Lecture 22 - Oral versus parenteral management of CVD / Enzymology Flashcards
What are the advantages of parenteral drug administration?
- Drug not broken down in GI tract
- 100% bioavailability
- Localised effect – eg injections into joint, ocular, intradermal
- Systemic effect – IV injection drug delivered directly into circulation
- Rapid onset of effect (iv injection)
- Drug administered in unconscious patient
- Delayed onset of effect of effect/ few dosing (IM injection once a month)
What are the disadvantages of parenteral drug administration?
-Use of needle (needle phobia, needlestick injury)
- Painful
- Preparation needs to meet stringent specifications (expensive)
- Limited self-administration
What is an intravenous injection?
Administration into easily accessible vein
What is the volume of an IV injection?
1ml
What is the volume of IV infusion?
Several litres
What is thrombophlebitis?
Damage to vein
How is thrombophlebitis minimized?
With the use of a central line
What causes damage to veins?
- Drugs with high/ low pH
- Hypertonic solutions
How is thrombophelitis minimised?
With the use of a central line
Can suspensions be administered via central line?
No - particles block capillaries
What is required for central dosing?
Emulsion
How are most paranteral drugs administered?
IV
What is intracardiac administertration?
Drug administration directly into the heart
When is intracardiac administration used?
Only for life threatening emergancy
What is the injection volume for intradermal administartion?
0.2ml
What is intradermal administration typically used for?
Vaccination
What angle is intradermal administered at?
10 to 15 degreeds
What angle is subcutaneous administered at?
45 degrees
What angle is intramuscular administered at?
90 degrees
What layer is intradermal administered into?
Dermis
What layer is subcutaneous administered into?
Subcutaneous tissue
What layer is instramuscular administered into?
Muscle
What is subcutanous also known as?
Hypodermic
Where are subcutanous injections administed into?
Subcutaneous fat
What is the injection volume for subcutaneous administration?
1ml
What are the advantages for subcutanous administration?
- Quite fast administration
- Predictable eg insulin
What formulation are subcutaneous injections?
- Aqueous solutions
- Suspensions
Where are intramuscular injections administered?
- Buttock
- Thigh
- Shoulder muscle
What is the volume of intramuscular injections?
Up to 4ml
Is intramuscular administration faster or slower than subcutaneous administration
Slower
What is the injection volume of intrathecal injections?
Up to 10ml
What formulation are intrathecal injections?
Aqueous solutions
Where are intrathecal drugs administered?
Into cerebrospinal fluid
What are the two intermost protective membranes of spinal chord?
- Arachnoid mater
- Pia mater
Where is the cerebrospinal fluid?
In the subarachnoid space between arachnoid mater and pia mater
What are intrathecal drugs used for?
To introduce drugs that cannot cross the blood brain barrier eg antibiotics to treat menengitis or anticancer agents
Where are epidural injectios administered?
Into epidural space eg spinal anaesthesia
Where are intra articular injections delivered?
Into synovial fluid of jount cavities
What drugs are usually given via intra-articular injections?
Anti-inflammatory drugs to treat arthritic conditions
Where are opthalmic injections administered?
Around on into the eye
What is the volume of ophthalmic injections?
1ml
Where are intracameral injections administered?
Into anterior chamber of the eye - infront of lens
What is the maximal volume of ophthlamic injections?
0.1ml
What happens if ophthalmic injections exceed the maximum volume?
Rise in intra ocular pressure
What are the pharmacopoeial requirements for injections?
- Sterility
- Excipients
- Containers - transparent to permit inspection of contents
- Free from endotoxin and pyrogens
- Free of particles
- For emulsions for IV injection droplet less than 3nm to prevent oil embolism
What can injections be?
- Solutions
- Emulsions
- Suspensions
What injections are used for local action?
- Intra articular
- Intra ocular
What injections need to be absorbed for systemic effect?
- Intramuscular
- Subcutaneous
How long do IM and SC injections of solutions usually take to absorb?
Within 30 mins
How long do IM injections of suspensions take to act?
1 - 7 days
How long do IM oily injections take to act?
Up to 4 weeks
How long do intra-articular injections of suspensions take to act?
Act over many weeks
What are three vehicles for injections?
- Water for injections (highly purified water)
- Solubelising agents (eg cyclodextrins)
- Oils
Give examples of oils used for injections
- Lecithin
- Sorbitan fatty acids
- Arachis oil
- Sesame oil
What is the pH of plasma?
7.4
What pH can injections be?
Between 3 and 9
What is used to adjust the tonicity of injections?
- Dextrose
- Mannitol
What is the purpose of enzymes?
- Powerful catalysts
What do catalysts do?
Increase the rate of a reaction by up to 1 million fold but don’t change the equillibrium of the reaction
How do catalysts accelerate reactions?
By stabilising the transition state
Describe the transition state?
- Highly unstable
- Energetically unfavourable
- Reaction intermediate
How do enzymes affect the activation energy?
Lower the activation energy of a reaction but G stats the same
What is the reaction surface for enzyme catalysis?
The active site
What is a suitable environment for enzyme catalysis?
Hydrophobic
What is the active site?
Small hyrdrophobic hollow or cleft on the enzyme surface
What does the active site contain?
Amino acids
What do amino acids in the active site do?
- Bind reactants (substrates and cofactors)
- Catalyse the reaction
What are the models of active site binding?
- Lock and key
- Induced fit
What is induced fit?
- The active site is nearly the correct shape for substrate.
- Binding alters the shape of the enzyme
- Strains bonds in substrate: involves intramolecular bonds between function groups in substrate and active site
What are the strongest bonding forces?
Ionic
What are the weakest bonding forces?
Van der waals
