Showing posts with label Pharmacology. Show all posts
Showing posts with label Pharmacology. Show all posts

10 July 2009

Drugs Affecting Respiratory System



Drugs Affecting Respiratory System
By:Jan Bazner-Chandler MSN, CNS, RN, CPNP

Common Cold
* Most cold are caused by viral infections
o Rhinovirus
o Influenza
* Virus invade the mucosa of the upper respiratory tract, nose, pharynx and larynx which leads to the upper respiratory system.
* Signs and symptoms: excessive mucous production leads to sore throat, coughing, upset stomach.
* Treatment: reduce symptoms
* Note: antibiotics do not help viral infections

Echinacea
* Herbal Therapy
* Has been shown in clinical trials to reduce cold symptoms and recovery time when taken early in the illness.
* Adverse effects: dermatitis, upset stomach, dizziness, headache, and unpleasant taste.

Antihistamines
* Action: act directly on histamine receptor sites H1 blockers.
* Used as an inflammatory mediator for allergic disorders, allergic rhinitis (hay fever and mold, and dust allergies), anaphylaxis, angioedema, insect bites and urticaria (itching).

Antihistamines
* Antihistamines associated with sedation (CNS)
* Non-sedating antihistamines

Antihistamines: sedating
* Classification: H1 antihistamine
o chlorphenramine (Chlor-Trimeton)
o dephenhydramine (Benadryl)
diphenhydramine

* Trade name: Benadryl
* One of the oldest anti-histamines
* Action: Antagonizes the effects of histamine at the H1 receptor sites.
* Adverse Effects: Significant CNS depressant: drowsiness, dizziness, hypotension, dry mouth.
o Onset: immediate to 60 minutes
o Peak: 1-4 hours
o Duration: 4-8 hours

Non-sedating Antihistamine
* The drugs were developed to eliminate the unwanted adverse effects; mainly sedation.
* Action: Works peripherally (do not cross the blood brain barrier) to block the actions of histamine.

loratadine
* Generic name: loratadine
* Trade name: Claritin
* Action: blocks peripheral effects of histamine released during allergic reactions.
* Therapeutic Effects: decreased symptoms of allergic reactions (nasal stuffiness, red swollen eyes)
o Onset within 1-3 hours
o Peak within 8-12 hours
o Duration: > 24 hours

cetirizine
* Trade name: Zyrtec
* Therapeutic classification: allergy, cold, and cough remedies, antihistamine
* Action: Antagonizes the effects of histamine at H1-receptor sites; anticholinergic effects are minimal.
o Onset: 30 minutes
o Peak: 4-8 hours
o Duration: 24 hours

Decongestants
* Nasal congestion is due to excessive nasal secretions and inflamed and swollen nasal mucosa.
o Three types of decongestants
+ adrenergic
+ anticholinergic
+ corticosteroids

Route of administration

* Orally to produce systemic effect
* Inhaled: directly to lungs with some systemic effects
* Nasally: local with some systemic effects

Nasal Drugs

* Adrenergic Drugs: topical application directly into the nares provides a very potent decongestive effect.
* Main side effect: rebound effect (after a few days of use if discontinued can have rebound congestion).

Adrenergic Nasal Drugs
* Afrin
* Neo-Synephrine
* Sinex

Intranasal Steroids
* Often used prophylactically to prevent nasal congestion in patients with chronic upper respiratory tract infections.
* Action: aimed at the anti-inflammatory response
* Trade names
o Nasacort
o Flonase
o Nasalide

Drugs to Treat Coughs
* Antitussives
o Opioid
o Non-opioid
* Expectorants

Antitussive Drugs
* Opioid drugs all have antitussive effects
* Codeine is the only opioid used as a cough medicine
* Action: suppress the cough reflex through direct action on the cough center in the CNS (medulla).
* Adverse effects: CNS and respiratory depression and addictive potential

Antitussive Drugs
* Non opioid
* Generic: dextromethorphan
* Trade names:
o Vicks Formula 44
o Robitussin DM
o Safe, non-addicting and does not cause CNS or respiratory depression.

Expectorants
* Aid in the coughing up and spitting out of the excess mucous that has accumulated in the respiratory tract by breaking down and thinning the secretions.
* Action:
o Loosening and thinning the respiratory tract secretions
o Direct stimulation of the secretory glands in the respiratory tract.
* Guaifenesin is the only drug currently available.
* Trade names: Robitussin, Humibid, Guiatuss
* Therapeutic effect: relief of respiratory congestion and cough suppression

Bronchodilators and Other Respiratory Drugs
Lungs
* Right side has 3 lobes
* Left side 2 lobes
* Contains the lower respiratory structures

Bronchi
* Definition: The bronchi are small air passages, composed of hyaline cartilage, that extend from the trachea to the bronchioles. There are two bronchi in the human body that branch off from the trachea. The bronchi are lined with mucous membranes that secrete mucus and cilia that sweep the mucus and particles up and out of the airways.

Alveoli
* Have a very thin membrane that allows rapid diffusion of oxygen and carbon dioxide between capillary blood and alveolar air spaces.
* Lined with surfactant to prevent alveolar collapse.

Surfactant
* Essential fluid that lines the alveoli and smallest bronchioles.
* Reduces surface tension of the lung allowing the oxygen and carbon dioxide across the membrane.

Lack of Surfactant
Nervous System Role
* Nervous system regulates the rate and depth of respirations.
* Medulla oblongata is the respiratory control system of the brain.
* Cough reflex is stimulated by nervous system.

Diseases of Respiratory System
* Upper respiratory tract: colds, rhinitis, hay fever
* Lower respiratory tract: asthma, emphysema and chronic bronchitis
o All involve obstruction of airflow through the airways.

Bronchial Asthma

* Recurrent and reversible shortness of breath that occurs when the bronchi and bronchioles become narrow as a result of bronchospasm, inflammation, and edema of the bronchial mucosa, and the production of viscid (sticky) mucous.

Allergic Asthma

* Caused by hypersensitivity to an allergen or allergens in the environment.
o Allergen is substance that elicits an allergic reaction.
o Antigen: Substance (usually a protein) that causes the formation of an antibody and reacts with the antibody.
o Antibody: Immunoglobulins produced by Lymphocytes in response to bacteria, viruses, or other antigen substances. (IgE)

Stepwise Therapy for Management of Asthma
* Step 1: mild intermittent
Treatment of mild intermittent Asthma
* Quick relief:
o Short-acting inhaled B2 agonists
+ Albuterol or Proventil

Albuterol (short acting bronchodilator)
* Therapeutic classification: bronchodilators
* Pharmacologic classification: adrenergic
* Indications: Used as a bronchodilator in the management of reversible airway obstruction.
* Action: Binds to beta 2-adrenergic receptors in airway smooth muscle.
* Therapeutic effects: bronchodilator

Albuterol
* Adverse effects:
o Nervousness, restlessness, tremor, headache, insomnia
o Cardiovascular: chest pain, palpitations, angina, hypertension, tachycardia

Albuterol
* Inhaled:
o Onset 15 to 30 minutes
o Peak: 2-3 hours
o Duration: 8 hours

Inhaler
Albuterol INH - Nebulizer
Teaching
* May give up to 3 treatments at 20 minute intervals
* If taking more than one inhaled medications take 5 minutes apart
* Encourage fluid intake
* Signs and symptoms of respiratory distress
* If no relief need to call PMD or go to ED

Mild Persistent Asthma
* Step 2:
o Short acting inhaled B2 agonist prn
+ Proventil (albuterol)
+ Xopenex (levoalbuterol)
o Low dose inhaled corticosteroids (beclomethasone, fluticasone, triamcinolone
+ Pulmicort, Flovent, Azmacort
o Cromolyn (particularly in children)

cromolyn
* Classification: Mast cell stabilizer
* Trade name: Intal, NasalCrom
* Indications: adjunct in the prophylaxis (long-term control) of allergic disorders including rhinitis and asthma
* Action: prevents the release of histamine and slow-reacting substance of anaphylaxis (SRS-A) from sensitized mast cells.
* Route: inhalation, solution for nebulization or nasal solution.

Inhaled Corticosteroids
* Generic name: fluticasone
* Trade name: Flovent
* Action: potent locally acting anti-inflammatory and immune modifier.
* Therapeutic effects:
o Decrease frequency of asthma attacks
o Prevention of pulmonary damage associated with chronic asthma.

Inhaled Corticosteroids
* Adverse reactions and side effects:
o EENT: hoarseness, oropharyngeal fungal infections
o Dry mouth, esophageal candidia.

Client Teaching
* Take medication as directed.
* Do not discontinue without consulting MD
* When using corticosteroids and bronchodilators use bronchodilators first and follow 5 minutes later with corticosteroids.
* Rinse and spit after inhalation therapy to prevent oral fungal infections.
* Use a tight fitting mask in infant / small child

Oral Thrush
Moderate Persistent Asthma
Antileukotriene Drugs
Severe Persistent Asthma
Corticosteroids
Prednisone
Exercise Induced Asthma
Chronic Bronchitis
COPD
Moderate COPD
Treatment of COPD
Salmeterol

Drugs Affecting Respiratory System.ppt

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24 June 2009

Treating Ulcerative Colitis



Treating Ulcerative Colitis
By:Robert Theobald III, D.O.
Vein Associates, P.A.

Introduction
* Ulcerative colitis is a chronic inflammatory disease of unknown etiology
* Primarily affects the colon and rectum
* Lesions are characterized by superficial infiltration of the bowel wall by inflammatory white cells
* Results in mucosal ulcerations and crypt abscesses
History
Epidemiology
Clinical Presentation
Clinical Presentation Symptoms
Colitis Activity Assessment
Diagnosis
* The diagnosis of UC is based on the clinical picture, stool examination, colonoscopic appearance, and histologic assessment of biopsied specimens
* The differential diagnosis includes infectious, chemical, IBS, ischemia, and miscellaneous
Disease Distribution at Presentation
Current Pharmacotherapy
Fallingborg Study
Steroids
Immunomodulators
New Therapy for Treatment of UC
Natural Remedies

Treating Ulcerative Colitis.ppt

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17 June 2009

Pharmacology Review of Everything



Pharmacology Review of Everything 2003-2004

Abacavir
Antiretroviral
Nucleoside reverse transcriptase inhibitor (NRTI)

Abciximab
Antiplatelet
Anti-GPIIb/IIIa receptor antibody

Acarbose
Oral hypoglycemic
Alpha-glucosidase inhibitor
Inhibitor of intestinal glucose absorption

Acebutolol
Sympatholytic
1 adrenergic antagonist
Class II antiarrhytmic

Antihypertensive
Antianginal
Bronchoconstrictor

Acetaminophen
Analgesic, Antipyretic

Acetazolamide
Diuretic
Carbonic anhydrase inhibitor


Acetylcholine
Cholinomimetic
Antigluacoma
Muscle contraction (nicotinic receptor)

Activated charcoal
Antidote

Acyclovir
Antiherpes
Purine analog
Phosphorylated to inhibitor of viral DNA polymerase

Adenosine
Antiarrhythmic
Miscellaneous
(does not fit class I-IV organization)

Adrenocorticotropin
(ACTH)
Anterior pituitary hormone
Anticonvulsant

Stimulates synthesis
and release of cortisol


Albendazole
Antihelminthic
Treatment of intestinal roundworms

Albuterol
Sympathomimetic
2 adrenergic agonist
Short acting bronchodilator
Used in asthma

Aldosterone
Adrenocorticosteroid
Mineralocorticoid

Alemtuzumab
Antineoplastic
Anti-CD52 antibody

Alendronate
Anti-osteoporesis

Bisphosphonate
Inhibitor of osteoclast-mediated bone resorption

Alfentanil
Opioid
General anaesthetic
Intravenous anaesthetic

Allopurinol
Antigout
Antineoplastic (supporting agent)

Folic acid analogue
Xanthine oxidase inhibitor


Alteplase
Thrombolytic
Tissue plasminogen activator (tPA)

Aluminum hydroxide
Antiulcer
Antacid

Amantadine
Antiviral
Antiparkinson

Treatment of Influenza A
Inhibits replication
at the stage of uncoating

List goes A-Z. This is very exhaustive presentation.

Pharmacology Review of Everything 2003-2004

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Designing Anti-Tumor Drugs Using Natural and Synthetic Agents



Designing Anti-Tumor Drugs Using Natural and Synthetic Agents
By:Herman L. Holt, Jr.
University of North Carolina, Asheville

Medicinal Chemistry Folklore
Famous for Synthesis and Discovery of the Mechanism of Action of:
Indomethacin
Sulindac
Diflunisal
Other anti-inflammatory-analgesic (NSAIDS) and immunoregulators
More than 210 U.S. Patents and scientific publications


* Medicinal Chemistry is defined as an interdisciplinary science situated at the interface of organic chemistry and life sciences (such as biochemistry, pharmacology, molecular biology, immunology, pharmacokinetics and toxicology) on one side and chemistry-based disciplines (such as physical chemistry, crystallography, spectroscopy and computer-based information technologies) on the other.

Chemistry based disciplines
Organic Chemistry
Life Sciences
Medicinal Chemistry
Definition and Objectives
Challenges for Medicinal Chemistry
TUBULIN
* Globular Protein
* Taxoid Site
* Vanca Alkaloid
Domain
* Colchicine Site
MICROTUBULES
* Tubulin Polymers
MITOTIC SPINDLE
* Composed of Microtubules and associated proteins
* Needed for cellular division
* Tubulin Polymers

What is the MTT assay?
CISPLATIN
* Anti-cancer agent
* Ovarian
* Testicular
* Lung
* Breast
* Cleaves DNA

TAXOL
* Anti-cancer agent
* Pacific Yew Tree
* Ovarian
* Testicular
* Lung
* Breast

VANCOMYCIN
COLCHICINE
COMBRETASTATIN
HETEROCYCLE ANALOGS OF COMBRETASTATIN
COMBRETASTATIN AND TRIAZOLE SYNTHESIS
AZIRIDINE ANALOGS OF COMBRETASTATINS
AZIRIDINE TYPE ANALOGS OF COMBRETASTATINS
MITOMYCINS
REFERENCES

Designing Anti-Tumor Drugs Using Natural and Synthetic Agents.ppt

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Pharmacology of Drugs Used to Treat Respiratory Disorders



The Pharmacology of Drugs Used to Treat Respiratory Disorders

Stuff about inverse-agonist beta-blockers (nadolol) and asthma
Asthma
COPD
Rhinitis & rhinorrhea
Cough

Asthma

“Obstruction of the airways (3rd to 7th generation of the bronchi) that is reversible with time or in response to treatment.”
Causes

* Allergens
* Cold air
* Exercise
* Upper respiratory infections
* Genetics

Features of asthma
Breathlessness
Cough
Wheezing
Chest tightness
Hyper-responsive lower airway
Hyperinflated lungs
Treatment

Remodeled airway
Poor distensibility of airway lumen on inspiration
Submucosal swelling internal to rigid zone with edema
Limited response to bronchodilator or anti-inflammatory therapy

Cells Recruited During Asthmatic Inflammation
Modulators of BSM contraction Contraction
Smooth muscle cell
Inflammatory mediators (e.g., histamine)
Goals of Therapy

Pharmacologic Therapy of Asthma
Anti-inflammatory
Bronchodilation
Prophylaxis
Anti-inflammatory Glucocorticoids
* Corticosteroids: the most effective anti-inflammatory agents.
* Primary action is to regulate gene expression.
Pharmacologic Actions
Anti-inflammatory Glucocorticoids
Inhalation of corticosteroids minimizes side effects
Disposition of Inhaled Drugs
Glucocorticoids Pharmacologic Actions
Inflammation Bronchonstriction
Mechanism of Action
Glucocorticoid Toxicity Administration by Inhalation
Toxicity: Inhalation
Glucocorticoid Toxicity: Systemic administration
Toxicity: Chronic systemic
Precautions/Contraindications
Therapy of Asthma
Long-acting(prophylaxis)
Short-acting(symptomatic)
and more topics are covered

The Pharmacology of Drugs Used to Treat Respiratory Disorders.ppt

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CANCER CHEMOTHERAPY



CANCER CHEMOTHERAPY
By:Dr. Debra Laskin
Rutgers.edu

Cancer (Neoplastic Disease)
Types of Cancers
Hematologic Malignancies
Leukemias
Lymphomas
Hodgkin’s Disease
Non-Hodgkin’s Lymphoma
Solid Tumors
Carcinomas
Sarcomas
Hematologic Malignancies
Tumors of blood forming organs and cells
* Leukemias: Proliferation of immature progenitors which circulate in blood
o Acute lymphocytic leukemia (ALL, BM lymphblasts)
o Chronic lymphocytic leukemia (CLL- immature B cells)
o Acute myelocytic leukemia (AML, BM myeloid cells)
o Chronic myelocytic leukemia (CML, myeloid cells; Philadelphia chromosome)
* Lymphomas: Lymph System
o Hodgkin’s Disease: lymph nodes
o Non-Hodgkin’s lymphoma: lymphocytes (CLL)
Solid Tumors
Can occur in any organ or tissue; malignant (metastatic and invasive)
* Carcinomas: Arises from epithelial cells; malignant by definition
* Sarcomas: Cancer of connective or supportive tissue (bone, cartilage, fat, muscle, blood vessels) and soft tissue

Cancer Chemotherapy Versus Antimicrobial Chemotherapy
I. Goal
II. Selective Toxicity
III. Immune System
IV. Kinetics of killing

Goal
* ACT: Get rid of invading organisms, restore health
* CCT: Kill as many tumors cells as possible without killing too many normal cells; tumor regression, increased patient survival time, alleviation of symptoms

Selective Toxicity
* ACT: Exploit biochemical differences between pathogenic organism and host; selective toxicity
* CCT: Only quantitative differences between normal and neoplastic cells; differences in growth rate, treatment is nonselective

Immune System
Kinetics
Tumor Cell Killing: First Order Kinetics
Tumor burden
Time
Stationary phase
New steady state
Determinants of Responsiveness to Cancer Chemotherapy
Tumor Determinants of Responsiveness
Total Tumor Burden (Size)
Cell Cycle
Cell Cycle Phase
Phases of Cell Cycle
Cancer Chemotherapy
Cell Cycle Specific Agents (self limiting)
Cell Cycle Nonspecific Agents
Drug Resistance
Mechanisms vary with drug
Host Determinants
General health status of patients
Immune status
General Considerations Cancer Chemotherapy
Adjuvant Therapy
Drug Toxicity
Most CCT agents:
Cytotoxic agents- kill all rapidly growing cells, nonselective
Side Effects of Anticancer Drugs
Cancer Chemotherapeutic Agents
Alkylating Agents
Mechanism of Action
Evidence in mammalian cells
Bi-functional: more toxic can cross link DNA
Resistance: excision/DNA repair enzymes; get rid of alkylated DNA
Cell cycle nonspecific
Classes of Alkylating Agents
Nitrogen Mustards
Classes of Alkylating Agents
Nitrosoureas
Classes of Alkylating Agents
Methane sulfonate esters (Alkyl sulfonates)
Folic Acid Analogs-Antifolates
Mechanism of Action
Cytotoxic Effects of Inhibiting DHFR
Leucovorin Rescue
Combination chemotherapy
Adjuvant to surgery
Antimetabolites
DNA Synthesis
Salvage Pathways
Purine Analogs
Mechanisms of Cytotoxicity
Resistance
Lethal Synthesis
Irreversible Ic
5-Fluorouracil
Mechanism of Action
Microtuble Inhibitors: Taxanes
Chromatin Function Inhibitors
Chromatin Function Inhibitors
Antibiotics
Steroid Hormones
Estrogens and Androgens
Immunotherapy: Monoclonal Antibodies
Monoclonal Antibodies
Targeted Therapy
Traditional CCT
Drugs inhibit proliferation

CANCER CHEMOTHERAPY

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Clinical Pharmacology of Anti-cancer Chemotherapeutic Agents



Clinical Pharmacology of Anti-cancer Chemotherapeutic Agents
By:Dr. Jeff R. Wilcke

Therapeutic Principles Diagnosis & Drug Selection
Absorption
Distribution
Metabolism
Elimination
Toxicity &/OR
Efficacy
Pharmacokinetics
Pharmacodynamics
Therapeutic Endpoints
* Efficacy without toxicity
o Human medicine: palliative therapy only
o Veterinary medicine: palliative therapy probably?
* Efficacy AND toxicity
o Human and veterinary medicine: aggressive, curative therapy
* Toxicity without efficacy
o Tentative administration
+ You may affect bone marrow ONLY rather than bone marrow AND tumor
o Drug Resistance
+ Reduces tumor response, bone marrow still sensitive
* Neither toxicity nor efficacy

Dosing v. P’kinetic End Points
Dose vs AUC Target
Peak Concentration
AUC
Intensity / Time Above
Absorption
* Oral
* Intramuscular
Activation
* Hepatic
* Intracellular phosphorylation
* Tissue metabolism with free radical production
Distribution
Elimination
Dosing Chemotherapeutics
Body Surface Area
Oral Chemotherapy
IM Chemotherapy
Intravenous Chemotherapy
Gemcitabine
Dose Form Manipulation

Clinical Pharmacology of Anti-cancer Chemotherapeutic Agents.ppt

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12 June 2009

Pharmacology presentations



Pharmacology presentations
by:Karyn Mills, RN, BSN
coastalbend.edu

Drugs for Hypertension
Drugs for the Reproductive System
Drugs for Bacterial Infection
DRUGS FOR SEIZURES
WHAT HAPPENS AFTER A DRUG HAS BEEN ADMINISTERED
Drugs for Heart Failure
Drugs for Dysrhythmias
Drugs for Anxiety, Daytime Sedation, and Insomnia
Drugs for Pulmonary Disorders
Drugs for Psychoses & Degenerative Diseases of the Nervous System
Drugs for Pain Control
Drugs for Skin Disorders
DRUGS FOR COAGULATION DISORDERS
Drugs for Inflammation, Allergies, & Immune Disorders
Drugs for Muscle, Bone & Joint Disorders
DRUGS FOR ENDOCRINE DISORDERS
Drugs for the ANS Autonomic Nervous System
Drugs for Kidney, Acid-Base, and Electrolyte Disorders
Drugs for GI Disorders
Drugs for Lipid Disorders
INTRODUCTION TO PHARMACOLOGY: DRUG REGULATION & APPROVAL
Drug Classes, Schedules, & Categories

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28 May 2009

Routes of Drug Administration



Routes of Drug Administration
By:Robert L. Copeland, Ph.D.
Department of Pharmacology, Howard University

Drug Absorption

* Absorption is the process by which a drug enters the bloodstream without being chemically altered or
* The movement of a drug from its site of application into the blood or lymphatic system
* Factors which influence the rate of absorption
* The rate at which a drug reaches it site of action depends on:
* Mechanisms of solute transport across membranes
Ion Trapping:
Kidney:
Lipid-Water Partition Coefficient
Enteral Routes
Sublingual/Buccal
Oral
First-pass Effect
Parenteral Routes
Intravascular
Absorption phase is bypassed
Intramuscular
Subcutaneous
Inhalation
Topical
Time-release preparations

Routes of Drug Administration.ppt

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SEDATIVE/HYPNOTICS ANXIOLYTICS



SEDATIVE/HYPNOTICS ANXIOLYTICS
By:Martha I. Dávila-García, Ph.D.
Department of Pharmacology, Howard University

Optimal Performance Nervous Breakdown
Performance Anxiety GOAL
SEDATIVE/HYPNOTICS ANXIOLYTICS
Manifestations of anxiety:
Pathological Anxiety
Causes of Anxiety
1). Medical:
o Respiratory
o Endocrine
o Cardiovascular
o Metabolic
o Neurologic.

2). Drug-Induced:
o Stimulants
+ Amphetamines, cocaine, TCAs, caffeine.
o Sympathomimetics
+ Ephedrine, epinephrine, pseudoephedrine phenylpropanolamine.
o Anticholinergics\Antihistaminergics
+ Trihexyphenidyl, benztropine, meperidine diphenhydramine, oxybutinin.
o Dopaminergics
+ Amantadine, bromocriptine, L-Dopa, carbid/levodopa.
o Miscellaneous:
+ Baclofen, cycloserine, hallucinogens, indomethacin.

3). Drug Withdrawal:
Anxiolytics
Sedative/Hypnotics
Properties of Sedative/Hypnotics in Sleep
1) The latency of sleep onset is decreased (time to fall asleep).
2) The duration of stage 2 NREM sleep is increased.
3) The duration of REM sleep is decreased.
4) The duration of slow-wave sleep (when somnambulism and nightmares occur) is decreased.
Other Properties of Sedative/Hypnotics
GABAergic SYSTEM
Benzodiazepines
* Diazepam
* Triazolam
* Lorazepam
* Alprazolam
* Clorazepate => nordiazepam
* Halazepam
* Clonazepam
* Oxazepam
* Prazepam
Barbiturates
* Phenobarbital
* Pentobarbital
* Amobarbital
* Mephobarbital
* Secobarbital
* Aprobarbital
Respiratory Depression
Coma/Anesthesia
Ataxia
Sedation
Anxiolytic
Anticonvulsant
DOSE
RESPONSE
BARBS
BDZs
ETOH
GABAergic SYNAPSE
GABA
glutamate
glucose
GAD
GABA-A Receptor
GABA AGONISTS BDZs
Mechanisms of Action
Benzodiazepines
PHARMACOLOGY
* BDZs potentiate GABAergic inhibition at all levels of the neuraxis.
* BDZs cause more frequent openings of the GABA-Cl- channel via membrane hyperpolarization, and increased receptor affinity for GABA.
* BDZs act on BZ1 (1 and 2 subunit-containing) and BZ2 (5 subunit-containing) receptors.
* May cause euphoria, impaired judgement, loss of cell control and anterograde amnesic effects.

Pharmacokinetics of Benzodiazepines
CNS Effects
Lipid solubility
Biotransformation of Benzodiazepines
Properties of Benzodiazepines
Side Effects of Benzodiazepines
Toxicity/Overdose with Benzodiazepines
Drug-Drug Interactions with BDZs
Pharmacokinetics of Barbiturates
Properties of Barbiturates Mechanism of Action.
Toxicity/Overdose
Miscellaneous Drugs
* Buspirone
* Chloral hydrate
* Hydroxyzine
* Meprobamate (Similar to BARBS)
* Zolpidem (BZ1 selective)
* Zaleplon (BZ1 selective)
Properties of Other drugs.
OTHER USES
ANXYOLITICS
Alprazolam
Chlordiazepoxide
Buspirone
Diazepam
Lorazepam
Oxazepam
Triazolam
Phenobarbital
Halazepam
Prazepam
HYPNOTICS
Chloral hydrate
Estazolam
Flurazepam
Pentobarbital
Lorazepam
Quazepam
Triazolam
Secobarbital
Temazepam
Zolpidem
References:

SEDATIVE/HYPNOTICS ANXIOLYTICS.ppt

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ANTIEPILEPTIC DRUGS



ANTIEPILEPTIC DRUGS
By:Martha I. Dávila-García, Ph.D.
Department of Pharmacology, Howard University

Epilepsy

A group of chronic CNS disorders characterized by recurrent seizures.
* Seizures are sudden, transitory, and uncontrolled episodes of brain dysfunction resulting from abnormal discharge of neuronal cells with associated motor, sensory or behavioral changes.

Causes for Acute Seizures
* Trauma
* Encephalitis
* Drugs
* Birth trauma
* Withdrawal from depressants
* Tumor
* High fever
* Hypoglycemia
* Extreme acidosis
* Extreme alkalosis Hyponatremia
* Hypocalcemia
* Idiopathic
Seizures
* The causes for seizures can be multiple, from infection, to neoplasms, to head injury. In a few subgroups it is an inherited disorder.
* Febrile seizures or seizures caused by meningitis are treated by antiepileptic drugs, although they are not considered epilepsy (unless they develop into chronic seizures).
* Seizures may also be caused by acute underlying toxic or metabolic disorders, in which case the therapy should be directed towards the specific abnormality.

Neuronal Substrates of Epilepsy
The Brain
The Synapse
The Ion Channels/Receptors
ions
Cellular and Synaptic Mechanisms of Epileptic Seizures
I. Partial (focal) Seizures
II. Generalized Seizures


Classification of Epileptic Seizures
Scheme of Seizure Spread
Simple (Focal) Partial
Contralateral spread
I. Partial (Focal) Seizures
Scheme of Seizure Spread
Complex Partial Seizures
Complex Secondarily Generalized Partial Seizures

I. Partial (focal) Seizures
II. Generalized Seizures
* Generalized Tonic-Clonic Seizures
* Absence Seizures
* Tonic Seizures
* Atonic Seizures
* Clonic and Myoclonic Seizures.
* Infantile Spasms

II. Generalized Seizures
Neuronal Correlates of Paroxysmal Discharges
B. Absence Seizures (Petite Mal)
Treatment of Seizures
Goals:
* Block repetitive neuronal firing.
* Block synchronization of neuronal discharges.
* Block propagation of seizure.
Strategies:
* Modification of ion conductances.
* Increase inhibitory (GABAergic) transmission.
* Decrease excitatory (glutamatergic) activity.

Actions of Phenytoin on Na+ Channels
* Resting State
* Arrival of Action Potential causes depolarization and channel opens allowing sodium to flow in.
* Refractory State, Inactivation
Sustain channel in this conformation
GABAergic SYNAPSE
Drugs that Act at the GABAergic Synapse
* GABA agonists
* GABA antagonists
* Barbiturates
* Benzodiazepines
* GABA synthesizing enzymes
* GABA uptake inhibitors
* GABA metabolizing enzymes
GLUTAMATERGIC SYNAPSE
* Excitatory Synapse.
* Permeable to Na+, Ca2+ and K+.
* Magnesium ions block channel in resting state.
* Glycine (GLY) binding enhances the ability of GLU or NMDA to open the channel.
* Agonists: NMDA, AMPA, Kianate.
Chemical Structure of Classical Antiseizure Agents
Treatment of Seizures
* Hydantoins: phenytoin
* Barbiturates: phenobarbital
* Oxazolidinediones: trimethadione
* Succinimides: ethosuximide
* Acetylureas: phenacemide
* Other: carbamazepine, lamotrigine, vigabatrin, etc.
* Diet
* Surgery, Vagus Nerve Stimulation (VNS).
* Most classical antiepileptic drugs exhibit similar pharmacokinetic properties.
* Good absorption (although most are sparingly soluble).
* Low plasma protein binding (except for phenytoin, BDZs, valproate, and tiagabine).
* Conversion to active metabolites (carbamazepine, primidone, fosphenytoin).
* Cleared by the liver but with low extraction ratios.
* Distributed in total body water.
* Plasma clearance is slow.
* At high concentrations phenytoin exhibits zero order kinetics.

Pharmacokinetic Parameters
Effects of three antiepileptic drugs on high frequency discharge of cultured neurons
Block of sustained high frequency repetitive firing of action potentials.
PHENYTOIN (Dilantin)
* Oldest nonsedative antiepileptic drug.
* Fosphenytoin, a more soluble prodrug is used for parenteral use.
* “Fetal hydantoin syndrome”.
* Manufacturers and preparations.
* It alters Na+, Ca2+ and K+ conductances.
* Inhibits high frequency repetitive firing.
* Alters membrane potentials.
* Alters a.a. concentration.
* Alters NTs (NE, ACh, GABA)
Toxicity:
* Ataxia and nystagmus.
* Cognitive impairment.
* Hirsutism
* Gingival hyperplasia.
* Coarsening of facial features.
* Dose-dependent zero order kinetics.
* Exacerbates absence seizures.
* At high concentrations it causes a type of decerebrate rigidity.
CARBAMAZEPINE (Tegretol)
* Tricyclic, antidepressant (bipolar)
* 3-D conformation similar to phenytoin.
* Mechanism of action, similar to phenytoin. Inhibits high frequency repetitive firing.
* Decreases synaptic activity presynaptically.
* Binds to adenosine receptors (?).
* Inh. uptake and release of NE, but not GABA.
* Potentiates postsynaptic effects of GABA.
* Metabolite is active.
Toxicity:
* Autoinduction of metabolism.
* Nausea and visual disturbances.
* Granulocyte supression.
* Aplastic anemia.
* Exacerbates absence seizures.
OXCARBAZEPINE (Trileptal)
* Closely related to carbamazepine.
* With improved toxicity profile.
* Less potent than carbamazepine.
* Active metabolite.
* Use in partial and generalized seizures as adjunct therapy.
* May aggravate myoclonic and absence seizures.
* Mechanism of action, similar to carbamazepine It alters Na+ conductance and inhibits high frequency repetitive firing.
Toxicity:
* Hyponatremia
* Less hypersensitivity and induction of hepatic enzymes than with carbamazepine
PHENOBARBITAL (Luminal)
* Except for the bromides, it is the oldest antiepileptic drug.
* Although considered one of the safest drugs, it has sedative effects.
* Many consider them the drugs of choice for seizures only in infants.
* Acid-base balance important.
* Useful for partial, generalized tonic-clonic seizures, and febrile seizures
* Prolongs opening of Cl- channels.
* Blocks excitatory GLU (AMPA) responses. Blocks Ca2+ currents (L,N).
* Inhibits high frequency, repetitive firing of neurons only at high concentrations.
Toxicity:
* Sedation.
* Cognitive impairment.
* Behavioral changes.
* Induction of liver enzymes.
* May worsen absence and atonic seizures.
PRIMIDONE (Mysolin)
* Metabolized to phenobarbital and phenylethylmalonamide (PEMA), both active metabolites.
* Effective against partial and generalized tonic-clonic seizures.
* Absorbed completely, low binding to plasma proteins.
* Should be started slowly to avoid sedation and GI problems.
* Its mechanism of action may be closer to phenytoin than the barbiturates.
Toxicity:
* Same as phenobarbital
* Sedation occurs early.
* Gastrointestinal complaints.
VALPROATE (Depakene)

ETHOSUXIMIDE (Zarontin)
CLONAZEPAM (Klonopin)
VIGABATRIN
LAMOTRIGINE (Lamictal)
FELBAMATE (Felbatrol)
TOPIRAMATE (Topamax)
TIAGABINE (Gabatril)
ZONISAMIDE (Zonegran)
GABAPENTIN (Neurontin)
Status Epilepticus
Treatment of Status Epilepticus in Adults
DIAZEPAM (Valium) AND
LORAZEPAM (Ativan)
Treatment of Seizures
PRIMARY GENERALIZED TONIC-CLONIC SEIZURES (Grand Mal)
GENERALIZED ABSENCE SEIZURES
ATYPICAL ABSENCE, MYOCLONIC, ATONIC* SEIZURES
INFANTILE SPASMS
Treatment of Seizures in Pregnancy
INTERACTIONS BETWEEN ANTISEIZURE DRUGS
ANTISEIZURE DRUG INTERACTIONS
With other drugs:

ANTIEPILEPTIC DRUGS.ppt
http://www.med.howard.edu/pharmacology/handouts/ANTIEPILEPTICS_OL2003.ppt

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Antiviral Agents



Antiviral Agents
By:Jillian H. Davis
Department of Pharmacology, Howard University

Viruses
* Obligate intracellular parasites
* Consist of a core genome in a protein shell and some are surrounded by a lipoprotein
* lack a cell wall and cell membrane
* do not carry out metabolic processes
* Replication depends on the host cell machinery
* Steps for Viral Replication

Sites of Drug Action
Antiviral Agents
Antiherpes Agents
* Acyclovir- prototype
* Valacyclovir
* Famciclovir
* Penciclovir
* Trifluridine
* Vidarabine
Mechanism of Action Acyclovir
* an acyclic guanosine derivative
* Phosphorylated by viral thymidine kinase
* Di-and tri-phosphorylated by host cellular enzymes
* Inhibits viral DNA synthesis
* Alteration in viral thymidine kinase
* Alteration in viral DNA polymerase
* Cross-resistance with valacyclovir, famciclovir, and ganciclovir

Clinical Uses Acyclovir
* Oral, IV, and Topical formulations
* Cleared by glomerular filtration and tubular secretion
* Uses:
o Herpes Simplex Virus 1 and 2 (HSV)
o Varicella-zoster virus (VZV)
* Side Effects: nausea, diarrhea, headache, tremors, and delirium

Valacyclovir
* L-valyl ester of acyclovir
* Converted to acyclovir when ingested
* M.O.A.: same as acyclovir
* Uses:
o 1) recurrent genital herpes
o 2) herpes zoster infections
* Side Effects: nausea, diarrhea, and headache

Famciclovir
* Prodrug of penciclovir (a guanosine analog)
* M.O.A.: same as acyclovir
* does not cause chain termination
* Uses: HSV-1, HSV-2, VZV, EBV, and hepatitis B
* Side Effects: nausea, diarrhea, and headache

Trifluridine
* Trifluridine- fluorinated pyrimidine
o inhibits viral DNA synthesis same as acyclovir
o incorporates into viral and cellular DNA
o Uses: HSV-1 and HSV-2 (topically)
Vidarabine
* An adenosine analog
* inhibits viral DNA polymerase
* incorporated into viral and cellular DNA
* metabolized to hypoxanthine arabinoside
* Side Effects: GI intolerance and myelosuppression

Anti-Cytomegalovirus Agents
* Gancyclovir
* Valgancyclovir
* Cidofovir
* Foscarnet
* Fomivirsen

Ganciclovir
* An acyclic guanosine analog
* requires triphosphorylation for activation
* monophosphorylation is catalyzed by a phosphotransferase in CMV and by thymidine kinase in HSV cells
* M.O.A.: same as acyclovir
* Uses: CMV*, HSV, VZV,and EBV
* Side Effect: myelosuppression

Valgancyclovir
* Monovalyl ester prodrug of gancyclovir
* Metabolized by intestinal and hepatic esterases when administered orally
* M.O.A.: same as gancyclovir
* Uses: CMV*
* Side Effect: myelosuppression

Cidofovir
* A cytosine analog
* phosphorylation not dependent on viral enzymes
* Uses: CMV*, HSV-1, HSV-2, VZV, EBV, HHV-6, adenovirus, and human papillomavirus
* Side Effects: nephrotoxicity (prevented by admin. of probenecid)
* Resistance: mutation in DNA polymerase gene

Foscarnet
* An inorganic pyrophosphate
* inhibits viral DNA polymerase, RNA polymerase, and HIV reverse transcriptase
* does not have to be phosphorylated
* Uses: HSV, VZV, CMV, EBV, HHV-6, HBV, and HIV
* Resistance due to mutations in DNA polymerase gene
* Side Effects: hypo- or hypercalcemia and phosphotemia

Fomivirsen
* An oligonucleotide
* M.O.A.: binds to mRNA and inhibits protein synthesis and viral replication
* Uses: CMV retinitis
* Side effects: iritis and increased intraocular pressure

Antiretroviral Agents
1) Nucleoside Reverse Transcriptase Inhibitors (NRTIs)
2) Nonnucleoside Reverse Transcriptase Inhibitors (NNRTIs)
3)Protease inhibitors

Reverse Transcriptase Inhibitors
* Zidovudine (AZT)
* Didanosine- causes pancreatitis*
* Lamivudine- causes pancreatitis
* Zalcitabine- causes peripheral neuropathy*
* Stavudine- causes peripheral neuropathy*
* Abacavir

Mechanism of Action Zidovudine (AZT)
* A deoxythymidine analog
* enters the cell via passive diffusion
* must be converted to the triphosphate form by mammalian thymidine kinase
* competitively inhibits deoxythymidine triphosphate for the reverse transcriptase enzyme
* causes chain termination

Mechanism of Resistance Zidovudine
* Due to mutations in the reverse transcriptase gene
* more frequent after prolong therapy and in persons with HIV

Clinical Uses Zidovudine
* Available in IV and oral formulations
* activity against HIV-1, HIV-2, and human T cell lymphotropic viruses
* mainly used for treatment of HIV, decreases rate of progression and prolongs survival
* prevents mother to newborn transmission of HIV

Side Effects Zidovudine
* Myelosuppression, including anemia and neutropenia
* GI intolerance, headaches, and insomnia

Other NRTIs
* Didanosine- synthetic deoxy-adenosine analog; causes pancreatitis*
* Lamivudine- cytosine analog
* Zalcitabine- cytosine analog; causes peripheral neuropathy*
* Stavudine- thymidine analog;causes peripheral neuropathy*
* Abacavir- guanosine analog; more effective than the other agents; fatal hypersensitivity reactions can occur


Nucleotide Inhibitors
* Tenofovir
* Adefovir

Nonnucleoside Reverse Transcriptase Inhibitors (NNRTIs)
* Nevirapine
* Delavirdine
* Efavirenz
Mechanism of Action NNRTIs
Nonnucleoside Reverse Transcriptase Inhibitors (NNRTIs)
Protease Inhibitors
Indinavir and Ritonavir
Saquinavir
Nelfinavir and Amprenavir
Fusion Inhibitors
Anti-Hepatitis Agents
Interferons
Ribavirin
Anti-Influenza Agents
Amantadine and Rimantadine
Zanamivir and Oseltamivir
Antifungal Agents
Fungal Infections
Systemic Antifungals
Amphotericin B
Flucytosine
Azoles
Differences in Azoles
Mucocutaneous Antifungals
Topical Antifungals

Antiviral Agents.ppt

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Anticoagulant, Antithrombotic and Anti-Platelet Drugs



Anticoagulant, Antithrombotic and Anti-Platelet Drugs
By:Robert Taylor, MD, Ph.D.
Department of Pharmacology, Howard University

Clinical Thrombosis
Indications For Antithrombotic Therapy
* Venous thromboembolic disease
o Deep venous thrombosis (DVT)
o Pulmonary embolism (PE)
o Primary prophylaxis of DVT or PE
* Arterial thromboembolic disease
o Prosthetic heart valves
o Mitral valve disease, especially with atrial fibrillation
o Congestive cardiomyopathies, especially with atrial fibrillatio
o Atrial fibrillation
o Mural cardiac thrombi
o Transient ischemic attacks
o Stroke in evolution
* Disseminated intravascular coagulation
* Maintenance of patency of vascular grafts, shunts, bypasses

Recombinant Human Activated Protein C
* Drotrecogin alfa (activated)- Xigris
* Indicated for Severe Sepsis in Adults with Acute Organ Dysfunction with High Risk of Death
* Reduction in Death as Primary End Point
* Antithrombotic, Antiinfammatory, Profibrinolytic Properties
* Serious Bleeding is Major Side Effect

Antithrombin III Inhibits the Following Serine Proteases
* Coagulation
* Factor XIIa
* Factor XIa
* Factor IXa
* Factor Xa
* Thrombin
* Fibrinolysis
* Plasmin

Inhibitory activity against all these enzymes is substantially accelerated by heparin

Heparin
Anticoagulant Properties of Heparin
* Inhibits the thrombin-mediated conversion of fibrinogen to fibrin
* Inhibits the aggregation of platelets by thrombin
* Inhibits activation of fibrin stabilizing enzyme
* Inhibits activated factors XII, XI, IX, X and II
* Biologic Sources
* Bioavailability
* Metabolism
* Elimination
* Side Effects
* Overdose
* Contraindications
* Pregnancy- YES

Unfractionated Heparin
* High Dose
Monitoring of Anticoagulant Therapy
Heparin
Low Dose Unfractionated Heparin
Indications for and Contraindications to Parenteral Anticoagulant Agents
Regional anesthesia
Pregnancy
Prosthetic Heart Valves
Regional anesthesia
Antithrombin III inhibitor
Low-molecular-weight heparin
Unfractionated heparin
Enoxaparin(Lovenox)
Dalteparin(Fragmin)
Tinzaparin(Innohep)
Contraindication
Approved & Appropriate Indications
Class
Anticoagulant Agent
Thrombocytopenia other than heparin-induced thrombocytopenia
Direct thrombin inhibitor
Heparinoid
Hirudin derivative
Synthetic factor Xa inhibitor
Ardeparin
Lepirudin
Argatroban
Danaparoid
Bivalirudin
Fondaparinux(Arixtra)
Heparin-Antibiotic Interactions
Mechanisms of HIT
Therapy of HIT
Warfarin
* Bioavailability
* Metabolism
* Serum Protein Binding
* Vitamin K Status
* Protein C Effects
* Elimination
* Side Effects
* Overdose
* Contraindications
* Pregnancy- NO
Contraindications to Antithrombotic Therapy
Platelet Receptor Mediated Pathways: Drugs
GP IIB/IIIA Inhibitors
Abciximab (ReoPro)
Eptifibatide (Integrilin)
Tirofiban
Thrombin
-Final Common Pathway
-Promotes Platelet Adhesion (Fibrinogen, vWF)
Ticlopidine
Clopidogrel
ADP
ASA
NSAIDs
Arachidonic Acid
Anti Platelet Drugs
CAD
Stroke-TIAs
Permanently inhibits COX-1 and COX-2
Aspirin
TIAs;Stroke
CAD;PVD
Inhibits ADP PlatAg;active metabolite
Ticlopidine
Clopidrgrel
TIAs
Inhibits PDE; increases cAMP
Dipyridamole
Limited Reversibly inhibits COX-1
NSAIDs
Uses
Mechanism
Drug

Anticoagulant, Antithrombotic and Anti-Platelet Drugs.ppt

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19 May 2009

Pharmacology Basics



Pharmacology Basics

First rule of thumb:
NEVER EVER ADMINISTER A DRUG YOU ARE UNFAMILIAR WITH
* Ancient vs. Modern Pharmacology
o Pharmekos-study of medicine/drug
o Ology-study
* Studies effects of drugs/how they exert their effects

Therapeutic Purposes of Medications
* Prevent disease
* Diagnose disease
* Cure disease
* Relief of symptoms

Drugs
* A drug may be defined as:
o Any substance taken by mouth; injected into a muscle, blood vessel, or cavity of the body; inhaled, or applied topically to treat or prevent a disease or condition.
* Drug- any substance that alters physiologic function w/potential for affecting health
* Drug interaction
* Adverse drug reaction-undesirable drug effect

Sources of Drugs
* Plants
* Animals
* Minerals or mineral products
* Synthetic chemical compounds
* Biotechnology

Drug Nomenclature
Drug Classification Indicates
Forms or Preparations of Drugs
* Liquid (solution, elixir, emulsion, spirit, syrup, suspension)
* Solid (tablet, capsule, powder, granules)
* Suppository (rectal, vaginal)
* Creams or lotions
* Aerosol
Sources of Drug Information
* Pharmacology textbook
* Pharmacists
* Internet sources
* Journal articles
* Drug reference books

Drug Standards Ensure
* Strength or potency
* Purity
* Efficacy
* Safety
* Bio-availability

Federal Drug Laws in the USA
Categories of Controlled Substances
* Schedule I - not approved for medical use and have high abuse potential
* Schedule II - used medically and have high abuse potential
* Schedule III - less potential for abuse but may lead to physical or psychological dependence
* Schedule IV - some potential for abuse
* Schedule V - contain mod. amounts of controlled substances, limited abuse potential

Scope of Management
Medication Assessment
Name of Medication
Include Generic & Brand Name Classification
Ordered Dose & Route
Is Dose Safe?
Standards of Practice
* Information for Administering Medications
o Generic Name/Trade Name/Classification
o Clinical Uses/Safe Dosage
o Mechanism of Action
o Side Effects/Adverse Effects
o Contraindications/Precautions
o Significant Drug Interactions
o Monitoring Needs/Client Teaching
o Evaluation of Effectiveness

N.C. Nursing Practice Act
Routes of Administration
Three Phases of Action
Pharmaceutics
Pharmacokinetics
Factors Which Influence Drug Absorption
Factors Which Influence Drug Distribution
Protein Bound Drugs
Highly protein bound drugs
First Pass Effect
Serum Half-Life
Pharmacodynamics
Time Intervals of Drug Action
Therapeutic Index
Drug interactions:
Drug Effects
Non-therapeutic Drug Use
Common or Serious Side Effects
Drug Related Variables Affecting Drug Actions
Client Variables Affecting Drug Actions
Nursing Process
Assessment
Planning
Implementation
Evaluation

Pharmacology Basics.ppt

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05 May 2009

Monitoring tissue drug levels by microdialysis



Monitoring tissue drug levels by microdialysis
Presentation lecture from: Universitätsklinik für Klinische Pharmakologie
Conventional Assumption
“Blood / Target equilibrium can be taken for granted”
Drug distribution can solely be explained by laws of diffusion

Active Transporters

Distribution is not always driven by instantaneous diffusion
Equilibrium at steady state (but delayed)
* capillary density and blood flow (Krogh cylinder)
* capillary permeability

Inequilibrium at steady state
* active transporters (e.g. P-GP)
* pH - partition
* Gibbs-Donnan inequilibrium
* filtration gradient (may decrease/reverse)
* Starling laws (oncotic pressure)
* elimination by lymph vessels

Conventional Assumption

“Tissue is a homogenous matrix”
The misleading partition coefficient / Binding issues
Interstitium
Capillary
Cell
Regulatory View
“Distribution studies should be done”
Critical Path
2003 CDER Report to the Nation

We continue ... to extend our long-standing interest in the application of dose-response principles by viewing drugs and their actions directly at the level of the drug target, rather than indirectly via plasma concentrations

Insertion of a microdialysis probe

Probe
Guide cannula
Interstitium
Capillary
Cell
Perfusate
Dialysate
Interstitial concentration in vivo (PK)
Concentration in culture in vitro (PD)
PK in Drug Resistant Tumors
Future Concepts
* Biomarkers in tissues
* Topical BE
* Dose finding (PK / PD)
* “Critical Path”
* Preclinical screening (CNS)

Where are my keys?
PET scanner
GE Advance
Siemens µPET Focus 220


Conclusions

* µD is a safe, reproducible, ethically acceptable and realtively inexpensive technique for studying tissue distribution in humans
* µD is a well established technology with standard clinical applications
* Most organs can be studied today in appropriate clinical situation
* Regulatory documents indicate a rationale for µD
* µD affects decision making in clinical R&D and routine practice

Monitoring tissue drug levels by microdialysis.ppt

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Microdialysis



Microdialysis
Presentation by:Steve Milway

Microdialysis A technique used to study the biochemical activity in the extracellular space.

Micro : refers to the extremely small scale.
Dialysis: the movement of chemicals across a permeable membrane.
Microdialysis allows us to monitor chemical changes in a behaving animal Most commonly, a concentric microdialysis probe is used. Usually the fluid flows in the opposite direction to the arrows in the diagram, but it doesn’t really matter as long as the fluid flows by the membrane.

A microdialysis probe is similar in size to a bipolar stimulating electrode.
It can therefore be implanted stereotaxically for both Acute and Chronic experiments.
The fluid circulating through the dialysis probe is artificial cerebrospinal fluid (ACSF). ACSF is very similar to the CSF in the extracellular space so a negligible amount of ACSF or CSF will cross the membrane. There is thus very little tissue damage or trauma.
Soluble molecules will cross the membrane down their concentration gradient.
Molecules can cross in either direction. A dialysis probe can be used to deliver chemicals to the brain. If a higher concentration of the chemical of interest is in the probe, it will tend to cross the membrane and enter the extracellular space.
This application is often called Retrodialysis.


Calibration

The recovery capabilities of probes vary. Before a microdialysis probe can be used, it must be calibrated. This is done in vitro by testing the probe with a known concentration of the molecule of interest in ACSF.
The recovery in brain will not be as efficient as the recovery in vitro.
Once the probe has been calibrated it can be used.
Before samples are collected, ACSF is run through the probe for approx. 20 minutes to allow the probe to equilibrate.

Factors influencing the dialysis rate
* Surface area of dialysis membrane.
* Magnitude of concentration gradient.
* Rate of flow through the probe.
* Type of dialysis membrane. Different membranes have different pore sizes
* The size of the molecule.

Applications

* Temporal characteristics of a drug crossing the BBB.
* Release of neurotransmitters during behaviour.
* Activation of brain areas by various agonists (Retrodialysis)
* Activation of one brain area with one probe. Recording neurotransmitter release from another area with a second probe.
* Mixed use? Using a probe to both deliver and sample.

Pitfalls

* Although microdialysis provides the sample, you still need a suitable method to analyze the sample.
* Some methods require only microlitres of solution while others might require millilitres. Temporal resolution will be limited. If it takes 10 minutes to collect a sample, that is the temporal resolution.
* Some areas of interest are too small for the probe.

Microdialysis.ppt
Microdialysis lecture

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04 May 2009

Toxicity Study of DC-D3T in Rats



Toxicity Study of DC-D3T in Rats

PRE-CLINICAL TOXICOLOGICAL EVALUATION OF 5,6-DIHYDRO-4H-CYCLOPENTA-1,2-DITHIOLE-3-THIONE, A POTENTIAL CANCER CHEMOPREVENTIVE DRUG, IN RATS
Rajabather Krishnaraj1, Izet M. Kapetanovic2, Robert L. Morrissey3, Thomas Kensler4, James Crowell2, Barry S. Levine1
1Toxicology Research Laboratory, University of Illinois at Chicago, Chicago, IL; 2NCI, Bethesda, MD; 3Pathology Associates, Chicago, IL; 4Johns Hopkins University, Baltimore, MD.

ABSTRACT

The purpose of this study was to examine the in vivo toxicity of 5,6-dihydro-4H-cyclopenta-1,2-dithiole-3-thione (DC-D3T), a potential cancer chemopreventive drug that may act primarily as a phase II enzyme inducer, in normal CD rats. Based on a 14-day range finding study, DC-D3T was administered daily by oral gavage (20/group/sex) for 28 days at 0, 3,12 and 50 mg/kg bwt/day. Endpoints included daily clinical signs, weekly body weight and food consumption, week 4 clinical chemistry, hematology, coagulation, ophthalmology, and necropsy at week 5 and histopathology. The mean plasma DC-D3T levels (measured 2 hours post-dosing in week 4) in the 3 (low), 12 (mid) and 50 (high) mg/kg/day dose groups were 0.28, 0.77 and 1.83 μg/mL for males and 0.24, 0.70 and 2.05 μg/mL for females, respectively. No mortalities or clinical signs of toxicity were seen. Reduced body weight gains and food consumption occurred in the high dose group males. At the high dose, hepatic effects were seen: elevated serum ALT, bilirubin (in the high and mid dose group females), protein, albumin, globulin, cholesterol and decreased triglycerides, and hepatomegaly. Mild renal injury was inferred from hypochloremia in the high dose group and creatininemia in high and mid dose group males. Decreased weights of heart and thyroid/parathyroids noted in the high dose group rats were unaccompanied by histologic changes. Splenomegaly (high dose), dose-dependent increases in the incidence and severity of follicular center hyperplasia of spleen and mesenteric lymph node (at low, mid and high doses), mild monocytosis and reticulocytosis (high dose group females) were also observed. Chronic perivascular inflammation (presence of lymphocytes around small arteries) of epididymis and kidney was noted at 3, 12 and 50 mg/kg/day of DC-D3T. The preliminary data on the effect of DC-D3T on lymphoid tissues could be interpreted as either general immunomodulation or toxicity of DC-D3T. Additional studies are needed to define the threshold for the tissue inflammatory reactions and possible direct immunologic effects of DC-D3T. Under the conditions of this study, a NOEL was not found for DC-D3T in male and female rats. (Supported by NCI contract No.N01-CN-0512).

CONCLUSIONS

* Toxicity of 5,6-dihydro-4H-cyclopenta[1,2]-dithiole-3-thione (DC-D3T) was tested in CD® rats after 28 days of daily gavage administration at 0, 3 (low dose), 12 (mid dose) and 50 (high dose) mg/kg/day.
* Neither mortalities nor drug-related clinical signs were seen at any dose.

* Reductions in weekly body weight gains accompanied by reduced food consumption occurred in the high dose group males, culminating in 25% decrease in total body weight gain.
* Elevated serum total bilirubin levels (high & mid dose group females) and elevated %reticulocytes (high & mid dose group males) were noted. There was no unequivocal evidence for mild hemolytic anemia.
* Mild hepatic injury was evident from the raised serum ALT levels (high dose group), hepatomegaly (high & mid dose group), and a dose-dependent increase in the incidence & severity of centrilobular hypertrophy in males. Hyperproteinemia, hypercholesterolemia and hypotriglyceridemia were also noted at high dose.
* Mild renal injury was suggested by elevated serum creatinine (at high dose), and chloride levels (in high and mid dose group males).
* Mean plasma drug levels in the low, mid and high dose groups were 0.284, 0.767 and 1.831 µg/mL (males) and 0.239, 0.700 and 2.045 µg/mL (females).
* Hyperglobulinemia, splenomegaly (high dose group), dose-dependent increase in the incidence and severity of follicular center hyperplasia of spleen (all DC-D3T treated groups) and mesenteric lymph node (low, mid and high dose group females) were also noted. These effects were accompanied by dose-dependent chronic perivascular inflammation of epididymis and kidney in all dose groups. These findings could be interpreted as either immunostimulatory or toxic effect of DC-D3T. A comprehensive evaluation of the immunomodulatory effect of this chemopreventive agent is needed.

* Under the conditions of this study, a No-Observed-Effect-Level was not found for DC-D3T.

Summary of Treatment-Related Lesions
* Incidence (severity range)
LYMPH NODE, MESENTERIC

-Hyperplasia, follicular center
-Inflammation, chronic, perivascular
-Hyperplasia, follicular center
-Hypertrophy, centrilobular
-Vacuolation, centrilobular

ORGAN - lesion
Dose (mg/kg/day DC-D3T)
Summary Of DC-D3T-Treatment Related Changes
Hematology
Clinical Chemistry
Food Consumption
Total Body Weight Gain
EXPERIMENTAL DESIGN

During the quarantine/pretest period, 80 male and 80 female rats were randomized using a computer-generated randomization program, stratified on the basis of body weight, and animals were assigned to 4 treatment groups of 20 males and 20 females per group. The study was stagger-started over two consecutive days beginning with the males.
Dose Concentration
Dose Volume
LIST OF ORGANS AND TISSUES EVALUATED FOR LESIONS

Abnormal lymph nodes Pancreas
*Adrenal glands Pituitary
Aorta (thoracic) Prostate
*Brain (fore-, mid-, hind-) Salivary gland (mandibular)
Cecum Sciatic nerve
Colon Seminal vesicles
Duodenum Skeletal muscle
Epididymides Skin
Esophagus Spinal cord (cervical and Eyes thoracolumbar segments)
Femur (with marrow) *Spleen
Gross lesions Sternum (with marrow)
*Heart Stomach
Ileum *Testes
Jejunum Thymus
*Kidneys *Thyroid/parathyroids
*Liver *Tissue masses
*Lungs/Bronchi Trachea
Lymph node (mesenteric) Urinary bladder
Mammary gland Uterus (corpus and cervix)
*Ovaries/Fallopian tubes Vagina
* Organs weighed.

Toxicity Study of DC-D3T in Rats.ppt

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02 May 2009

Pharmacy and Pharmacology videos



Pharmacy and Pharmacology videos from: University of Wisconsin–Madison


04/17/2009 Picture from Secondary Prevention: Recent Antithrombotic Trials video
R. Levine
03/19/2009 Picture from Chemotherapy-Related Cardiomyopathy: An Update video
S. Ewer
02/25/2009 Picture from Clinical Research from Industry's Perspective video
M. Westrick
11/16/2008 Picture from Can Drug Regimens be Adapted to Patients, or Vice Versa? video
N. Britten
09/17/2008 Picture from A Global Strategic Plan for Hospital Pharmacy Practice video
L. Vermeulen
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As the complexity of medication therapy has increased for hospitalized patients, the importance of skilled pharmacists and advanced pharmacy services in hospitals has become critical. In August 2008, the Hospital Pharmacy Section of the International Pharmaceutical Federation (FIP) will host a Global Conference on the Future of Hospital Pharmacy, bringing hundreds of delegates from over 100 nations to Basel, Switzerland to address issues that will shape the future of hospital pharmacy practice. Lee Vermeulen, who chaired the Steering Committee for the Conference, presents a summary of the Conference consensus statements. In addition, a global survey of hospital pharmacy practice was conducted by the Vermeulen in preparation for the Conference, and a summary of the results are presented.
06/12/2008 Picture from Overview of Translational Research: Type 1 (Efficacy) and Type II (Effectiveness) video
M. Smith, R. Marnocha

Picture from Introduction to Clinical Trials video
C. Sorkness
02/28/2008 Picture from Cardiovascular Prescription Development and Pitfalls video
R. Harrington
01/22/2008 Picture from Management of Pain in the Ambulatory Care Setting video
M. Backonja
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In this presentation participants will: * Learn the pharmacological treatment options for acute and chronic pain and highlight the role of opioid analgesics * Discuss practical challenges when prescribing opioids and point to the opioid risk management issues including underuse, overuse and misuse * Learn regulatory and practice management issues when prescribing chronic opioid therapy
11/20/2007 Picture from Medical Student Oral Presentations - Session I video
C. Baggot, D. Fadowole, E. Fish, R. Johnson, W. Truong
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Hear the following presentations from the 2007 Medical Student Research Fall Forum: "Cation-Dependent Chloride Transporters in Neuropathic Pain Following Spinal Cord Injury" Christopher Baggott, Mentor: Dandan Sun, MD, PhD "Collaborative Health Care: The Implications of Using the Internet as a Health Resource on Doctor-Patient Relationships" Deborah Fadowole, Mentors: Kim McDowell, MD, PhD; Mary Michaud "Vitamin D Status of Morbidly Obese Bariatric Surgery Patients" Emily Fish, Mentor: Jon Gould, MD "Use of Thiopurines as Antiviral Agents for Hepatitis C Virus and Dengue Virus" Ryan Johnson, Mentor: Robert Striker, MD, PhD "The Effects of Metacarpal Shortening on Flexor Tendon Efficiency" William Truong, Mentor: Robert Ablove, MD, MA
11/13/2007 Picture from Cannabis and Cannabinoids in the 21st Century: Medical Marijuana video
D. Bearman
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David Bearman, MD, a Santa Barbara, California physician and surgeon with Wisconsin roots, speaks on "Cannabis and Cannabinoids in 21st Century Medicine: Medical Marijuana in the Clinic". Bearman is one of the leading physicians in the U.S. in the field of medical marijuana. He has spent 40 years working in substance and drug abuse treatment and prevention programs. Bearman was a pioneer in the free and community clinic movement.
11/02/2007 Picture from The Truth about Drug Companies video
M. Angell
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Paying for prescription drugs is no longer a problem just for poor people. As the economy continues to struggle, health insurance is shrinking. Employers are requiring workers to pay more of the costs themselves, and many businesses are dropping health benefits altogether. Since prescription drug costs are rising so fast, payers are particularly eager to get out from under them by shifting costs to individuals. The result is that more people have to pay a greater fraction of their drug bills out of pocket. And that packs a wallop.
10/10/2007 Picture from Pain Policy Project - Sierra Leone video
R. Buitrago, G. Madiye
10/04/2007 Picture from Diabetes Management - What Physicians Should Know video
M. Meredith, G. Klinkner
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The objectives of this presentation are to discuss: 1) Insulin use in the hospitalized patient, adjusting insulin for patients who are NPO, transitioning patients off an insulin drip and using correction insulin 2) UWHC on-line diabetic management resources 3) Diabetes Management Service ... scope and purpose
07/06/2007 Picture from Essentials of Order Writing video
C. Kraus
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Connie Kraus, PharmD, BCPS, speaks on "Essentials of Order Writing" at the Transitional Clerkship Orientation on July 6, 2007.
11/20/2006 Picture from Medical Student Oral Presentations I video
A. Gepner, D. Hirsch, D. Friedman
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Hear the following presentations from the 2006 Medical Student Research Fall Forum: "An Abbreviated Ultrasound Scanning Protocol For Atherosclerosis Screening" Adam Gepner, Mentor: James Stein, MD "Pioglitazone Helps to Restore Insulin Secretions & Insulin Secretory Reserve in Islet Transplant Recipients: Preliminary Results" David Hirsch, Mentor: Luis Fernandez, MD "Relationship between HIV-1 Subtype, Antiretroviral Response and Resistance in a Ugandan Pediatrics Clinic" DeAnna Friedman, Mentor: Frank Graziano, MD, PhD
10/17/2006 Picture from Emergency Contraception as an Over-the-counter Drug video
S. Schrager
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Emergency Contraception was recently approved with Over-the-counter status. Sarina Schrager , MD, MS discusses the road here, what the new status means, and obstacles that remain (i.e. age limit, financial, etc).
08/24/2006 Picture from PCI, Drug-Eluting Stents, and Adjunctive Medical Therapy for Patients with CVD video
S. King, III
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23 April 2009

Medicare Prescription Drug Coverage



Medicare Prescription Drug Coverage

Prescription drug coverage will be a new benefit offered by Medicare in January 2006. This program offers an extensive overview of the new prescription drug benefit, available options and a workshop. App. one hour video

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22 April 2009

Drugs for Circulatory Disorders



Drugs for Circulatory Disorders

Presentation covered the following topics.

* Drugs used are to maintain, preserve or restore circulation
* Anticoagulants & antiplatelets (antithrombotics), thrombolytics, antilipemics, peripheral vasodilatiors
* Anticoagulants - prevent formation of clots that inhibit circulation
* Antiplatelets - prevent platelet aggregation
* Thrombolytics (clot busters) - attack/dissolve formed clots
* Antilipemics - decrease bld. lipid concentration
* Peripheral vasodilators - promote dilation of vessels narrowed by vasospasm

Thrombus Formation
Risk Factors for Deep Vein Thrombophlebitis and Thromboembolism
Anticoagulants
Heparin
Circulatory - LMWH
LMWHs
Warfarin
Antiplatelet Drugs
Thormbolytics
Circulatory - Thrombolytics
Antilipemics
Circulatory - Antilipemics
Peripheral Vasodilators

Drugs for Circulatory.ppt

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All links posted here are collected from various websites. No video or powerpoint files are uploaded on this blog. If you are the original author and do not wish to display your content on this blog please Email me anandkumarreddy at gmail dot com I will remove it. The contents of this blog are meant for educational purpose and not for commercial use. If you use any content give due credit to the original author.

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