Pharmacology-condensed (Melega) Flashcards
Pharmacokinetics
What the body does to the drug
Absorption, distribution, metabolism and excretion (ADME)
Pharmacodynamics
What the drug does to the body
Potency
Effective dose or concentration that produces 50% of its maximal response (ED50)
Good for comparing two drugs with same efficacy
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)
4 targets of drugs
1) Receptors: Ligand-gated ion channels
2) Receptors: G-protein coupled receptors
3) Enzymes
4) Transporters
Bioavailability
(AUCoral)/AUCiv) x 100%
Fraction of administered dose that reaches the systemic circulation (plasma)
IV has 100% bioavailability b/c injected directly
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
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
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
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
Phase II metabolism
All drugs must go through Phase II
“Conjugation” with polar group
Glucuronidation is most common, also can add AA or sulfate
Drug in system after X half lives
3.3 half lives: 90% drug eliminated
6 half lives: more than 98% drug eliminated
What determines the time to get to Css?
Kel
Severe vs. serious side effects
Severe describes intensity of symptom, but serious is based on outcome (death or hospitalization)
Severe headache is not serious
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)
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)
Chelators (EDTA)
Complexes metal within molecule and complex gets cleared
Has different affinity for different ions
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
UVA/UVB
UVA: long-term sun damage; not always targeted by sunscreens
UVB: causes erythema of sunburn
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)
