Drugs Affecting Motor Function
The smallest structural unit of skeletal musculature is the striated muscle fiber. It contracts in response to an impulse of its motor nerve. In executing motor programs, the brain sends impulses to the spinal cord. These converge on a-moto-neurons in the anterior horn of the spinal medulla. Efferent axons course, bundled in motor nerves, to skeletal muscles. Simple reflex contractions to sensory stimuli, conveyed via the dorsal roots to the motoneurons, occur without participation of the...
iron Compounds
Not all iron ingested in food is equally absorbable. Trivalent Fe3 is virtually not taken up from the neutral milieu of the small bowel, where the divalent Fe2 is markedly better absorbed. Uptake is particularly efficient in the form of heme present in hemo- and myoglobin . Within the mucosal cells of the gut, iron is oxidized and either deposited as ferritin see below or passed on to the transport protein, transferrin, a Pi-gly-coprotein. The amount absorbed does not exceed that needed to...
Diuretics of the Sulfonamide Type
These drugs contain the sulfonamide group -SO2NH2. They are suitable for oral administration. In addition to being filtered at the glomerulus, they are subject to tubular secretion. Their concentration in urine is higher than in blood. They act on the luminal membrane of the tubule cells. Loop diuretics have the highest efficacy. Thiazides are most frequently used. Their forerunners, the carbonic anhydrase inhibitors, are now restricted to special indications. Carbonic anhydrase CAH inhibitors,...
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Rapid and complete conversion in liver to hydrophilic metabolite Rapid and complete conversion in liver to hydrophilic metabolite A. Elimination of hydrophilic and hydrophobic drugs Drug Concentration in the Body as a Function of Time. First-Order Exponential Rate Processes Processes such as drug absorption and elimination display exponential characteristics. As regards the former, this follows from the simple fact that the amount of drug being moved per unit of time depends on the...
B Antiarrhythmics of the Nachannel blocking type
Electrophysiological Actions of Antiarrhythmics of the Na -Channel Blocking Type Action potential and ionic currents. The transmembrane electrical potential of cardiomyocytes can be recorded through an intracellular microelectrode. Upon electrical excitation, a characteristic change occurs in membrane poten-tial the action potential AP . Its underlying cause is a sequence of transient ionic currents. During rapid depolarization Phase 0 , there is a short-lived influx of Na through the membrane....
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Glyceryltrinitrate nitroglycerin Algocor, Corgal, Procorum, Wingom Cytovene, Vitrasert Gelafundin, Haemaccel Lopid Cidomycin, Garamycin, Refobacin, Sulmycin Daonil, DiaBeta, Euglucon, Glynase, Micronase Amaryl Glucotrol Ang-O-Span, Nitrocap, Nitrogard, Nitroglyn, Nitrolingual, Nitrong, Nitrostat Robinul Factrel, Kryptocur, Relefact Zoladex Gramoderm Kytril Fulvicin, Grisovin, Likuden Wytensin Ismelin, Visutensil Tenex
Coumarin Derivatives A
Vitamin K promotes the hepatic Y-car-boxylation of glutamate residues on the precursors of factors II, VII, IX, and X, as well as that of other proteins, e.g., protein C, protein S, or osteocalcin. Carbox-yl groups are required for Ca2 -mediat-ed binding to phospholipid surfaces p. 142 . There are several vitamin K derivatives of different origins K1 phy-tomenadione from chlorophyllous plants K2 from gut bacteria and K3 menadione synthesized chemically. All are hydrophobic and require bile...
Drugs Used to Influence Smooth Muscle Organs
Bronchodilators. Narrowing of bronchioles raises airway resistance, e.g., in bronchial or bronchitic asthma. Several substances that are employed as bronchodilators are described elsewhere in more detail 2-sympathomimetics p. 84, given by pulmonary, parenteral, or oral route , the methylxanthine theo-phylline p. 326, given parenterally or orally , as well as the parasympatholytic ipratropium pp. 104, 107, given by inhalation . Spasmolytics. N-Butylscopolamine p. 104 is used for the relief of...
Calcium Antagonists
During electrical excitation of the cell membrane of heart or smooth muscle, different ionic currents are activated, including an inward Ca2 current. The term Ca2 antagonist is applied to drugs that inhibit the influx of Ca2 ions without affecting inward Na or outward K currents to a significant degree. Other labels are Ca-entry blocker or Ca-channel blocker. Therapeutically used Ca2 antagonists can be divided into three groups according to their effects on heart and vasculature. I....
B 1
Bacitracin Baclofen Basiliximab Beclomethasone Bismuth subsalicylate Bisoprolol Bitolterol Bleomycin Aldecin, Beclovent, Beconase, Becotide, Propaderm, Madopar plus Levodopa Bicillin, Megacillin, Tardocillin Cogentin Desuric, Narcaricin, Normurat, Uricovac Anaesthesin, Americaine, Anacaine Betoptic, Kerlone Befizal, Bezalip, Bezatol, Cedur Amycor, Bedriol, Mycospor, Mycosporan Akineton, Akinophyl Bicol, Broxalax, Durolax, Dulcolax, Laxanin, Laxbene, Concor, Detensiel, Emcor, Isoten, Soprol,...
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Noradrenalin Norepinephrine Norethisterone Norethindrone Norfloxacin Anabolin, Androlone, Deca-Durabolin, Hybolin Decano-ate, Kabolin Niclocide, Yomesan Adalat, Procardia Nimotop Sular Atempol, Mogadon Bayotensin, Baypress See Glyceryl trinitrate Nipride, Nitropress Axid Tranxilium N, Vegesan Arterenol, Levophed Micronor Norlutin, Nor-Q D Noroxin Korostatin, Mycostatin, Mykinac, Nilstat, Nystex, O-V Statin
Treatment of InsulinDependent Diabetes Mellitus
Juvenile onset type I diabetes mellitus is caused by the destruction of insulin-producing B cells in the pancreas, necessitating replacement of insulin daily dose approx. 40 U, equivalent to approx. 1.6 mg . Therapeutic objectives are 1 prevention of life-threatening hypergly-cemic diabetic coma 2 prevention of diabetic sequelae angiopathy with blindness, myocardial infarction, renal failure , with precise titration of the patient being essential to avoid even short-term spells of pathological...
Diuretics An Overview
Diuretics saluretics elicit increased production of urine diuresis . In the strict sense, the term is applied to drugs with a direct renal action. The predominant action of such agents is to augment urine excretion by inhibiting the reabsorption of NaCl and water. The most important indications for diuretics are Mobilization of edemas A In edema there is swelling of tissues due to accumulation of fluid, chiefly in the extracellular interstitial space. When a diuretic is given, increased renal...
Systems Pharmacology
In the course of phylogeny an efficient control system evolved that enabled the functions of individual organs to be orchestrated in increasingly complex life forms and permitted rapid adaptation to changing environmental conditions. This regulatory system consists of the CNS brain plus spinal cord and two separate pathways for two-way communication with peripheral organs, viz., the somatic and the autonomic nervous systems. The somatic nervous system comprising extero- and interoceptive...
Antidiarrheal Agents
Causes of diarrhea in red Many bacteria e.g., Vibrio cholerae secrete toxins that inhibit the ability of mucosal ente-rocytes to absorb NaCl and water and, at the same time, stimulate mucosal secretory activity. Bacteria or viruses that invade the gut wall cause inflammation characterized by increased fluid secretion into the lumen. The enteric musculature reacts with increased peristalsis. The aims of antidiarrheal therapy are to prevent 1 dehydration and electrolyte depletion and 2...
Nonsteroidal Antiinflammatory Antirheumatic Agents
At relatively high dosage gt 4 g d , ASA p. 198 may exert antiinflammatory effects in rheumatic diseases e.g., rheumatoid arthritis . In this dose range, central nervous signs of overdosage may occur, such as tinnitus, vertigo, drowsiness, etc. The search for better tolerated drugs led to the family of non-steroidal antiinflammatory drugs NSAIDs . Today, more than 30 substances are available, all of them sharing the organic acid nature of ASA. Structurally, they can be grouped into carbonic...
Hoch2ch2nch3
A. Examples of chemical reactions in drug biotransformation hydrolysis A. Examples of chemical reactions in drug biotransformation hydrolysis Oxidation reactions can be divided into two kinds those in which oxygen is incorporated into the drug molecule, and those in which primary oxidation causes part of the molecule to be lost. The former include hydroxylations, epoxidations, and sulfoxidations. Hydroxylations may involve alkyl substitu-ents e.g., pentobarbital or aromatic ring systems e.g.,...
Inhibitors of Tetrahydrofolate Synthesis
Tetrahydrofolic acid THF is a co-enzyme in the synthesis of purine bases and thymidine. These are constituents of DNA and RNA and required for cell growth and replication. Lack of THF leads to inhibition of cell proliferation. Formation of THF from dihydrofolate DHF is catalyzed by the enzyme dihy-drofolate reductase. DHF is made from folic acid, a vitamin that cannot be synthesized in the body, but must be taken up from exogenous sources. Most bacteria do not have a requirement for folate,...
a Small Bowel Irritant Purgative Ricinoleic Acid
Castor oil comes from Ricinus communis castor plants Fig sprig, panicle, seed it is obtained from the first cold-pressing of the seed shown in natural size . Oral administration of 10-30 mL of castor oil is followed within 0.5 to 3 h by discharge of a watery stool. Ricinoleic acid, but not the oil itself, is active. It arises as a result of the regular processes involved in fat digestion the duodenal mucosa releases the enterohormone cholecystokinin pancreozymin into the blood. The hormone...
Drugs for Treating Endo and Ectoparasitic Infestations
Adverse hygienic conditions favor human infestation with multicellular organisms referred to here as parasites . Skin and hair are colonization sites for arthropod ectoparasites, such as insects lice, fleas and arachnids mites . Against these, insecticidal or arachnici-dal agents, respectively, can be used. Endoparasites invade the intestines or even internal organs, and are mostly members of the phyla of flatworms and roundworms. They are combated with anthelmintics. Anthelmintics. As shown in...
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D. Protein synthesis-regulating receptor Mode of Operation of G-Protein-Coupled Receptors Signal transduction at G-protein-cou-pled receptors uses essentially the same basic mechanisms A . Agonist binding to the receptor leads to a change in receptor protein conformation. This change propagates to the G-protein the a-subunit exchanges GDP for GTP, then dissociates from the two other subunits, associates with an effector protein, and alters its functional state. The a-subunit slowly hydrolyzes...
Info Pxe
Tertatolol Carvedilol Esmolol Bopindolol Bisoprolol Celiprolol Betaxolol Befunolol Carteolol Mepindolol Penbutolol Carazolol Nadolol Acebutolol Bunitrolol Atenolol Metipranol Metoprolol Timolol Sotalol Talinolol Oxprenolol Pindolol Bupranolol Alprenolol B. Avalanche-like increase in commercially available -sympatholytics Antiadrenergics are drugs capable of lowering transmitter output from sympathetic neurons, i.e., sympathetic tone. Their action is hypotensive indication hypertension, p. 312...
Local Anesthetics
Local anesthetics reversibly inhibit impulse generation and propagation in nerves. In sensory nerves, such an effect is desired when painful procedures must be performed, e.g., surgical or dental operations. Mechanism of action. Nerve impulse conduction occurs in the form of an action potential, a sudden reversal in resting transmembrane potential lasting less than 1 ms. The change in potential is triggered by an appropriate stimulus and involves a rapid influx of Na into the interior of the...
Info Hqc
Drops, mixture, effervescent solution A. Oral administration drug release and absorption A. Oral administration drug release and absorption the rectum or vagina. The resulting oily film spreads over the mucosa and enables the drug to pass into the mucosa. Powders, ointments, and pastes p. 16 are applied to the skin surface. In many cases, these do not contain drugs but are used for skin protection or care. However, drugs may be added if a topical action on the outer skin or, more rarely, a...
Nondepolarizing muscle relaxants
Curare is the term for plant-derived arrow poisons of South American natives. When struck by a curare-tipped arrow, an animal suffers paralysis of skeletal musculature within a short time after the poison spreads through the body death follows because respiratory muscles fail respiratory paralysis . Killed game can be eaten without risk because absorption of the poison from the gastrointestinal tract is virtually nil. The curare ingredient of greatest medicinal importance is d-tubocurarine....
Antitubercular Drugs 1
Drugs of choice are isoniazid, rifampin, ethambutol, along with streptomycin and pyrazinamide. Less well tolerated, second-line agents include p-aminosal-icylic acid, cycloserine, viomycin, ka-namycin, amikacin, capreomycin, ethi-onamide. Isoniazid is bactericidal against growing M. tuberculosis. Its mechanism of action remains unclear. In the bacterium it is converted to isonicotinic acid, which is membrane impermeable, hence likely to accumulate intracellu-larly. Isoniazid is rapidly absorbed...
Antimalarials
The causative agents of malaria are Plasmodia, unicellular organisms belonging to the order hemosporidia class protozoa . The infective form, the sporozoite, is inoculated into skin capillaries when infected female Anopheles mosquitoes A suck blood from humans. The sporo-zoites invade liver parenchymal cells where they develop into primary tissue schizonts. After multiple fission, these schizonts produce numerous mero-zoites that enter the blood. The pre-erythrocytic stage is symptom free. In...
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Ephedrine Eprosartan Eptifibatide Ergocalciferol Etodolac Etomidate Etoposide Etretinate Ecostatin, Gyno-Pevaryl Phospholine Iodide Vasotec, Xanef Ethrane Adrenalin, Bronchaid, Epifin, Epinal, EpiPen, Epitrate, Lyophrin, Simplene, Suprarenin, Vaponefrine Ergotrate Maleate, Ermalate Ergotrate Ergomar, Gynergen, Migril E-mycin, Eryc, Erythromid Dowmycin, Ilosone, Novorythro EES, Erythrocin, Wyamycin Cimetrin Delestrogen, Dioval, Femogex, Progynova Apocretin, Effontil, Effortil, Ethyl Adrianol,...
S 1
Sulfadoxine Pyrimethamine Sulfamethoxazole Sulfapyridine Sulfisoxazole Azaline, Azulfidine, S.A.S.-500, Salazopyrin Proventil, Novosalmol, Ventolin Acnex, Sebcur, Soluver, Trans-Ver-Sal Serevent Black Draught, Fletcher's Castoria, Genna, Gentle Kabikinase, Streptase Strepolin, Streptosol Zanosar AK-Sulf Forte, Cetamide, Sulamyd, Sulair, Sulfex, Sulten Gamazole, Gantanol, Methanoxanol Dagenan
Follicular Growth and Ovulation Estrogen and Progestin Production
Follicular maturation and ovulation, as well as the associated production of female gonadal hormones, are controlled by the hypophyseal gonadotropins FSH follicle-stimulating hormone and LH luteinizing hormone . In the first half of the menstrual cycle, FSH promotes growth and maturation of ovarian follicles that respond with accelerating synthesis of estradiol. Estradiol stimulates endometrial growth and increases the permeability of cervical mucus for sperm cells. When the estradiol blood...
Opioid AnalgesicsMorphine Type
Source of opioids. Morphine is an opium alkaloid p. 4 . Besides morphine, opium contains alkaloids devoid of analgesic activity, e.g., the spasmolytic pa-paverine, that are also classified as opium alkaloids. All semisynthetic derivatives hydromorphone and fully synthetic derivatives pentazocine, pethidine meperidine, l-methadone, and fentanyl are collectively referred to as opioids. The high analgesic effectiveness of xenobiotic opioids derives from their affinity for receptors normally acted...
Pharmacokinetics of Benzodiazepines
All benzodiazepines exert their actions at specific receptors p. 226 . The choice between different agents is dictated by their speed, intensity, and duration of action. These, in turn, reflect physico-chemical and pharmacokinetic properties. Individual benzodiazepines remain in the body for very different lengths of time and are chiefly eliminated through biotransformation. Inactivation may entail a single chemical reaction or several steps e.g., diazepam before an inactive metabolite suitable...
inhibitors of the RAA System
Angiotensin-converting enzyme ACE is a component of the antihypotensive renin-angiotensin-aldosterone RAA system. Renin is produced by specialized cells in the wall of the afferent arteriole of the renal glomerulus. These cells belong to the juxtaglomerular apparatus of the nephron, the site of contact between afferent arteriole and distal tubule, and play an important part in controlling nephron function. Stimuli eliciting release of renin are a drop in renal perfusion pressure, decreased rate...
Insulin Therapy
Insulin is synthesized in the B- or p- cells of the pancreatic islets of Langerhans. It is a protein MW 5800 consisting of two peptide chains linked by two disulfide bridges the A chain has 21 and the B chain 30 amino acids. Insulin is the blood-sugar lowering hormone. Upon ingestion of dietary carbohydrates, it is released into the blood and acts to prevent a significant rise in blood glucose concentration by promoting uptake of glucose in specific organs, viz., the heart, adipose tissue, and...
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A. Chemical structure of catecholamines and affinity for a- and -receptors Enteral absorbability CNS permeability Catecholamine-O-methyltransferase Enteral absorbability CNS permeability Catecholamine-O-methyltransferase I I Affinity for a-receptors I I Affinity for -receptors I I Resistance to degradation I I Absorbability B. Structure-activity relationship of epinephrine derivatives Apart from receptors, adrenergic neurotransmission involves mechanisms for the active re-uptake and re-storage...
Info Vvh
B. Bronchial asthma treatment algorithm In emesis the stomach empties in a retrograde manner. The pyloric sphincter is closed while the cardia and esophagus relax to allow the gastric contents to be propelled orad by a forceful, synchronous contraction of abdominal wall muscles and diaphragm. Closure of the glottis and elevation of the soft palate prevent entry of vomitus into the trachea and nasopharynx. As a rule, there is prodromal salivation or yawning. Coordination between these different...
A Wgf
Abacavir Abciximab Acarbose Acebutolol s-Aminocaproic acid Thromboplastin denotes investigational drug status in USA Monitan, Sectral Sintrom see Paracetamol Diamox, Glaupax Airbron, Fabrol, Mucomyst, Parvolex Acylanid Aspirin, Arthrisin, Asadrine, Ecotrin, Entrophen, Pyronoval, Supasa Zovirax Alloprin, Novopurol, Urosin, Zyloprim, Zyloric Xanax Aprobal, Aptine, Gubernal Prostin VR, Minprog Activase Aldrox, Alu-Tab, Amphojel, Fluagel Solu-Contenton, Virofral, Symmetrel Ambril, Bronchopront,...
Events Underlying Contraction and Relaxation B
The signal triggering contraction is a propagated action potential AP generated in the sinoatrial node. Depolarization of the plasmalemma leads to a rapid rise in cytosolic Ca2 levels, which causes the contractile filaments to shorten electromechanical coupling . The level of Ca2 concentration attained determines the degree of shortening, i.e., the force of contraction. Sources of Ca2 are a extracellular Ca2 entering the cell through voltage-gated Ca2 channels b Ca2 stored in membranous sacs of...
Info Hbq
Accumulation in airways of mucus, inadequate expulsion by cough IgE-mediated allergic reactions p. 72 involve mast cell release of histamine p. 114 and production of other mediators such as leukotrienes, p. 196 . Resultant responses include relaxation of vascular smooth muscle, as evidenced locally by vasodilation e.g., conjunctival congestion or systemically by hypotension as in anaphylactic shock enhanced capillary permeability with transudation of fluid into tissues swelling of conjunctiva...
I J
An agonist has affinity binding avidity for its receptor and alters the receptor protein in such a manner as to generate a stimulus that elicits a change in cell function intrinsic activity. The biological effect of the agonist, i.e., the change in cell function, depends on the efficiency of signal transduction steps p. 64, 66 initiated by the activated receptor. Some agonists attain a maximal effect even when they occupy only a small fraction of receptors B, agonist A . Other ligands agonist B...
Inhibitors of Cell Wall Synthesis
In most bacteria, a cell wall surrounds the cell like a rigid shell that protects against noxious outside influences and prevents rupture of the plasma membrane from a high internal osmotic pressure. The structural stability of the cell wall is due mainly to the murein peptidoglycan lattice. This consists of basic building blocks linked together to form a large macromolecule. Each basic unit contains the two linked aminosug-ars N-acetylglucosamine and N-acetyl-muramyl acid the latter bears a...
Depolarizing Muscle Relaxants
In this drug class, only succinylcholine succinyldicholine, suxamethonium, A is of clinical importance. Structurally, it can be described as a double ACh molecule. Like ACh, succinylcholine acts as agonist at endplate nicotinic cholino-ceptors, yet it produces muscle relaxation. Unlike ACh, it is not hydrolyzed by acetylcholinesterase. However, it is a substrate of nonspecific plasma cholin-esterase serum cholinesterase, p. 100 . Succinylcholine is degraded more slowly than is ACh and therefore...
Flucortisone Against Blackouts Bradycardia
Coronary atherosclerosis angina pectoris, myocardial infarction, arrhythmia Atherosclerosis of cerebral vessels cerebral infarction stroke Cerebral hemorrhage Atherosclerosis of renal vessels renal failure A. Arterial hypertension and pharmacotherapeutic approaches The venous side of the circulation, excluding the pulmonary circulation, accommodates 60 of the total blood volume because of the low venous pressure mean -15 mmHg it is part of the low-pressure system. The arterial vascular beds,...
Organic Nitrates
Various esters of nitric acid HNO3 and polyvalent alcohols relax vascular smooth muscle, e.g., nitroglycerin gly-ceryltrinitrate and isosorbide dinitrate. The effect is more pronounced in venous than in arterial beds. These vasodilator effects produce hemodynamic consequences that can be put to therapeutic use. Due to a decrease in both venous return preload and arterial afterload, cardiac work is decreased p. 308 . As a result, the cardiac oxygen balance improves. Spasmodic constriction of...
Damage to the mitotic spindle B
The contractile proteins of the spindle apparatus must draw apart the replicated chromosomes before the cell can divide. This process is prevented by the so-called spindle poisons see also col-chicine, p. 316 that arrest mitosis at metaphase by disrupting the assembly of microtubules into spindle threads. The vinca alkaloids, vincristine and vin-blastine from the periwinkle plant, Vinca rosea exert such a cell-cycle-specific effect. Damage to the nervous system is a predicted adverse effect...
Drugs Used in the Treatment of Fungal Infections
Infections due to fungi are usually confined to the skin or mucous membranes local or superficial mycosis. However, in immune deficiency states, internal organs may also be affected systemic or deep mycosis. Mycoses are most commonly due to dermatophytes, which affect the skin, hair, and nails following external infection. Candida albicans, a yeast organism normally found on body surfaces, may cause infections of mucous membranes, less frequently of the skin or internal organs when natural...
Antianginal Drugs
, -Dimethylcysteine chelation with Cu2 and Pb2 Antidotes for cyanide poisoning A . Cyanide ions CN- enter the organism in the form of hydrocyanic acid HCN the latter can be inhaled, released from cyanide salts in the acidic stomach juice, or enzymatically liberated from bitter almonds in the gastrointestinal tract. The lethal dose of HCN can be as low as 50 mg. CN- binds with high affinity to trivalent iron and thereby arrests utilization of oxygen via mitochondrial cytochrome oxidases of the...
Antidiuretic Hormone ADH and Derivatives B
ADH, a nonapeptide, released from the posterior pituitary gland promotes reabsorption of water in the kidney. This response is mediated by vasopressin receptors of the V2 subtype. ADH enhances the permeability of collecting duct epithelium for water but not for electrolytes . As a result, water is drawn from urine into the hyperosmolar inter-stitium of the medulla. Nicotine augments p. 110 and ethanol decreases ADH release. At concentrations above those required for antidiuresis, ADH stimulates...
Info Kxa
REM-sleep Rapid Eye Movement sleep NREM A. Succession of different sleep phases during night rest A. Succession of different sleep phases during night rest B. Effect of hypnotics on proportion of REM NREM B. Effect of hypnotics on proportion of REM NREM C. Concentration dependence of barbiturate and benzodiazepine effects C. Concentration dependence of barbiturate and benzodiazepine effects
Inhalational Anesthetics
The mechanism of action of inhalational anesthetics is unknown. The diversity of chemical structures inert gas xenon hydrocarbons halogenated hydrocarbons possessing anesthetic activity appears to rule out involvement of specific receptors. According to one hypothesis, uptake into the hydrophobic interior of the plasmalemma of neurons results in inhibition of electrical excitability and impulse propagation in the brain. This concept would explain the correlation between anesthetic potency and...