week 10 CTL Flashcards
Describe the main routes of drug administration and their
advantages and disadvantages
Oral : +) Quick easy safe to administer -) depends on a range of chemical (formulation of the drug, solubility and ionisation) and physiological factors (first pass metabolism, GI contents, GI motility, splanchnic blood flow, metabolism of the drug by GI enzymes)
Intravenous +) allows for immediate effect of drug +) allows large amounts of drug to be administered over time +) can be used for drugs that cannot be administered orally due to first pass metabolism -) difficult to administer and has potential risk of overdose, thrombosis and infection e.g antibiotic IV or thiopenton (anaesthetic)
Intramuscular/ subcutaneous +) allows for gradual slow absorption and therefore longer duration of drug action -) intramuscular can be painful e.g. insulin
Intrathecal (epidural) +) administered directly into the subarachnoid space to provide localised pain relief e.g bupivacaine in labour
Inhalation: only used in inhalation anaesthetics or when the site of action of the drug is the lungs e.g. bronchodilators
Epithelial: skin, cornea, nasal mucosae. Used usually when a local effect is desired e.g. oestrogen stick on patches
Sublingual: +) Rapidly absorbed directly into the systemic circulation without passage through the liver e.g. glycerol trinitrate (angina)
Rectal: +) used usually when GI tract is the site of action of the drug or when oral/ IV admin is not possible e.g anti-inflammatory drugs for inflammatory bowel disease
Explain the main factors that affect drug absorption including effects of pH on ionisation
- Main factors that affect absorption are lipid solubility and ionisation
- As pH drops for weak bases less of the drug will be unionised therefore less permeable
- As pH drops for weak acid more of the drug will be unionised therefore more permeable
Remember:
- ACIDIC drugs will be ionised when the PH is more basic (less permeable)
- BASIC drugs will be ionised when the PH is more acidic (less permeable)
Define volume distribution and explain how it is used
This is the amount of fluid in which the amount of the drug would need to be uniformly distributed in order to produce the observed concentration in blood.
It is used to determine the accumulation of the drug in tissue compartments
It is a major determinant of the half life of a drug
It is also used to calculate loading
- The Volume distribution is determined by the relative stregnth of binding of the drug to tissue compartments (tightly bound to plasma proteins means it stays largely in circulation so volume is close to blood volume) wheras tightly bound to tissue means less of the drug in circulation and larger volume
What is the role of phase 1 and phase 2 metabolism
Phase 1 metabolism: Reactions reactions that add functional groups to drugs. Oxidation, reduction, hydrolysis. Catalysed by a group of hepatic microsomal enzymes known as CYP450 - cytochrome P450-mono oxygenase system. Generally, results in loss of pharmacological activity. This is important for pro-drugs.
Phase 2 metabolism: Reactions where a covalent bond is made between functional groups on a drug or phase 1 metabolite. ROLE IS TO conjugate a functional group. Makes a highly polar chemical that is rapidly cleared.
Describe the factors that affect drug metabolism and the impact of these on plasma drug concentrations
Age - decreases liver and renal function therefore increases plasma drug concentrations as metabolism is prolonged.
Drug induced alterations in liver enzymes: drugs or toxins can inhibit the production of microsomal enzymes like CYP450 this can seriously alter the effect of other drug metabolism therefore decrease alter drug concentrations.
Disease status e.g liver or kidney disease would increase the plasma drug concentration less metabolism of drug.
Nutritional status
Hormonal status/gender
Define drug clearance
The ability of an individual organ or the body to eliminate a drug
Volume of blood cleared of drug per unit of time is either in L/h or Ml/Min
Total body clearance is the sum of all the different clearance processes for a given drug
CL(total body) = CL(hepatice) + CL(renal) + CL(other)
It is constant for a particular drug and a specific rate varies with plasma concentration
CL (L/Hour) = Elimination rate (mg/hour) / plasma drug concentration C
Define drug bioavailability
This is the amount of drug that reaches the systemic circulation following oral administration.
How is bioavailability measured
Systemic circulating drug - how much escapes the first-pass metabolism and how much is absorbed into GIT
Name the major routes of excretion
Urine
Bile
Expired in air
Faeces
Excretion is the irreversible loss of chemically unchanged drug via these routes.
Define half-life and its relation to drug clearance and distribution
Half-life is the amount of time taken for the amount of drug in the body to fall by half.
HALF LIFE = 0.693 x Vd/ CL
- The half life increases if the volume distribution of the drug is higher
- A decrease in drug clearance also increases half life
What is first pass metabolism?
When drugs administered orally are INACTIVATED by liver or intestines before it enters the systemic circulation.
