pharmacology Flashcards
what is a drug
this is a chemical that is used to prevent , diagnose, treat or cure pathological issues.
drug action
drug binding onto a molecule.
drug affinity
ability of a drug to bind onto a receptor and elicit a response
efficacy
ability of a drug to cause a response after binding onto a receptor.
factors that pharmacological effect depend on
affinity
efficacy
residence time
what is meant by residence time
total time spent by the drug on the receptor
factors that can influence receptor response
1.polymorphic variation - different people have different genes that code for the receptor proteins .
2.age -older people less receptors that are expressed.
3.disease
4.drug treatment for example clonidine is a drug for hypertension and addition of this molecule is seen as not balancing in homeostasis.
agonist receptors
they bind to the receptor and they cause a response
antagonists ligand
bind to the receptor and causes no activation
competitive ligand
competes with the other ligands for site for binding while the non - competitive changes the shape of the binding site.
pharmacodynamics
effects of the drug on a specific site
what is meant by pharmacokinetics
what the body does to the drug that is ADME
Biophase
the effect site of the drug (the physical region in which the
drug target is located)
bioavailability
this is the extent and rate at which the drug reaches its site of action
how is bioavailability measured
measured by injecting the drug in the systemic circulation through IV administration.
best routes of administration
IV
SC/IM
PR/PO
what is meant by half life of a drug
that is the time it takes to reach half it concentration in the blood.
methods of drug lost
through barriers that is why IV route is usually the best option .
bioavailability and the mode of administration
IV has the highest bioavailability because there is no loss of the drug
what is the benefit of a half life
adjustment of a dose
concentration max interpretation
too low means there is no therapeutic effect while too high means toxicity.
what is meant by therapeutic index
this is the ratio of the the dose that causes therapeutic effect to the dose that causes toxicity
narrow therapeutic index
prescription with care
very large therapeutic effect
not so many problems
movement of the drug from the plasma
-plasma to interstitial fluid
then to intracellular fluid which has to cross the cell membrane .
-sometimes has to cross other fluids such as CSF, peritoneal , humours etc.
movement of plasma to interstitial fluid
filtration
paracellular movement
filtration
transcellular movement
from the interstitial fluid to the intracellular
types of barriers to be crossed during drug penetration
passage through the basement membrane to the epithelial cell
types of movement that occur
movement by diffusion
facilitated diffusion
active transport
factors that affect movement of drugs into the cell
1.lipophilicity
2.ionisation
3.blood supply and perfusion.
4.size of a drug
5.existence of some transport mechanism.
6.
elimination of a drug
this refers to metabolism and excretion
body`s mechanism of preventing the exposure to alien molecules.
1.blood brain barrier
2.physical removal of a drug through urine, blood , sweat and breath.
3.characteristics that promote entry limit exit such as size , lipophilic or not etc.
metabolism are easily excreted than parent
metabolites render the drug more polar
phases of metabolism of drug
Phase I (functionalisation); Phase II (synthetic)
organ for drug metabolism
liver
what is metabolism of a drug
breaking the drug to a form that can easily be eliminated by the body .
examples for enzymes that are used to metabolise the drugs
cytochrome 450
what are the main routes of administration of a drug
Intravenous: not absorbed
* Oral (most common)
* Subcutaneous
* Intramuscular
* Other GI (rectal, sublingual)
* Nasal
* Inhalation
* Transdermal
what is absorption of a drug
this is the process of mass transfer from site of administration to bloodstream
factors that affect the process of absorption of a drug
1.physio-chemical properties ( eg polarity , size, charge etc)
2.bioavailability
3.physiological factors.
4.anatomical factors.
topical administration of a drug
-Topical “of a place”
-Skin, mucous membranes, ears, eyes.
reason for topical administration of a drug
1.Adverse events: Excess effect at site of action… but can be “off-target”
2. Aim: to reduce exposure beyond site of action
rationale of local anaesthetics
they cause the blockage of potassium ion channels.
factors to consider before administering local anaesthetics
1.dosing which depends on :
patient factors eg children , elderly and pregnant women.
2.inject only in superficial not deep.
3.co administer with adrenaline
4.avoid highly vascularised tissue
routes for absorption
1.Enteral (oral; sublingual; rectal).
2. Parenteral (SC; IM; pulmonary? Nasal?)… IV.
3. Oral: Most common, most desirable.
why oral administration
1.cheapest
2.easiest and doesn`t require equipment.
3.higher compliance that is it is non invasive.
factors affecting oral absorption
1.solubilty ; some drugs are affected by gut contents( tetracycline)
2.gastric emptying time this will affect the time required for the drug to reach the SI for metabolism.
3.pH change in the gut leading to ionisation and less ability to move into the cell.
4.gut flora
5.lung phase 1 and liver phase 2
illness
which drugs can be affected by gut contents
tetracyclines
crossing barriers for for drugs
paracellular
transcellular
fick`s first law application
1.Diffusion coefficient
2* (Size etc)
3* Partition coefficient
4* Thickness of membrane
5* Total membrane area
6* Driving force is the drug
concentration
7* ‘Sink’ condition
first order kinetics
-for diffusion of drugs into the cell membrane.
the rate of absorption is directly proportional to the rate of concentration of the drug.
door theory
facilitated diffusion for bigger sized molecules
molecules used for facilitated transport
-Channel proteins: molecules of
appropriate size and charge.
-Carrier proteins.
curve for the facilitated diffusion
there is saturation whereby even the increase in the concentration will not lead to an increase in the rate of absorption.
tissues where there are barriers for distribution
brain
testes
ovary
placenta
how are the drugs distributed in the body
1.they bind onto the plasma protein and are transported through that .
2.they also bind on lipoproteins .
3.also bind on glycoproteins.
what is the volume of distribution
this is a proportionality constant between a total amount of drug in the body and the amount in the plasma at any one time.
importance of volume of distribution
1.drugs with a low volume of distribution remain in the plasma
drugs
2. high volume of distribution tend to leave plasma ie there is more distribution.
how does volume of distribution influence plasma
1.the drug is cleared form the plasma and redistributed from other tissues.
2.because of this the plasma volume declines slowly .
drugs with high volume of distribution have a longer elimination half life.
what is a steady state of a drug
the rate of drug administration is equal to the rate of drug elimination.
what happens if a half life is long
there is a maintenance dose that is added.
factors affecting the choice administration
- Oral route – much is about cost, convenience, acceptability etc
- Drawbacks: first pass metabolism; factors that affect absorption
- IV – speed; criticality of Cp
- Drawbacks: 100% bioavailability means rapidly perfused
compartments get rapid exposure; needs to be aqueous solution;
acceptability - IM – usually safer than IV; rapid absorption of aqueous drugs
- Drawbacks: Painful; clots, abscesses etc; dependence on blood flow
- SC – Similar to IM, but less painful etc
- Drawbacks: Irritation; impact on local tissue
inhaled medications
metabolism or absorption in the lung
oral bioavailability
manipulation of the dosage form
LADME ; liberation and absorption
reason why there is no absorption of drugs in the oral cavity
because there is limited contact in the mouth so although the mouth is highly vascularised there is less absorption.
absorption of drugs
absorption of drugs mainly takes place in the small intestines.
how does gastric emptying affect the absorption of a drug
time taken for the drug to reach the main absorption site that is the small intestine.
factors that affect the rate of gastric emptying
food for example fatty food slows down gastric emptying.
how does food affect the extent of absorption
Food may enhance the extent of absorption for poorly soluble drugs (eg, griseofulvin), reduce it for drugs degraded in the stomach (eg, penicillin G), or have little or no effect.
reason why most absorption is in the small intestine
In the GI tract, the small intestine has the largest surface area for drug absorption, and its membranes are more permeable than those in the stomach
pH affects absorption
Certain pH promote ionisation of drug and this leads to changes in the solubility of the drug.
blood flow and absorption
Decreased blood flow (eg, in shock) may lower the concentration gradient across the intestinal mucosa and reduce absorption by passive diffusion.
Gut bacteria and absorption of drugs
GI microflora may reduce absorption.
absorption of drugs that have been administered through the lymphatic system
If protein drugs with a molecular mass > 20,000 g/mol are injected IM or sc, movement across capillary membranes is so slow that most absorption occurs via the lymphatic system. In such cases, drug delivery to systemic circulation is slow and often incomplete because of first-pass metabolism (metabolism of a drug before it reaches systemic circulation) by proteolytic enzymes in the lymphatics.
a drug that is bound to a protein is inactivee
yes
a drug with a high volume of distribution
there is a high concentration of drugs that is in circulation and that means there is less drug concentration in the plasma .
half life for volume of distribution
- Half-life = 0.693 x (Vd
/Clearance)
what is the significance of volume of distribution
dosing that is to understand how fast or slow a drug is retained in the blood system.
what is meant by loading dose
this is the dose that is initially put into the system .
calculation of loading dose
volume of distribution by concentration of the drug in the plasma
when is steady state achieved
after approximately 4 half lives
what is drug metabolism
process of converting medication into a less or more active form
reason for metabolism
create metabolites that can be excreted.
