4- Pharmacology 1 Flashcards
What is the Medicines Act 1998
It regulate the use of medicines in the UK
Before any medicine can be supplied it is required to have marketing authorisation
This is granted by the Medicines and Healthcare Products Regulatory
What are the three categories for medications as shown in the SmPC?
Prescription only (POM)
Pharmacy medicine (P)
General sales list (GSL)
What is a POM
Prescription only medicine
Can only be obtained with a prescription
What is a P medicine
Pharmacy medicine
Can only be purchased under the supervision of a pharmacist in registered premises
What is a GSL medicine
General sales list
Can be sold in general shops with no supervision
What is an OTC medicine
It has no legal meaning
What are the recommendations from the Crown Reviews (1998/99) regarding medication without a prescription?
Recommendations about the use of medication without a prescription under Medicines Act exemptions.
Support for non-medical (independent) prescribing.
What is the legal authority granted to new professional groups under amended legislation?
Authority to prescribe or authorise NHS expenditure for medicines in specific therapeutic areas related to their competence and expertise.
Includes prescription-only medicines (POMs) within those areas.
Name some healthcare professionals who can supply or administer POMs under exemptions.
POPM
Paramedics
Orthoptists
Podiatrists
Midwives
Define pharmacokinetics.
The movement of drugs into, around, and out of the body. “What the body does to the drug.”
Define pharmacodynamics.
How drugs work when they reach their site of action. “What the drug does to the body.”
What is the difference between local and systemic drug action?
Local action: Effects confined to a specific area (e.g., topical application).
Systemic action: Drug enters the blood supply for delivery to body tissues.
Can eye preparations act locally or systemically?
Eye preparations often act both locally and systemically.
What is bioavailability?
The fraction of the administered dose that reaches the systemic circulation.
Dosage of drugs with short half life
Given more frequently
E.g. paracetamol t 1/2= 2-4 hours
Dose- 1g every 4 to 6 hours
Dosage of drugs with long half life
Given less frequently
E.g. Warfarin t 1/2 = 24 hours
Dose- Once daily
What is a drugs half life?
Half life is the time required to reduce the plasma concentration to half of its original value
Also time taken for drugs concentration in the blood to fall by half
Routes of drug absorption
S, B, R, R
Sublingual- under tongue
Buccal- oral mucosa
Rectal- Lower GIT
Respiratory tract- Nasal passages or lungs
Advantages of oral drug administration
Convenient
Self administration
Simple
Economical
Liquids often available
“first pass metabolism
Disadvantages of oral drug administration
Not all drugs active orally e.g. insulin
Unpredictable absoprtion
Delayed onset of action
Gastrointestinal side effects
“first pass metabolism”
Advantages of intravenous drug adminstration
Immediate
Predictable effect
Large volumes
Infusion allows maintenance of effect
Avoids ‘1st pass’ metabolism
Disadvantages of intravenous drug administration
Risky
Infection
Phlebitis
Preparation time
Anaphylaxis
Infusion calculations
Expensive
Staff involvement
Incompatibilities
What are the topical drug therapies that can be applied to the affected area
Creams
Ointments
Nasal sprays
Eye drops / ointment
Ear drops
Inhalers
Transdermal Patches (Buprenorphine, fentanyl, hyoscine, HRT)
What are the advantages of topical drug therapies
4
↓ systemic side effects
Useful if swallowing difficulties
Onset of action may be quicker
Compliance and comfort
Disadvantages of topical drug therapy
Compliance?
Physical difficulties?
Reactions at site
Staining of clothing
Delayed onset of action
Misconception that topical = safe
What is half life also referred to as
t ½
What are the variabilities of half life (t 1/2)
Can be categorized into physiological, pathological, genetic, and drug-related factors:
1. Physiological Variabilities
Age:
Neonates- longer half-life.
Elderly- shorter half life
Sex:
Body Composition: some drugs have longer half-life in obese individuals due to fat storage.
Metabolic Rate:
Higher metabolism shorter half-life
2. Pathological Variabilities
Liver Disease, Kidney Disease, Heart Failure longer half-life.
3. Genetic Variabilities
Pharmacogenetics:
4. Drug-Related Variabilities
Route of Administration:
IV administration avoids first-pass metabolism, leading to faster peak concentration but may not alter half-life.
What is half life used for
Used to calculate dosage frequency / time to ‘steady state’
Bioavailabilty changes between IV and Oral administration-
2 drug examples P, F
Propanolol
100% IV and 30-40% Oral
Fluconazole
100%IV and >90% Oral
What must oral medicines pass through before reaching systemic circulation (bloodstream)?
Medicines must pass through the semi-permeable (lipid) membrane of the gut before reaching systemic circulation (bloodstream).
What factors affect drug absorption?
Route of administration
Lipid solubility (absorption of non-ionised molecules is favoured due to higher lipid solubility)
Food/drink interactions
Formulation of the medicine
Blood flow at the absorption site
Presence or absence of specific receptors needed for absorption
Gastric emptying time
GI motility
Drug inactivation in the gut or liver
Pre-existing medical conditions
Drug interactions
What is unique about intravenous injection in terms of absorption?
It bypasses absorption barriers and directly enters the bloodstream, resulting in rapid distribution to tissues.
List barriers to absorption.
Concordance (patient adherence to medication)
Food/drink interactions
Formulation of the drug
Blood flow at the site of absorption
Route of administration
Absence of specific receptors
Gastric emptying rate
GI motility
Inactivation in the gut or liver
Pre-existing medical conditions
Drug interactions
What is distribution in pharmacokinetics?
The process by which a **drug moves from its site of absorption to other tissues **in the body to achieve systemic action
What determines how a drug is distributed in the body?
(3)
LRP
The drug’s lipid solubility (some go into fat, others stay in extracellular fluid).
Regional blood flow.
Plasma protein binding (free drug is active; bound drug is inactive).
What is the role of plasma protein binding in drug distribution?
bound v free drug- which one is active and which one is inactive
-Drugs bind to plasma proteins in the blood
-Bound drug: Inactive
-Free drug: Active
Why is lipid solubility important for distribution?
Increased lipid solubility improves penetration of drugs, especially through barriers like the blood-brain barrier.
What are the major barriers to drug distribution?
CCB
Cell membranes
Capillaries
Blood-brain barrier
What conditions affect drug distribution?
LRR
**Liver disease: **Can cause low plasma protein levels, reducing drug binding.
**Renal disease: **High blood urea levels may affect distribution.
Reduced regional blood flow: Common in conditions like diabetes.
What is ADME
This is the internal processes that describe how a drug moves throughout and is processed by the body.
Absorption
Distribution
Metabolism
Excretion
More routes of drug absorption
IISEII
Intravenous- directly into venous blood
Intramuscular- muscles
Subcutaneous- into blood from skin layers
Epidural- epidural space
Intrathecal- directly into cerbro-spinal fluid
Intravitrial- into vitreous space near retina
What is the primary site of drug metabolism?
The liver is the main site of drug metabolism, though the gastrointestinal system and lungs also have significant metabolic activity.
What is the purpose of drug metabolism?
To make drugs as water-soluble as possible for elimination by the kidneys.
How does drug metabolism affect activity?
Metabolites are usually less active than the parent compound.
Some are active metabolites, which may be more potent if the parent drug was a pro-drug (inactive on administration, activated by metabolism).
What is first-pass metabolism?
the process by which** a drug is metabolized in the liver and intestines **before reaching systemic circulation
What factors affect drug metabolism?
Genetic factors: E.g., acetylation status (fast/slow metabolizer).
Age:
Impaired enzyme activity in the elderly.
Immature hepatic enzymes in children <6 months (especially premature infants).
Drug interactions:
Hepatic enzyme inducers.
Hepatic enzyme inhibitors.
Why do cells require membrane transport
To transport molecules into and out of the cell, which is essential for maintaining cellular function and homeostasis.
What determines whether a molecule can pass through a cell membrane?
Molecules can pass based on their size – smaller molecules pass more easily.
On which cellular components can drugs act?
Components of the cell membrane.
Critical chemical pathways within the cell.
Transport mechanisms for molecules entering and exiting cells.
Chemical messaging systems between cells.
DNA/RNA replication processes.
What is osmosis?
The spontaneous movement of a solvent (e.g., water) through a semi-permeable membrane from a less concentrated solution to a more concentrated solution, aiming to equalize solute concentrations on both sides.
What drives the osmosis process
The concentration gradient between the two sides of the semi-permeable membrane.
What is the primary organ responsible for drug elimination?
The kidneys
How are water-soluble and lipid-soluble drugs handled during renal elimination?
Water-soluble compounds: Excreted in urine via glomerular filtration.
Lipid-soluble compounds: Reabsorbed by passive diffusion into the renal tubules.
What is enterohepatic recirculation?
Some drugs are concentrated in bile and excreted into the intestine.
They may be reabsorbed into the circulation (increasing the drug’s persistence in the body) or eliminated in feces.
What are other routes of drug elimination besides renal and biliary?
STGB
Sweat
Tears
Genital secretions
Breast milk
How can enterohepatic recirculation affect drug action?
It can prolong the drug’s presence in the body, potentially increasing its effect or toxicity.
What decreases with age
GF
Glomerular filtration
Example of Glomerular filtration decrease
1y/o- 140 ml
80 y/o- 60ml
What is Glomerular filtration
A process by which blood plasma is filtered through the glomerular filtration membrane. This is the first step of urine formation, by which the kidney starts to eliminate toxins from blood plasma.
which drug administration routes avoid first pass metabolism
IV, sublingual, and rectal (lower rectum)
routes avoid first-pass metabolism because they bypass the liver’s initial processing.
A medication with a half-life of 6 hours is administered at 8 AM. Approximately what percentage of the drug will remain in the plasma at 8 PM?
25%
Explanation:
A drug with a half-life of 6 hours will reduce by half every 6 hours:
8 AM → 100%
2 PM → 50%
8 PM → 25%
Advantage of Topical Drug Administration
Avoidance of first-pass metabolism
Dosing Frequency for Long Half-Life Drugs
Once daily
e.g., warfarin, digoxin) are typically given once daily to maintain therapeutic levels without excessive accumulation.
A 70-year-old patient with reduced kidney function is prescribed a renally excreted drug. What adjustment may be necessary?
Decrease the dose
For drugs that are renally excreted what can impaired kidney function cause
-drug accumulation, increasing toxicity risk
-dose reduction prevents this
A drug is 90% bound to plasma proteins. What effect would severe hypoalbuminemia have on the drug’s action?
Increased free (active) drug concentration
Low albumin reduces plasma protein binding, increasing free drug concentration, leading to enhanced drug effects and toxicity risk.
Where Highly Lipid-Soluble Drugs Accumulate
fat tissues
Example of a Prodrug
Enalapril
A patient is taking a drug that undergoes enterohepatic circulation. What does this mean?
The drug is continuously recycled between the liver and intestines
Which of the following drugs would have the highest likelihood of crossing the blood-brain barrier?
A drug with high lipid solubility
What kind of drugs does the blood brain barrier allow to enter the brain
lipid-soluble drugs (e.g., benzodiazepines)
