2) Pharmacotherapeutics Flashcards
Volume of distribution (Vd)
- Volume of body fluid into which a drug is dissolved or distributed
The most common site for drugs metabolism
- Liver
- A detoxifying machine via chemical reactions of CYP450
Cytochrome P450 (CYP)
- Important group of enzymes responsible for a variety of Phase I reactions (1st step reactions of metabolism that biotransforms drugs, typically to MORE POLAR compounds)
Superfamily of CYP enzymes was classified into
subgroups using the following system
- Family (40% homology, number after CYP)
- Subfamily (60% homology, letter after CYP#)
- Genetic isoform/variant (number following CYP#X)
- Alleles (*# at the end)
Factors modifying drug actions
- Physiochemical
- Physiological
- Pathological
- Genetic
- Environmental
Age influence on drug actions
- Newborn babies & elderly are greater & more prolonged effect
- Less efficient drug metabolism & renal functions
Gender influence on drug actions
- Dose and response can differ between men & women
- Metabolism of some drugs less in women (more adipose tissues)
- Females may require doses that are on the lower side of the range
Pregnancy effects on drug actions
- Avoid certain drugs due to teratogenic effects
- Lipophilic drugs cross placental barrier
- Altered body physiology during pregnancy
- Increased cardiac output, GFR & renal elimination, volume of distribution
- Altered metabolism of certain drugs
Body weight and surface area effects on drug actions
- Concentration of drug at site of action = ratio of body wt. & amount of drug
- Quantity of drug for lighter vs heavier and smaller vs larger persons
Diarrhea increases the motility of the gut and can
- Decrease drug absorption
Liver disease leads to
- Decreased metabolism of drug and accumulation
Impaired renal function leads to
- Decreased drug excretion
- Drug accumulation
Cigarette smokers metabolize _____ more rapidly than non-smokers
- Olanzapine
Genetic polymorphism
- The variation/difference in genetic makeup
- Can affect patient response to a specific drug
Some drugs have a genetic testing requirement prior to use in order to avoid
- Inducing a fatal ADR
- Having no/low therapeutic effect
- Causing significant Drug-Drug Interactions (DDIs)
Poor Metabolizers (PM)
- Have two non-functional alleles
- Little to no enzyme activity
Intermediate Metabolizers (IM)
- Have one non-functional allele and one normally functioning allele
- Decreased enzyme activity
Extensive Metabolizers (EM)
- Have 2 normally functioning alleles
- Normal enzyme activity
Ultra-Rapid Metabolizers (UM)
- Have one or more alleles with a mutation type
- Increased enzyme activity compared to extensive metabolizers
CYP2B6 metabolizes 2 anti-HIV drugs
- Efavirenz
- Nevirapine
For drugs to exert a pharmacological actions, they have to
- Reach the systemic circulation
- Be in active form
- Be free (non-complexed)
If drugs are metabolized “prior to” reaching the circulation, they are said to
- Have gone through “first pass effect” or “pre-systemic” metabolism
Oral drugs may be exposed to first pass effect in
- Extra hepatic (outside the liver)
- Hepatic
Extra-hepatic first pass metabolism sites
- P-glycoprotein system (protein of the cell membrane that pumps many foreign substances out of cells)
- Intestinal metabolism
- Intestinal microflora
P-GlycoProteins (P-gp)
- Efflux (E for Exit, expulsion, pumping to outside) plasma membrane protein
P-GlycoProteins (P-gp) are implicated in many
- DDIs (Drug-Drug Interactions) since many CYP3A4 substrates are also P-gp substrates
In the gut, P-glycoprotein
- Pumps drugs back into the lumen
- Decreasing their absorption
Drugs which induce P-glycoprotein, such as rifampicin, can
- Reduce the bioavailability of some other drugs
Inhibitors of P-glycoprotein, such as verapamil,
- Increase the bioavailability of susceptible drugs
Intestinal mucosa is rich in
- CYP3A4 system
Many drugs like _____ and _____ can be affected if the gut
flora balance is disrupted
- Digoxin
- Estrogens oral contraceptives
Drugs secreted by the liver into bile are capable of undergoing
- Enterohepatic recycling
Enterohepatic recycling
- The circulation of biliary acids, bilirubin, drugs or other substances from the liver to the bile
- Followed by entry into the small intestine
- Transported back to the liver
Routes of administration available
- Intramuscular
- Subcutaneous
- Intravenous
- Intradermal
- Transdermal
- Sublingual
- Oral
- Rectal
- Parenteral
- Topical
