Drug Handling Of The Body Flashcards
What are the advantages of oral administration?
Convenient for patient
Absorption from small intestine- large surface area
What are the disadvantages of oral administration?
Not appropriate for all patients Absorption can be variable Absorption can depend of stomach contents Rate of gastric emptying Degradation in the stomach First pass metabolism
What does degradation in the stomach mean?
Parenteral cells secrets HCL
Chief cells secrete digestive enzymes this means the drug could have low bioavailability
What does bioavailability mean?
The amount of drug that reaches the circulation as intact drug
Want does first pass metabolism mean?
Drug gets lost in the liver due to hepatic first pass effect, low bioavailability
What are the advantages of topical administration?
Convenient
Poorly absorption means minimum risks of overdosing
What are the disadvantages of topical administration?
Negative effect on the skin- thinning of the skin
What are the advantages of transdermal administration?
Long acting
Useful for when you want low blood levels for a long period of time
Suitable for a wide range of patient groups
What are the disadvantages of transdermal administration?
Skin effects Variable absorption Lipid solubility Potent Expensive
What are the advantages of rectal administration?
Local effect
Useful for patient who cannot swallow
What are the disadvantages of rectal administration?
Need to be trained
Example of rectal drugs
Analgesics
Diazepam
Prednisolone
Antifungals
What are the advantages of inhalation?
Rapid changes in the plasma concentration of drug because of the high surface area of the lungs and good blood flow to area
Local or systemic effect
What are the disadvantages of inhalation?
Difficulties in ensuring the drug reaches the site of action
Example of inhalation drugs
Halothane
Salabutomol
Nitric oxide
GTN
What are Parenteral routes?
IV- thiopental, heparin
IM-pre-Meds
Intradermal- dentistry, local anaesthesia, allergy screening
SC- insulin
INTRATHECAL- antiviral agents, chemo drugs
Epidural- nerve blockers used during labour
What are the advantages of parenteral administration?
Rapid action
By pass stomach and liver
Lower doses is required
Patent controlled for analgesia- syringe drivers
What are the disadvantages of Parenteral administration?
Trained person needed
Extreme care required
Accidental overdose?
IM- painful
Explain the different types of formation of drugs
Tablets, gels, locations, aresols, suspensions. Powders. Granules. Capsules, lotions, patches, Inhalations, pastes, sprays, syrup, creams, gases
Can impact upon the bioavailability and sustained release
Explain the oral drug absorption
From tablet to granules to fine particles to solutions, then absorbed through stomach and small intestine
How does the drug cross the cell membrane?
If they are lipid soluble- can cross through the epithelial cell in the small intestine to get to the blood stream through diffusion
If water soluble cannot cross through
How is the drug absorbed whole it moves across membranes?
1 passage through water channels
2 endocytosis
3 passive diffusion
4 facilitated of active transport
What is facilities transport?
Drug moves down concentrated gradient
Proteins provide channels
No energy required
Staturable, selective, competitive inhibition by other substances
What is active transport?
Drug moves against the concentration gradient
Energy is required
Saturable, selective, competition inhibition
Example:lithium, levodapa, methyldopa
What happens when the drug has been absorbed?
Distributed via blood stream
Transferred into and out of various tissues in the body
Want affects extent of distribution?
Lipid solubility of drugs
Blood flow to organ/tissue
Binging of drugs to proteins
Explain the blood flow in these organs/tissues: liver, kidney, CNS, myocardium, fat, other I.e. Muscles
Liver: 680ml/min/kg
Kidney: 3,333 ml/min/kg: received the most blood flow
CNS: 615ml/min/kg
Myocardium: 833ml/min/kg
Fat and other: 25ml/min/kg each: here drugs are not distributed
Where does protein binding occurs?
Free drugs can bind to proteins in the plasma I.e. Albumin
Only free drugs can diffuse across membranes and have an effect
How is drug removed from the body?
Through metabolism and excretion
Most drugs are lipophilic and so will recirculate around the body
We excited water soluble drugs
Define drug metabolism
It is the enzyme-mediated conversion of a lipid soluble compound into a more water soluble one, ready for excretion
Where does metabolism take place?
Mainly in the liver : smooth endoplasmic reticulum Kidneys Lung GI tract Brain Plasma
What are the phases of metabolism?
There are two phases. Usually occur in a sequence, phase 1 then phase 11, however phase 11 can precede phase 1
What happens in phase 1?
Modify the chemical structure of drug
Makes drugs slightly more water soluble
Prepare for phase 11
Products can be more chemically reactive than the parent drug
What are pro-drugs?
Some drugs when metabolised can even more active than the original drug
Example: prednisone becomes prednisolone
Codeine become morphine
GTN becomes nitric oxide
What happens on phase 11 of metabolism?
Conjugate drug into large molecules- amino acid, sulphate groups
Product become water soluble and easily excreted
Increased molecular weight
Inactive , decrease receptor affinity and enhance excretion
Explain a how drugs interact.
Drugs metabolising enzymes can be a) induced I.e alcohol and carbamazepine induce liver enzymes and b) inhibited such as fluoxetine and grape juice
This will result in decrease of the duration of drug action
Explain the role of excretion
Removal of drugs: drug metabolic and water soluble drugs
Urine, bile, faeces, lungs, skin
To increase drug exception, increase blood flow to the kidneys, decrease plasma protein binding
Explain the dosage regimens
The therapeutic response of most drugs is related to the level of the drug in the plasma
We need to know the half life of a drug, this is the time it takes for the amount of drug to decrease to one half of the peak level
The rate at which drugs are eliminated from the body
How much drug remains if the half life is 2hours for 20mg drug?
After 2 hours: 10mg drug will remain 4hrs: 5mg 6hrs: 2.5mg 8hrs: 1.25mg 10hrs: 0.625mg After 10 hrs sufficient to say all the drug has gone
How much of the drug is eliminated in 5 half lives?
97%
Why do we care about half lives?
To avoid drug interactions
Estimating how long it will take for toxic concentration to be eliminated from body
What is drug disposition?
What the body does to the drug compared to what the drug does to the body
Intake–>absoprtion–>distribution–>drug-cell interaction–>metabolism –> excretion
Explain the therapeutic window
A range of doses that produces therapeutic response without causing any significant adverse effect in patients.
Generally therapeutic window is a ratio between minimum effective concentrations (MEC) to the minimum toxic concentration (MTC).
I.e. Warfarin and phenytoin have narrow therapeutic window and so need close monitoring
What happens if a patient has renal or hepatic disease?
The plasma half life increase and drug concentrations may reach a toxic level
