Pharmocology Flashcards
What is pharmacokinetics?
Non-specific general processes
- absorption from site of administration
- time to onset of effect
- elimination from the body
What are the categories of drug names?
- generic name
- trade or brand name
- chemical name
- use name
- effect name
What is the generic name?
Approved or official name e.g. Paracetamol
What is the trade or brand name? Example with Paracetamol?
‘Propietary’ name given to a drug by its pharmaceutical producer e.g. panadol
What is the chemical name? Example with Paracetamol?
Each drug has its own chemical structure and is given an appropriate chemical name e.g. N-(4-hydroxyphenyl)ethanamide
What is the use name? Example with Paracetamol?
Commonly drugs are categorised according to the use for which they are prescribed such as anti-hypertensives, contraceptives, anti-inflammatories e.g. pain-killer
What is the effect name? Example with Paracetamol?
For some drugs, the categorisation relates to the physiological or biological response in the body e.g. pain killer
What are the ten routes of administration of drugs?
- Oral
- intramuscular
- subcutaneous
- intravenous
- buccal
- transdermal
- inhalation
- intrathecal
- epidural
- topical
What is the advantage of oral administration?
Convenient, safe, economical
What is the disadvantage of oral administration?
Cannot be used for drugs inactivated by 1st pass metabolism or that irritate the gut
What is the advantage of intramuscular administration?
- Suitable for suspensions and oily vehicle
- rapid absorption from solutions
- slow and sustained absorption from suspensions
What are the disadvantages of intramuscular administration?
- May be painful
- May cause bleeding at site of injection
What is the advantage of subcutaneous administration?
Suitable for suspensions and pellets
What are the disadvantages of subcutaneous administration?
- cannot be used to deliver large volumes of fluid
- cannot be used for drugs that irritate cutaneous tissue
- poses more risk for toxicity
What are advantages of intravenous administration?
- bypasses absorption yielding immediate effect
- 100% immediate bioavailability
What is the disadvantage of intravenous administration?
Poses more risk for toxicity
What are the advantages of buccal administration?
- rapidly absorbed
- avoids 1st pass metabolism
What are the disadvantages of buccal administration?
- effective only for low doses
- drugs must be water and lipid soluble
What is the advantage of transdermal administration?
Avoids 1st pass metabolism
What is the disadvantage of transdermal administration?
Effective only for low doses of drug that are highly lipid soluble
What is the advantage of inhalational administration?
Produce a localised effect
What are the disadvantages of inhalational administration?
- drug particles must be the correct size
- dependent on parient technique
What is the advantage of intrathecal administration?
Local and rapid effects
What are the disadvantages of intrathecal administration?
- requires expert administration
- May introduce infection/toxicity
What is the advantage of epidural administration?
Provides a targeted effect
What are the disadvantages of epidural administration?
- risk of failure
- risk of infection
What is the advantage of topical administrations?
Non-invasive and easy to administer
What ate the disadvantages of topical administration?
- poorly lipid soluble nor absorbed via skin or mucous membranes
- very slow absorption
How are oral drugs administered?
Taken in through the mouth
How are intramuscular drugs administered?
Injection of substance into the muscle
How are subcutaneous drugs administered?
Injected directly under dermis and epidermis layer
How are intravenous drugs administered?
Directly delivered into the vein
How are buccal drugs administered?
Drugs applied or administered in the cheek and enter directly into the bloodstream
How are transdermal drugs administered?
Delivered across the skin into the blood
How are inhalation drugs administered?
By inhalation
How are intrathecal drugs administered?
injection into the spinal canal or subarachnoid space so that it reaches the cerebrospinal fluid (CSF)
How are epidural drugs administered?
injected into epidural space around the spinal cord
How are topical drugs administered?
Application on body surfaces
What are the advantages of using modified dose forms?
improved patient adherence
reduction in incidence and severity of GIT (gastrointestinal) effects
improved control over therapeutic plasma concentrations :
- Improved treatment of chronic conditions in which steady plasma concentration required
- Maintenance of therapeutic action overnight
- Minimise adverse effects associated with high plasma concentrations
What are the disadvantages of using modified dose forms?
- Cost more per unit dose than conventional forms
- Possibility of unsafe over dosage if used incorrectly or in failure of MR tablet
- Rate of transit through GIT limits the max period for which a therapeutic response can be maintained
- Variability in physiological factors e.g. GIT pH, enzymes, food etc influence drug bioavailability
What can occur due to the incorrect route of administration?
Adverse effects and death
What are examples of incorrect routes of administration?
- Oral medications given intravenously
- Intermuscular preparations administered intravenously
- epidural and intravenous lines mix-up
- Using intravenous medications given orally
- Intrathecal administration instead of intravenous administration e.g. Vincristine which is a anti-cancer drug
What does ADME stand for?
- Absorption
- Metabolism
- Distribution
- Excretion
What is the ADME for an orally administered drug?
- Absorption
- (First pass) metabolism in the liver
- Distribution to systemic circulation = pharmacological action in the target tissue, metabolised in the liver and excretion via kidneys, lungs, faeces etc
What is the ADME for injected drugs?
- No first pass
- Distribution to systemic circulation = pharmacological action in the target tissue, metabolised in the liver and excretion via kidneys, lungs, faeces etc
What is absorption and the types?
Transfer of the drug from the site of administration into the general or systemic circulation
- absorption from the gut (approx. 75% of orally given drug will be absorbed in 1-3 hours)
- Absorption from other routes
What are the factors affecting oral absorption?
- Particle size and formulation
- GIT enzymes/acid
- GIT motility
- Physicochemical factors
- Food
What are acids? Dissociation formula?
compounds that can dissociate to donate one or more protons
HA <–> H+ + A-
What are bases? Formula?
Bases are proton acceptors
BH+ <–> B + H+
As drugs are either acids or bases what is their degree of ionisation based on?
Dependent on the pH of their environment
What type of drugs cannot cross the cell membrane?
Charged fractions of any drug cannot cross
What is distribution?
The process by which the drug is transferred reversibly
- from the general circulation into the tissues as concentrations in blood increase
- from the tissues into blood as blood concentrations decrease
How does distribution mainly occur?
Mainly occurs by passive diffusion of un-ionised form across the cell membrane
What is the volume of distribution?
Volume of plasma that accounts for total amount of drug
What is the volume distribution used for?
- Used to determine the loading dose necessary for a desired blood concentration of a drug
- Also used for estimating a blood concentration in the treatment of overdose
What are factors affecting drug distribution?
- plasma protein binding
- specific drug receptor sites in tissues
- regional blood flow
- lipid solubility
- disease
What does perfusion mean?
The passage of fluid through the circulatory or lymphatic system
What are some well perfused organs?
- lung
- adrenals
- kidneys
- thyroid
- liver
- heart
- intestines
- brain
- placenta
What are examples of poorly perfused organs?
- skin
- skeletal muscle
- fat
What is the formula for drug-protein binding?
Drug + protein <–> Drug - protein complex
What is drug-protein binding?
- Binding of drugs with albumin and glycoprotein
- reversible structure
What happens if there is administration of a highly bound protein drug to a patient who is already taking a drug that is highly protein bound?
- Results in displacement of drug already bound to protein
- Produces increased unbound concentration of drug and biological activity
What happens with plasma protein binding?
If drug is widely distributed in tissues, the increase in unbound drug is rapidly redistributed to body tissues and unbound plasma concentration rapidly returns to negligible amount
What happens with unbound plasma concentration if the drug is 20% bound?
- Reduction of 5% in bound drug
- Unbound plasma concentration increases from 80% to 85% (negligible)
What happens with unbound plasma concentration if the drug is 95% bound
- Reduction of 5% in bound drug
- Unbound plasma concentration increases from 5% to 10% (significant)
What are characteristics of passive diffusion?
- Molecules move from an area of high concentration to an area of low concentration
- Ion channels may facilitate passive diffusion down a concentration gradient
What are characteristics of facilitated diffusion?
- Molecules combine with membrane-bound carrier protein
- Movement still dependent on concentration gradient
Slightly faster than passive diffusion
What are characteristics of active transport?
- Requires energy
- Molecule transported can be transported against concentration gradient
What are characteristics of pinocytosis?
- Molecules engulfed by cell membrane and vesicle formed
- Vesicle moved into the cell
Molecule may then be released within the cell
What is the process of altering drugs to remove them from the body?
- Activation of inactive drug
- Production of active drug with increased activity from active drug
- Inactivation of active drugs
- Change in the nature of the activity
When does metabolism occur?
Prior to and during absorption
What are the 4 major metabolic barriers before they reach the general circulation?
- Intestinal lumen = digestive enzymes secreted by the mucosal cells and pancreas, certain enzymes break down proteins and stop them from being absorbed
- Intestinal wall = Rich in enzymes that further metabolise drugs
- Liver = Major site of drug metabolism
- Lung = Cells of the lung have high affinity for many drugs and are the site of metabolism for many local hormones.
What are the phases of metabolism?
- lipophilic (fat soluble) drug undergoes reaction (oxidation, reduction and hydrolysis)
= more reactive drug which undergoes reaction (conjugation)
= hydrophilic (water soluble) drug
= excreted by kidneys
What are the factors (6) affecting drug metabolism?
- First pass effect
- Hepatic blood flow
- Liver disease
- Genetic factors
- Other drugs
- Age
What is the cytochrome P450 (CYP450) system?
A large family of enzymes and individual one is called an isoenzyme. Isoenzymes are named using an agreed method of nomenclature.
What is the substrate for cytochrome P450?
Drug metabolised by isoenzyme
What are the enzyme inducers for the cytochrome P450 system?
- Enhance production of liver enzymes which breakdown drugs
- faster rate of drug breakdown
What are the enzyme inhibitors of the cytochrome P450 system?
- Inhibit production of enzymes which breakdown drugs
- Reduced rate of drug breakdown
How is paracetamol metabolised?
Conjugation = paracetamol glucuronide, paracetamol sulphate
Oxidation = N-acetyl-p-benzoquinoneimine (NAPQI) = cysteine/ mercapturate derivatives with glutathione acting on reaction to produce this
What is bioavailability?
Proportion of a dose that reaches systemic circulation
What are the examples of bioavailability with digoxin and atenolol?
- Digoxin 125 micrograms oral dose = 93.75 micrograms in plasma = bioavailability is 75%
- Atenolol oral bioavailability is 100mg = 45-60mg in the plasma = bioavailability of 46-60%
What is bioequivalence?
Two or more chemically or pharmaceutically equivalent products (so one can be replaced with another product without causing clinical problems)
What does drug elimination via the liver depend on?
- blood flow to the liver
- activity of the enzymes in the liver
How does drug elimination by the liver work?
Liver enzymes will chemically alter the drug to form ‘metabolites’ which are:
- inactive or
- equally or more active than the parent drug
Elimination of drugs via kidney?
- filtration into bowman’s capsule, go into peritubular capillaries for reabsorption and then secretion from renal vein and also then urinary excretion after it exits peritubular capillaries.
What is clearance?
Volume of blood/ plasma cleared of drug per unit time
- This includes metabolites as well as renal and biliary clearance
- Clearance does not indicate the amount being removed
What is half life (T 1/2)
Time taken for the concentration to reduce by 50%
What is the substance produced in skeletal muscle which is excreted through the kidneys?
Creatinine
How is creatinine absorbed and secreted?
It is neither passively reabsorbed nor actively secreted
What does estimation of creatinine clearance do?
Estimates clearance of drugs filtered at the glomerulus
What is is the Cockcroft Gault equation and what does it tell you?
Estimated Creatinine clearance in mL/min
= (140-Age) x Weight x Constant/ Serum Creatinine
- Age in years, weight in Kg, serum creatinine in micromol/litre, constant 1.23 in men and 1.04 for women
What is absorption like in children vs elderly?
- Unreliable in neonates and greater transcutaneous absorption
- In general, unchanged
What is distribution like in children and the elderly?
Fat components of body mass tends to be proportionately greater, acting as a reservoir
What is metabolism like in children?
Reduced capacity due to immature liver in infants – drug effects prolonged or excessive
What is metabolism like in the elderly?
Slight reduction due to impaired liver function, so drug effects more pronounced and longer lasting
What is excretion like in children?
Reduce capacity due to immature kidneys in infants
What is excretion like in the elderly?
Reduction due to impaired glomerular filtration rate
