Pharm week 1-6 Flashcards
pharmacokinetics vs phamacodynamic
pharmacokinetics
ADME
absirption
distribution
metabolism
excretion
phamacodynamics
-receptor binding
-signal trasnduction
-pharmacological effects
-dose responseh
how are most drugs absorbed
passive diffusion
which form of drugs can pass through lipid bilayer
non ionized formed (no charge)
many drugs are weak acids and bases
where are most drugs metabolized
liver via enzymes
**prodrugs need to be activated by metabolism
make it more water soluble to be excreted bye kidneys
first pass effect
Drugs absorbed via the gut reach the liver via the portal vein before entering the systemic circulation
The degree to which the drug is inactivated by liver enzymes prior to entering the systemic circulation substantially alters the drug’s bioavailability
phase 1 vs phase 2 metabolism
phase 1
–>Primary goal is to introduce or open up a binding site for hydrophilic compounds to be added later by phase II mechanisms
–>Oxidative reactions by far the most common
–>Microsomal cytochrome P450 (CYP450) system
phase 2
–>Not all drugs require phase I metabolism prior to phase II but most do
–>These reactions essentially conjugate a water-soluble molecule to the spot opened up by phase 1 reactions
–>In many instances, this means conjugating something to an available hydroxyl group
–>Each phase 2 mechanism has its own enzyme that catalyzes the reactions
phase 1 is oxidative to make binding site
phase 2 is conjugation to increase solubility
enterohepatic circulation
Glucuronide conjugates are excreted in bile (fat soluble drugs)
Some commensal gut bacteria have glucuronidase enzymes which can cleave the glucuronide off the metabolite resulting in the parent drug being able to be reabsorbed
elimination
water soluble via kidney
lipid soluble via feces
Most water-soluble drug metabolites are excreted by the kidneys
Various mechanisms exist throughout the sections of the nephron
Lipid-soluble drugs are excreted in the distal tubule if they’re small enough
Lipid-soluble drug metabolites and glucuronide-conjugates are excreted by the liver into bile and are excreted in feces
agonist vs antagonist
Agonist – a substance that initiates a physiological response when combined with a receptor
Antagonist – a substance that interferes with or inhibits the physiological action of another substance
competitive vs allosteric
Competitive – used to describe when two substances use the same binding site on a receptor
Allosteric – used to describe when a substance binds to a receptor away from an active binding site but still alters the physiological effect
measure of safety
Therapeutic Index (TI)
LD50 – dose at which causes death in 50% of individual (animal)
ED50 – dose at which causes a therapeutic response in 50% of individuals (human)
TI= LD50/ED50
beta lactam antibitocs
β-lactam antibiotics are antibiotics that contain a beta-lactam ring in their chemical structure. This includes penicillin derivatives, cephalosporins
most common bacterial pathogens of acute otitis media
Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis
watchful waiting and who should never do it
Withhold antibiotic prescriptions for 48 hours in children over 6 months of age provided they have:
Nonsevere illness (mild pain and fever < 39°C)
Uncomplicated AOM (no episode in the preceding month, no acute facial nerve palsy, mastoiditis, meningitis, or labyrinthitis)
Infants under 6 weeks of age should be immediately referred to the nearest emergency department
Patients aged 6 weeks to 6 months should begin antibiotic therapy immediately
Patients with 3 or more episodes in 6 months or 4 or more within a year should begin antibiotic therapy immediately
how to overcome antibiotic resistance in strep pneumonia
and influenza and catarhalis
S. pneumoniae resistance is a result of the alteration of penicillin-binding cell wall proteins leading to decreased drug affinity
This is overcome by doubling the dose of amoxicillin
–
H. influenzae and M. catarrhalis produce beta-lactamases which confer resistance
This is overcome by using a beta-lactamase inhibitor called clavulanate
what is the first line therapy fro acute otitis media
amoxicillin
what are alternative for acute otitis media
cephalosporins !!
Cefuroxime axetil and Cefprozil
Second-generation cephalosporins have reasonable activity against H. influenzae and M. catarrhalis as they are more resistant to bacterial beta-lactamases
Less effective against S. pneumoniae Considered second-line agents
what is type 1 hypersensitivity to penicillin/ amoxicillin
macrolides –>
Azithromycin and Clarithromycin should be reserved for patients with type 1 hypersensitivity reactions to beta- lactam antibiotics
lincosamides –>Clindamycin can be used for patients with type 1 hypersensitivity reactions to beta-lactam antibiotics
It does not cover H. influenzae or M. catarrhalis
The resistance mechanism produced by H. influenzae can be overcome by which of the following strategies?
A. Doubling the dose of amoxicillin
B. Giving amoxicillin and clavulanate together
C. Using clindamycin as an alternative to amoxicillin D. Giving cefprozil and clavulanate together
B. Giving amoxicillin and clavulanate together
2 types of corticosteroids and what are the different mechanisms
- Glucocorticoids – effect carb, fat, protein metabolism + anti inflame, immunosuppress
- Mineralcorticoids – effect electrolytes by renal excretion
when can get adverse effects from corticosteroids
too high potency or too long
systemic suppression of HPA axis
use finger tip units !
topical drug vehicles
- Creams (least effective at penetrating skin)
- Gel (for hairy and oily areas)
- Lotion (for large and hariy areas)
- Ointment (thick and greasy; emollient effect, best permeability)
- Foam (greasy spray for hard to reach areas)
potency for topical corticosteroids
Class 1 is the highest potency also called the superpotent or ultra-high class.
Class 2 – high,
Class 3 – medium-high,
Class 4/5 - medium
Class 6/7 – low potency
which potencies for which parts of body
low potency on face and skin folds with thin skin
medium potency on body and scalp
high potency on palms and soles
A high-potency topical corticosteroid would be an appropriate initial recommendation for the treatment of which of the following body areas?
A. Face B. Elbow C. Palm D. Scalp
C. Palm
what are the 2 types of NSAIDs
and what are they inhibiting
o Non specifc COX inhibitor: acetylsalicylic acid (ASA) and ibuprofen
o COX 2 specific inhibitor: celecoxib
COX1 can increase GI bleeds
both have CVD risk
which COX do you want to inhibit for anti inflammatory
the inducible COX2
because COX2 prostaglandins are inflammatory which can thus cause pain
what are the side effects of inhibiting COX1
GI function; mucous secretion in stomach
ulcers and GI bleeds
which non opioid analgesics inhibit COX 1 and have side effects of GI bleeds
ASA and ibuprofen
what non opioid analgesics inhibit COX 2
celecoxib
acetylsalicylic acid (ASA) is an NSAID that binds…
irreversible inhibition of COX vis covalent bond
non competitive inhibitor
activates COX binding site
short half life; became salicylic acid then eliminated in urine
contraindicated in kids with viral infection
GI bleeds
tinnitus
aspirin is aka…
acetylsalicylic acid (an NSAID)
what drug has an affinity for COX3
and what are its effects
acetaminophen (tylenol_)
Little anti inflammatory effect
Analgesic and antipyretic
FOR PAIN AND FEVER; not inflame
acetaminophen (tylenol_) is absorbed where
and what are the intermediates
absorbed rapidly in the gut
toxic intermediates formed with CYPs
what is a disease celecoxib can be used for
osteoarthritis
its a cox2 Non-steroidal anti-inflammatory drugs (NSAIDSs)
how to help w gastroprotection when using NSAIDs
1.Using COX-2 selective NSAIDs
- Using prostaglandin analogues: misoprostol
3.Using proton pump inhibitors: omeprazole
Which of the following NSAIDs acts through non- competitive inhibition of COX enzymes?
A. Acetaminophen
B. Acetylsalicylic acid
C. Ibuprofen
D. Celecoxib
B. Acetylsalicylic acid
what are gaba derivatives? what are they used for? where do they act?
a. Pregabalin
b. Gabapentin
i. For soft tissue and hyperalgesic pain, neuropathic pain
ii. Act centrally
what receptors do gaba derivatives act with
voltage gated calcium channel
–> dorasl horn of spinal column
NOT gaba receptors
GABA derivatives side effects
sedation, GI, tremors, weight gain
cannot abruptly discontinue
types of muscle relaxants
a. Antispasmodics
i. Benzodiazepines or non-benzodiazepines (methocarbamol) (work via CNS not muscle contraction fibers)
b. Antispastics (baclofen) (help with muscle rigidity)
what is methocarbamol
non benzodiazepine muscle relaxant (antispasmodic)
doesnt effect muscle fiber contractions
works via CNS depressant and block reflexes, prolong refractory period
what is baclofen
anti spastic muscle relaxant
GABA receptor agonist on beta subunit (on pre or post synaptic neruron) causes K+ influx and hyper polarization and decrease Ca2+ influx = reduce AP and activation of muscle
Which of the following drugs is classified as a non- benzodiazepine antispasmodic?
A. Gabapentin
B. Baclofen
C. Pregabalin
D. Methocarbamol
D. Methocarbamol
