Quiz 2 Flashcards
1
Q
Agonism
A
- ligand binds and stimulates R
- drug on R activates
- mol/cel resp
- intrinsic activity = 1
2
Q
Partial Agonism
A
- drug on R activates
- partial efficacy
- intrinsic activity 0-1 or <1
3
Q
Antagonism
A
- drug on R prevents agonist binding
- no resp to agonist
- Also blocks baseline stim, so can take below baseline
4
Q
Irreversible Antagonism
A
- stays bound to R
- high conc agonist may overcome
5
Q
Competitive Antagonism
A
- ag/ant both act on same R
6
Q
Noncompetetive Antagonism
A
- ant binds to one R preventing ag binding to different R
- ag must not be bound for ant to bind
7
Q
Opioid example of degrees of R activation
A
- Methodone = full ag
- high R activation
- Buprenorphine = partial ag
- medium activation
- partial efficacy
- Naloxone = antagonist
- higher affinity
- blocks/prevents ag activity
8
Q
Pharmacologic Antagonism
A
- antagonism at the R level
- competetive and noncompetetive
9
Q
Effect Antagonism
A
- system level antagonism
- ex: one drug works in brain to incr BP, a different one works in the heart to decr BP
10
Q
Drugable Targets
A
- places in proc we can aim to intervene with drug to effect system
11
Q
Ligand-Gated Ion Channels
A
- R binding causes ion channel to open
- ions flow down a pre-established gradient to produce effect
- ex: ACH opens channel, Na+ flows in depolarizing memb
-> initiates action potential
12
Q
Voltage-gated Ion Channel
A
- nearby memb pot changes conformation of channel
- open/closed
- Sz drugs stabilize hyper-exitable membranes
13
Q
Na/K pump
A
- Pump -> energy consuming
- E required
- moves ions against gradient
- ex Dig inhibits NaKATPase
- Na out/K in against gradient/establishing gradient
- inh causes >Na inside, slowing export of Ca out
- >Ca inside >contractility (force of contraction)
14
Q
Enzymes
A
- Catalyze rxn: A(substrate) + B(substrate) <=>C(product)
- enz inhibitors
- inh substrate from entering enz active site
- ex AChE inhibitor: slows cleavage of ACH inc amt in syn cleft
- also activators
15
Q
RAAS
A
- angiotensinogen —renin–> angiotensin I —ACE–> ang II
- need quick response from system so gen is available to be converted rather than having to start from scratch
- 3 targets
- renin inhibitor = tecterna
- ACEi’s
- ARB’s
16
Q
Pharmaceutics
A
- Science of dosage form design
- preparing drugs for administration
17
Q
Absorption
A
- moving drug from outside to inside of body
- across a bio memb
18
Q
Enteral Absorption
A
- Gut is most convenient
- mouth to rectum
- mouth
- stomach
- SI
- rectum
19
Q
Enteral: mouth
A
- thin lining, rich blood supply -> rapid action
- sublingual/buccal routes
- swallowing not req
- antiemetics
- >compliance
20
Q
Enteral: stomach
A
- medium SA, rich blood supply, acidic pH
- most drugs dis better in base
- drugs don’t stay here long
- variable with food in stomach/empty stomach
21
Q
Enteral: small intestine
A
- huge SA
- rich blood supply
- basic pH
22
Q
Enteral: rectal
A
- small SA, rich blood supply, basic pH
- uses:
- N/V
- local effect to rectum/colon (ulcerative colitis)
23
Q
Parenteral Administration
A
- Bypasses membranes
- IV
- IA (artery)
- IM
- IT (inside thecal sac/spinal canal, also bypass BBB)
- SQ
- Epidural (next to thecal memb)
- Intra-articular
- low blood supply so little circulating drug gets there
- ex: lubricant to knee
24
Q
Topical Administration (sites)
A
- Skin
- Eyes
- Ears
- Intranasal
- Inhalation
- Vaginal
25
Topical: skin
* ointments, creams, patches
* local and systemic
26
Patches
1. doesn't rub/wash off
2. ~occlusive dressing - changes skin properties \>abs
3. control dose, preloaded in patch
27
Topical: eyes
* drops, ointments
* local
28
Topical: ears
* local
29
Topical: intranasal
* sprays and drops
* local
* steroid
* systemic - when it allows to bypass injection
* narcan
* migrane med
* vaccines
30
Topical: inhalation
* local
* asthma drugs
* systemic - difficult to predict absorption
* inhaled insulin
31
Topical: vaginal
* Local primarily
* Systemic (contraceptives, primarily local w/systemic effects)
32
Pharmaceutical Phase
* Disintegration
* tablet to particles
* \>SA -\> dissolves faster
* Dissolution
* particles to molecules in solution
* Must be in solution to cross memb
33
Oral dosage forms - fastest to slowest
1. dissolved liquid (elixer, syrup)
2. suspension
3. powder
4. capsule
5. tablet
6. coated tablet/caplet
7. enteric coated tablet
8. sustained release
34
Dissolved liquid
1. inconvenient
2. tastes bad
3. patient controls dose
4. abs faster
35
Suspensions
* chunks of drug floating in liquid
* drug settles
* may be more conc toward end if not always mixed properly before use
* taste bad/bad mouth feel
* patient controls dosage
36
Powders
* in powder papers
* unit dose
* tear corner and pour into water
* not really used any more
37
Capsules
* powder inside
* modern "powder paper"
38
Tablets
* compressed powder
* with exipients
39
Coated tablets/Caplets
* slower dissolving,
easier to swallow
40
Enteric-coated Tablets
* don't dis in acid
* protects dosage (panc enz: act in duo, destroyed in stom)
* else 50x dosage and hope some gets to duo
* else enz w/antacid (inconvenient)
* for drugs that upset stomach (ASA)
41
Sustained Release
* slow abs/time
* short duration drugs -\> long duration (ex procardia q6h or XL daily)
1. allergy capsule w/colored beads
1. red = IR
2. blue = 4-8 hr coverage
3. green = 8-12 hr coverage
2. layered tablets - outer, inner, center layers
3. GI transport system - procardia/nifedipine
* water absorbing matrix - water in a constant rate
* pushed memb up at constant rate, pushing drug out hole
* Theo-24: dose dumping-\>arrhythmias, sz, death
42
Pharmacokinetics
* what body does to drug
* mathematical models to make predictions
* pharmacokinetic phase = absorption
43
Diffusion: passive v. facilitated
* most are passive diffusion
* facilitated
* membrane carrier molecule binds outside and releases inside
* not against gradient
* no energy expenditure
44
Rate of absorption determines...(3)
1. onset of action - faster abs -\> faster onset
2. duration of action - slower -\> extended duration
3. Intensity of response - faster -\> inc levels, same dose \>intense resp
* ex: beer over 1/2h, 5min, beer bong
45
Variables affecting absorption (4)
1. nature of absorbing surface - skin v intestinal mucosa
2. SA - small v large intestine
3. blood flow (PIV not so good for patients in shock)
4. pH as site
46
Bioavailability
* % of dose that reaches systemic circ (F or f in dec form)
* First Pass Effect
47
First Pass Effect
* Factors affecting dose before it reaches sys circ
1. stomach **acid**
2. stomach **enz**
3. slow/poor diffusion across **memb**
4. liver **met**
* ex:
* ganciclovir poorly abs f=0.09 =\> 10x dose
* propanolol hepatic met f=0.26 =\> ~75% removed first pass
48
Distribution
* ka = rate abs (drug in)
* ke = rate elimination (drug out)
* ka = ke =\> constant levels
* One compartment model
* one central compartment = blood
* Two compartment model
* administered to central compartment = blood
* redistributes to second "tissue" compartment
* skel m, fat, etc \<=\> in equilibrium
* conc proportional between 2 compartments at a certain time
* Dig @ 3-4h blood conc~heart tissue conc
* earlier would give false high
* not toxic in blood, toxic in heart
49
Drug Elimination
* "Removal of **_activity_** of drug"
* biotransformation
* excretion
50
Biotransformation
1. inactivating drug (active to inactive = eliminating)
* hepatic met
* cytochrome P-450
* Ox/Red
* Conjugation
* Tissue enz
* GI tract
* Lungs
* Kidneys
2. activating drug also
51
Excretion
* Removal of still active drug
1. kidneys
2. Gi tract
3. lungs (exhaled as in breathalyzer)
4. sweat glands
5. salivary glands
6. mammary glands - active form?.. to baby
52
Clearance
* clearance is abstract
* half-life is more common
* time to reduce circulating amount by 50%
* short half-life = more frequent dose
* sometimes misleading -
* emeprozole
* short half-life, long duration of action
* enters cell and remains active
* propanolol - irreversible blocker, effects last longer
53
Creatinine Clearance
* change dose of renally excreted drugs based on renal fx
* assess renal fx
* serum Cr most commonly used
* not nec accurate
* CRCL
* Cr constant rate of prod, removed through Glom filt
* GF estimated by CRCL
* \>80 unlikely impairment
* 50-80 mild impairment (narrow tx range req change)
* \<50 moderate impairment (many may req dosage change)
* \<10 severe impairment (look up drugs)
54
Formula for CRCL
CRCL in ml/min
CLcr =
(140-age)IBW
------------------- x (\*.85 for females)
(Scr)(72)
IBW
* male 50kg + (2.3 x inches over 5ft)
* female 45kg + (2.3 x inches over 5ft)
55
When would you use actual BW v IBW?
* actual BW when excess wt is muscle, body builder
* Cr=1.2, CrCl=109
* IBW when excess wt is fat - doesn't give credit for fat towards renal fx
* Cr=1.2, Crcl=38 = moderate impairment
56
MDRD
* Modification of Diet in Renal Disease
* valid for GFR\<90ml/min
* not accurate for emaciated or cirrhotic pts
* more accurate but less common/less drug info provided
* so use CrCl
* GFR = (175)(Cr)-1.154(Age)-0.203(0.742females)(1.1212blacks)
* 175cr1154age02030742f11212b
* tickle cr to tell her age so name sake ron toten don
57
Time-Concentration Curve
* Concentration over time after dose is administered
58
Absorption Phase
* Drug is being absorbed faster than it is being eliminated
59
Cmax
* Maximum concentration
* End of abs phase
* Beginning of elim phase
60
Elimination Phase
* Drug is being eliminated faster than it is being absorbed
61
Minimum Effective Concentration
* MEC
* must be above this to get measurable effect of drug
62
Toxic Level
* concentration level where increased risk of toxicity is seen
63
Therapeutic Range
* between MEC and toxic level
* unimportant/unknown for many drugs
1. drug has such a wide range
2. blood level doesn't correlate to effect
64
Onset of Action
* Time when MEC is achieved
65
Duration of Action
* [Time when conc falls below MEC] minus [Onset of Action]
66
Drug-Drug Interactions
* give 2 drugs and something different happens then giving the 2 drugs alone
* antagonism - one offsets the activity of the other
* synergism - one enhances the other
* idiosyncratic - unpredictable
67
Drug-Food Interactions
* oral phenetoin + enteral feedings
* head injury, sz
* enteral feedings
* 300mg normal, 2g required to overcome interaction
* then enteral feeding stops or decreases -\> overdose
68
Drug-herbal interactions
* herbal medication interacts with prescription drug
69
Drug-laboratory Interactions
* Drug interferes with results of a particular assay
70
Pharmacokinetic Drug Interaction
* levels
* one drug causes the blood level of another drug to change +/-
* alters rate or extent of absorption, dist or met of other drug
71
Object Drug
* drug whose level is changed by another, precipitant drug
* the victim
72
Precipitant Drug
* Causes a change in the levels of the object drug
73
Pharmacodynamic Interaction
* actions
* one drug causes a change in patient response to another drug without altering the object drug's kinetics
* Pharmacological interaction
* 2 drugs for BP cause greater drop than expected, no change in blood concentration = synergistic pharmacodynamic interaction
74
Pharmaceutical Interactions
* physical and chemical incompatibilities
* IV admixtures -\> precipitates
75
Potential for Interactions
* 4,000 drugs available in U.S.
* 25% of pop on 5+ products
* Possible combinations... too big to say
* So identify patients and drugs at greatest risk
76
Patients at Greatest Risk
* multiple meds #1-more drugs, more risk
* multiple docs
* multiple pharmacies
* elderly - more meds, worse response to rxn
* obese - generally less healthy, multiple diseases, more meds
* critically ill - more susceptible, less tolerance to rxn
77
Object drug characteristics
* narrow therapeutic range, ex coumadin
* steep dose response curve - 2x dose -\> 4x response
* hepatically met drugs
* chronic use drugs
* interactions are usually slow to develop so chronic use drugs increase that risk
78
Clinical Significance
1. level goes from sub-therapeutic to therapeutic, could be clinically sig in a good way
2. level goes from low therapeutic to mid therapeutic, probably not clinically sig
3. level goes from low therapeutic to toxic, clinically sig, bad
\*therapeutic range based on averages of thousands, so a particular pt may need "toxic" levels to be therapeutic, etc.
79
Points of Caution in Assessing Patient Risk
* over/under-estimation of clinical importance based on personal clinical experience
* ex 1/10,000 rxn seen, withold proper tx for 9,999
* ex clinician who says 'I use those drugs together all the time'
* clinical outcomes are highly situational
80
Predicting Clinical Relevance
* wide therapeutic range object, small change caused by precipitant
* unconcerned
* narrow range object, small change
* medium caution
* wide range, big change
* more caution
* narrow range, big change
* worst case
81
Absorption Interactions
* primary site of abs is small intestine, but interactions can occur anywhere in the bowel
* result of interaction
1. changes in extent of abs
2. changes in rate of abs
82
Mechanisms of Altered Absorption
* complexation
* pH changes
* GI motility changes
* altered drug transport
* enzymatic metabolism
83
Complexation
* drugs that form chemical complexes with other agents may lower the rate and extent of absorption - keeps obj drug from abs
* Bile acid resins
* Cholestyramine
* Colestipol
* divalent and trivalent metal ions
* Mg, Ca, Zn, Fe, Al - ex Ca decr tetracycline abs
* in many antacids and multivitamins
* Give at different times could solve problem
84
Changes in pH
* Drugs that change gastric pH
* H2 R blockers - cimetidine, ranitidine
* PPI's - omeprazole, lansoprazole
* Antacids
* Drugs that need acid pH for dissolution
* ketoconazole, itraconazole
* AID's pt on ketoconazole for fungal infection starts taking antacid and ends up dying
* Fe suppliments
85
Changes in GI motility
* Drugs that slow GI motility
* narcotics
* anticholinergics - antihistamines, tricyclic antidepressants, phenothiazines
* Drugs that speed up GI motility
* laxatives
* metoclopramide
* erythromycin
* More time in gut may mean more destroyed by bact, so not nec more absorbed d/t time
* One predictable example: less time in gut for time released=less absorption
86
Altered Drug Transport
* Transport systems in gut wall can be influenced
* not practical... yet
87
Enzymatic Metabolism
* contribute to drug metabolism and the first pass effect
* highest concentration in duodenum
* effect metabolism moreso than absorption
88
MEC
* min eff conc
