pharmacokinetics Flashcards
—- action of the drug on the body
- physiological and biochemical effects of drugs
- interactions w macromolecular targets
- specific to drug or drug class
pharmacodynamics
—– effects of the body on drugs
- drug movement ( movement of drugs into , around , out of the body )
- change in concentration of drugs
- non-specific , general process
pharmacokinetics
the 4 process of pharmacokinetics include:
1. —– : the transfer of drugs from the site of administration to the general circulation ( bioavailability F )
2. —– : the transfer of drug from the general circulation into different organs of the body ( apparent volume of distribution Vd )
3. —— : refers to the removal of drugs from the body this involves ——
- clearance Cl
- plasma-half life ( t 1/2)
- absorption
- distribution
- elimination ( this needs metabolism or excretion )
—– movement from the site of administration into the body
——- moving between locations within the body
—— moving out of the body by both :
1. —- the conversion to another chemical entity / biotransformation
2. —– irreversible loss of unchanged drug
All of the process are defined relative to the site of — which is usually —-
- absorption
- distribution
- elimination
1. metabolism
2, excretion - measurement
- plasma
drug passage across membrane ( absorption process ) :
1- through pores or ion channels : By diffusing through aqueous pores formed by special proteins (‘aquaporins’) that traverse lipid.
Passive movement along conc gradient
Water soluble small molecules e.g. lithium
2. passive diffusion: diffuses directly through the lipid , passive movement along the concentration gradient and drug must be somewhat lipid soluble
3. carrier mediated process: either bt facilitated diffusion e.g. levodopa & blood-brain barrier or through active transport as: 5-fluorouracil
4. pinocytosis
- most drugs are —- acids and bases that are present in solution as both —- and —- forms
- ionised molecules are usually —- to penetrate the lipid cell membrane bc they are —- and — lipid soluble
- unionised are usually lipid —– and can diffuse across the cell membrane
- weak
- ionised
- unionised
- unable
- hydrophilic
- poorly
- soluble
drug absorption:
Routes of administration ( ROA) can be divided into :
1. —- local effect , substance is applied directly where its action is desired
2. —— where desired effect is systemic ( non local ) and substance is given via digestive tract
2. —— desired effect is systemic and substance is given by routes other than digestive tract
- tropical
- internal
- parenteral
( The U.S. Food & Drug Administration (FDA)
recognises >100 distinct routes of administration.)
- local effect
- substance is applied directly where its desired
- Application to epithelial surfaces (e.g. skin, cornea, vaginal, nasal mucosa)
this is — route
topical
- desired is non local
- through digestive tract
- Oral - (per os / PO), by mouth
- Sublingual - (SL) placed under the tongue
- Rectal - (per rectum), suppositories or enemas
enteral
- systemic and is given other than digestive tract
-* Inhalation - Injection:
Intravenous - most certain route
Subcutaneous
Intramuscular
Intrathecal - injection into subarachnoid space via a lumbar
puncture needle to access cerebrospinal fluid (CSF)
parenteral
—- injection gives in a large muscle mass ( delta or gluteals ) which is best for larger volumes and when fast absorption desired eg. antibiotics
—– directly into the vein
—– into the dermis and just below the epidermis , the longest absorption time of all the parasternal routes and used for allergy tests and local anaesthesia.
——- below the dermis and epidermis when a slower , more prolonged effect is desired as insulin , many immunisation m heparin
- IM
- IV
- intradermal
- subcutaneously ( SC/SQ)
The most common and convenient administration is —-
oral
factors affecting the drug absorption from the gut:
- Drug structure:
– Highly polar/ionized compounds poorly absorbed
– Weak acids and weak bases undergo pH partitioning/ion trapping
– Peptides broken down by digestive enzymes (e.g. insulin) - Formulation:
– Capsule/tablet must disintegrate
– Modified release formulations - Gastric emptying can effect rate but not quantity
– Food, generally slows absorption rate due to delayed gastric emptying
and stimulation of gastric acid secretion
– Fasting, malnutrition - First-pass metabolism
1.drug is absorbed from —- and passes via —- into the —- where some drugs are metabolised via enzymes ( CYP450)
2. results in only a — of the drug reaching the circulation
3. first pass metabolism can occur in:
4. Alternative ROAS to avoid first pass effect as:
- Gi tracts
- portal vein
- liver
- proportion
- Gut e.g. for benzylpenicillin and insulin
– Intestinal lumen (digestive enzymes, bacterial enzymes)
– Intestinal wall (MAO)
– Lung (MAO, peptidases) - alternatives: tv , intramuscular , sublingual )
( the first pass metabolism is aka presystsemic metabolism )
the route of administration is determined by :
1. —- charcatertsics of the drug
2. the — of the drug is absorbed and/or released
3. the need to bypass — metabolism and achieve high concentration at particular sites
-physical
- speed
- hepatic
