Pharmacology Flashcards

Question

Calcium release receptors

Answer 1

Calcium-induced calcium release (CICR) describes a biological process whereby calcium is able to activate calcium release from intracellular Ca²⁺ stores e.g. calcineurin, nitric oxide synthase, cytokines

Answer 2

Intracellular receptors are receptors located inside the cell rather than on its cell membrane. Classic hormones that use intracellular receptors include thyroid and steroid hormones.

Answer 3

* Direct: e.g. Isoproterenol(Beta blocker) * Indirect: e.g. Cocaine * a substance that enhances the release or action of an endogenous neurotransmitter but has no specific agonist activity at the neurotransmitter receptor itself * Mixed: e.g. Tamoxifen * a drug which under some conditions behaves as an agonist while under other conditions, behaves as an antagonist. * Inverse: e.g. Emedastine * a drug that binds to the same receptor as an agonist but induces a pharmacological response opposite to that of the agonist. * Partial: e.g. Buspirone * drugs that bind to and activate a given receptor, but have only partial efficacy at the receptor relative to a full agonist ## Footnote **Inverse agonist can produce a lower response than antagonist**

Answer 4

* Binds reversibly and ireversibly * Binding site selectivity: * Competitive (compete for the same binding site used by an endogenous agonist) * Non-competitive (allosteric)- implies that the antagonist, while still opposing the action of the agonist, does so without competing with it for the binding site. The agonist may bind there all it wants; it will still do no good. Unaffected by agonist dose. Binds to site distinct from agonist binding site, causes changes in agonist binding site * Uncompetitive (allosteric binding in presence of substrate slows ligand dissociation and response rate) require agonist. Locks receptor with agonist attached so agonist cannot disassociate and restimulate

Answer 5

[affinity] X [intrinsic activity]

Answer 6

* Ligand gated ion channels * Receptors interact with substrate In ways that allow channel opening for a specific ion to create a flow of ions in a specific direction * Eg GABAA, AChN, glutamate * G-protein coupled * 7 transmembrane domains * Most common receptor type targeted by ophthalmic drugs * Eg AChM, rhodopsin * Phosphorylation of G protein to GTP * Enzymatic * Single transmembrane spanning domain * Eg insulin, epidermal growth factor * Calcium release * Interacts with a receptor in the cell that releases Ca from sarcoplasmic reticulum * Eg calcineurin, nitric oxide synthase, cytokines * Intracellular or nuclear * Substrates must be able to readily pass through the lipid bilayer * Eg steroids and hormones

Answer 7

congential malformation

Answer 8

Cornea is a thick barrier - important as an immune barrier Stroma has little resistance to the passage of drugs, esp water soluble AC has little resistance for water soluble drugs Iris is quite porise, can absorb drugs readily to enter systemic circulation Anterior lens is a good means of protection Vitreous has low profusion resistance ILM of retina is not much of a barrier, retinal BVs have tightly knit walls to prevent absorption of drugs here - Blood retinal barrier Choroidal vessels are fenestrated and absorb and release drugs readily

Answer 9

The large majority of drugs are weak acids or bases Their ionization constant pKa defines the pH at which ionized and unionized forms are equal in concentration Only uncharged drugs are lipid soluble; charged drugs are water soluble In increasingly acidic environments, the above rxn will move to the left as excessive levels of protons flood the environment Log[protonated/unprotonated] = pKa -pH

Answer 10

Normal test pH is aroung 7.1-7.6, ie slightly basic Strongly buffered drugs can alter teat pH Weak bases are most stable at low pH since protonated charged state reduces metabolism Inflammation creates an acidic environment Charged drugs accumulate in aqueous media Uncharged drugs readily leave aqueous environments to cross lipid barriers pH = pKa + log ([A-]/[HA]) [H+] = Ka + ([HA]/[A-])

Answer 11

Corneal tear drainage, episcleral blood flow and intraocular convection limit influx of locally administered drugs into the posterior segment Size of drug plays a role in which can penetrate ILM

Answer 12

Drug metabolism rates: each drug has an absorption (and elimination) half-life describing the time it takes for 50% of the drug to be processed Absorption, clearance and elimination kinetics are unique to a given drug and assume two distinct profiles; Zero order and 1st order - In some cases, drugs follow both zero order and 1st order kinetics depending on their concentration; in this case they are classified as mixed order For drugs with 1st order kinetics, their concentration exponentially impacts their rate of processing by a given receptor (aka carrier) - During the metabolic phase, when the levels of a carrier far exceed its substrate drug concentration, the kinetics are said to be non-saturable For drugs with zero-order kinetics (like ethanol and salicylates) their rate of processing is independent of their concentration, so doubling a dose means it will take twice as long to metabolize - With Zero-order kinetic drugs, there is a greater demand for dose modification: loading VS maintenance

Answer 13

Dosing schedule First order Kinetics: - Steady state is achieved when rate of intake = rate of elimination Zero order kinetics: - Greater demand for dose modification (loading vs maintenance) - Doubling a dose calls for twice the time to be metabolized

Answer 14

To best avoid undesired fluctuation of plasma drug levels, dosing intervals are recommended at less or equal to a drug's half-life; in this way drug concentration never drops lower then 50% - Dosing according to a drug's half-life is readily accomplished with sustained release drugs Dosing intervals less than 1/3 of a drugs half-life results in plasma drug levels that are similar to those seen with continuous infusion - Because most antibiotics have a high therapeutic index (very safe), dosing schedules for severe infection is often don’t in a loading dose fashion since large peaks in plasma levels are not toxic

Answer 15

1st order kinetics - Steady state is reached in this case in 3-5 drug half lives with first order kinetics - Conversely a 3-5 half-lives following the last dose, 90% of a systemic drug is eliminated

Answer 16

One way to achieve the designated therapeutic drug level is to modulate the dose concentration Another way is to modulate dose frequency OR do both - Greater frequency --\> less potential for toxicity

Answer 17

* Steroids: long term topical or oral - Cataracts and glaucoma risks * Beta-blockers - Cardiovascular & respiratory risks * Mitotic - Retinal detachment risk * Oral carbonic anhydrase inhibitors - Electrolyte imbalance risk

Answer 18

4 components of a malpractice case * Standard of care: what standard of care is expected? * . Present once a relationship is established with patient, regardless of fees or setting * Informed consent in a language the patient comprehends involves a discussion of alternative therapies, drug or procedure risks and warnings, abnormal findings * Breach of care: did the level of care not meet the standard? * Evidence of injury: how was the patient affected? * Proximate cause: did the injury occur around the same time as the breach of care took place?

Answer 19

In order of most to least common * Failure to diagnose * Glaucoma, tumors of the visual system, retinal detachment * Delayed diagnosis * Misdiagnosis * . Herpes keratitis, fungal disease, pseudomonas ulcers * Improper management * Failed/delayed referral or consultation * Schedule follow-up before patient leaves office

Answer 20

The DEA has established 5 distinct categories or schedules for drugs which relate to the drug's acceptable medical use as well as its abuse or dependency potential I: no currently accepted medical use and a high potential for abuse (eg heroin) II: a high potential for abuse, with use potential leading to severe psychological or physical dependence (eg hydrocodone, Adderall) III: A moderate to low potential for physical and psychological dependance (eg testosterone) IV: A low potential for abuse and low risk of dependence (eg Valium) V: Lower potential for abuse than schedule IV drugs (eg penicillin)

Answer 21

Category Warning A No evidence of risk in women B No evidence of risk in animals C Animal toxicity evidence D Risks may be about equal to benefits X Risks outweigh benefits

Pharmacology Flashcards

(47 cards)