Intro to pharmacology Flashcards
what is pharmacology
study of drug action ( how drug interacts with living organisms and influences physiological function. More drug focused
What 2 concepts are pharmacology split into
pharmacodynamics ( effect of drug on body) + pharmacokinetics ( how body breaks down drug)
What is pharmacodynamics
effect of drug on body
What is pharmacokinetics
how body breaks down drug
what is the study of therapeutics
Drug prescription and treatment of disease. More ppl focused
What questions must you ask in pharmacodynamics
Where is the effect produced ?
Remember drugs can have different effects good and bad
Must be specific about location
What is the target for the drug ?
Remember in order for a drug to have an effect it must bind to a target
What response produced after interaction with the target ?
Where does cocaine act
Dopaminergic neurons in the nucleus accumbent to produce high
How does cocaine produce a high
Cocaine blocks dopamine reuptake protein on pre synaptic terminal hence dopamine not removed for synapse → more dopamine can bind to D1 receptor ( Dopamine 1) and cause euphoria
What are the 4 types of drug targets and name an example of a drug that woks on each
Receptors - nicotine
Enzymes - aspirin
Ion channels - local anaesthetic
Transport proteins - prozac (antidepressant)
What is drug selectivity
Effective drugs must bind with high selectivity for a target but may be hard in real life as a lot of things are structurally similar
Remember lock and key effect → if a drug is selective the drug ( the key) will only bind to one target ( the lock)
Why does dopamine antagonists produce side effects
Ie . Dopamine , Noradrenaline and serotonin and similar shapes so dopamine antagonists may also produce side effects due to reactions with noradrenaline + serotonin receptors
What is dose and how do you find out the correct dose for a drug
Dose helps with selectivity → first find the dose at which the drug is only selective for the intended receptor then you can find out what
dose the drug will have to be to get side effects ( acting on side receptors)
What are the 4 interaction drugs have with their receptors
Electrostatic interactions → most common . H bonds + van der waals
Hydrophobic interactions → important for lipid soluble drugs
Covalent bonds → least common as interactions tend to be irreversible
Stereospecific interaction → drugs exist as stereoisomers and interact with specific receptors
when a drug binds to a receptor what is formed
what happens if you increase conc of a drug
Drug receptor complex
Remember this is like an equilibrium reaction if increase conc of drug then equilibrium shift to right as more drug avialable to bind to receptors so more drug receptor complexes formed
What can drug interactions be divide
ntagonists + Agonists. Both can bind to receptors but only agonists can activate them. ( Lock and key mechanism : agonist ( key) that can open the receptor ( lock) but antagonists can fit but would jam the lock
What is affinity
: Strength of binding of drug to receptor. Linked to receptor occupancy aka the higher the affinity the more the drug binds with receptor
What is efficacy
ability of an individual drug molecule to produce and effect once bond to a receptor . Drugs can produce: complete , no or partial responses
Remember a drug can have no efficacy but high affinity
What are the 2 classes of agonists
Partial + full
What is potency
Conc / dose of a drug to produce a 50% tissue response ( EC50 / half maximal effective conc or ED 50 / half maximal effective dose)
What is the difference betweeen ED50 and EC50
look at example on docs
Which is more important potency or efficacy
efficacy is more important as you want to know if a drug can give max response. If 2 drugs have equal efficacy potency doesn’t matter as you can still prod max response in the less potent drug but administering it at a higher conc
What are the 4 factors to consider in pharmacokinetics
Absorption
Distribution
Metabolism
Excretion
What are the 4 most important carrier systems in pharmacokinetics
Renal tube ( allow excretion of drugs from body)
Biliary tract
Blood brain barrier ( allow drug access to certain tissues)
GI tract ( allow drug access to bloodstream due to absorption here + allow extrection)
What is absorption
Passage of drug from administration site into plasma aka process for drug transfer into blood. Linked to Bioavailability
what is bioavailability
fraction of initial dose that gains access to systemic circulation aka outcome/ how much drug transferred into blood
What are 5 ways to administer a drug
Intravenous → bioavailability is 100% as all drug passes into circulation ( bulk transfer) Oral Inhalational Dermal ( percutaneous Intranasal
what are the 2 ways that drugs can move around the body
Bulk flow transfer ( ie in bloodstream) Diffusional transfer ( movement across shot distances)
What are the 4 types of diffusional transfer
Pinocytosis ( vesicle transfer of drug ( drug surrounded by broken cell membrane ) ( RARE)
ie insulin access to brain
Diffusion across aqueous pores ( gapes in epi/endothelial cells) ( Uncommon as drugs unlikely to be smaller than 0.5nm in diameter)
Simple diffusion ( drug must be lipid soluable)
Carrier mediated transport ( sometimes need ATP)
why is bioavailality <100% for non IV drugs
Due to diffusion of drug through lipid membranes before it can get to bloodstream
What are the 2 formes a drug is able to exist in
weak acid or base meaning that they will be Ionised / unionised
Why are most drugs water soluble
Most soluble in water not lipid as most are orally administered and need to be dissolved in the GI tract
What form are drugs more lipid soluble
Unionised form
What 2 factors does ionisation of a drug depend on
Dissociation constant ( pKa) of drug Most Weak acids have pka of 3 -5 Most Weak bases pka of 8-10 PH of body Remember if Pka of drug = pka of tissue then durg will be equally dissociated aka 50% ionised/ 50% unionised
what happens to solubility of weak acids as PH
a) increases
b) decreases
For weak acids as PH decreases = unionised form dominated, PH increases = more ionised form
what happens to solubility of weak bases as PH
a) increases
b) decreases
For weak bases PH increases - unionsed from more , PH decrease = ionized form more
Where are weak acids more unioinsed
areas of low Ph like stoma
Where are weak bases more unioinsed
Areas of higher Ph like blood and urine
what is the pka of aspirin and morphine
Aspirin = weak acid. In ionised state donates H+ . has a Pka of 3.5 aka at PH 3.5 equally dissociated. Morphine = weak base. The ionised state accepts H+ . Has Pka of 8
Will weak bases be trapped in stomach and weak acids trapped in blood?
No→ weak base may be poorly absorbed in stomach but when it enters the SI it will have access to transport proteins . Weak acids can be absorbed in stomach and move into blood but won’t remain trapped there due to tissues having transport proteins moving the drug from the blood into the tissue
what are factors effecting distribution of drugs
1) Regional blood flow
2) Plasma protein binding
3) capillary permeability
4) tissue localisation
What factors do amount of drug bound depend on
Free drug conc
Affinity for protein binding sites
Plasma protein conc
Why is binding capacity important
Why is binding capacity important?
Albumin has 2 binding sites and a conc in the blood of 0.6mmol/ bringing the binding capacity to 1.2mmol/L
Plasma conc required for all drugs is less than 1.2mmol/l ⇒ therefore plasma proteins are NEVER saturated with drugs so they don’t get harmed. Differences are due to different affinity of drugs to receptors
Note → only free drugs can diffuse out of blood into tissue. Drugs bound to plasma proteins can’t leave until it dissociated from the protein
how does regional blood flow effect distribution of drugs
Different tissues receive diff cardiac output. Higher cardiac output = higher blood flow = more drug distributed to those tissues
Remember distribution can increase / decrease depending on circumstance ie exercise will increase blood to muscles and decrease to stomach
how does plasma protein binding effect distribution of drugs
Drugs can bind to plasma proteins in circulation ( albumin is V good at binding to acidic drugs so acidic drugs tend to be more heavily plasma protein bound) Amount of drug bound depends on : Free drug conc Affinity for protein binding sites Plasma protein conc
What are the 4 capillary types and how does they effect distribution of drugs?
Continuous structure ( most cap have this) this means that lipid soluble drugs can diffuse through. If drugs aren’t lipid soluble then they will either be v small ( pass through gap junctions) or be transposed into tissues via carrier proteins
Blood brain barrier has tight junctions which makes it hard for drugs to access the brain as they can’t move through
Fenestrated →Circular winders in endothelial cells that allow for passage of small mr substances ie bloods example : kidney glomerulus ( important for excretion of drugs → small drugs can pass through in kidney tubules increase excretion )
Discontinuous → allows big gaps between capillary endothelial cells so drugs can easily diffue out of blood . example : Liver ( important as liver is key for metabolising drugs)
how does tissue localisation effect distribution of drugs
Make up of the tissue determines diffusion gradient for lipid and water soluble substances
Ie Lipid soluble delta9 - TCH active component of cannabis diffuses into brain → equilibrium established → brain has higher fat content → diffusion grad weights towards higher retention in the brain → more localisation in brain
Water soluble drug diffuses into brain → equilibrium established → brain has lower water content → different grad means more of drug stays in plasma
What is drug metabolism
Breaking down of the drug. Ideally want drugs to be lipid insoluble so they can stay in bloodstream and get excreted but this means they will have to effect. Metabolism involves conversion drugs → metabolites that are water soluble so easier to excrete
What organ is the site for major drug metabolism
liver
What enzyme n the liver is responsible for drug metabolism
Cytochrome P450
What are the 2 stages of drug metabolism
Phase 1 and 2
What happens in phase 1 of drug metabolism
Phase 1 ( want to introduced a reactive group to drug) Introduce reactive polar groups . Can occur by reduction , oxidation , hydrolysis Most common is oxidation → note all oxidation reactions start with a hydroxylation step by CP450 system. Aim is to incorporate O into non activated hydrocarbons
What enzyme carries out phase 1 drug metabolism
c P450
What are prodrugs and when are they made
phase 1 can make pharmacologically active drug metabolites ( aka drug that only become active one metabolised. These are known as PRODRUGS . Active metabolites my also damage things ie ( liver damage in paracetamol overdose is due to metabolite not paracetamol)
What happens in phase 2 of drug metabolism
Phase 2 ( add a conjugate to reactive grp)
Attachment of conjugate to make resulting metabolite inactive ( mostly) and less lipid soluble for excretion in urine . bile
Done using transferases enzymes ! rather then cp540 enzymes like in phase1
qhat is first pass hepatic metabolism and why is this a problem
First pass hepatic ( presystemic ) metabolism :
Problem with oral drugs
Oral drugs administered → absorbed mostly from SI → enter hepatic portal blood supply → pass through liver → systemic circulation
This causes drug to be heavily metabolised so little active drug may reach systemic circulation ( note presystemic metabolism is needed for Prodrug activity)
What is the solution to presytemic metabolism and why is this solution not perfect
Solution : increase dose
Prolem : extent of metabolism varies in ppl so amount of drug reaching systemic circulation also varies→ causes hard to predict drug + side effects
What enzyme carries out phase 2 of drug metabolism
Transferases not cp540 like in phase 1
What are 4 routes for excretion of drugs
Routes for excretion: Excreted via lungs ( ie alcohol → think alcohol breath test) Breast milk Urine ( *) Bile (*) *most excreted this way
what are the 3 mayor ways for drugs to exit the kidney ( most effective secretion method)
Glomerular filtration
active tubular secretion ( reabsorption_ ,
passive diffusion across tubular epithelium
What happens in glomerular filtration
Allows drug molecules of molecular weight <20,000 to diffuse into glomerular filtrate. → therefore smaller drugs are excreted quicker
What happens in active tubular secretion
Most important method as 80% of renal plasma passes onto blood supply to PCT and isn’t filtered out by glomerulus so more drugs are delivered to PCT
PTCT capillary endothelial cells have 2 active transport systems to transport drugs against conc grad : 1 for acidic drugs and the other for basic
what happens in passive diffusion across tubular epithelium
Generally leads to reabsorption from kidney tubule. 99% of water filtered is reabsorbed and lipid soluble drugs go back into the blood
Factors influencing reabsorption:
Drug metabolism → phase 2 metabolites more water soluble than parent drug → less well reabsorbed
Urine PH → can vary from 4.5 - 8. Acidic drugs better absorbed at lower PH and basic drugs at higher PH
What causes variation of excretion of drugs
Drugs used these 3 processes of excretion by the kidney differently which causes variation of excretion of drugs ( this is also impacted on by metabolism. Phase 1 + 2 produce more water soluble metabolites that are easier to excrete)
How do drugs get excreted in biliary excretion
Liver cells transport drugs from plasma to bile ( use transported similar to kidney)
Is really good at removing Phase 2 glucuronide metabolites
Drugs go into bile → intestine → excreted in faeces
What is enterohepatic recycling and what does it do
Prolongs drug effect
Glucuronide metabolite transported to bile
Metabolite excreted into SI where it is hydrolysed by hut bac releasing glucuronide conjugate
Loss of glucuronide conjugate increase lipid solubility of molecules
Increased lipid solubility increase reabsorption from SI back into hepatic portal blood system for return to the liver
Molecule reuters to liver where a probation will be metabolised by a proportion ma escape back into system circulation to continue having effects
Extra
Extra
Extra
Extra
Extra
Extra
Extra
Extra
Extra
Extra
Extra
Extra
