1.1-1.3 general pharmacology Flashcards
Provide and discuss a comprehensive individual risk benefit analysis for a given drug!
In general: - medical indication: severity of indication (headache vs oncology) consequences of no therapy (therapeutic nihilism)
drug application severity of adverse drug reactions (GI disturbances vs cardiac arrest) propabiliby of occurrence of adverse drug reactions
Which factors have to be considered to wisely choose an individually optimal route
of application? Discuss those factors with different drugs and patient situations.
Factors that influence
- route of application: ability to swallow, urgency of the situation, interval of application (Cp must be maintained in therapeutic window), chemical properties of the certain drug, local vs. systemic effects, is patient conscious?, should the patient be able of apply drug himself?, status of liver, kidney and GI mucosa of the patient
Janna: physical/chemical properties of drug (size, soluability, pH stability)
urgency of situation
local vs. systemic effects
condition of the patient (consciousness, ability to follow instructions, dysphagy)
other medications
system application (oral, sublingual, rectal, parenteral, transdermal, local)
Give a detailed discussion of advantages and disadvantages of transdermal
therapeutic systems.
Advantages: constant drug level in the blood (smooth plasma levels) , no swallowing, no first pass effect, little GI irritation, no food interactions, improved compliance (every 72h), possible self-administration
Disadvantages: Expensive, precise patch changing time needed, slower onsetof drug, local irritation, suitable just for a few drug and small amounts
Effect can vrie through:
1.) biological: skin condition, skin age, regional skin site, skin metabolism
2.)physicochemical: skin hydration, temperature and pH, diffusion coefficient, drug concentration, partition coefficient, molecular size
3.) environmental: sunlight, room temperature, clothing
(eg tight-fitting vs sloppy)
For eg. Fentanyl, nicotine, estradiol
Explain half-life
The halt life of a drug is the time that is needed to halve the concentration of the drug. It depends on time course of drug elimination and accumulation and influences the choice for the dose interval
Explain Cmax
Cmax is the maximum concentration of drug in the plasma that occurs after taking the drug
Explain tmax
the time needed to achieve Cmax
Explain steady state (Css)
Is the concentration when an equilibrium is reached (after 5 half life periods) so there is no infinite accumulation due to concentration-dependend elimination (first order kinetics and t1/1 dependent).
Explain drug clearance
Drug clearance (CL) is the plasma volume form which the drug is completely removed per time (L/h or ml/min). It is NOT excretion (mg/min)! = important for maintainance
Total body clearance: Hepatic + renal + lung clearance (depending on organ functions)
CL (l/h) = Rate of elimination (mg/h) / Cp (mg/l)
Cp = plasma concentration
Can be determined from:
Vo and t1/2 or form AUC using trapezoidal rule (drug concentration and time after administration)
Explain first pass effect
The first pass effect sums up the presystemic eleimination of a drug in the GI mucosa and the presystemic liver metabolism. Only a fraction of drug occurs in systemic circulation (Portal vein is NOT systemic, as it is before the liver metabolism)
Closely related to bioavailability
What are prodrugs? Explain active metabolites in this context
Coumpounds that need to undergo biotransformation before exhibiting pharmacological effects.
Can be used to improve availability when the active compounds BA is too low: Absorption of inactive prodrug (BA good) –> transformation to active compound after absorption
Active metabolite: Is a compound that exhibts pharmacological effect after it got transformed by reactions in the body. One (pro)drug can have many active metabolites (cocktail effect)
Explain mechanisms of plasma protein binding
drugs are reversibly attached to plasma proteins (eg. hydrophobic drugs: to enhance hydrophilicity)
Drug + protein and Drug-complex are in a equilibrium
Most important plasma proteins are albumins (rest: globulins)
Protein bound drugs cant leave the vasculat system and serve as a drug-depot
–> prolenged half-life, serves as mechanism for drug-drug interactions, medical conditions as hyperalbuminea (dyhydration or Vit A defiencency) and hypoalbuminea affect albumin levels and therefore affect free drug concentration
(so pharmacological drug effect may change despite unchanged drug dose)
Explain volume of distribution (Vd)
Vd= (total amount of drug in the body)/ (drug plasma concentration) in liters
Decribes distribution of drug between blood and tissues
Vd is a theoretical volume (as there are many different compartments) depending on hydro-/lipophilicity and plasma protein binding
It is useful for prediction of half life and dose adjustment for body weight (adipositas)
Explain therapeutic window/therapeutic index
The therapeutic window is the relation between the minimum toxic dose (MTD) and the minimum effect dose (MED) = so a dose that exhibits effect without being toxic
Can be shown in a grpah from lag-phase to rise/onset (where absorption>elimination) followed by peak effect and then elimination>absorption
Therapeutic index (TI)
Decribes the realtion between therapeutic and toxic effect
LD25/ED75 or LD5/ED95 (Letal and effective doses)
When TI is narrow, there is a higher risk of overdosing
Can be differentiated in narrow, medium and broad
Explain therapeutic drug monitoring (TDM)
Therapeutic drug management: indivudaize drug dose
in difficult to manage medications when you need optimal dosage regimen in special drugs
1) measurement of drig concentrations in various body fluids
2) interpreting concentrations
3) individual modification of dosage
–> reqiures multidisciplinary expertise!
Explain modified-release dosage
via different Controlled release systems to have zero order kinetics (opposite of immediate release)
–> drug delivery is delayed, prolonged/sustained and targeted
Used to achieve:
improved compliance (in l-thyroxine)
improved symptom control (eg opioids)
improved efficacy (eg colon-targeted mesalazine)
reduced toxicity (avoidance of toxic Cmax)
- ) Diffusion systems: reservoir (porous polymer coating: acrylates) or matrix devices (drug ins solved gelling agent)
- -> pH depended (PPI!) dose dumping with alcohol or high fat) - ) Dissolution systems: sustained release due to salts with reduces solubility or slowly dissoluing coatings
(e. g. insulin: normally a dime, but through adding zinc it forms slow soluble hexamers = depot)
3.) Osmotic release oral delivery systems (ORODS): semi permable outer membrane with laser holes (as weter flows into GI through osmosis drug is pushed out)
