Pharmacology-condensed (Melega) Flashcards Preview

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Flashcards in Pharmacology-condensed (Melega) Deck (20):
1


Pharmacokinetics


What the body does to the drug

Absorption, distribution, metabolism and excretion (ADME)

2


Pharmacodynamics


What the drug does to the body

3


Potency


Effective dose or concentration that produces 50% of its maximal response (ED50)

Good for comparing two drugs with same efficacy

4


Affinity vs. Efficacy


Affinity (recognition): Agonists and antagonists have binding affinity

Efficacy (signal transduction): Only agonists have efficacy

(Also remember, agonists have varying degrees of efficacy)

5


4 targets of drugs


1) Receptors: Ligand-gated ion channels

2) Receptors: G-protein coupled receptors

3) Enzymes

4) Transporters

6


Bioavailability


(AUCoral)/AUCiv) x 100%

Fraction of administered dose that reaches the systemic circulation (plasma)

IV has 100% bioavailability b/c injected directly

7


First Pass Effect


Some of the drug is degraded by the liver and GI tract before the drug gets to the general circulation

Additionally, some of the drug is never even absorbed in the GI tract and is excreted right away

8


Cytochrome P450 (CYP enzymes)

Phase I metabolism ("functionalization")

Imbedded in ER of many cells, especially liver

Monooxygenase

Heme protein (has Fe)

Uses oxygen to oxegynize the drug and reduce the other atom to a hydroxyl (adds OH)

Creates more polar metabolite

9

Induction of CYP enzymes

Makes drug metabolism by CYP faster, and thus drug effect is lower

Increase in synthesis of CYP protein (so this is slow)

Ex: anticonvulsants phenobarbital and phenytoin induce CYP3A4; ethanol induces CYP2E1 (alcohol + acetominophen = bad news; cigarette smoke induces CYP1A1

10


Inhibition of CYP enzymes

Makes drug metabolism by CYP slower, and thus drug effect is stronger

Competitive or non-competitive binding of drug to CYP, so faster and usually reversible

Ex: Cimetidine (H2 blocker); ketoconazole; desipramine; fluoxetine

11


Phase II metabolism


All drugs must go through Phase II

"Conjugation" with polar group

Glucuronidation is most common, also can add AA or sulfate

12


Drug in system after X half lives


3.3 half lives: 90% drug eliminated

6 half lives: more than 98% drug eliminated

13


What determines the time to get to Css?


Kel

14

Severe vs. serious side effects


Severe describes intensity of symptom, but serious is based on outcome (death or hospitalization)

Severe headache is not serious

15


Iatrogenic vs. Nosicomical


Iatrogenic: adverse effects caused inadvertently by physician's advice or medical treatment

Nosicomical: originated or acquired in the hospital (ex: hospital-acquired infections)

16


Adverse drug interactions


Usually with Phase I enzymes

Elderly people have the most problems (higher fat:lean ratio, decreased protein/albumin, decreased oxidation/reduction, decreased renal clearance)

17


Chelators (EDTA)

Complexes metal within molecule and complex gets cleared

Has different affinity for different ions

18


Transdermal Patch


High potency drug

High concentration of drug

Lipophilic

Neutral drugs

Small molecules

Rapid penetration

Note: takes longer to get to steady state, but then is constant concentration

 

19


UVA/UVB


UVA: long-term sun damage; not always targeted by sunscreens

UVB: causes erythema of sunburn

20


Skin pigmentation/natural mechanism to protect yourself from skin damage


1) UV light triggers DNA damage in nucleus of keratinocytes

2) p53 activated, and upregulates transcription of proopiomelanocortin (POMC)

3) POMC post-translationally processed to produce melanocyte-stimulating hormone (MSH) and beta endorphin

4) MSH acts on melanocortin 1 receptor on melanocytes at basal layer of epidermis and induces production of pigment melanin

5) Melanin is transported to keratinocytes where melanin vesicles coalesce over sun-exposed side of the nucleus and cause tanning (and protect against UV)