Pharm terms (Block 1) Flashcards
1
Q
How are drugs classified?
A
- Based on their main effect (analgestics)
- Based on their clinical/therapeutic use (antivirals)
- Based on their mechanism of action (beta-blockers)
2
Q
Drug size & molecular weight
A
- Less than a 100 not selective for receptors
- Greater than a 1000 poorly absorbed & poorly distributed
- Smaller = BETTER
3
Q
Chemistry of Drugs
A
- Inorganic
- Small/large organic
-Bio macromolecules = recombinant proteins, antibodies, polysaccharides, nucleic acids
4
Q
Stereoisomers
A
- 1/4 to 1/2 of all drugs exist as this
- same molecular formula and sequence of bonds BUT different 3D shape
- Structural isomer = same molecular formula, BUT bonded together in different orders
- Racemic mixture of drug’s steroisomer
5
Q
Pharmacokinetics
A
-What does the body do with the drug
- Absorption
- Distribution
- Metabolism/Biotransformation
- Elimination
6
Q
Enteral administration
A
- Delivery of drugs via GI tract
- Oral, sublingual, rectal
7
Q
Pareneteral administration
A
-Delivery NON GI tract
-Injections (most common) Subcutaneous, Intradermal, Intramuscular, Intravenous
-Cutaneous: Topical or transdermal (systemic)
-Mucous membrane: Eyedrops, ear drops, throat sprays, inhaled, vaginal, urethral
8
Q
Bioavailability
A
- quantitative measurement of drug absorption also called volume of distribution (VD)
- fraction of a drug dose reaches systemic circulation unchanged
- Each drug possess different bioavailability depending on route of admin.
-IV is 100% bioavailability
9
Q
What are the 3 major areas that drugs are administrated?
A
-Therapeutic sites: tissues/organs where drug can function
-Tissue réservoirs: tissues/organs where drug can be stored (drug depot)
-Unwanted sites of action: Tissues/organs where drug is able to elicit unwanted effects this leads to adverse effects/toxicities
10
Q
Drug metabolism, Biotransformation, Clearance
A
- May activate, inactivate, or maintain drug activity
- Major organ involved is liver
- Major enzyme involved cytochrome P450 (located in smooth endoplasmic recticulum of hepatocytes)
- Clearance = majority Renal OTHERS are intestines, lungs, skin, sweat
- Quanitative measurement = Clearance of drug (CL)
11
Q
Pharmacodynamics
A
-What Drug does to the body
- Study of the effects, actions, and mechanisms of drug
- Receptors, mediators, targets, toxicity
- Binding of drugs to receptors done by non-covalent bonds (hydrogen, ionic)
12
Q
Pharmacodynamics (Mech of Action)
A
- Molecular mods cause pharm action of drug
- Drugs do NOT interact with organ as a whole BUT w/molecules in tissue
- Drug receptors = bio macromols (reg. proteins, ion channels, cell surface, carrier proteins)
- Drugs binding to receptors = noncovalent bonds (H bonds, van de waals, ionic)
- Non covalent = Specific / selective & reversible action
- Covalent = less specific & irreversible
13
Q
Pharmacodynamics (Bound drugs)
A
- Full agonist - Drug when bound = activates receptor to produce MAX response
- Partial agonist - Drug when bound = activates receptor to produce BELOW max level
- Antagonist - Drug when bound = fails to completely to make activate receptor
- Inverse agonist - Drug when bound to active receptor (intrisic or basal activity) decreases basal activity
14
Q
Pharmacodynamics (Drug interaction)
A
- Mechanism of action - Drug X functions as a full agonist of Beta-receptors
- Pharmacological action - (functional or physio effect) Drug X increases frequency of spontaneous depolarization of SA node
- **Pharmacological effect - (observed effect) **Drug X induces tachycardia
- Drugs targeting self - primary use to manipulate physio of body
- Drugs targeting NON-self - Chemotherapy or target other foreign organisms in body
15
Q
Pharmacodynamics (Contraindications & Precautions)
A
- Condintion makes use of drug INADVISABLE
- Absolute contraindication = makes use of drug absolutely inadvisable under ALL circumstances
- Relative contraindication = makes use of drug SOMEWHAT in advisable BUT does not rules it out (precaution)
16
Q
Pharmacodynamics (Reproductive Toxicity)
A
- Teratogenic = Effect in the uterodevelopment of organism resulting in abnormal structure or function. NOT heritable
- Mutagenic = Effect on inheritable characteristics of cell/organism. Mutations in DNA
- Ames test-invitro = test for mutagenicity & carcinogenesis
- Dom. lethal test-invivo = males exposed to substance & observed for progeny (Offspring)
17
Q
Schedule 1-5 Drugs
A
- Heroin, LSD, Cannabis, peyote, EX - NO current medical use in US
- Hydromorphone, oxycodone, fentanyl, morphine, adderal - High potential for abuse (narcotis/Stimulants)
- Vicodin, high dosage of tylenol, Ketamine, steroids, benzphetamine - Moderate/low dependence or HIGH physio dependence
- Xanax, klonopin, diazepam, lorazepam - LOW potential abuse
- Cough syrup or has limited narcotics (100 ml of codeine per 100 grams)- LOW abuse potential
- Analogs - drugs whose structure is related to another drug BUT pharm & chem properties differ
- Congener- Drug made by same chem rxns & same pharm effect
18
Q
Route of Admin (Enteral & Parental)
A
- Enteral- Sublingal, oral, buccal, rectum
- Mouth, Stomach, SI (big SA & most drugs absrobed here), Colon, rectum
- Parental- Injections, pulmonary admin, cutaneous admin, mucoud membrane
- Used for drugs poorly absorbed in GI tract, QUICK onset, HIGH bioavailability
- Can cause local tissue damage = Nerve damage in subcutenous injection
19
Q
1st pass effect
A
- Prodrugs use to their benfit
- Greater the 1st pass the LESS the agent will reach the systemic circulation when administered orally
- Primary enzymes affect metab = GI lumen, Gut wall, bacterial, hepatic
- Oral preps - Enteric coated = chem envelope resists action of fluids & enzymes in stomach BUT dissolve in Upper Intestine & Extended release = Special coating control how fast drug is released to body
20
Q
Pharmcokinetics (Drug absorption)
A
- Acidic drugs (HA) release a proton (H+) = charged anion to make = A-
- Basic drugs (Bh+) release proton causing UNCHARGED base = B
- **Uncharged substances can cross hydrophobic cellular membrane **
- **Charged is better excreted **
- Conc of permeable form of drug is determined by ratio of carged to uncharged forms
- Ratio = Depends on PH absorption site & ionization constant (pKa)
- LOWER pka = more acidic
- HIGHER pka = more basic
21
Q
Ion Trapping
A
- Body fluids vary in PH difference from blood PH will favor trapping or reabsorption
- Small intestine
- Breast Milk
- Aqueous humor
- vaginal secretions
- prostatic secretions
- Acidic drugs are ionized (charged) = cant cross membrane MOST found in urine
- Basic drugs concentrated in LOW ph enviroment = Gastric bile
22
Q
Determinants of drug absorption
A
- P-glycoprotein - transmembrane transporter protein expressed through out body, when HIGHLY expressed reduces drug absorption
- Functions = Liver (transports bile for excretion)
- Kidneys (pumps drugs into urine)
- Placenta (transports drugs into maternal blood)
- Intestines (transports drugs into lumen & reduces drug absoption into blood)
23
Q
Volume of distrubution (Vd)
A
- Vd=Amount of drug in body / plasma drug conc @ time 0 or (X/C0)
- A drug binds to blood components remains confined to blood & has small volume distrubution
- Drugs that have extra-vascular tissue binding have large VD
- Plasma compartment = Drugs w/large mol weight or drugs that bind to plasma proteins are TRAPPED
- Extracellular fluid = Low Mol weight drugs are hydrophilic can move into interstitial fluid, BUT no crossing lipid
- Total body water = Low mol weight drugs hydrophobic move across cell membrranes
- HIGH AVD values = 100-1000’s long 1/2 life use loading doses
24
Q
BBB
A
- Tighter endothelial arrangement leaving NO gaps
- Absence of transport systems & membrane channels
- Presence of acid pumps (like in kidney) active transport out of CNS into blood
25
Special Tissues
* **_Placenta =_** Drugs w/ mol wt. less than 1000 daltons & moderate high lipid cross barrier w/Simple diffusion
* **_Blood-cerebrospinal fluid =_** HIGH lipd soluble drugs can cross - CSF barrier
* **_Testis =_** Tight junctions between sertoli cells - restricts passage of drugs to spermatocytes & spermatids
26
Phase 1 metabolism
1. Functionalization rxns
2. Converts parent drug to more POLAR by introducing finctional group (OH, NH2)
3. Results in loss of pharm activity
4. = or more active than parent
5. Almost all oxidative enzymes local to endoplasmic reticulum
* Mixed function enzymes found in microsomes of many cells - performs diff functions rxns
* Oxidation, reduction, hydrolysis, hydration
* If compound is NOT completely secreted THAN on to phase 2
27
Phase 2 metab
* Conjugation rxns
* Enzymes located in cytosol
* **_RXNS:_**
* Glucuronic acid (glucuronidation)
* Sulfate (sulfation)
* Acetic Acid (acetylation)
* AA (glutathione/glycine conjug.)
* Alkyl group (methylation)
* HIGHLY polar - rapidly excreted in urine/feces
* Usually inactive - exception morphine
28
Cytochrome P450
* Metab of diverse endogenous & exogenous compounds
* Drugs, enviromental chems, xenobiotics (chem found in body not normally produced)
* Catergorized into 17 families (cyps#) 40% identical
* Subfamilies 55% identical CYP#A, B, C
* Isoforms CYP#A#
* **St. John's wort INDUCES P450**
* Grapefruit inhibits P450
29
Biliary Excretion
* Similar to kidneys (ACTIVE)
* Lipid soluble drugs filter intially, get reabsorbed along with water, NOT excreted effciently
* Acid/Bases active secretion WORKS effectively if MW high enough
* Conjugation to glucoronide increase MW for bilary excretion
30
Zero & 1st order kinetics
* **_1st order =_** amount of drug metabolized or excreted in given period of time DIRECTLY proportional to PLASMA conc. 1/2 life is constant
* **_Zero order =_** Saturation kinetics = ehtanol. Constant amount of drug eliminated PER unit time
31
Pharmacodynamics (receptors)
* **Drugs can INHIBIT enzymes -** enzymes control # of metabolic processes, very common mode of action
* **Drugs BIND to** - Proteins, genome (cyclophosphamide), microtubules (Vincristine)
* **Receptors located** - IN or ON cells, tight bonds w/ligand, requirements (size,shape,stereospecificity), signal transduction
* **Proteins act as -** Regulatory, enzymes, transport, structural
32
Pharmcodynamics (Drug interaction)
* **Affinity =** measurement of drug binding to receptor - _covalent_ = STRONG/irreversable & _Electrostatic bonds_ = strong or weak/reversible.
* Inverse of Kd like Km 1/2 max binding
* **Efficacy (intrisic activity) =** ability of drug to change the receptor in a way that MAKES an effect, SOME drugs have affinity BUT no efficacy
* Like Vmax and closer to Y axis = MORE efficacy
33
Second Messengers
* Small, nonprotein, water-soluble
* Rapidly spread thoughout cell by DIFFUSION
* **C-AMP -** reg. protein phospho -
* **Ca+2 ions -** more common than C-AMP used in NT, GF
* Increases in Ca+2 = Muscle contraction, secretion, cell division
34
Spare Receptors
* Max drug response obtained @ less than max occupation of receptors
* NOT qualitatively different from NON-spare receptors
* Effect may presist longer than interaction
* Insulin = 99% are spare & Beta on heart
* Compare Max binding (kD) with conc (Ec) w/spare receptors
35
Agonists & Antagonists
* **Agonist** - Binds to receptor directly or indirectly = FULL activation of effector systems
* **Partial agonist -** makes LESS than full effect EVEN when saturated receptors, acts as inhibitor in presence of full agonist
* **Antagonist-** BINDS no activity to receptors = BLOCKS or competes w/agonist
* Repeated admin of agonist or antagonist = changes in responsiveness @ receptor
1. Down-regulated
2. Endocytosis inside cell
3. Unresponsive to ligand
* Inert binding site = Albumin (no effect when bound)
36
Comp. Antagonists
* Competes w/agonist receptor
* Binds reversibly w/o activating effector system
* Atagonists increase agonist conc needed for REPONSE
* CONC-effect curve shift to HIGHER doses
* Effects are overcome by adding MORE agonist
* Increases median effective dose = ED50
* **Irreversible antagonist =** more dependent on turnover of receptors & works w/spare receptors
37
Graded Dose Response
* Relationship between drug & receptor is graded
* Continuous & gradual
* Semi-logrithmic plots due to range of doses & conc. can vary = sigmodial shape
* **_Potency =_** EC50 amount of drug needed to make effect - use 50% of max dose
* **Smaller the value** for EC50 **greater the potency**
* **_Efficacy =_** Emax magnitude of drug effect can cause at max dose = ALL receptors occupied= NO reponse with dose increased
* _Potent drugs =_ make less of demand on metabolic enzymes = lesser side effects
38
Drug receptor binding
* **_Law of mass action -_** Relationship between drug conc & receptor occupancy (insertion of 1 mol will NOT alter binding of other mols)
* **DR/Rt = D/Kd + D **
* _DR_ = conc of bound drug
* _D =_ Conc of free drug
* _Rt = t_otal conc of receptors (bound & unbound)
* _Kd =_ dissociation constant of receptor for drug
39
Dissociation constant (Kd)
* Strength of interaction between ligand & receptor = conc of drug required to bind 50% of receptors
* Kd= D\*R/DR
* **HIGH Kd** = weak interaction & low affinity
* **LOW Kd** = strong interaction & high affinity
* Mag of response is proportional to amount of receptors bound or occupied
* Emax = all receptors bound
* binding of receptors exhibits NO cooperativity
* E/Emax = D/Kd+D (E=effect on drug conc (D))
40
Effectiveness, Toxicity, Lethality
* **ED50 = Median effective dose** (dose which 50% of pop manifests given effect)
* **TD 50=Median Toxic dose** (dose which 50% of pop manifests toxic effect)
* **LD50 = Letal dose** (dose which kills 50% of subjects)
* _Theraputic index =_ Ratio of TD50 or LD50 to ED50
* _Increased index =_ wider margin of safety (represents safety of drug)
* Ex of safe drug is very LARGE toxic dose & small effective dose (ED50 of 3mg & LD50 of 150mg)
* **_Theraputic window =_** doage range is minimum effective conc (MEC) & max toxic conc (MTC)
* Ex. MEC = 7-10mg/L (average 8mg/L) & MTC = 15-20mg/L (average 18mg/L) = Window 8-18mg/L
* Warfarin SMALL theraputic index & Penicillin LARGE theraputic index
41
Frequency of Distrubution
* **NOT cumulative**
* Plots # of responders @ each dose increment OR dose LVL (conc)
* **Bimodal response curves** = heterogeneity in pop w/respect to response of drug
42
Terminology of Drig Effects
1. **Side effects =** Not intended or desired, Minor problem
2. **Adverse effects =** Undesirable, more serious
3. **Toxic effecets =** Serious undesired effects, potentially FATAL
* _On target =_ excessive actions, Inappor conc, suboptimal kinetics, incorrect tissue (Diphenhydramine + H1)
* _Off target =_ Effects unrelated to action, binds to unintended receptor (Terfenadine + Cardiac K+ channel)
43
Idiosyncratic Rxns
* G6PD def - 6-phosphogluconate synthesis via G6PD produces NADPH required maintaining GSH LVLs
* When **LACKING cannot protect against RBC oxidative stress = G6PD def**
* Protect against maleria
44
Hypersensitivities 1-4
1. **Immediate hyper -** atophy, anaphylaxis, asthma - _Mediators (IgE)_
2. **Antibody mediated hyper -** Autoimmune, hemolytic anemia - _Mediators (IgG or IgM)_
3. **Immune complex mediated hyper -** Serum sickness, Lupus - _Mediators (IgG)_
4. **Delayed hyper -** Transplant reject, dermatitis, tuberculosis - _Mediators (Tcells, macrophages, histocyctes)_
