pharma sem 2 block 1 Flashcards
what is pharmacokenetics?
its what the body does to the drug and includes absorption, distribution and metabolism and excretion
what is pharmacodymanics?
its what the drug does to the body
what is the shape of the concentraion-time curve shaped by?
the rate of absorption, how quickly its distributed and how quickly its eliminated
what is first pass metabolism?
its how much of the drug is directly excreted before going into the circulation
what are the characteristics of a drug formulation if its to be administered orally?
solid aggregates (usually cristalline)
water soluble salts
What does pharmacokinetics study?
Drug absorption, distribution, metabolism, excretion, and how the body affects the drug.
What is clinical pharmacokinetics?
The application of pharmacokinetic methods to ensure patients are treated safely and effectively.
What is drug absorption?
The transportation of the unmetabolized drug from the administration site to the body circulation system.
List the mechanisms of drug absorption.
- Passive diffusion
- Carrier-mediated membrane transport
- Active diffusion
- Facilitated diffusion
What factors can affect drug absorption?
- Drug-specific factors
- Patient-specific factors
What is bioavailability?
The rate and extent of a drug’s absorption.
What is the primary route of drug administration discussed in the article?
Oral route.
What is passive diffusion?
The most common mechanism of absorption for drugs, explained through the Fick law of diffusion.
What is Fick’s law of diffusion?
The principle that a drug moves according to the concentration gradient from higher concentration to lower concentration.
What is the role of P-glycoprotein in drug absorption?
It is an energy-dependent efflux transporter that restricts overall drug absorption.
How does active diffusion differ from passive diffusion?
Active diffusion requires energy and moves drugs against a concentration gradient, while passive diffusion does not.
What are physicochemical variables that affect drug absorption?
- Drug solubility
- pH and pKa
- Particle size
- Surface area
- Dissolution rate
- Polymorphism
What is the significance of drug solubility in absorption?
Ionized drugs are hydrophilic and cannot cross cell membranes, while non-ionized drugs are lipophilic and can penetrate easily.
What is polymorphism in pharmacokinetics?
The existence of more than one crystalline form of a solid substance.
What physiological factors affect drug absorption?
- Age
- Gastric emptying time
- Intestinal transit time
- Blood flow
- Presystemic metabolism
How does age affect drug absorption?
Physiological changes with increased age may lead to decreased drug absorption.
What is first-pass metabolism?
The metabolism of orally administered drugs within the gut wall or liver before reaching circulation.
What is absolute bioavailability?
The bioavailability of an orally administered drug compared to its bioavailability following IV administration.
What is relative bioavailability?
The comparison of the bioavailability of an orally administered drug with that of an oral standard of the same drug.
What is the order of bioavailability among different routes of administration from highest to lowest?
- Parenteral
- Rectal
- Oral
- Topical
Why are IV drugs administered?
For rapid onset of response, in unconscious patients, or when the GI tract is non-functional.
What are bioequivalence studies?
Studies conducted to differentiate between two drug products with the same active ingredients.
True or False: Bioavailability directly affects the therapeutic range of a drug.
True.
what is the route most drugs take to systemic circulation?
through the portal blood vessel
what is the rate limiting step for the absorption of tablets?
the rate at which it dissolved
is the unionised form of the drug good or bad for absorption?
good as its got good lipophilicity for absorption
what determines the extent of ionisation of a drug?
the pH of the GIT fluid and the pKa of the drug
what is the bioavailability of the drug?
its the amount of drug which is still around after the drug has passed through the liver
what is the difference between the oral and IV administration called?
the bioavailability of the drug
what factors do you have to consider for oral administration?
food incompatibilities
first pass effects
irritability of the drugs
incompatible physico-chemical properties i.e. non-ionic highly lipophilic drugs wont be able to pass through membranes in the gut to be absorbed
the chemical stability
the onset of action i.e. opioids are usually IV as theyve got a faster onset
location of action- asthma and acute pain
systemic or local effects- i.e. steroids for rashes
what are enteric coated tabs used for?
to avoid being broken down in the acidic stomach environment
what is the positive of buccal/sublingual administration?
it avoids the first pass effects and has a fast onset
why administer omeprazole at the same time as ibuprofen?
as its a proton pump inhibitor so it stops the harmful gastric effects of the ibuprofen
what helps with the formation of a dynamic equlibrium for the drug?
the binding of drug molecules to plasma proteins, only unbound molecules are able to leave the circulation and cause a theraputic effect
how does plasma albumin contribute to drug interactions?
the drugs compete for the same binding sites on the plasma albumin and can result in changing the free concs of the drugs in circulation
what effects on the drug distribution does plasma protein binding have?
it makes the action of the drugs longer and less intesnse as theres less free drug available
how is the volume of distribution measured?
Vd = dose/ plasma conc
what are the four patterns of distribution?
in the vascular system (i.e. warfarin) where drugs stay in the bloodstream due to them being strongly bound to the plasma protein
in the extracellular fluid where they dont usually do into the cells (streptomycin)
uniformly distributed (paracetamol) low molecular weight and easily moves through tissues
concentrated in specific tissues (chloroquine an anti-malarial is concentrated in the liver)
however most drugs are a combo of these and have non-uniform distribution throughout the whole body and can pass through membranes when the carry a positive charge
why are there high levels of bound drug on plasma albumin?
as plasma albumin has a naturally positive charge due to the high percentage of amines and positive proteins making it good for binding high levels of negatively charged ionised drugs
why does it take longer for acidic drugs to distribute round the body?
as theres lower levels of free drug due to the majority of acidic drugs binding to plasma proteins such as albumin
what is the absorption of drugs from the blood stream into the tissues determined by?
the high levels of phosphilipid content in the cellular membranes meaning that basic drugs can easily pass through due to the mutual attraction to the pps
what are some examples of acidic drugs?
gentamycin, ibuprofen and naproxen
what are some examples of basic drugs?
paracetamol, ketamine and morphine, theyve all got Vd>0.7
what characteristics affect Vd?
the drugs relative water and lipid solubility
the plasma/tissue binding properties
if it required loading doses to establish theraputic drug concentrations
what drugs need loading doses?
amiodarone or digoxin
what ways can drugs get through the BBB?
through tight junctions- water soluble drugs
through the membrane of the endothelium- lipid-soluble drugs
transport proteins
by specific receptor mediated endocytosis- i.e. transferrin (rivagastine binds to transferin through its Fab fragment to allow the mAb ganterneumab to clear amyloid-beta aggragates in AD)
cationisation of native plasma proteins increases their uptake by absorptive-mediated endocytosis
why is the uptake of drugs through the BBB much smaller than other lipid membranes?
because the tight junctions only allow in very small molecules and normal blood proteins arent able to cross
what clinical considerations do you have to have when thinking about drug distribution?
how widely distributed it is, the wider its distributed, the harder it is to remove from the body as its far away from the liver
if certian disease states affect its metabolism and excretion
how the drug will get to the target tissue
how available it is in the circulation, very available and its effects will wear off quickly and will be vv strong
what are compartment models in pharmacokenetics?
its the model used to investigate the distribution of drugs accross the fast and slow distributing tissues
fast= muscle
slow=fat
just think of athletes and obese people
what is the three compartment model?
its the distribution of drugs between the central compartment of blood, brain and liver with the slow redistributing tissues of adipose tissue and the fast redistributing tissues of muscle and vicera
what diseases impact pharmacokenetics?
diabetes, liver and renal diseases, heart failure and sepsis, dysregulation of hepatic enzymes
what are the things to think about when it comes to pharmacokenetics?
Absorption
Distribution
Metabolism
Excretion
how does diabetes alter PK?
Absorption, due to changes in subcutaneous adipose blood flow, muscle blood flow and gastric emptying;
(ii) distribution, due to non-enzymatic glycation of albumin;
(iii) biotransformation, due to regulation of enzymes/transporters involved in drug biotransformation; and
(iv) excretion, due to nephropathy
how does age alter PK?
it leads to changes in drug deposition and sensitivity due to physiological chnages in childhood and as a result of ageing which impact the dynamics of compounds
what is ageing associated with?
a reduction in first-pass metabolism
what is the irrational use of medicines?
the over or underuse or misuse of drugs and expensive drug administration i.e. drugs given via IV when they can be given orally
what are the most common measures of inequality?
Life Expectancy
Infant Mortality
Obesity and Overweightness (BMI)
Mortality Rate
Regular smokers/tobacco consumption
Self-perceived health
what are some factors in improving lifespan?
hygine and clean water
treatment of infectious diseases
treatment of CVD
effective cancer treatments
what are some reasons for inequalities in health?
bad environments
poor conditions during development
income differences
educational differences
what are the inequalites relative to birth?
theres more adversde intra-uterine conditions in more deprived areas due to more chronic illness, poor maternal nutrition (linked with T2D) low birth weight- heart problems and vascular problems
what are the effects of neglect?
alteration of the HPA axis - alters the natural biological stress response, risk factor for anxiety, depression, CVD and chronic health impairments
learning difficulties leading to reduced attainment
what are the effects of alcohol on health?
liver disease
cancer risks
CV effects- hypertension, stroke, arrhythmia and MI
neurological degeneration leading to dementia
fetal alcohol syndrome
what are the effects of the health inequality life cycle on adults?
smoking
obestity
alcohol dependance
drug abuse
what are the effects of obestity on health?
less heathy eating, nutrition and excersize increase levels of adipose tissue leading to increased rates of cancer, death + T2D+ CVD+ muscoskeletal diseases
impacts on PK due to increases in slow redistributing adipose tissue, difficulty with IV access + incr absorption due to increased gastric emptying, increased elimination of drugs
what treatments are there for AD?
lecanumab- mAb which binds AB with high affinity
sage-718 - modulates NMDA receptors
beta-secretase inhbitors
gamma-secretase inhibitors
gamma secretase
AChE inhibitors
NMDA antagonists
what drugs are given on the NHS for AD?
AChE inhibitors like donepzil, galantmine and rivastigine
NMDA antagonists like memantamine for severe AD
what are the reccomendations for SZ treatments?
give a 1st gen typical anti-psycotic such as chloropromazine, haloperdiol, levopromazine or sulpride
OR give a 2nd gen atypical antipsycotic if 1st gen didnt work like amisupride, clozapine, olnazepine or rispodarone
or for noncompliant patients, consider giving a depot-injection such as haloperdiol or rispodarone
what is the only anti-psychotic which is suitable for anyone with psychosis?
clozapine but should not be considered before giving two other anti-psycotics with one of them being a non-clozapine 2nd gen
what else should be given in addition to an antipsycotic drug?
psycological therapies incluiding CBT for the patient and family therapy
also a healthy eating plan and an excersize plan should be reccommended in addition to the anti-psycotic
