Pharmacology Midterm Flashcards
Cardinal Signs of Inflammation
Dolor (pain)
Rubor (redness)
Calor (heat)
Tumor (swelling)
*5th sign is loss of function, added later
Inflammation Cell Types
- Granulocytes
- neutrophils
- eosinophils
- basophils
- Monocytes
- Mast cells
Which granulocyte is increased during allergic and parasitic reactions?
Eosinophils
Which granulocyte contains histamine?
Basophils
Types of Chemical Mediators
- vasoactives
- chemotactic factors
- plasma proteases
- reactive molecules
Phases in Inflammatory Response
- Vasodilation
- Chemotaxis
- Phagocytosis
- Resolution
Pharmacology for Inflammation
- Steroids
- NSAIDS
- DMARDS
- disease modifying anti-rheumatic drugs
Steroids used in Inflammation
- Corticosteroids or glucocorticoids
- induce calcium and lipocortins
Types of NSAIDS
- salicylates (acetylated and non-acetylated)
- selective COX-2 inhibitors
- non-selective COX-2 inhibitors
Pharmacokinetic features of Anti-Inflammatories
- weak acid
- well absorbed in GI
- highly protein bound
- extensive liver metabolism
Non-Steroidal Anti-Inflammatory Drugs (NSAIDS)
- COX inhibitors
- COX catalyzes formation of prostanoids
- Drugs:
- acetylsalicyclic acid
- ketorolac
- Celecoxib
- Meloxicam
Adverse Effects of NSAIDS
- CNSH
- headaches, tinnitus, and dizziness
- Cadiovascular
- fluid retention, hypertension, and edema
- Gastrointestinal
- abdominal pain, nausea, vomiting, ulcers, bleeding
- Hematological
- thrombocytopenia, neutropenia, aplastic anemia
- Hepatic
- abnormal LFT and rare liver failure
- Pulmonary
- airway hyper-reactivity
- Integumentary
- pruritis
- Renal
- insufficiency, failure, hyperkalemia, and proteinuria
Cyclooxygenase-1 (COX-1)
- expressed gene
- generates prostanoids for “housekeeping”
Cyclooxygenase-2 (COX-2)
- inducible gene
- major route by which prostanoids involved in inflammation are synthesized
- selective NSAIDS target only COX-2
Non-Selective NSAIDS Drugs
- Acetylsalicyclic acid
- ketorolac
Selective NSAIDS Drugs
- Celecoxib
- Meloxicam
Acetylsalicylic Acid adverse effects
- unwanted bleeding
- gastric upset and ulcers
- angioedema, hives, and rashes
- nephrotoxicity, hepatotoxicity
- airway hyperreactivity
- salicylism
- Reye’s syndrome
Salicylism
toxicity associated with high doses of aspirin
headache, vomiting, tinnitus, vertigo, fever, seizures, respiratory depressions
Reye’s Syndrome
Aspirin use in young children
vomiting, encephalopathy, hepatotoxicity
Ketorolac mechanism of action
reversible inhibitor of COX-1 and COX-2
Ketorolac duration of use
up to 5 consecutive days
Celecoxib Black Box Warning
- risk of thrombosis, MI
- contraindicated in CABG surgery
- serious GI effects
Precautions of Steroidal Anti-Inflammatory Drugs
- Children: growth retardation
- elderly: osteoporosis
- diabetes: increase blood glucose
- psychosis: exacerbation
- myasthenia gravis: muscle weakness
- hypertension: sodium/water retention
- systemic infections: immunosupression
- pregnancy: catgeory C
Acetaminophen
- COX-1, COX-2, and COX-3 inhibitor
- analgesic and antipyretic
Meloxicam
(Mobic)
- COX-2 inhibitor
- arthritis
Cyclooxygenase (COX)
catalyzes formation of prostaglandins, thromboxane, and prostacyclin
Celecoxib
(celebrex)
selective COX-2 inhibitor
broad-spectrum anti-inflammatory
used off-label for prophylaxis of colorectal cancer
clinical characteristics of Asthma
- shortness of breath
- chest tightness
- wheezing
- coughing
pathological characteristics of asthma
- hyper-responsive airways
- inflammation, bronchoconstriction
- vascular remodeling
- collagen deposition, cellular hyperplasia
Model of Asthma
- initial exposure produces IgE antibodies
- IgE binds to FceRI receptors on mast cells
- reexposure releases stored mediators of inflammation
Early asthmatic response
- immediate airway constriction
- histamine, prostaglandin, D2, leukotriene C4, tryptase, platelet activating factor (PAF)
- immediate fall in FEV1
Late asthmatic response
- elevated mucus production, edema, sustained bronchoconstriction
- delayed fall in FEV1
Formoterol
(Foradil)
long-acting ß2-agonist (LABA)
Salmeterol
(Serevent)
long-acting ß2-agonist (LABA)
Theophylline
bronchodilation and antiinflammatory
- increases intracellular cAMP
- via phosphodiesterases
- adenosine antagonist
*narrow therapeutic index
Ipratropium
COPD and asthma
structurally simila to atopine
Glucocorticoids for Asthma
- Budesonide
- Dexamethasone
- Fluticasone
- Mometasone
(7) ß2-agonist
- Albuterol
- Formoterol
- Levalbuterol
- Metaproterenol
- Pirbuterol
- Terbutaline
- Salmeterol
Zileuton
(Zyflo CR)
asthma
reduces airway inflammation
Leukotriene synthesis (5-LOX) inhibitor
(2) Leukotriene receptor antagonists for Asthma
Montelukast (Singulir) and Zafirlukast (Accolate)
* Know where Zileuton and Montelkast/Zafirlukast
Omalizumab
(Xolair)
IgE antibody
treats asthma
Cromolyn
treats asthma
alters Cl- channels
- inhibits mast cell degranulation
- inhibits eosinophil responses
- inhibits cough
Endogenous opioid peptides
produced in the human body
General mechanism of Opioids
Mu (u) agonist
General effects of Opioids
- analgesia
- cough suppression
- hypotension
- nausea
- miosis
- constipation
- tolerance
General Indications for Opioids (5)
- analgesia
- cough suppression
- diarrhea
- shivering
- acute pulmonary edema
Elimination of Opioids
mainly by the kidney
In kidney disease, Meperidine may cause seizures and Codeine may enchance opioid action
Morphine
full agonist
phenanthrenes
Methadone
Full opioid agonist
phenylheptylamine
Opioid Phenylpiperidines (3)
- Fentanyl
- Meperidine
- Remifentanyl
Codeine
partial opioid agonist
phenanthrenes
Opioid Phenylpiperidines
(partial)
Diphenoxylate and Loperamide
treat diarrhea
Nalbuphine
(Nubain)
mixed opioid agonist
Absorption of Opioids
first-pass effect
interpatient variability
Which sedative drug has a linear relationship between dose and stage of anesthesia?
Barbituates
(5) Benzodiazepines for Sedation
- Diazepam
- Midazolam
- Lorazepam
- Temazepam
- Triazolam
(4) Barbituates for Sedatin
- Methohexital
- Pentobarbital
- Secobarbital
- Thiopental (Pentothal)
Therapeutic Indications for Sedatives
- anxiety
- insomnia
- epilepsy
- nausea
- control of ethanol withdrawal
- spasticity
Schedule III Drug
barbituates
prescriptions with refills