Lecture 1 - Introduction to Pharmacology Flashcards
What is the basic model for pharms working on the body?
Lock and Key Model.
Note: different substrates are used
Why are leaky blood vessels a problem?
They have proteins which will latch onto a membrane receptor and causes a response.
What is a leaky blood vessel describe?
Inflammation.
What is affinity?
potential for drug receptor binding
What is a receptor?
binding site w/ biological effect
What is Intrinsic activity?
Capacity to prduce a biological effect
What is an Agonist?
Having an intrinsic activity and affinity
What is an Antagonist?
Affinity without intrinsic activity
Note: Efficacy is zero for antagonists
What is an allostery?
Stereospecific phenonmenon whereby a bound ligand influeneces specificity of a 2nd site
What is efficacy?
Affinity x Intrinsic activity
Note: Does dependent. As long as the same response is generated in contrast to potency which is does dependent
What is EC50?
“effective” concentration in 50% of subjects
Whats is ED50?
“effective” does in 50% of subjects
What is IC50?
“Inhibitory” concentration in 50% of subjects
What is a receptor?
Any cellular macromolecule to which a drug binds to initiate its effects
What is hypersensitivity?
Result of chronic antagonism
What is maximum dose?
Minimum amount of drug producing max. therapuetic effect
What is partial agonist?
low intrinsic activity with potency and affinity within therapeutic range
What is pharmacodynamics?
Drug –> Body
What is Pharmacokinetics?
Body –> Drug (Absorption
Distribution
Metabolism
Eliminated - Charged molecules will be eliminated via. Urine
Lipid based would be eliminated in the feces)
What is pharmacotherapeutics?
Drug –> Disease
What is posology?
science of drug dosing
What is Potency?
response to a given dose
Note: Inversly related to EC50 for agonists
Note: Inversly related to IC50 for antagonists
What is resistance?
loss of pharmacological effect
What is selectivity?
Ability to produce a desired effect vs. adverse effect
ex. how good is a drug that can eliminate a headache but not cause another issue.
Ibuprofen will cure a headache and will not cause an adverse reaction
What is specificity?
ability to act at a specific receptor
What is tachyphylaxis?
rapidly decreasing therapuetic response
or resistance
What is teratogenesis?
Congenital malformation
What is bioavailablity?
Amount of active drug reaching target tissue
What is therapeutic index?
LD50:ED50 or TD50:ED50
Note: We would like the TD high, keeping it a safe drug
What is DPA?
Diagnostic pharmaceutical agent?
What is TPA?
Therapeutic pharmaceutical agent
What is a supplement?
Ex. insulin
Involves in the addition of a substance that is normally required by the body but exsists in insuffiecient amounts
What does supportive mean?
Ex. glucose
Aimed at releiving symptoms or helping pts. cope with them rather than focusing on a cure
What is a prophylactic?
low dose aspirin - reduce the likely hood of something occuring
Why is methotrexate important?
antimetabolic/antineoplastic: inhibitor of dihydrofolate reductase, preventing folate reduction to tetrahydrofolate, thus stopping DNA synthesis in the sysnthesis phase of the cell cycle; used in various cancers, psoriasis and rheumatoid arthrisitis
What is symptomatic?
Ex. Olopatadine
Not a cure/
What is a diagnostic?
to complete a test.
Ex. fluorescein
What is a therapeutic?
Ex. Methodtrexate
Name the super families.
Hint: there are 5
1) Nuclear: Intracellular receptors with DNA binding domain; cytokines, Ex. steroids, hormones (these are lipophilic)
2) G-protein coupled: MOST COMMON.
Ex. ACH and Rhodopsin
-G-protein (guanosine nucleotide-binding proteins) coupled receptors are the most common target of ophthalmic therapeutic & diagnostic agents; when activated they bind GTP and hydrolyze it to GDP (aka GTPase)
ACh (acetylcholinergic); M (muscarinic); N (nicotinic)
3) Ligand-gated ion channels: GABA, ACH, Glutamate, voltage gated ion channels respond to change in membrane potential
4) Enzymatic: Insulin, epidermal growth factor.
Lipophilic, can cause transcriptional change. Can turn insulin on and off
5)Calcium release: calcinerurin, nitiric oxide synthase
Key: Ca very toxic to cells, apotosis can occur.
Name 4 various binding interactions.
Covalent, Ionic, Hydrogen, Van der Waals
What are the 4 protein structural configuration?
Primary, secondary, tertiary and quaternary
What is a direct agonist?
Isoproterenol, which is adernergic beta receptor
What is an indirect agonist?
Cocaine
What is mixed agonist/antagonist?
Tamoxifen, which is a estrogen receptor anatgonist in breast cancer, agonist in bone (inhibits osteoclast indiced osteoporosis, partial agonist in endometrium (risk in endometrial cancer)
What is an inverse agonist?
reverse contitutive receptor activity. The background stimulation, the supression of the constiutive product.
What are the 2 types of binding integrity?
Reversible (binds to receptor and cannot function not more) and Irreversible
What are the 3 typse of site binding site selectivity?
1) Competitive - endogenous agonist
- competes against the agonist, thus fighting for the same site
2) Non-competitive (allosteric) - don’t bind to the original site but bind to another. Not competing, and changes the structure of the binding site for the substrate in an indirect fashion prevents from further interaction of the agonist
3) Uncompetitive - Memantine is used to treat alzheimers.
- Binds only when the agonist has been bound, but shuts down the reaction by the agonist.
What are the 3 types of mode of action?
Biological - PCN
Chemical - Alka Seltzer, chelators
Physiological - ACH, Epi, Histamine
What is an allosteric mechanism
the effect of the antagonist is to stabilize the binding of the agonist and receptor such that sustained reaction through the binding of subsequent agonists is delayed
What is absorption influenced by?
First pass metabolism,
Barriers: vascularity at site of adminisitration
Pt. age, gender, weight, pregnancy and health
Note: An eye that has a leaky blood vessel, the inflammation occurs even further
What is the pharmacokinetics for distribution?
Volume of Distribution (Vd); dose/(drug in plasma)
What is the pharmacokinetics for metabolism?
Drug 1/2 life must be considered
-influenced greatly by health of metabolizing organ
What is the pharmacokinetix for elimination?
Routes may include fecal, urinary, sweat, respiration and saliva
Drug clearance = (drug volume eliminated)/(time)
What is an ocular drug barrier?
Tear film
-mucin layer in both water and lipid soluble
If a pt. has keratitis, what could cause a problem, in regards to regards to the tear film?
The damage to the cornea, can cause the aqueous products entering the epithelium
What 2 parts of the eye that are most absorbing?
Corneal epi and RPE.
What is a poor area for drug passage of the eye?
The corneal endothelium due to the fact there are lack of tight junctions.
What is the tear film volume?
10ul (on the eye) vs. 30ul max (how much room we have on the eye) vs. 25-56uL gt
Basal tear flow 0.5 -2.2 ul/min - if you had to move the entire replacement of the tear. 60 minutes to replace the entire 30 uL
What is the main drug barrier for the cornea?
Epithelium; thick in diabetes; thin in keratoconus
Stroma
What is the % of topical drug lost to evaporation?
90%
What is the % eliminated by the nasolacrimal drainage system?
80% in 2 minutes
What is the barrier for the Conj. and sclera?
20% of drug passage to iris and CB
What is the Iris barrier
Lipophilic pigment is a color-sensitive depot
What is a amphipathic drug?
Both aqueous and lipophillic. Work really well.
True or False. A pt. with brown eyes absorb drugs more than a blue eyed individual?
True.
What is the normal tear pH?
7.1 to 7.6
What does pH = pKa mean?
50% dis-association
If you have a drug that is an acetate, acetone and alcohol be the reason?
It is the charge of the chemical.
What antibodies/protein that can build up in contact users?
Immunoglobulins
What is the volume in the anterior chamber?
200 micro liters/50 mins
This means that the drug that is with it, the drug will go with it
What is the most metabolically active part of the lens?
Crystalline lens
What is the primary drug metabolism site?
Ciliary body
Note: the CB is the entry point for systemic meds to the anterior and posterior chamber
What type of drug can reduce the blood aqueous barrier?
steroid
What structures of the eye can limit the influx of locally administered drugs into the posterior segment of the eye?
Cornea, Tear Drainage, Episcleral blood flow.
What is zero order
it is concentration independent. Has a CONSTANT amount of clearance
ELIMINATION PER UNIT TIME IS LINEAR
What drugs follow zero order kinetic?
Alcohol, ASA, phenytoin, fluxetine and verapamil
T or F, if you double the dose of alcohol, it will take twice the time to metablize
True.
What is 1st order kinetics?
Most drugs are 1st order. its is concentration dependent.
- Has non saturable carrier
- eliminated per unit time is exponential
What is mixed order kinetic?
Saturable carrier at high concentration only
What would you consider the dosing schedule for first order kinetics?
Steady state. Intake must equal rate of elimination
What would you consider to be the dosing schedule for zero order kinetics?
Greater demand for dose modification.
Loading dose vs. Maintenance
Loading dose which is to get levels high by giving a higher than normal dose and then giving maintenance by keeping to the dose that is needed.
When you increase the dose, it will the plasma equilibrium level increase or decrease?
Decrease
True or False.When dosing done more frequently can raise equilibrium level without elevating the individual dose?
True
What is major side effect of steroids?
Cataracts and Glaucoma
What are certain monitoring systems you could do, in regards to Beta Blockers?
Monitor pulse, BP and Respiratory status
Note: Interfere with the cardiovascular system.
What are certain health issues that can arise using Miotics?
Spasming of Ciliary muscles, retinal detachment
Note: Lattice - pilocarpine can induced a retinal detatchment
What type of drug can cause open angle glaucoma?
Oral carbonic anhydrase inhibitors
Not used often, they are dangerous and manipulate ion levels in the body.
What does proximate cause mean?
When did the injury occur.
What are common Tx. negligence?
1) Failure to diagnose
- OAG, tumors of the visual system and retinal detachment
2)Delayed diagnosis
3) Misdiagnosis
- HSV keratitis, Fungal disease, Pseudomonas ulcers, abrasions and Contact Lens Extended Wear)
4) Improper management - did you get help when you needed
5) Failed/delayed referral or consultation
Which is safer, schedule 3 or 4?
4.
Which is a safer drug for a pregnant women, B or C?
B would be safer
What is anaphylaxis?
An acute, emergent inflammation. You must give Epineprine.
Usually anaphylaxis is caused by allergies
What do you if a respiratory tubulation is inflammed?
Lie them on their back and do NOT give water, but Epineprine pen must be inserted into a fatty region.
Epineprine will get the blood flow to increase.
If you have given a pt. a epi pen, and sweating is exaggerated in a pt. , what maybe occuring?
An anaphylactic shock
Can DR. prescribe a off label drug?
Yes.
Note:
What is off label drug use?
Practice of prescribing a drug for a non-FDA approved indication
What are the 3 major FDA requirements for drugs?
1) Min. 90% activity
2) > 18 month shelf life
3) Antimicrobial preservation vs. non-preserved unit dosing vials
What are the 8 areas for ocular drug delivery sites?
1) Eye drops
2) Scleral plug
3) Subconj. Implant
4) Suprachrodial implant
5) Suprasceleral injection
6) Intravitreal implant
7) Intravitreal injection
8) Oculex products
What are the 6 routes of injection?
1) Subconj. - lower dose, high local concentration, no compliance issues
2) Subtenons - steroids for equatorial uveaitis
3) Retrobulbar - into muscle, high penetration, very low usage now a days
4) Peribulbar - Anesthesia
5) Intracameral - endophtalmitis
6) Intravitreal
What is a benefit with using a gel\?
Thicker and can be used with higher dosed products
What is an ointment?
Oil base. Can penetrate the fatty layer of the skin
Cream is a water base
What is a solid drug delivery system?
Contact lenses, collagen shields (biodegradable-protect the eye but disolve), filter strips (strip onto the eye and slowly release drug), cotton pledgets (available to apply drug to the eye - localize the area of dilation), lacrisert (meant for dry eyes, put into the fornix ), vitrasert (vitreous insertion) and lucentis (injection into the eye and treat neovascular diseases)
What are solutions?
Water soluable, homogenous
What is a suspension?
A solution that is not a solvent???? Not sure on this.
What is a colloid?
Must be uniform in every single drop
What is a spray?
Its a spray
What is an emollient and what is the effect it has on skin?
Oil based cream. Meant to soothe the skin
What is a demulcent?
A substance that helps with an irritation in the mouth.
What is the major function of an emuslsifier?
Keeps solids in liquids well dispersed
What polymer is used to prolong tear film wetting time and enhance corneal penetration of Fluorescein and Dexamethasone?
HPMC: Hydroxypropylmethlcellulose
This compund differs from HPMC by carrying a greater negative charge and enhances mucoadhesion?
Carboxymethylcellulose
What compund enhances surface retention time and is a viscosity enhancer?
PVA (Polyvinyl alcohol)
What is a good vehicle that assists in pt. who suffer from discomfort of blinking and is found in joints?
Hyaluronate
-Made yo of glycosaminoglycans
What is a function of chelator?
Binds to metals and won’t allow the bacteria to enrichs its self, thus dying off.
What is a brief definition of a disinfectant?
Bacteriostatic
Note: An antiseptic is a disinfectant
What is a scientific name for a soap like product, that has a fatty component to it?
Surfactant
What is the number 1 preservative used in all eye drops?
What is a less allergenic material compared to this compound?
BAK (Benzalkonium Chloride
and Chlorobutanol is less allergenic than BAK
What is PVP (Povidone) used for during WW2?
Reduction of toxicity and allows preservation of bactercidal action
Why should an OD monitor the use of sodium perborate products on a dry eye?
inactivation is pH sensitive thus questioned in use on dry eyes; metabolized from hydrogen peroxide to water and oxygen
If a pt. opens a resealable self-preserved artifical tears, how long can they be used for, once opened?
12 hours
