Intro to pharmacology Flashcards

Question

what is bioavailability

Answer 1

fraction of initial dose that gains access to systemic circulation aka outcome/ how much drug transferred into blood

Answer 2

``` Intravenous → bioavailability is 100% as all drug passes into circulation ( bulk transfer) Oral Inhalational Dermal ( percutaneous Intranasal ```

Answer 3

``` Bulk flow transfer ( ie in bloodstream) Diffusional transfer ( movement across shot distances) ```

Answer 4

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)

Answer 5

Due to diffusion of drug through lipid membranes before it can get to bloodstream

Answer 6

weak acid or base meaning that they will be Ionised / unionised

Answer 7

Most soluble in water not lipid as most are orally administered and need to be dissolved in the GI tract

Answer 8

Unionised form

Answer 9

``` 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 ```

Answer 10

For weak acids as PH decreases = unionised form dominated, PH increases = more ionised form

Answer 11

For weak bases PH increases - unionsed from more , PH decrease = ionized form more

Answer 12

areas of low Ph like stoma

Answer 13

Areas of higher Ph like blood and urine

Answer 14

``` 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 ```

Answer 15

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

Answer 16

1) Regional blood flow 2) Plasma protein binding 3) capillary permeability 4) tissue localisation

Answer 17

Free drug conc Affinity for protein binding sites Plasma protein conc

Answer 18

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

Answer 19

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

Answer 20

``` 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 ```

Answer 21

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)

Answer 22

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

Answer 23

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

Answer 24

Cytochrome P450

Answer 25

Phase 1 and 2

Answer 26

``` 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 ```

Answer 27

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)

Answer 28

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

Answer 29

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)

Answer 30

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

Answer 31

Transferases not cp540 like in phase 1

Answer 32

``` Routes for excretion: Excreted via lungs ( ie alcohol → think alcohol breath test) Breast milk Urine ( *) Bile (*) *most excreted this way ```

Answer 33

Glomerular filtration active tubular secretion ( reabsorption_ , passive diffusion across tubular epithelium

Answer 34

Allows drug molecules of molecular weight <20,000 to diffuse into glomerular filtrate. → therefore smaller drugs are excreted quicker

Answer 35

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

Answer 36

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

Answer 37

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)

Answer 38

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

Answer 39

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

Intro to pharmacology Flashcards

(71 cards)