Pharmacology-condensed (Melega)

Question 1

Pharmacokinetics

Answer 1

What the body does to the drug

Absorption, distribution, metabolism and excretion (ADME)

Question 2

Pharmacodynamics

Answer 2

What the drug does to the body

Question 3

Potency

Answer 3

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

Good for comparing two drugs with same efficacy

Question 4

Affinity vs. Efficacy

Answer 4

Affinity (recognition): Agonists and antagonists have binding affinity

Efficacy (signal transduction): Only agonists have efficacy

(Also remember, agonists have varying degrees of efficacy)

Question 5

4 targets of drugs

Answer 5

1) Receptors: Ligand-gated ion channels
2) Receptors: G-protein coupled receptors
3) Enzymes
4) Transporters

Question 6

Bioavailability

Answer 6

(AUC_oral)/AUC_iv) x 100%

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

IV has 100% bioavailability b/c injected directly

Question 7

First Pass Effect

Answer 7

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

Question 8

Cytochrome P450 (CYP enzymes)

Answer 8

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

Question 9

Induction of CYP enzymes

Answer 9

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

Question 10

Inhibition of CYP enzymes

Answer 10

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

Question 11

Phase II metabolism

Answer 11

All drugs must go through Phase II

“Conjugation” with polar group

Glucuronidation is most common, also can add AA or sulfate

Question 12

Drug in system after X half lives

Answer 12

3.3 half lives: 90% drug eliminated

6 half lives: more than 98% drug eliminated

Question 13

What determines the time to get to C_ss?

Answer 13

K_el

Question 14

Severe vs. serious side effects

Answer 14

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

Severe headache is not serious

Question 15

Iatrogenic vs. Nosicomical

Answer 15

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

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

Question 16

Adverse drug interactions

Answer 16

Usually with Phase I enzymes

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

Question 17

Chelators (EDTA)

Answer 17

Complexes metal within molecule and complex gets cleared

Has different affinity for different ions

Question 18

Transdermal Patch

Answer 18

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

Question 19

UVA/UVB

Answer 19

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

UVB: causes erythema of sunburn

Question 20

Skin pigmentation/natural mechanism to protect yourself from skin damage

Answer 20

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)