Pharmacology Flashcards
What is the therapeutic window?
The area between the MEC for adverse responses and the MEC for therapeutic response (desired response)
What factors affect pharmacokinetics?
Age, liver/renal function, BMI
How do most drugs interact with the plasmalemma?
Via surface receptors since they’re polar and cannot diffuse across
What are most drugs conceptualized as, as far as their interactions with the cell?
Ligands for surface receptors
Which kinds of drugs are lipid soluble? Water soluble?
Uncharged (hydrophobic)
Charged (hydrophilic)
What is ion trapping and how does it work?
Ion trapping is the use of a drug’s pKa to change its charge to transport it to the desired location (like into the blood stream from the GI tract)
When pKa is greater than its environment, the charge is hydrated and it becomes nonpolar. THEN it can be transported across lipid bilayers.
(TLDR: pKa=4.4 in stomach, uncharged. Transported to blood. In blood, regains charge)
What is a prerequisite for CNS active drugs?
Must be hydrophobic (due to BBB)
What are the main uptakes for drugs from slowest to fastest?
Oral, Transdermal, IM, IV and intrathecal
What is the reason oral intake is slow?
Has to go through first-pass metabolism (via portal circulation)
How is bioavailability calculated?
F=
Quant of drug reaching system circulation
OVER
Quant of drug administered
What route of intake has the highest bioavailability? Lowest?
Intravenous; oral
What is the issue with inhalation as a route of intake?
Patient education and patient technique
Where is a drug located if the Vd is 4L (equal to blood plasma volume)?
ALL OF IT is in the blood
Where is a drug most likely located if the Vd is 250?
Extravascular spaces (muscle, tissues, adipose, etc)
Where is a drug mostly located if the Vd is low?
Blood plasma (vascular compartment)
What is the Vd of drugs that are most likely to need a loading dose?
High Vd may need loading dose to increase plasma levels to the therapeutic range
Describe first order kinetics in regards to elimination of a drug?
drug concentration determines how much drug is eliminated (like a constant 16% elimination per half life. The plot’s slope gets smaller as more drug is eliminated)
What are zero-order kinetics in relation to drug elimination?
A constant amount of drug is eliminated regardless of concentration (very linear elimination line)
What is steady state?
Rate of elimination= rate of administration (takes 4-5 half lives)
maintains concentration in the blood plasma through multiple maintenance doses
What is the formula for clearance?
Clearance= metabolism plus excretion, divided by the concentration of drug in plasma
How does drug binding to proteins affect its activity?
Protein bound drugs (like bound to albumin in the blood) are INACTIVE
What is protein binding’s effect on Vd?
More protein binding= lower Vd
Less protein binding= higher Vd
How can disease-state modifications of proteins affect drug action?
Less protein= greater risk of toxicity due to incr free drug in plasma
More protein= higher conc needed for therapeutic range (not as important)
What drugs are most susceptible to dangerous effects when protein is low?
Those with a low therapeutic index
How is dosing calculated for pediatric patients?
Mg/kg (as compared to standard dose for adults)
More drugs are unbound (more active), average Vd for hydrophilics are higher, average Vd for lipophilics are lower
What does alpha-1-glycoprotein bind? Albumin?
A1GP- basic drugs
Albumin- acidic drugs
How is dosing for elderly patients different than adults?
Body composition changes drug distribution
- lower Vd for hydrophilic drugs (more in serum)
- higher Vd due to more fat stores (prolongs half life)
- acute illnesses more prevalent=more changes in plasma protein and binding
What order of kinetics are most drugs?
First-order
How is half life calculated?
(Ln(2))(Vd) / clearance
Where are CP450 enzymes found?
Smooth ER of liver
What are the most potent CYP enzymes for drug clearance?
3A4, 2D6, 2C19, 2C9, 2E1, 1A2
How does variation factor into first-pass metabolism?
Some people met faster or slower than average (via induction or inhibition)
How does induction of CYP change drug interaction?
Decreases response/efficacy
What are some outcomes metabolism can have on drugs?
- Inactivates an active free drug
- activates an inactive free drug
- turns an active free drug into an active metabolite (incr drug effect)
- turns active drug to a toxic metabolite
What are the phase one and two reactionsof CYP enzymes?
P1: redox reactions
P2: conjugation/hydrolysis actions
What does phase 1 and 2 reactions in CYP metabolism do?
Increases hydrophilicity (promotes excretion)
What are the names of the three conjugation reactions?
Glucuronidation, acetylation, sulfation (increases solubility in urine or bile for excretion)
How do P450 enzymes react to aging?
Decreases
