hr |

| | |

|Desloratadine |Longer T ½ |

| | |

|Fexofenadine |Highly selective for H1 receptor |

|Cromolyn | |

| |Mast cell stabilizer |

| |Prevents asthma, does not stop attack |

|Nedocromil |Prevents mediator release from mast cells |

| |Inhalation or eye drops |

|Montelukast (Singulair) |Leukotriene Receptor Blockers |

| | |

| |Prevents exercise and aspirin-induced asthma |

| |Antagonist of LTD4 at cysteinyl LT receptor |

| | |

|Zileuton (Zyflo) |5-Lipoxygenase Inhibitor |

| | |

| |Prevents production of all leukotrienes |

| |Not useful for treatment of attacks |

|Barbiturates |General inhibition of the CNS w/ |

| |sedative-hypnotic actions Augments |

| |GABA responses (by potentiating GABA |

| |signal) and mimics GABA (by opening |

| |Cl-channels in the absence of GABA). |

| |Keeps Cl channels open longer, |

| |hyperpolarizing the cell preventing |

| |further excitation. Alsoblocks excitatory |

| |glutamate receptors |

|phenobarbital |Barbituates |

| |epilepsy (phenobarbital) and anesthesia induction (thiopental) |

|thiopental |Side effects/Risks: |

| |high risk of dependence (severe/lethal withdrawal symptoms) |

|Amobarbital |may lead to cardio-respiratory depression |

|Pentobarbital |potent inducers of P450 enzymes; drug interactions (contraceptives, etc.) |

|Secobarbital | |

|Benzodiazepines |Seven-membered ring fused to aromatic ring, Selective activates GABA receptor operated |

| |Cl channels, Increase affinity of GABA for rec., Treat Anxieties, fewer side effects |

|Chlordiazepoxide, Diazepam, Lorazepam, Flunitrazepam, Alprazolam, Triazolam |than barb., anterograde amnesia |

|MAO Inhibitors as Antidepressants |Increase norepinephrine, serotonin, and dopamine (prevents metab) |

|Tranylcypromine |Side effects high |

|Phenelzine |Food-drug interaction: cheese |

|SSRIs |Increase serotonin levels by preventing neuronal reuptake |

| |Same efficacies as TCAs, fewer side effects |

|Fluoxetine |Inhib sexual climax, can cause aggression |

|Paroxetine | |

|Sertraline | |

|Clotalopram | |

|Tricyclic Antidepressants |Increase norepinephrine and serotonin by preventing neuronal reuptake, strong |

|Imipramine |interaction with alcohol. Sedation=side effect |

|Desipramine | |

|Clomipramine… | |

|Phenothiazines |Treat Schizophrenia |

| |1st gen: neuroleptic |

|Butyrophenones |Block dopamine receptor on post synaptic vesicle, Cause acute dystoni, akathesia, |

| |tardive dyskinesia, sedation, dry mouth, lactation, interaction with alcohol |

|Clozapine |Atypical Neuroleptics (2nd gen) |

| |Inhibit 5-HT and D2 receptors, act mostly on limbic system, not in striatum (fewer side |

|Olanzapine |effects) |

|L-dopa (Levodopa) |Treat Parkinsons Disease |

| |Metabolic precursor of dopamine, often combined with Carbidopa (LDOPA decarboxylase |

|Carbidopa |inhib). Increases amt of L-Dopa that reaches the brain |

|Bromcriptine |Dopamine Agonists |

| |Similar to L-dopa |

|Pergolide |D2 agonists, treat Parkinsons |

| | |

|Pramipexole | |

| | |

| |Inhib of MAOb, extends half-life of dopamine, Indirect dopamine agonists, Treats |

| |Parkinsons, also antidepressant |

|Selegiline | |

| |Muscarinic acetylcholine receptor antagonist. |

| |Reduces cholinergic signals in the CNS (responsible for stimulating GABA output |

|Atropine |suppressing the thalamus) |

| | |

| |No longer used for Parkinson’s disease |

| |Blocks voltage gated Na channels that are in the inactivated state, preferentially |

| |blocks high frequency discharges. (use-dependent inhibition) |

| |(does not elevate seizure threshold, limits the propagation and spread of seizure), Zero|

|Phenytoin |order kinetics, Indicated for convulsive seizures, Side Effect: hyperplasia |

| |Treats Epilepsy, inhib of ca channels, |

|Ethosuximide |Etho=blocks T-type channels, drug of choice for absence seizures |

| | |

|Valproate |Val=mech unclear, good for convulsive and absence seizures |

| |Hepatotoxic |

| |Treats alcholoism |

| |inhibits aldehyde dehydrogenase; leading to acetylaldehyde accumulation causing |

| |“hang-over” |

|Disulfuram |-also blocks the conversion of dopamine to NE, rise in dopamine levels causes |

| |schizophrenic symptoms |

| | |

| | |

|Naltrexone |Treats Alcoholism |

| |opiod receptor antagonist; inhibiting the reward response that normally results for |

| |alcohol consumption |

| |IV anesthetic |

| |Rapid onset with high lipid solubility (accumulates in fat); slow recovery |

|Thiopental |Narrow therapeutic range |

|(barbiturate) |No analgesic effect |

| |IV anesthetic |

| |Rapidly metabolized for quick recovery. |

|Propofol |Used for same-day surgery |

| |IV anesthetic |

| |Phencyclidine (PCP) analogue; may cause hallucinations during recovery |

|Ketamine |Have both anesthetic and analgesic properties |

| |-often used in veterinarian medicine and in tranqulizers |

| |IV anesthetic |

| |Benzodiazepine. Very short-acting. |

|Midazolam |Have all benzodiazepine properties, often used for anesthesia induction |

| | |

| | |

|Ether |Obsolete |

| |Slow onset and recovery |

| |Post operative nausea, vomiting |

| |Low potency (must be combined with other agents to achieve anesthesia) |

|Nitrous Oxide |Rapid induction and recovery |

| |Both anesthetic and analgesic properties |

| |High potency anesthetic; combined w/ N2O |

| |No analgesic properties. |

|Haloethanes |Some hepatic metabolism occurs; repeated use causes hepatoxicity |

| |Also causes hypotension (thru vasodilation and cardiac suppression) |

| | |

| |High potency anesthetic; similar to haloethanes |

|Enfluran |Fewer side effects because less metabolized by liver. |

|Isofluran | |

|Desfluran | |

| |CNS – sedation, nausea, and cough suppression |

|Morphine |Respiratory System – reducing frequency and depth of breathing |

| |GI Tract – increases segmentation and decreases peristalsis (constipation) |

| |Eyes – papillary constriction (due to parasympathetic activation) |

|Codeine |Pro-drug, that is converted into morphine by CYP2D6. |

| |CYP2D6 inhibitors may reduce codeine efficacy, Genetic polymorphism may also explain |

| |codeine resistance |

| |Little euphoric effect, so low risk for addiction.Used as an anti-tussive (cough |

| |suppressant) |

| | |

| |Synthetic morphine derivative that does not act thru opioid receptors. |

|Dextromethrophan |Same efficacy as codeine |

| |No GI or analgesic effect |

|Heroin |Diamorphine; diacylated-morphine is more lipophilic than morphine so it crosses the |

| |blood-brain barrier more rapidly producing a greater rush. |

| |2x more potent than morphine |

|Hydrocodone | |

| | |

| |Vicodin; often combined w/ NSAIDs for synergistic effect |

| | |

| |Indicated for chronic pain. |

|Oxycodone |Addicts chew thru the slow release formulation to obtain immediate release to mimic |

| |heroin rush |

| | |

| |Similar to morphine, but shorter duration. |

|Meperidine |Used during labor. |

| |Similar to morphine, but much longer duration. |

| |Used to treat morphine/heroin addiction |

| | |

|Methadone | |

| |High potency. Can be used transdermally. |

| |Short-lasting. Used in anesthesia and patient controlled infusions. |

| | |

|Fentanyl | |

| | |

| |Opiate Antagonist |

|Naloxone |Short-acting competitive antagonist used to rapidly reverse opioid induced analgesia and|

| |respiratory suppression |

| | |

| |Opiate Antagonist |

|Naltrexone |Long-acting competitive antagonist |

| |Used to protect detoxified addicts from relapsing |

|Cocaine |-contains ester bond; rapidly metabolized by non-specific esterases in the plasma |

| |-cocaine’s CNS effects are independent from its analgesic effect |

| |(blocks reuptake of DA, 5-HT, NE) |

|Lidocaine |-contains amide bond; longer acting compared to local anesthetics w/ ester bonds |

|Classification of |Cell wall synth inhib |

|Antibiotics | |

| |Protein synth inhib |

| | |

| |Folate antagonists |

| | |

| |Quinolones |

|Penicillins | |

|Cephalosporins | |

|Carbapenems |All Beta-Lactam Antibiotics |

|Monbactams | |

|Vancomycin, Bacitracin | |

| |Penicillins, cell wall synth inhib |

|Benzylpenicillin |Inhibit transpeptidase, cant make cell wall |

| |Beta-lactamase sensitive |

|Phenoxymethylpenicillin |Narrow spectrum |

| |Phenoxy has better oral avail |

| |G+ bacteria |

| | |

|Methicillin |Narrow spectrum, b-lactamase resistant |

|Oxacillin |Cell wall synth inhib |

|Cloxacillin |G+ bacteria |

|Dicloxacillin |Methicillin=poor oral avail |

| |Oxacillin=good oral avail |

| | |

| | |

|Ampicillin |Broad spectrum, penicillinase sensitive |

| |Cell wall synth inhib |

|Amoxicillin |Amp=good oral avail, G+ and G-, entero |

| |Amox=excellent oral avail |

|Carbenicillin |Extended spectrum, b=lactamase sensitive, cell wall synth inhib |

|Ticarcillin |Carb=poor oral avail, G+ and G-, pseudomonas, Klebsiella |

|Mezlocillin | |

|Pipercillin | |

| | |

| |B-lactamase sensitive |

|Cefazolin |Cell wall synth inhib |

|Cephalexin |1st generation cephalorsporins |

| |Cross allergies with pen. |

| |G+ bacteria |

| | |

|Cefaclor |2nd generation Cephalosporins |

| |B-lactamase sensitive |

|Cefamandole |Cell wall synth inhib |

| |Some G-, mostly G+ |

|Cefoxitin | |

| | |

|Clavulanic Acid |B-lactamase inhib, cell wall synth inhib |

| |Irreversible inhib, good oral absorption |

|Sulbactam |Often combined with amoxicillin or ticarcillin |

| | |

|Vancomycin |Cell wall syth inhib |

| |Vanc=only effective against G+, poor oral absorption, used to treat GI infections |

|Bacitracin |Bacitracin=mixture of polypeptides, serious nephrotoxicity |

| | |

|Aminoglycosides |Protein synth inhib |

|Tetracyclins |Inhibit either 30s or 50s ribosomal unit |

|Macrolides |Drugs need to enter bacteria (point of resistance) |

|Chloramphenicol | |

|Clindamycin | |

|Gentamicin | |

|Tobramycin |Aminoglycosides (protein synth inhibitors) |

|Streptomycin | |

|Neomycin | |

|Kanamycin | |

|Amikacin | |

| |Tetracyclines, energy dependent transport, oral absorption impaired by food (antacids, |

| |Ca) |

|Tetracycline |Incorp into teeth and bones=staining, causes photosensitivity |

|Oxytetracycline |Broad spectrum antibiotics |

|Minocycline | |

|Doxycycline | |

| |Macrolides |

|Erythromycin |Narrow spectrum, good alternative for patients with allergy to pen, few side effects |

|Azithromycin |Azi=long T ½ , convenient 6 pills regimen |

|Clarithromycin |Clarith=used for H. pylori infection |

| |Protein synth inhib |

|Chloramphenicol |Chlor=broad spectrum, severe side effects, reserved for life threatening situations |

| |Clind=medium broad spectrum, treat pen resistant cocci |

|Clindamycin |Side effect=collitis |

|Sulfonamides | |

| |Folate antagonist, blocks folate synth=blocked replication |

|Sulfadiazine |Structural analogues of PABA |

|Sulfadimidine | |

|Sulfamethoxazole | |

| | |

|Trimethroprim |Competes with folates fro Dihydrofolate-reductase (folate antag), Similar to |

| |sulfonamides, combined with Sulfomethoxazole |

| |Treat UTIs |

| | |

| | |

|Quinolones |Inhibit DNA-Gyrase (Topoisomerase II), very broad spectrum, bactericidal, usually |

|Nalidixic acid |fluorinated |

|Ciprofloxacin |(Fluoroquinolones) |

|…floxacin | |

| | |

| | |

| | |

| | |

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