Pharmacology Nu 420 1st exam

what the body does to a drug

Absorbtion-transfer of a drug from site of administration to the blood  (must cross cell membrane- active/passive transport)

distribution: moving of drug from blood to various compartments in the body

drug metabolism: biotransformation and excretion

what drug does to the body

Hypersensitivity:if a receptor’s activity is chronically reduced by antagonists, a state of up-regulation may occur and the if the drug is rapidly withdrawn the receptors react strongly to the natural agonists, resulting in an exaggerated response

• Continual bombardment of receptors causes and decrease in the total receptor thereby decreasing the overall effect of the medication.
• AKA desensitization.

Actions ends when the drug leaves the receptor site.

A drug that binds and occupies the receptor permanently.

A drug that works opposite of the antagonist and competes with the agonist at the receptor sites, will occupy the same site as the antagonist.

A drug that irreversibly binds to a receptor and has a greater affinity to the receptor than does the other drug it is inhibiting.

A drug that when bound to a receptor only exerts a partial effect when compared to a full agonist.

A sudden decrease in the response to a drug following administration.

Phase I: Oxidation, hydrolysis, or reduction to increase water solubility of drug.

Phase II: conjugation or union with water soluble molecule.

Metabolism of orally administered drug before it reaches the systemic circulation.  If the drug is absorbed via the stomach, or intestine then it will pass through the liver first.

After passing through the liver and circulation to the systemic circulation the drug then return back to the liver and be "re-phased."

CYP 450

Drug that is administered in it's inactive form and the through biotransformation is turned into the active form.

Most ACEI

• Passive Glomerular filtration
• Active tubular secretion
• tubular re-absorption

Biliary excretion.

100%

75-100%

75-100%

30 to <100%

5 to <100%

5 to<100%

80 to 100%

• Dose response relationship
• therapeutic index
• plasma level profile
• Half-life
• Bioavailability

the amount of drug needed to produce an effect.

The maximum effect that can be produced by a drug.

the time between administration and first sign of drug effect.

• Th time required to meet the maximum concentration of drug.
• -amount of drug being absorbed and distributed is equal to the amount being metabolized and and excreted.

Time that the blood levels are above the minimum effective concentration(MEC).

The drug level drops below the MEC.

• Onset of action
• peak of action
• duration of action
• termination action

MTC-MEC

• (MEC)- level below which therapeutic effects will occur
• (MTC)- level above which toxic effects begin

• Physicochemical Characteristics:
• Lipid Solubility
• Protein Binding
• Molecular Size
• Distribution by Compartment:
• Plasma: low molecular weight, high protein binding, hydrophilic
• ECF: low molecular weight, lipophilic

pharmacokinetics, pharmacodynamics, therapeutic issues, safety, and cost

• Standardization of nomenclature
• Approval process for new drugs and indications
• Official labeling  
• Surveillance of adverse drug events
• Methods of manufacture and distribution
• Regulation of advertisements for prescription drugs

• A schedule 1 drug is a drug that is:
• No accepted medical use
• No legal use permitted
• For registered research facilities only
• Examples are:
• Heroin, LSD, mascaline, peyote, marijuana

• No refills permitted
• No telephone orders unless true emergency and followed up by written prescription within 7 days
• Electronic prescribing permitted as of 2011 with specific software and secure identification processes
• Examples:
• Narcotics:  (morphine, codeine, meperidine, opium, hyromorphone, oxycodone, oxymorphone, methadone, fentanyl)
• Stimulants:  (cocaine, amphetamine, methylphenidate)
• Depressants:  (pentobarbital, secobartial)

• Prescription must be rewritten after 5 months or 5 refills
• Telephone or fax prescription okay
• Examples:
• Narcotics: (Codeine in combination with non-narcotic ingredients not to exceed 90 mg/tab; hydrocodone not to exceed 50mg/tab)
• Stimulants: (Benzphetamine, chlorpehniramine, diethylpropion)
• Depressants: (butabarbital)

• Prescription must be rewritten after 5 months or 5 refills
• Telephone or fax prescription okay
• *Penalties differ for illegal possession*

Penazocine, propoxyphene, phentermine, benzodiazepines, meprobamate

May be dispensed without a prescription unless regulated by the state

• Indications:
• Allergic rhinitis, Vasomotor rhinitis, pruritis, conjunctivitis, upper respiratory allergies
• Action:
• Complete antagonist of histamine at the H1 receptor sites in the GI, uterus, large vessels and bronchial muscle. Binds non-selectively to central H1 receptors; can cause cns depression and stimulation.

• Action:
• Complete antagonist of histamine at the H1 receptor sites in  the GI, uterus, large vessels and bronchial muscle. Binds non-selectively to central H1 receptors; can cause cns depression and stimulation.

• sedation and anticholinergic side effects common (drymouth, urinary retention, dysuria
• Central: dizziness, tinnitus, lassitude, disturbed coordination, fatigue, headache, irritability, nervousness, blurred vision, diplopia, and tremors
• GI related: increased or decreased appetite, nausea, epigastric distress, vomiting, constipation, diarrhea

• In patients with narrow-angle glaucoma, lower respiratory tract infections (thicken secretions and impair expectoration), stenosing peptic ulcer, symptomatic prostatic hypertrophy, bladder neck obstruction, pyloroduodenal obstruction, and MAOI use
• Newborns and premature infants: may convulsions

Seasonal or perennial rhinitis, chronic uticaria, pruritis, allergic rhinitis

• Selective for peripheral H1 receptors and therefore as a group are less sedating
• They do not cross the blood-brain barrier in appreciable amounts

Minimal compared to first generation: benefit incidence of drowsiness greatly reduce, tolerated well in GI system, minimal incidence of dry mouth.

• In patients with significant hepatic dysfunction
• Number of drugs in this class cannot be used in conjunction with: mycins, zoles, quinine, HIV drugs, SSRI’s

• Long term asthma care
• first-line agent for long term prophylactic therapy of moderate asthma

Coughing, throat irritation, wheezing

• Inhalation Mechanism:
• Suppressing inflammation
• Stabilizing the cytoplasmic membrane of mast cells preventing release of histamine and other mediators
• Suppressive effect on other inflammatory cells (macrophage, eosinophils, monocytes)

Hypersensitivity.

• Bronchospasm associated with asthma, COPD, and bronchitis
• Maintenance therapy of chronic stable asthma
• Oral theophylline is indicated for patients that experienced nocturnal attacks of asthma
• Used to be widely used, now being replaced with safer and more effective medications
• second line, low dose treatment for COPD

• plasma levels at <20 mcg/ml: adverse effects are uncommon
• plasma levels 20-25 mcg/ml: nausea, vomiting, diarrhea, insomnia, restlessness
• plasma levels >30 mcg/ml: Seizures, tachycardia, arrhythmias
• CNS stimulant: cause insomnia, excitability, tremors, increase gastric secretions, increased sodium and chloride secretion, causes diuresis

• Bronchodilation by relaxing smooth muscle of the bronchi
• Possible mechanisms include blockade of receptors of adenosine, inhibiting phosphodiesterase enzyme

hypersensitivity to xanthine, peptic ulcer disease, and underlying seizure disorder

• Long term treatment of
• allergen-, exercise-, histamine-, and methacholine- caused bronchospasm

• Effects are delayed but persist for up to 12 hours
• exert long-lasting bronchoprotection effects against allergen-, exercise-, histamine-, and methacholine- caused bronchospasmNOT first choice agent for long term controlDosing on a fixed schedule, not PRN

may increase the risk of severe asthma, asthma-related intubation and death

• avoid concurrent use with Beta blockers, causes mutual inhibition
• MAOIs, Tricyclic antidepressants
• should be used only in patients taking a recommended medication for long-term control, and only if that medication has been inadequate by itself

• reversible bronchoconstriction caused by asthma or restrictive airway disease
• control episodic bronchoconstriction
• Preventative for exercise-induced asthma

• act on smooth muscle to reverse bronchospasm
• stimulate beta 2 adrenergic receptors in the lung to increase production of cyclic adenosine monophosphate (cAMP): increased cAMP concetrations relax bronchial smooth muscle and inhibit release of mediators of immediate hypersensitivity from cells, especially from mast cells
• Effects begin immediately, peak in 30-60 minutes, and persist for 3-5 hours

Cardiac arrhythmias- tremor, tachycardia,hypotension, angina, headache, dizziness, nausea, etc.

• Diabetics potential for drug induced hyperglycemia
• Any patients with digoxin therapy or cardiac history: contraindicated due to this drugs effect on the cardiovascular system (Albuterol increases the volume of distribution of Digoxin)
• Hypothyroidism- adverse reactions more likely to occur with use of bronchodilator
• Pheochromocytoma- severe hypotension can occur when Bronchodilator used

Asthma, Allergic Rhinitis

• Primary action is anti-inflammatory: ibhibit IgE and mast cell mediated migration of inflammatory cells into the bronchial tissue
• Most potent and effective anti-inflammatory medication currently available
• lead to reduction in the severity of asthma symptoms, increased peak flow readings, and decreased airway hyperresponsiveness

• Xerostomia, hoarseness, tongue and mouth irritation, flushing, dysgeusia, rash, uticaria
• Local immunosuppression can lead to oral candidiasis
• Cataracts can be induced with corticosteroid use
• Systemic: Adrenal suppression, bone loss, can slow growth rate of children, but does not reduce adult height

• Contrindicated in acute status asthmaticus
• Adrenal insufficiency when switching from inhaled to oral
• Avoid use in patients with Cushings Syndrome
• In combination with other steroids, risk for hypothalamic pituitary adrenal suppression is increased

Prophylaxis and chronic treatment of asthma

• Suppresses the effect of leukotrienes
• Maximum effect develop within 24 hours of the first dose, and are maintained once daily dosing in the evening

• Reported adverse reactions of those taking montelukast are similar to those taking placebo
• In leukotrience modifiers:
• Neuropsychiatric events have been reported: agitation, aggression, anxiousness, dream abnormalities, hallucinations, depression, insomnia, irritability, restlessness, suicidal ideation, tremor

Contraindicated in patients with hypersensitivity to any of the components of the medication

Bronchospasms associated with asthma or COPD

• Blocks muscarinic cholinergic receptors
• Blocks the effects of acetylcholine released from cholinergic nerves in the airways
• Block reflex bronchoconstriction caused by inhaled irritants
• Less potent bronchodilators than inhaled beta-2 agonists, in general, have a slower onset of action (Atrovent: alternative bronchodilator for patients who experience adverse effects from beta 2 agonists)

• Most common side effect is cough
• Dryness of the mouth, bitter taste, hoarseness, throat irritation, dysgeusia, nausea, vomiting, dyspepsia
• Systemic effects are minimal

• Contraindicated in patients with hypersensitivity to atropine, atropine derivatives, and bromine sensitivity
• Inhaled anticholinergics should be avoided for patients with urinary retention, bladder neck obstruction, or prostatic hypertrophy, and closed angle glaucoma (can increase intraocular pressure)
• Safety has not been established for children under 12 years old

• B-2 Aderenergic agents
• Anti-colinergics

• B-2 Adrenergic Agents
• Methylxanthines
• Cromolyn sodium
• leukotriene inhibitors
• anti-IgE monoclonal antibodies

caused by M. Tuberculosis; inhaled into the alveolus and spread from lungs; grows slowly; infection is spread almost exclusively by aerosolization of contaminated lung secretions

Accurate diagnosis: PPD screenings, chest xray; Completion of the recommended therapy; Effective treatment to treat patients and prevent transmission; Risk stratifications: HIGH RISK: children <4 years, HIV/AIDS patients, foreign-born patients

• 1. Regimen to contain multiple drugs to which the organisms are susceptible to.
• 2.The drugs must be taken regularly
• 3. Drug therapy must continue for a sufficient period of time
• 4. Never add a single drug to a failing regimen

• 1. Initiation phase for the first 2 months
• 2. continuation phase for the last 4-7 months

• INH-Isoniazidi: risk for hepatitis, and peripheral nueropathy
• RIF-Rifampin
• EMB-Ethambutol
• PZA-pyrazinamide

• Sputum cultures monthly until negative, TB-free after two months of treatment
• Chest xray at completion of therapy to document post TB CXR
• Monitor for drug adverse effects: Baseline liver enzymes, bilirubin, creatinine, CBC, platelets

INH alone for 6-9 months, monitor monthly, directly observed therapy if necessary, successful treatment is determined by absence of the disease, patient education is CRITICAL to a successful treatment

• Exogenous morphines and their derivatives (opiates): MODERATE TO SEVERE PAIN
• Anti-inflammatory agents

mu receptor

• Morphine
• hydromorphone
• levorphanel

• buprenorphine
• Because it is only a partial agonist, it does not produce as much euphoria but it does suppress withdrawal and cravings. (http://www.buppractice.com/howto/whatisbup/mechanism)

meperidine, methadone, tramadol, tapentadol

euphoria, respiratory depression, constipation, urinary retention, drug dependence

• Strong agonist: morphine, pentazocaine, nalbuphine, butorphanol
• Little or no activity: methadone, levorphanel,
• meperidine

produce sedation but NO euphoria, respiratory depression, constipation, or urinary retention

Aspirin, salicylates, NSAIDS, acetaminophen, corticosteroids

Inhibition of COX enxymes, prostoglandin synthesis. Because of prostoglandin inhibition may predispose patient to peptic ulcers.

Inhibition of COX enxymes, prostoglandin synthesis. Because of prostoglandin inhibition may predispose patient to peptic ulcers.

• Exact mechanism unknown, thought to increase the pain threshold.
• Limited anti-inflamitory effect.

point at which a stimulus is experienced as pain

• Sensory/discriminatory system
• motivational/ affective system
• congnitive//evaluative system

If there are multiple "pains" that a person is experiencing, only the strongest stimulation will be reported.

duration or intensity of pain that a person will tolerate before seeking action to relive it?

up to 6 months

Tissue injury

Pain caused by a lesion or dysfunction in the CNS (infarction, hemorrhage, abscess, degeneration, tumors, or traumatic injury); migraines and headaches also fall into this category.

Nonneuropathic Pain- results of any lesion that is noncancerous and not the result of nerve damage. The most common causes are inflammatory in nature, but the exact physiological basis may be unclear; fibromyalgia, myositis, myalgia, and muscle strain fall into this category

Result of trauma or disease of the peripheral nerves; pain is often paroxysmal, burning, or shooting; examples include hyperesthesias, phantom limb pain

pain related to a psychological disorder, pain that is purely psychogenic (conversion disorder) is extremely rare.

• reduction or elimination of the pain sensation with a minimum of adverse reactions
• Because acute pain is a short-term phenomenon, lifestyle modifications are largely directed toward reduction of the source of the painful stimulus, rest or immobilization of the affected part, elevation when possible, ice, or compession.
• Oral administration of any pain drug is route of choice if the patient has a functioning GI system

• would prefer elimination of the pain, but with chronic pain this may not be possible. An acceptable goal for treatment in chronic pain is the reduction of pain to level that the patient finds tolerable with a minimum of medication side effects.
• Goals should be: (1) negotiated between the patient and provider (2) specific (3) measurable