1.6 General principles of drug action Flashcards
a) routes of adminestration b) + and - c) bioavailability and distribution d) pKa and pH, movement e) distribution of drug f) volume of distribution
what are the common routes of administration?
oral route (swallow) IV cutaneous sublingual vaginal/anal
1) Why would you want to use the oral route?
2) Why would oral route not be used?
1) – safe
– convenient
– economical
2) – Irritant drugs cause sickness
– Not possible in vomiting patients
– Some drugs destroyed by gut acid/flora
– Intestinal absorption can be erratic
In oral route what types of drug are absorbed in the stomach?
2) in the intestine
1) acidic drugs absorbed here, mainly weak acids, small amounts of aspirin , NSAIDS, alcohol
2) • Site of absorption of most exogenous compounds taken orally, Preferentially weak bases (most drugs are)
What is the pH of of the duodenum and terminal ileum?
pH ranges from 6 (duodenum) to 7.4 (terminal ileum),
What affects the rate of absorption if the drug is to be absorbed in intestines?
1) rate of gastric emptying
2) number and type of transported in enterocytes of epithelium, if drug is hydropholic
3) gut motility
4) gut pH
5) physico-chemical interactions i.e. has it bound to substances in lumen of intestine e.g. tetracycline and Ca, bile-acid-binding resins and other drugs
6) particle size and formulation i.e. how its been prepared pharmaceutical e.g. fast or slow release particles, e,g. resistance coating
What is bioavailability (F)?
The fraction of the administered dose which enters the systemic circulation.
What is first-pass metabolism?
Occurs in both intestine and liver before drug reaches systemic circulation.
How do you calculate F (fraction of drug absorbed)?
2) What is AUC?
3) What does F represent?
AUC (oral) / AUC (IV)
2) the area under the curve where x is time and y concentration in plasma.
3) bioavailability
What are the limitations of calculating bio availability
• Does not consider inter and intra individual variations in; – enzyme activity – Gastric pH – Intestinal motility • Does not consider rate of absorption
How do you find
a) Cmax
b) Tmax
read a graph x=time and y=Cp
a) Maximum concentration of compound after administration
– Concentration units (i.e. mg/mL, ng/mL, etc.)
b) Time at which Cmax is reached
– Time units (usually hours)
What are the advantages of rectal/vaginal route of aministration?
b) what do blood vessels drain into?
1) • Absorption may be rapid and extensive, but depends on drug and formulation
– pH 7-8
2) bu passes GI/hepatic first pass effects
3) rich blood supply
b) middle and inferior rectal veins, • Superior rectal vein
• Portal (to liver)
What are the advantages of sublingual administration?
b) describe drainage
1) Required for fast/rapid response
2) avoids first pass metabolism as …
b) Utilises venous drainage from the mouth to the superior vena cava. going almost directly to the heart through the superior vena cava.
When is vaginal/rectal administration useful>
Useful when drug causes nausea and vomiting, or if the patient is already vomiting
e. g. HIV patients , some antiviral drug causes necrosis of tissues so can’t be given IV
b) also avoids 2/3 of first pass metabolism
What are the advantages of IV injection?
• predictable, very rapid action,
• alternative route for drugs which are
irritant by (im)
• iv infusion for ill, hospitalised patients
What are the disadvantages of IV?
- difficult /painful,
- risk of infection,
- cost and safety,
- immediate adverse effects
compare subcantaneous injection with intramuscular:
2) Do subcutaneous injections have systemic or local affect?
1) intramuscular has faster absorbtion (unless deep) than subcutanous due to better blood supply
2) either, subcutanous injection usually systemic, except in dentistry where its a local anaesthetic
How can absorbtion of a subcutanous injeciton be increased?
2) how can it be reduced?
1) enzyme hyaluronidase
2) co-injection with vasoconstritor e.g. epinephrine (adrenaline), this is done in dentistry
enteral vs parenteral
enteral uses GI tract, parenteral doesn’t
Give 4 enteral routes of administration:
oral, sublingual, rectal, vaginal
Give 5 parenteral routes of administration:
- Intravenous
- Intramuscular
- Subcutaneous
- Transdermal
- Inhaled
Which administration method is absorbtion not releavant to ?
IV injection
What are the ways can drugs cross a cell membrane?
- passive diffusion through lipid
- diffusion through aqueous channel
- carrier mediated transport
- Membrane engulfment
- Pinocytosis: rare form of absorption however.
What factor about the drug determines rate of absorbtion if drug diffueses through lipid?
lipid solubility, effected by pKa of drug, so if the drug is ionised (due to being an acid in alkali or vice verse) not absorbed as well
How do you find percentage ionisation/ un-ionised?
pH-pKA
eg. Warfarin= pKa=5
pH is 5
5-5=0
Therefore, using table it shows ionisation is 50%. You must use table to find it.
Remember to match up heading and units of the table with blank space
e.g. if pH is 3, then it will be 1% ionised and 99% un-ionised.
What is the term guven to when acids accumulate in basic fluid compartment and vise versa
pH partitioning
What affects how much a drug is distributed to other tissues?
– Its ability to cross cell membranes (based on physiochemical properties)
– Blood flow to individual tissues
– Extent of its plasma protein binding
What is drug distribution?
reversible transfer of drug from one location to another within the body either blood plasma, intersticial fluid or intracellular
What are the 2 things drugs bind to plasma?
- albumin
2. – Alpha 1 acid glycoprotein (AAG)
Where is Alpha 1 acid glycoprotein (AAG) synthesised?
2) What does it bind to?
3) What effects it conc. in blood?
4) what is the normal range?
liver
• Binds mostly basic and some neutral drugs
• Acute phase protein, elevated in some diseases (cancer), inflammation
• Normal range: 0.4 - 1.1 mg/mL
Where is albumin synthesised?
2) what does it bind to?
3) What causes its conc to be reduced?
4) What is the normal range?
1) liver
2) Binds mostly acidic and some neutral drugs
3) Decreased in malnutrition and cirrhosis
4) Normal range: 3.5 – 5 g/dL
What form of drug is not active or absorbed in blood?
2) Which form is?
1) plasma protein bound
2) free drug
How do you calculate volume of distribution?
2) describe the units
total amount of drug in body/ drug blood plasma
2) units of volume (usually L or mL), sometimes per unit of weight (i.e. L/kg)
will Vd value be big or small if..
1) drug is confined to plasma compartment
2) accumulate outside plasma
1) small
2) big
Another calculation of Vd is…. (involves a plus sign)
Vp+ Vt(fu/fUt) Vp= plasma volume of drug Vt=tissue volume of drug fu= fraction unbound in plasma fut= fraction unbound in tissue
Give volume in :
a) total body water
b) intracellular
c) extracellular volume
- d)intersitial volume
- e) plasma volume
a) 42 litres
b) 28 litres
c) 14 litres
- d) 10 litres
- e) 4 litres
What sort of drug is distributed throughout body water?
lipid soluble drugs
What sort of drug is distributed throughout extracellular compartment?
low lipid solibility so cannot easily enter cells
What sort of drugs accumulate in plasma compartment?
are too large to cross capillary wall easily or bound to plasma proteins
