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Hoff Exam 4
Telgenhoff Exam 4 (Nov-Dec 2012)
231
Pharmacology
Graduate
11/12/2012

Additional Pharmacology Flashcards

 


 

Cards

Term
Factors affecting ventilation
Definition
airway diameter
contraction and relaxation of smooth muscle
ANS input
Term
obstructive disorders
Definition
asthma
chronic bronchitis
emphysema
Term
COPD
Definition
Chronic bronchitis + emphysema
Term
Asthma
Definition
from Greek "panting"
Respiratory system disorder characterized by episodes of difficulty in breathing
Term
PEF
Definition
peak expiratory flow
maximum flow of forced expiration
Term
FEV1
Definition
Bronchial hyper-reactivity
Fall in Forced Expiratory Volume in 1 sec provoked by inhaling histamine or methacholine
Term
Immunologic mediators responsible for the early reactions
Definition
diffuse throughout airway wall
cause muscular contraction and vascular leakage
immediate bronchoconstriction (histamine, leukotriens, prostaglandings)
Term
Epinephrine
Definition
rapid-acting bronchodilator
SQ or inhaled
stimulates B1, B2 and alpha
max bronchodilation in 15 min
60-90 min duration
Dose: 320mcg/puff
adverse effects: tachycardia, arrhythmia, worsening of angina
Term
Isoproterenol
Definition
potent bronchodilator inhaled as a microaerosol from a pressurized canister dose: 80-120 mcg cause max bronchodilation in 30 min 60-90 min duration of action adverse effects: increases mortality, arrhythmias
Term
Salmeterol ans Formoterol
Definition
Long acting B2 agonists
duration - 12 hrs
high lipid solubility
dissolve in membrane and slowly release to receptor
Term
Beta 2 selective sympathomimetic agents
Definition
most widely used for asthma
most aerosol
max effect in 30 min, duration 3-4 hrs
Ex; albuterol, isoproterenol, terbutaline - available parenteral
Term
Oral inhalation
Definition
Greatest airway effects
aerosol deposition depends on Particle size (2-5 microns), patterns of breathing, geometry of airways
80-90% of total dose deposited in mouth and pharynx
Term
Methylxanthines
Definition
Theophylline, Theobromine, Caffeine
possible inhibit PDE, adenosine receptors, have anti-inflammatory action
Produce bronchodilation,stimulate CNS, kidney, heart + ionotpic, + chronotropic.
Term
Theophylline
Definition
Most selective for smooth muscle effects out of methylxanthies
PDE inhibitor
Therapeutic dose 5-20 mg/L
Toxic >20 mg/L - low therapeutic effect
Toxic effects: HA, N/V, tremors, seizures
Metabolized by liver
available in tea
effective for mild asthma
Term
Muscarinic Antagonists
Definition
Compete with ACh at muscarinic receptors
Block contraction of airway smooth muscle
Block mucous secretion
poorly absorbed in aerosol
Term
Atropine
Definition
bronchodilator
parenteral
doses for bronchodilation much lower than cardiac
equivalent to beta agonist
duration:5 hrs
adverse effects: parasympathetic blockade
Term
Ipratropium Bromide
Definition
more selective than Atropine
no CNS effects
used in pts intollerable of Beta-agonists
can combine with Beta agonist for synergistic effect
Term
Tiotropium
Definition
muscarinic antagonist
longer acting
24 hrs
used in COPD
Term
Corticosteroids
Definition
"controller therapy" - long term control
anti-inflammatory: inhibit production of cytokines, lymphocytic eosinophilic airway mucosal inflammation
Term
the good of corticosteroids
Definition
- reduce bronchial activity
- increase airway caliber
- reduce frequency of asthmatic exacerbations
- improve quality of life
Term
the bad of corticosteroids
Definition
- may increase osteoporosis
- slow the rate of growth in children
Term
the ugly of corticosteroids
Definition
oropharyngeal candidiasis
Term
long term use of corticosteroids
Definition
- reduces symptoms
- improves pulmonary function
- reduces need for oral steroids
- reduces bronchial reactivity
Term
Cromolyn and Nedocromil
Definition
mast cell stabilizers
prophylactic drugs
inhibit exercise induced asthma
No Direct effect on airway smooth muscle
Term
Leukotrienes cause...
Definition
Bronchoconstriction
increased bronchial reactivity
mucosal edema
mucus hypersecretion
Term
Leukotriene Pathway Inhibitors
Definition
taken orally
reduce frequency of exacerbations
effect on airway less than with corticosteroids
Zileuton - inhibit 5-lipogenase
Zafirlukast, Montelukast - inhibit binding to the receptor
Term
Aspirin
Definition
can make asthma worse by making more Leukotrienes
Term
causes of seizures
Definition
infection
neoplasm
head injury
heredity
toxic effects
metabolic disorder
Term
antiseizure drugs used for:
Definition
febrile seizures
seizures as a part of an illness
epilepsy
Term
principle mechanism of action of antiseizure medication involve...
Definition
voltage-operated ion channels
excitatory synaptic function
Term
partial seizure
Definition
- begins in specific area of the brain
Term
simple partial seizure
Definition
- minimal spread of discharge
- does not affect consciousness or awareness
- may show normal discharge
Term
Complex Partial Seizure
Definition
- automatism : lip smacking, swallowing, fumbling, scratching, walking about)
Term
Partial seizures secondarily generalized
Definition
- begin as a simple or complex partial seizure, but then spread to rest of the brain
- look like tonic-clonic seizures
Term
Generalized seizures
Definition
begin over entire surface of the brain
Term
Generalized tonic-clonic (Grand Mal)
Definition
- pt falls to the ground
- entire body stiffens
- muscle jerk or spasm
- tongue or cheek may be bitten
- urinary incontinence
Term
atonic seizure
Definition
- generalized
- sudden loss of muscle tone
- patient falls without warning
- a drop attack
Term
Tonic seizure
Definition
- generalized
- muscle suddenly contract and stiffen
- often causes falls
- a drop attack
Term
Clonic and Myoclonic seizure
Definition
- generalized
- make body jerk like it is being shocked
Term
Infantile Spasms
(West's Syndrome)
Definition
- muscle spasms that affect a child's head, torso, and limbs
- usually begins before age of 6 months
- associated with cognitive dissability later in life
Term
Phenytoin
Definition
alters:
- Na+, K+, and Ca++ conductance
- membrane potentials
- Neurotransmitters NE, ACh, GABA
- primary effect of GABA - enhances its release
Term
GABA
Gamma-AminoButyric Acid
Definition
Major inhibitory NT in CNS in
- spinal cord
- Hypothalamus
- Hippocampus
- Sustantia Nigra
- Cerebral Cortex
Term
MOA of Phenytoin
Definition
- use dependent effect at normal concentrations
- binds to Na+ channels
- Causes prolongation of AP
- blocks sustained, high frequency repetitive firing of APs
Term
MOA of Phenytoin at high concentrations
Definition
- inhibit release of Serotonin
- promotes uptake of Dopamine
- inhibits MAO
- interacts with membrane lipids )may promote stabilization)
- causes excitation of some CNS neurons
Term
Therapeutic level of Phenytoin
Definition
10-20 mcg/ml
Term
Level of Free Phenytoin
Definition
1-2.5 mcg/ml
Term
Toxic level of Phenytoin
Definition
30-50 mcg/ml
Term
lethal level of Phenytoin
Definition
>100 mcg/ml
Term
toxicity of Phenytoin
Definition
-dose related
-NYSTAGMUS
- loos of extraocular pursuit of movement
- diplopia
- ataxia
- sedation
- gingival hyperplasia
- hirsuitism
- mild peripheral neuropathy (deep tendon reflexes in legs)
- abnormal Vit D metabolism (osteomalasia)
Term
Adverse drug reactions of Phenytoin
Definition
skin rash - hypersensitivity
fever
skin lesions
- teratogenic
- withdrawal
Term
MOA of Carbamazepine
Definition
- blocks Na+ channels at therapeutic level
- inhibits high frequency repetitive firing
- works presynaptically
- inhibits uptake and release of NE from brain synaptosomes
- does not influence GABA uptake
Term
Clinical Use of Carbamazepine
Definition
- drug of choice for partial seizures
- can be used with phenytoin
- effective in Trigeminal Neuralgia
- also useful for Bipolar Disorder
Term
Carbamazepine drug interactions
Definition
- exclusively related to drug's enzyme inducing properties
- autoinducer CYP450
- phenytoin, Phenobarbital, ethosuxemide, valprois acid
clonazepam
Term
Carbamazepine Toxicity
Definition
-Most Common: DIPLOPIA, ATAXIA
-GI uset, unsteadiness
- drowsiness in high doses
- Idiosyncratic blood dyscrasias
- mild leukopenia
- erythenmatous skin rash
in elderly pts with trigeminal neuralgia: Aplastic Anemia, Agranulocytosis
Term
Oxacarbazepine
Definition
-closely related to carbamazepine
- improved toxicity profile
- less potent
- less hypersensitivity
- less enzyme induction
Term
Phenobarbital
Definition
- oldest antiseizure drug
- one of the safest
- sedative effects
-drug of choice in infants
Term
MOA of Phenobarbital
Definition
- enhances inhibitory transmission
- decreases excitatory transmission
- may suppress abnormal neurons
- at high concentrations; suppresses high frequency firing, affects Na+ conductance, Blocks Ca++ currents ( N and L type)
- at therapeutic levels: prolongs opening of Cl- channels
Term
Half-Lives of Phentobarbital
Definition
adult: 53-140 hrs
Term
Clinical Use of Phenobarbital
Definition
partial and generalized tonic-clonic seizures
not useful in other types of seizures, can even worsen them
Term
Toxicity of Phenobarbital
Definition
Hepatic enzyme inducer, CYP450, lessens effects of other drugs
sedation
overdose: unsteady gate, slurred speech, confusion, respiratory depression, come
Term
Valproic Acid
Definition
- used in absence, myoclonic, grand mal, bipolar, migraine
- blocks sustained high frequency firing
- effects on Na+ currents
- increases GABA
- increases K+ conductance
- increases Free Phenytoin
- inhibits metabolism of other drugs
Tox: GI, sedation, tremors,can cause severe hepototoxicity in multi-drug patients.
Term
Perioperative Management of pts with seizures
Definition
- chronic Phenytoin Therapy makes pt resistant to neuromuscular blocking agents
- Phenytoin can enhance NMB
- avoid drugs that stimulate seizure activity - methohixital, sevofluorane
- ONLY narcotic that stimulate seizure activity is DEMEROL
Term

Inflammatory Response

-acute inflammation

Definition

-initial response to tissue injury

-Mediated by autocoid group

Histamine

serotonin

Bradyinin

Prostaglandins

Leukotrienes

Term

Chronic Inflammation:

Release of additional mediators

Definition

Interleukins

GM-CSF

TNF

Interferons

PDFG

 

Term
Cell damage- major pathways
Definition

Cyclooxygenase pathway

-arachidonic acid (AA) converted to PG by COX

 

Lipoxygenase pathway

-AA converted to leukotrienes by lipoxygenase

Term
COX isoforms
Definition

COX-1: Constitutive, wide distribution

 

COX-2: expression is stimulus dependent, facilitates inflammatory response

Term
Leukotrienes r/t NSAIDS
Definition

Powerful chemotactic effect on

-eosinophils

-neutrophils

-macrophages

Promote bronchoconstriction

Alters vascular permeability

 

Term
Other effects of Inflammatory Response (r/t NSAIDS)
Definition

Neutrophils produce ROS

-membrane damaging

(Hydrogen peroxide, Hydroxyl radicals)

 

ROS + AA = chemotacticmetabolites

Term
Therapeutic Strategies of Inflammatory Response (r/t NSAIDS)
Definition

Goals (pain relief, arrest tissue damage)

 

Strategy (reduce inflammation)

Term
Anti-inflammatory drugs
Definition

Nonsteroidal anti-inflammatory drugs (NSAIDS): relieve pain (acute and chronic)

 

Glucocorticoids: chronic use toxicities

 

Slow-acting antirheumatic drugs

 

Disease modifying antirheumatic drugs (DMARDs)

Term

NSAIDS

(general info & kinetic properties)

Definition

Suppress S/S of inflammation.

Antipyretic, Analgesic, original NSAID: ASA

 

-weak acids

-well absorbed

-highly metabolized

-renal and biliary excretion

-highly protein bound

Term
NSAIDS: pharmacodynamics
Definition
  • Inhibition of PG synthesis
  • Decreases sensistivity of vessels to bradykinin and histamine
  • Affect lymphokine production (reverse vasodilation)
  • Inhibit platelet aggregation (Not for COX 2 selective agents)

Other mechanisms:

-chemotaxis inhibition

-down regulation of IL1

-Decrease production of ROS

-Interfere with Ca++ mediated intracellular events

 

Term
NSAIDS: toxicity
Definition

All are gastric iritants (differeing degrees of irritation)

 

All can cause nephrotoxicity and/or hepatotoxicity

Term

ASA

general info and history

Definition

Acetylsalicylic acid

 

"gold standard"

 

First documented use in 1763 (willow bard extracts- antiquity)

 

Term

ASA:

Anti-inflammatory effects

 

Definition

Nonselective irreversible COX inhibitor

 

-inhibition of granulocyte adherence

-stabilized lysosomes

-inhibits migration of PMN and macrophages to sites of inflammation.

Term
ASA: antipyretic effects
Definition

Mediated by cOX and IL-1 inhibition

 

dissipation of heat caused by vasodilation of peripheral vessels

Term
ASA: platelet effect
Definition

Irreversible block of platelet cyclooxygenase (other NSAIDS are reversible block)

 

slight prolongation of bleed time

 

antiplatelet effect: 8-10 days

 

concern pre-surgery

Term
ASA: clinical use
Definition

Widely used, not for severe pain

(1200-1500mg TID)

 

Rheumatoid arthritis

 

Rheumatic fever

 

Fever

 

Clot prevention (81-325 mg/day)

Term
ASA: other effects
Definition

Decrease incidence: Transient ischemic heart attacks, angina, coronary artery thrombosis

 

Lower incidence: Colon CA

 

Enteric coated: prevent tablet from dissolving in stomach, adequate absorption in small intestine

Term
ASA: adverse effects
Definition

GI upset! (buffering may decrease)

~cause: irritaton of gastric mucosa, inhibition of GI protective PG


Increase incidence of gastric ulcers


Salicylism

-higher doses  -vomiting   -tinnitus    -decreased hearing   -vertigo



Increase liver enzymes      hepatitis      decreased renal function

bleeding                         rashes         asthma

Reye's syndrome

Term
ASA: toxicity
Definition

Mild: Respiratory alkalosis (increased respirations)

 

Moderate: Acidosis (SA derivatives, depression of resp. center)

 

Severe: restlessness, irritability fear or nervousness, dizziness, confusion, abnormally excited mood, hallucinations, LOC, fever, uncontrollable shaking, seizures, comiting, decreased urination, double vision

Term
Nonacetylated Salicylates
Definition

Mg++ choline salicylate

Sodium salicylate

Salicylsalicylate (effective anti-inflammatory, less effective analgesia)

 

Less effective COX inhibitors

-good for some patients (asthma, bleeding tendencies, renal dysfunction)

Term
COX-2 Selective Inhibitors
Definition

No effect on "housekeeping" COX-1

-analgesia

-antipyretic

-anti-inflammatory

 

Fewer GI side effects (halved)

 

No impact on platelet aggregation

Term
Celecoxib
Definition

Selective COX-2 inhibitor

 

Sulfonamide (allergies)

 

Use:

-Rheumatoid arthritis                    -Osteoarthritis 

                      -Decrease ulcer incidence

 

Black box warning: increased risk of serious adverse CV events

FDA: adverse CV events related to all NSAIDS (except ASA)

Term
Meloxicam
Definition

Inhibits COX-2 over COX-1

 

Not as selective as other COX inhibitors

 

Fewer GI effects


Texicities similar to other NSAIDS

Term
Diflofenac
Definition

Decreases arachidonic acid availability

 

Anti-inflammatory, analgesic, and antipyretic

 

20% of patients have adverse GI effects

(decreased with misoprostal: Cytotec)

Term
Ibuprofen
Definition

Less GI upset than ASA

(equivalent anti-inflammatory, analgesia)

 

Available OTC

 

Available oral, cream, gel, IV

 

Adverse effects and toxicity = NSAIDS

(agranulocytosis and aplastic anemia are rare)

Term

Indomethacin:

general info

Definition

Potent COX inhibitor

 

May also inhibit Phospholipase A and C

 

Reduce PMN migration

 

Decrease T & B cell proliferation

 

Use:

-Rheumatism       -Gout       -Patient ductus arteriosus

Term

Indomethacin:

uncommon conditions

 

Definition

Conjuctivitis (ointment)

 

Sweet's syndrome

 

Juvenile rheumatoid arthritis

 

Pleurisy

 

Nephrotic syndrome

Term

Indomethacin:

Adverse reactions

Definition

1/3 of patients at higher doses


GI effects:

-abdominal pain

-diarrhea

-GI hemorrhage

-pancreatitis

Term
Other Nonselective COX inhibitors
Definition

Diflunisal (Dolobid): Rheumatoid arthritis, CA pain

Etodolac (Lodine): Post-op pain relief

Flurbiprofen (Ansaid): Racemic mixture, IV for minor ear, neck and nose surgery

Ketoprofen: Both COX and lipoxygenase, surprisingly no better than other NSAIDS

Ketorolac: analgesic post-surgery, increased peptic ulcer if use >5 days

 

Naproxen     Oxaproxin     Sulindac    Tolmetin

Term
Acetaminophen: MOA
Definition
  • COX-2 selective
  • Weak PG inhibitor in peripheral tissues
  • No significant anti-inflammatory effect
  • PO or PR (newer IV formulation)
  • Metabolized by hepatic enzymes (toxic to both liver and kidney)
Term
Acetaminophen: Indications
Definition
  • Equivalent to ASA as analgesic and antipyretic
  • No effect on platelet aggregation
  • Mild to moderate pain (HA, myalgia, postpartum)
Term
Acetaminophen: preferred in patients...
Definition

allergic to ASA

 

asthmatics

 

hemophiloia

 

peptic ulcer

 

children

Term
Acetaminophen: adverse effects
Definition
  • Mild increase in hepatic enzymes
  • Larger doses: dizziness, excitement, disorientation
  • Fatal: 15gms, hepatotoxicity, ATN (renal)
Term
CNS drugs: general overview
Definition
  • Therapy
  • Sense of well being
  • Specific receptors modulating synaptic transmission
  • Drug effects elucidate disease mechanisms
Term
CNS drugs selectivity:
Definition
  • Different transmitters used in different areas
  • Neuronal systems control broadly different functions
  • Different signals:

EPSP (excitatory post synaptic potential,

IPSP (inhibitory post synaptic potential)

Term
Endogenous ligands (for pain)
Definition
  • Act as NTs for pain modulation
  • Released during: pain, expectation of pain, excitement, certain foods, exercise, love, orgasm
  • Types: Endorphins, Enkephalins, Dynorphins
Term
Opium
Definition

Opium poppy Papaver somniferum


Serturner, a German pharmacist (1803), isolated a pure active alkaloid from opium and named morphine

Term
Opium classification:
Definition

Agonists, partial agonists, antagonists

 

Receptor specificity

μ (mu):

full agonists: morphine, fentanyl

partial agonists: codeine, oxycodone

antagonist: naloxone (narcan)

 

δ (delta)

Κ (kappa)

Term

μ (mu)


Receptor functions & endogenous ligands

Definition

Supraspinal and spinal analgesia: sedation; inhibition of respiration; slowed GI transit; modulation of hormone and NT release

 

 

Endorphins>enkephalins>dynorphins

Term

δ (delta)


Receptor function & endogenous ligands

Definition

Supraspinal and spinal analgesia; modulation of hormone and NT release

 

Enkephalins > endorphins and dynorphins

Term


Κ (kappa)


Receptor function & endogenous ligand

Definition

Supraspinal and spinal analgesia; psychotommimetic effects; slowed GI transit

 

Dynorphins >> endorphins and enkephalins

Term
Opioid Pharmacokinetics:
Definition

A: Well absorbed (IM, SQ, Oral)

-nasal, patch- avoid first pass effect

-Codeine: low first pass metabolism

 

D: Highly perfused tissues- accumulation

-brain, heart, kidney, liver

-skeletal muscle-reservoir


M: Morphine: Phase 2 to active forms (M3G, M6G)

Esters (heroin): tissue esterases to morhine

Other-Phase 1 (CYP3A4, CYP2D6)


E: Mainly in urine

Term
Opioids: MOA
Definition

Bind to receptors in brain and spinal cord

 

modulation of pain


receptor effects:

-Reduce NT release (glutamate, ACh, NE, 5-HT, Substance P)

-Hyperpolarize postsynaptic neurons

Term

Opioids: Pharmacodynamics

 

differential receptor effects

Definition

Mu: analgesia, euphoria, respiratory depression, dependence

 

Delta: analgesia, enhance mu effects

 

Kappa: analgesia, enhance mu effects

Term
Opioids: CNS effects
Definition
  • analgesia: sensory and emotional aspects
  • Euphoria (dysphoria)
  • sedation
  • respiratory depression (brainstem)
  • cough suppression
  • miosis (always - marker)
  • increased muscle tone (trunk)
  • N/V
  • Hyperthermia (mu) or hypothermia (kappa)
Term

Opioids:

CV and GI effects

Definition

CV:

most have no direct effects

bradycardia (CNS)

Meperidine (Demerol) - tachycardia

 

GI:

constipation (ENS) - marked, no tolerance

Term

Opioids:

Other organ system effects

 

Definition

Kidneys: function depressed, increased retention

 

Uterus: may prolong labor

 

Flushing

 

Immune response: enhanced

Term

Pain assessment

(opioids)

Definition

Pathology

Patient history

Duration

Term
Opioids: analgesia
Definition

Severe, constant

Sharp, intermittent- not as effective

Terminal illness (fixed interval, sustained release)

Obstetrics- fetal monitoring

Renal or biliary colic

Term

Acute Pulmonary Edema

(opioids)

Definition

Dyspnea from LVF


MOA:

-reduced anxiety

-reduced preload (↓ preload)

-reduced afterload (↓ PVR)

Loop diuretics

Term
Other uses for Opioids:
Definition
  • Cough
  • Diarrhea
  • Shivering
  • Anesthesia:

Pre-op anxiety or post-op pain

peri-op: anesthetic (fentanyl)

epidural

Term

Opioid Toxicity:

 

Definition

Extension of therapeutic effects:

behavioral restlessness,    tremulousness, respiratory depression,    N/V,    increased ICP, constipation,    urinary retention,    postural hypotension (accentuated by hypovolemia),  itching around nose

Term
Tolerance vs. Dependence of Opioids:
Definition

 Tolerance:

~Fairly rapid
~multiple mechanisms (theories): receptor phosphorylation cAMP, internalization uncoupling with G-proteins

 

Dependence:

~Continuation despite negative effects
~Withdrawal symptoms

 

Term
S/S of withdrawal from Opioids:
Definition

Stems from physical and chemical dependence

  • Rhinorrhea
  • Lacrimation
  • Yawning
  • Chills
  • Hyperventilation
  • Hyperthermia
  • Mydriasis
  • N/V
  • Anxiety
  • Hostility
Term
Cautions using Opioids:
Definition

~Drug OD: Naloxone (Narcan)

~Head injuries: Opioids may enhance resp. depression

~Impaired pulmonary function

~Pregnancy: fetal dependence

~Impaired hepatic or renal function

~Endocrine disease: prolonged or exaggerated response to opioids

~Mixing: pure agonists (morphine) with partial (pentazocine) reduces analgesia

Term

Strong Agonists (opioids):

Phenanthrenes

Definition

~Use for severe pain

 

Morphine, hydromorphone

Heroin (diacetylmorphine)

(palliative care, UK)

[image]

Term

Strong Agonists (opioids):

Phenylheptylamines

Definition

Methadone:

Chronic pain (morphine tolerance)

duration of analgesia: 4-6 hrs

long half-life: 25-50 hrs

CYP3A4

 

Opioid abuse

Term

Strong Agonists (opioids):

Phenylpiperidine

 

Definition

Fentanyl:

Additionsl analogs (increased potency, rate)

Multiple routes of administration

 

Meperidine (Demerol):

antimuscarinic effects (tachycardia)

(-) inotrope,   seizures

usage decreasing due to side effects

 

 

Term
Moderate Agonists (opioids)
Definition

~Phenanthrenes: Codeine, Oxycodone

More effective as combinations:

Oxycodone + acetaminophen = Percocet

Oxycodone + Aspirin = Percodan


~Phenylheptaylamines:

Propoxyphene (Darvon)


~Phenylpiperidines:

Loperamide (immodium): diarrhea, low incidence of abuse

Term
Opioid Antagonists:
Definition

Derivative of morphine:

Naloxone, Naltrexone

 

Completely and dramatically reverses opioid effects in 1-3 minutes (short duration, Nalaxone, effect may return)

 

Little effect in absence of agonist

Term
Unites States of Addiction
Definition

90% of all drugs manufactured in the world are consumed by 10% of the American population

 

Today there are estimated 30 million chronic drug users in America

 

Most chronic abusers (addicts) started by using marijuana, alcohol, and tobacco in their youth

Term

Schedule of Controlled Drugs

(general info & history)

Definition
  • Controlled Substances Act (1970)
  • DEA, FDA, HHS
  • Drugs placed in schedules based on potential for abuse
  • Controversy
  • Exclusions: tobacco, alcohol
Term
Scheduled Drugs
Definition

Schedule 1: High abuse, no medical application

ie: heroin, GHB, marijuana

 

Schedule 2: High abuse, medical application

ie: Morphine, Amphetamines

 

Schedule 3: lower abuse, medical use

ie: Codeine (dose), ketamine, anabolic steroids

 

Schedule 4: Low abuse, medical use, low addiction

ie: Butorphanol (Stadol), Valium, Ambien

 

Schedule 5: Very low abuse, addiction, preparations of small amounts from other schedules (cough syrup with codeine)

ie: Pregabalin (Lyrica), Lomotil

Term

Opioid Dependence

 

Definition

Dependence:

Physical dependence, withdrawal symptoms

 

Addiction:

Psychological dependence, strong feelings of euphoria or reward

Term
Addiction of Opioids:
Definition

~dopamine mesolimbic system

 ~Reward processing system (animal modes(

 ~Associate drug with effects:

learning system

addiction- maladaptive learning (drugs of abuse, compulsive disorders (gambling))

~Few patients desire opioid after drug withdrawal

~1/6 becomes addicted to cocaine

~Addiction factors: deredity, environmental cues

Term
Non0addictive Drugs of Abuse
Definition

~Alter perception wihtout euphoria

 

~Little associated wiht mesolimbic dopamine system:

LSD: serotonin receptor

PCP, Ketamine: Dissociative, NMDA receptors

Term
Stages of Abuse:
Definition
  1. Initial use, experimentation
  2. Repeated or regular use
  3. Abuse
  4. Dependence
  5. Relapse
Term
Pharmacologic classification
Definition

All increase dopamine in mesolimbic system

 

Classify based on targets:

GPCR

Iontropic receptors or ion channels

Monoamine transporters

Term
GPCR's
Definition

Opioids: mu, kappa, delta

~Morphine, heroin, codeine, oxycodone, demerol

~strong tolerance and dependence

~withdrawal

~treatment:

OD: Naloxone

Substitution: Methadone

Term
Cannabinoids-CB1
Definition

GPCR

~Euphoria, relazation

~Duration: 2-4 hours

~toxicity: visual distortion, drowsiness, impaired memory

~Medical use: ↑ appetite, ↓IOP, ↓nausea

~Dependence (2 out of 5):

withdrawal- agitation, insomnia

Term

Gamma-hydroxybutyric acid (GHB)

Definition

GABAB, GHB receptor

~Endogenous: metabolism of GABA

~"date rape drug": euphoria, social closeness, sedation, amnesia

~10-20 mg/kg dose, 20-30 minute effects

~Toxicity: respiratory arrest

~Medical use: insomnia

Term
Nicotine
Definition

Nicotinic ACh receptors: Ionotropic

~High level of addiction

~common

~nAChRs on dopamine neurons

~cessation: nicotine patch, behavioral

~OD: Atropine

Term
Benzos
Definition

GABAA: Ionotropic

~Librium, Valium, Halcion

~Sedative-hypnotics: followed barbs

~Schedule IV (4)

~Sedative, retrograde amnesia

~OD: seizures, coma

Term
Alcohol
Definition

Many receptors (GABAA, NMDA, 5-HT): Ionotropic

~Common

~Dopamine release?

~Dependence, withdrawal:

tremors, anxiety, N/V, delerium tremens

~Treatment: benzos, counseling

Term

Phenyclidine (PCP)

Ketamine

Definition

NMDA Receptors: Ionotropic

 

Anesthetics

Hallucinogens

Term
Inhalants
Definition

NMDA: Ionotropic

 

Huffing, bagging

 

Aromatic hydrocarbons

 

Brain lesions, coma, death

Term
Cocaine
Definition

Monoamine transporters: Dopamine Transporter (DAT)

~Highly addictive (crack cocaine)- stimulant

~Peripheral effects:

NET, Na+ channels

Tachycardia, appetite suppression

~OD: Intercranial hemorrhage, MI, coma, death

Term
Amphetamine, Methamphetamine
Definition

Monoamine Transporters: Ionotropic

VMAT, NET, DAT

~Increase arousal, stimulant

~Euphoria

~Pill, smoke, injection

~Hypertension, tachycardia

~Neurotoxic

~"Meth Mouth"

Term
Ecstasy (MDMA):
Definition

Monoamine Transporters: Ionotropic:

SERT

~intimacy and empathy

~"Designer drug"

~hyperthermia

~dehydration?

~Serotonin syndrome

Term
Organizing bacteria
Definition

Morphology: Cocci, Bacilli, etc.

 

Arrangement

 

Metabolism: Aerobes vs. Anaerobes

 

Staining Characteristics: Gram, AF

Term
Gram Positive Cell Wall
Definition
Gram positive: Teichoic acid
Term
Gram Negative Cell Wall
Definition

Gram negative:

Additional outer membrane

contains lipopolysaccharide (LPS)

Term
Cell Wall Target
Definition

PCN: prevents peptidoglycan synthesis

 

Lysozymes: digests peptidoglycan

Term
Ribosomes
Definition

Protein synthesis

 

Sedimentation rate:

-70S (eukaryotes are 80S)

-subunits of 30S and 50S

-Eythromomycin and Streptomycin bind to 70S

Term
Organizing Bacteria
Definition

Hemolysis patterns

 

Spore Forming

 

Aerotolerance

 

Surface antigens (Group A and B Strep)

Term
Pathogens
Definition

Ability to invade tissues: bypass host defense, OIP-mycobacterium, viruses

 

Ability to produce toxin: endotoxin, exotoxin

 

Term
General Properties of Antimicrobial Agents
Definition

Selective Toxicity

 

Spectrum of Activity

 

Modes of Action

 

Side effects

 

Resistance of Microorganisms

Term
Inhibition of Cell Wall Synthesis
Definition

Inhibiting cell wall synthesis selectively damages bacterial and fungal cells

 

PCN and Cephalosporin: B-lactam ring

 

the B-lactam ring attaches to the enzymes that cross link peptidoglycans and prevent cell wall synthesis

Term

Clinical use:

PCN

Definition

Gram (+) cocci:

Group A strep (throat)

Group B prophylaxis

Viridans strep endocarditis

Enterococcal UTI

 

Anaerobes

Dental procedure prophylaxis

Aspiration pneumonia

Term
Beta-Lactamase Resistant PCN
Definition

Used against beta-lactamase producing streptococci

 

Methicillin

Nafcillin

Isozazol penicillins

Term
Extended Spectrum Penicillins
Definition

Greater activity against Gram (-) bacteria

(penetrate outer membrane)

 

Ampicillin/Amoxicillin

 

Pipercillin

 

Available with beta-lactamase inhibitor (clavulanic acid, sulbactam)

Term
Adverse reactivity to ATBs
Definition

-Hypersensitivity:

most common drug allergy

can cross react with similar antibiotics

 

-Allergic reactions:

anaphylactic shock (0.05%)

skin rash (<1%)

oral lesions

hemolytic anemia

interstitial nephritis

 

-GI upset

N/V

Term
First, Second, Third-line drugs
Definition

1930's: Sulfonamides

 

1940's PCN

 

1960's: MORE PCN

 

1970's: Spectinomycin

Term
Cephalosporins
Definition

-More resistant to b-lactamase

-Broader spectrum

-First generation:

better gram (+) activity

Cephalexin (Keflex), cefazolin

Uses: UTI, Staph, Alternative to PCN (less allergy)

Term
Carbapenems
Definition

Beta-lactam (more beta-lactamase resistant)

Very expensive

Wide spectrum of activity

Penetrate CNS

DOC for enterobacter

Imipenem, Meropenem

Term
Vancomycin
Definition

Resistant to beta-lactamase

Alternative to PCN resistant bacteria (MRSA)

"Drug of last resort"

10% of adverse rxns

irritating to tissues

chills/fever

ototoxicity, nephrotoxicity

"red neck" syndrome

Term
Disruption of Cell Membrane function
Definition

Polypeptide ATBs (polymyxins)

 

Act as detergents

 

Bind to phospholipids

 

Especially effective against gram-negative bacteria which have an outer membrane

Term
Inhibition of protein synthesis
Definition

selective toxicity

 

attach bacterial cells without significantly damaging animal cells

 

70S ribosomes (humans are 80S)

-subunits, 30S, 50S

Term
Tetracyclines: general info
Definition

Streptomyces,  Bacteriostatic

 

Pharmacokinetics: readily absorbed, widely distributed

 

Have the widest spectrum of activity of any ATB

 

however, they destroy the normal intestinal microbiota and often produce severe GI disorders

Term
Tetracyclines: ADR
Definition

-GI: Anorexia, N/V/D, stimulate gut motility

-bone

-liver: acute cholestatic hepatitis (hypersensitivity)

-kidney

-Drug interactions: inhibitor of CYP 450 enzymes

Term
Macrolides: general info
Definition

Protype drug: Erythromycin

(streptomyces erythreus)

 

Semi-synthetic derivatives: Clarithromycin (Biaxin) and Azythromycin (Zithromax(

 

 Chemistry: macrolide ring

Term
Macrolides: resistance
Definition

-Usually plasmia mediated

reduced permeability

active efflux

esterases that hydrolyze macrolides

modification of ribosome binding site

Term
Macrolides: clinical uses
Definition

Drug of choice: corynebacterial infections (diptheria)

 

Chlamydial infections (respiratory, neonate, ocular, genital)

Term
Additional inhibitors of Bacteria protein Synthesis
Definition

Aminoglycosides (streptomycin)

Clindamycin (anaerobes)

Chloramphenicol (serious toxicities)

Streptogramins

Oxazolidinones (Linezolid- MRSA, VRE)

Term

Hallucinogens

 

Definition

LSD, mescalin, psilocybin: 5HT2A agonist:

 

Natural and synthetic

No dependence/addiction

Duration: 6-12 hours

Inability to make rational judgements

Term
Inhibition of Nucleic Acid Synthesis
Definition

differences between the enzymes used by bacterial and animal cells

 

Rifamycin family bind to a bacterial RNA polymerase

Term
Flouroquinolones
Definition

Inhibit DNA gyrase (bacterial)

Excellent gram (-) activity

Good Gram (+)

Types:

Cipro, Levaquin, Floxin

UTI, RTI

Bone and joint infections

ADR

Term
Action as Anti-metabolites
Definition

competitive inhibition

 

incorporated into important molecules

Term
Sulfonamides
Definition

Structurally similar to PABA (synthesis of folic acid)

 

Pneumocystis, toxoplasmosis (conjunction with trimethoprim (Bactrim, Septra))

 

Toxicity: allergenic, may precipitate in urine, hematopoetic disturbances

Term
Antifungal agents
Definition

Imidazoles: creams for cell membrane inhibition (ketoconazol)

 

Polyenes: Amphotercin and Nystatin- systemic infections

 

Dermatophytes: Griseofulvin (oral), Lamisil (topical)

Term

Antiviral agents

 

Definition

Purine/Pyrimidine analogs (disrupt viral DNA replication (Acyclovir, AZT)

 

Relenza, Tamiflu (prevent influenze entering or exiting cell)

 

Cells infected with viruses produce proteins- interferons

Term
Antiprotozoan agents
Definition

Quinidine- malaria (second generation compounds)

 

Metronidazole (Flagyl):

Giardia, Trichomonas

Many side effects: birth defects, cancer, black hairy tongue

 

Term
Determining selection of ATBs
Definition

Comcomitant disease states?

 

Prior adverse drug reactions?

 

Impaired elimination or metabolism?

 

Age? 

Pregnancy status?

Genetics?

Term
Antibiotic Sensitivity
Definition

Most infections- presribe antibiotics

Severe infections: C&S:

culture tubes-aerobic and anaerobic

isolation

identification

antibiotic sensitivity

Term
Specialized Assay Methods
Definition

anaerobe culture

 

beta-lactamase assay

 

synergy studies

 

PCR identification of strain

Term
Antibiotic Synergy
Definition

Multiple antibiotics given together can have synergistic effect:

PCN damages cell wall, Streptomycin penetrates better

 

Antaonism:

Tetracyclines inhibit growth

PCN requires growth for effectiveness

Term

Endo    crine   System

"inside"  "secrete"            

 

Definition

Odd organ system

 

Endocrine glands usually not connected

 

Secrete chemical messages called hormones to target cells

 

ie: pineal gland, hypotlamus, pituitary gland, thyroid gland, parathyroid gland, thymus gland, adrenal glands, pancreas, ovary, testis

Term
Types of hormones
Definition

4 structural groups:


Amino acid based (amino acid derivatives, peptides and proteins (polypeptides))

 

Steroids (cholesterol based)

 

Fatty acid derivatives (eicosanoids)

Term
Pancreas: general info
Definition

Consists of two major types of secretory tissues which reflects its dual function

 

-Exocrine (digestive enzymes)

-Endocrine: islets of Langerhans

control centers for blood glucose

(insulin from beta cells,

Glucagon from alpha cells)

Term
Diabetes: general info
Definition

Elevated Blood Glucose

Four types:

Type 1: insulin dependent (IDDM)

 

Type 2: Non-insulin dependent (NIDDM)

 

Type 3: other causes elevated blood glucose (pancreatitis, drug therapy)

 

Type 4: gestational

Term
Type 1 DM
Definition

-Destruction of beta cells

-Severe or absolute insulin deficiency

-Immune (most common)

-Idiopathic

-Clinical manifestations: hyperglycemia

80-90% of the function of the insulin secreting beta cells in the islet of Langerhans is lost

-Polydipsia, polyuria, polyphagia, wt. loss, and fatigue

-Require insulin replacement (DKA)

Term
Type 2 DM
Definition

"Adult Onset Diabetes"

 

Genetic-environmental interaction

 

Metabolic syndrome

 

Combination of relative deficiency of insulin secreation with tissue insulin resistance

Term
Type 2 DM treatment
Definition

Exercise, lose weight, medication

 

Manifestations: recurrent infections, vision problems, neuropathy

dehydration: nonketotic hyperosmolar coma

Term
Chronic Complications of DM
Definition

-Hyperglycemia and nonenzymatic glycosylation


-Hyperglycemia and polyol pathway:

Sorbitol and fructose increase IC osmotic pressure (attracts water, leading to cell injury)


-Evident in the eye lens, nerves, RBCs


-Protein kinase C (enzyme inappropriately activated by hyperglycemia)


-Microvascular disease (retinopathy, diabetic nephropathy)

Term
Type 4 DM
Definition

Gestational: Hormones block- insulin release

 

7% of US pregnancies

 

Higher birthweight

 

Resolves after pregnancy

(increase risk for 2nd pregnancy, increase risk for Type 2 DM)

Term
Lab testing for Type 4 DM
Definition

Diagnosis:

Fast blood glucose, glucose tolerance test

 

Monitoring:

Self: glucose POC, HgB A1C, insulin

Term
DI
Definition

Insufficiency of ADH-Posterior Pituitary

-Polyuria and polydipsia

-Partial/total inability to concentrate the urine

-Neurogenic (insufficient amounts of ADH)

-Nephrogenic (inadequate response to ADH)

 

↑ADH = SIADH

↓ADH = Diabetes Insipidous

Term
Insulin: general info
Definition

Beta cells:

Proform, Activated in granules

 

C-peptide: no known function

 

Species differences

Term
Insulin secretion
Definition

Constituitive, low level release

 

Insulin secretagogues:

glucose (mannose, fructose)

amino acids

hormones

fatty acids

SNS (bet adrenergic)

Drugs- sulfonylureas, isoproterenol, ACh can release secretion of insulin

Term
Insulin Receptor
Definition

-Tyrosine kinase receptor

-Multiple effects:

 

membrane translocation of GLUT

 

increased glycogen formation

 

activation of multiple transcription factors

Term
Inhibition of Insulin secretion
Definition

insulin

Leptin

SNS (alpha adrenergic)

Chronically high glucose

Drugs: diazoxide, phenytoin, vinblastine, colchicine

Term
Insulin Preparations
Definition

Rapid acting: Lispro, Aspart

 

Short acting (Regular): Novolin, humulin

 

Intermediate acting: Neutral protamine Hagedorn, isophane

 

Long acting: Glargine, detemir

Term
Insulin delivery
Definition

SQ injection- hypodermic needle

 

Portable pen injectors

 

Continuous SC insulin infusion devices (CSII):

requires sterile change every 2-3 days

best for "tight" insulin control

Term
Insulin regimens
Definition

Inensive: IDDM: tight control,

basal + bolus (calculated)

 

Conventional: SSI

 

Illness: DKA, hyperosmolar hyperglycemic syndrome

Term
Hypoglycemia
Definition

Complication of treatment:

S/S: anxiety, blurred vision, palpitations, shaky, slurred speech, sweating

 

Treatment: glucose/simple sugars 3-4 tabs, 1/2 can of soda

Glucagon injections: 1 mg IM/IV/SQ may repeat in 20 mins prn

Term
Oral antidiabetic agents
Definition

Biguanides

Insulin Secretagogues

Incretin-based therapies

Amylin Analogs

Bile Acid Sequestrant

Thiazolidinediones

Term
Biguanides
Definition

First line therapy (NIDDM)

 

Reduction in hepatic glucose production (metformin/Glucophage)

 

500 mg prandial

 

GI toxicities

Term
Insulin Secretatgoges
Definition

Bind to K+ channels: Rectifier current, binding causes depolarization

 

Classes: Sulfonylureas, Meglitinide, Phenylalanine derivatives

Term
Thiazolidinediones (Tzds)
Definition

Decrease insulin resistance (PPAR mediated)

 

Increase insulin signal transduction

 

Risk of MI:

increase with insulin, nitrates

Avandia-Rosiglitazone

Term
Alpha-Glucosidase Inhibitors
Definition

Block digestion of complex carbs

 

Beneficial in Pre-diabetes

 

Prominent GI effects:

Flatulence, diarrhea, abdominal pain

Term
Bile Acid Binding Resins (r/t DM)
Definition

large cation exchange resins-not absorbed

 

Bind bile acids0 prevent reabsorption

 

GI upset

Term
Amylin Analog
Definition

Amylin also released by beta cells (suppresses glucagon release)

 

Decrease circulating glucose

 

Concomitant with insulin

Term
Incretin-Based Therapies
Definition

Incretins: GI hormones

 

Glucagon-like polypeptide-1 (GLP-1) Agonists

 

dipeptidyl Peptidase-4 (DPP-4) Antagonists

Term
Combination Therapy in NIDDM
Definition

Biguanide

 

Biguanide + insulin OR Biguani de + Decretagogue

 

Biguinide + 2-3 other classes

 

Intensive Insulin Therapy

Term
Adjunctive Therapy: Energy balance diet, dyslipidemia
Definition

Low-carb, low fat, calorie-restricted diet

 

Patients with type 2 DM have an LDL goal <100 mg/dL

 

wt. loss

First line therapy; statins

 

Fiber, Omega-3 fatty acids

Term

Adjunctive therapies for DM:

CV disease/HTN

Antiplatelet agents

Definition

SBP goal <130

ACE-II inhibitor is first line:

Renal protective

ARBs

 

Consider starting daily low dose ASA (81 mg/day) to prevent ischemic events

 

Term

Formula for BMI

 

Definition
Mass (kg)/(Height (m))2
Term
Overweight
Definition
If BMI 25 to 29.9 kg per m2
Term
Obesity
Definition
if BMI of 30 kg per m2 or more
Term
Body Volume Index
Definition

weight distrubution

concern over "central Obesity"

Term
Epidemiology of obesity
Definition
30% increase in the last 10 years
Term
What causes obesity?
Definition

1. Nutrient and Energy model: Metabolism, appetite regulation, energy expenditure

2. Genetics

3. Behavioral and cultural factors

Term
2 main weight loss strategies that should be targeted first
Definition

1. Diet Therapy

2. Increased Physical Activity

Term
Medications for weight loss
Definition

1. SNRI's - Pristique, Symbalta, Sibutramine

2. Orlistat - lipase inhibitor, decreases absorption of dietary fat ( 120 mg PO TID)

Term
2 part of lipoproteins
Definition

1. outer protein coating

2. Lipid core

Term
Mechanism of action of Niacin
Definition

inhibits VLDL secretion, which decreases production of LDL

Increases HDL

Incorporates into NAD

Term
Effects of Statins
Definition

LDL -40%

HDL +10%

Triglycerides ↓

Term
Effects of Niacin
Definition

LDL -20%

HDL + 25%

Triglycerides ↓↓

Term
Effects of Fibrates
Definition

LDL -10%

HDL +15%

Triglycerides ↓↓

 

Term
Effects of Binding Resins
Definition

LDL -20%

HDL +5%

Tryglycerides (-)

Term
Effects of Absorption Inhibitors
Definition

LDL -20%

HDL +5%

Triglycerides (-)

Term
What are the steps in Gram staining?
Definition

1) Crystal Violet: all cells turn purple

2) Iodine: all purple iodine acts as mordant to set stain

 

3) Decolorize with alcohol:

Gram (+): purple (because of the thick wall, not all the color is washed out)

Gram (-): turns clear

 

4)Safranin wash:

Gram (+): stays purple

Gram (-): turns pink

Term
What two drugs do you have to watch with pts with previous seizures?
Definition
Enflurane and Demerol
Term
How do we develop resistance to ATBs?
Definition
through the beta lactam ring (the part that binds to receptors)
Term
Inhibition of bacteria Protein Synthesis
Definition
Aminoglycosides (Streptomycin)
Clindamycin (Anaerobes)
Chlorampenicol
Streptogramins
Oxazolidinones (Linezoid)
Macrolides(Erythromycin,Azythromycin)
Tetracyclines
Term
Targeting Cell Wall
Definition
Penicillin
Cephalosporins
Vancomycin
Bacitracin
Methicillin
Ampicillin
Piperacillin
Carbapenems (Meropenem, Imiperem)
Term
Disruption of Cell Wall Function
Definition
Polypeptide antibiotics (polymyxins)
Term
Inhibition of Nucleic Acid Synthesis
Definition
rifamycin
Fluoroquinolones (Cipro, Levaquin, Floxin)
Term
Action as Anti-Metabolites
Definition
Bactrim
Septra
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