Drugs Flashcards
What needs to be considered when prescribing a drug?
Mode of action
Efficacy
Safety
Patient suitability
Formulation
Dose
Route
Frequency
Duration
What is efficacy?
Power to produce an effect- drugs ability to elicit a response when it binds to receptor
Prescribers normally choose drugs w/ greatest efficacy
May be appropriate, however, to compromise on efficacy if other drugs are more convenient, safer to use or less expensive.
how does formulation of drug affect prescribing?
Some drugs- choice of formulation- some are easier to ingest particularly by children
Formulation important when writing repeat prescriptions for drugs w/ low there-tunic index that come in different formulations
- Even if prescribed dose is same, an alternative formulation may differ in absorption & bioavailability- thus plasma drug conc.
What factors influence route of drug administration? What routes are possible?
Different routes:
- IM- intramuscular
- INH- inhalation
- IV- intravenous
- PR-per rectum
- SC- subcutaneous
- SL- sublingual
- Orally
Factors influencing route:
- Comfort- morphine SC rather than IV
- Ease of access- diazepam PR, adrenaline- IM
- Direct access to site of action
- Poor absorption
- Rapid action- haloperidol IM rather than oral
- Vomiting
- Certainty of effect
How does dosage differ depending on drug & patient?
Prescribers should start w/ low dose & slowly increase as necessary
-Important if patient is more sensitive to adverse pharmacodynamic effects e.g. delirium or hypotension in elderly.
However, some drugs must achieve therapeutic conc quickly because of clinical cirumstance g.g. antibiotics, flu corticoids
- When early effect is important but there may be delay in achieving steady state due to drug’s long half-life, a loading dose is given prior to establishing maintenance dose
If adverse effects occur, dose should be reduced or alternative drug should be prescribed
- lower drug may suffice if combined w/ another synergistic drug e.g. immunosuppressant azathioprine reduces glucocorticoid requirements in patients w/ inflammatory disease
Higher doses may produce little added therapeutic effects & might increase chances of toxicity- dose-response curve
How does frequency of drug doses differ?
Frequency of doses dictated by manufacturer’s recommendation
- Less frequent doses more convenient for patients but result in greater fluctuation in drug conc- transitions from peaks & troughs more frequent
- Issue if peaks associated w/ adverse effects e.g. dizziness w/ antihypertensives, or troughs associated w. loss of effects e.g. anti-parkinsonian drugs
Problems can be tackled by splitting dose or by employing modified release formulation.
How does duration of a drug differ between drugs & patients?
Some drugs require single dose e.g. thrombolysis post myocardial infarction
Others, the duration of course of treatment is certain at outset e.g. antibiotics
- duration will depend on prescriber’s discretion & will depend on response & disease progression e.g. antidepressants & analgesics.
Many treatments are long-term e.g. insulin, antihypertensives.
How does patient suitability affect what drugs are prescribed?
Age:
- drug metabolism is low in newborns, enhanced in young people & becomes less effective w/ age
- Drug excretion calls w/ age-related decline in renal function
Sex:
- women have higher body fat than men- increases vol of distribution & half-life of lipid-soluble drugs
Body weight:
- obesity increases vol of distribution & half life of lipid-soluble drugs
Smoking:
- tar in tobacco smoke stimulates oxidation of some drugs
Alcohol:
- consumption stimulates liver enzyme synthesis
- binge drinking may temporarily inhibit drug mechanism
Take into account patient’s
- features of disease- meds should be based on known or suspected sensitivity of infective organism
- Co-existing disease- may be either an indication or contraindication to therapy- hypertensive patients might be prescribed b-blockers if they also have left ventricular impairment but not have asthma.
Patient adherence to therapy - prescribers should choose drugs w/ a simple dosing schedule or easier administration e.g. ACE inhibitor lisinopril once daily rather than captopril 3 times daily for hypertension
How does patient safety determine which drugs are prescribed?
Prescribers should be wary of choosing drugs that are likely to cause adverse effect (e.g. cephalosporins rather than alternatives for patients allergic to penicillin) or worsen coexisting conditions (e.g. b-blockers as treatment for angina in patients w/ asthma)
Prescribers should avoid giving combo of drugs that might interact, directly or indirectly
Definition of pharmacodynamic?
What the drug does to the body.
Definition of agonist?
Bind to receptor to produce conformational change that is coupled to a biological response
As agonist conc increases, so does proportion for receptors occupied & thus biological effect.
Partial agonists activate receptor but cannot produce maximal signalling effect like full agonist, even when all receptors occupied.
Definition of antagonists?
Bind to a receptor but do not produce the conformational change that initiates an intracellular signal.
Competitive antagonist- competes w/ endogenous ligands to occupy receptor-binding sites w/ resulting antagonism depending on conc of drug & ligand.
Non-competitive inhibit effect of agonist y mechanisms other than direct competition for receptor binding w/ agonist.
Definition of potency?
The strength of a drug at a particular dosage.
Concentration/ dosage required to produce 50% of maximal effect.
- Drugs of different potencies will require different doses to elicit drug response required
- very potent drug= only small amount needed to achieve full effect
Definition of therapeutic index?
The ratio of the ED50 for therapeutic efficacy & for a major adverse effect.
- Usually based on adverse effects that might require dose reduction or discontinuation.
ED50- dose of a medication that produces a desired pharmacologic effect in 50% of the studied patient population that takes the medication
What are the mechanisms by which drugs ?
Pharmacokinetic
Pharmacodynamic
How does pharmacodynamics work?
When drug enters body, it interacts w/ receptor & creates signal
- This signal results in biological effect e.g. it can tell DNA to stop replicating.
Receptors can be divided into 4 types:
- Ligand-gated ion channels
- G protein-couples receptors
- enzyme-linked receptors
- intracellular receptors
Drugs interact w/ receptors which determines the effects of drugs:
- Selectivity- describes the propensity for a drug to bind to 1 target rather than another
- Affinity- describes propensity for a drug to bind to a receptor & is related to the molecular fit & strength of the chemical bond. Some drug-receptor interactions are irreversible, either due because affinity is so strong or because drug modifies structure of its molecular target.
- Agonist
- Antagonists
How do ligand-gated channel receptors work? Example of drugs that use this receptor?
ligand- molecule or ion
channel has Wigan binding site
-when ligand binds to it, channel opens - briefly
allows sodium, potassium, calcium
E.g. GABA receptor, nicotinic acetylcholine receptor
How do g-coupled receptors work? Examples of drugs w/ this receptor?
Pass through cell membrane 7 times
Composed of 3 sub-units: alpha, beta, gamma- together known as G-protien
- in inactive form, alpha subunit is attached to GDP
- When ligand attaches to receptor, affinity for GTP increases, so GTP replaced GDP
- This causes alpha subunit to dissociate from beta- game sub unit- both complex go on to interact w/ other enzymes & proteins (regulate), leading to some response.
3 types of G-protein:
- Gs
- Gi
- Gq
Gs:
- stimulative G- protein
- activates enzyme adenylyl cyclase- which produces cAMP from ATP
- cAMP (2nd messenger)- very important.
Gi:
- Inhibitory g-protein
- inhibits adenyl cyclase, thus lowering levels of cAMP in cell
Gq:
- activates enzymes called PLC
- PLC produces 2 second messengers- DAG & IP3
- DAG leads to different responses through activation of protein kinases
- IP3 produces responses by mediating intra-ceullar release of calcium
Have ability to amplify signals they receive e.g. 1 stimulated G-protein receptor can activate many adenylyl cyclase- results in more cAMP produced, thus amplifying response.
E.g. Acetylcholine receptors, B-adrenoceptors, dopamine receptors, opioid receptors
How do enzyme-linked receptors work?
Have extracellular binding sites (ligands) which hormones & growth factors bind to stimulate enzyme activity in cell.
Most enzyme-linked receptors are of tyrosine kinase type- means display kinase activity & amino acid tyrosine involved.
When ligand binds to 2 receptors, causes conformational change that results in aggregation of both receptors
- Dimer is formed & tyrosine regions get activated & cause ATP to become ATP- results in auto-phosphorylation of receptors.
- Once each tyrosine picks up phosphate group, different inactive intracellular proteins come up & attach to phosphorylated tyrosine
- this causes conformational change in attached protein leading to cascade of activations that produce cellar response
How do transcription factor receptors (intracellular receptors) work?
Located inside the cell rather on cell memorable like others
- ligand has to cross lipid membrane to bind to receptor
Once bonded, wigan-receptor complex moves to nucleus to bind to DNA & regulate gene expression
- lead to synthesis of specific proteins
Each cells DNA has code that synthesise proteins from which different receptors are assembled
-once assembled, receptors embedded into cell membrane & receive & respond to signalling molecules.
E.g. steroid receptors, thyroid hormone receptors, vitamin D receptors, retinoid receptors.
How do cells regulate themselves?
Cells can down-regulate receptors to prevent damaged (signal overload)
- they can be removed from membrane & recycled so fewer number are expressed- decreased sensitivity to signalling molecules
Cell up-regulates when
most receptors get blocked & cell receives weak signals
- means more receptors are inserted into membrane thus increasing sensitivity to signalling molecules.
What is the relationship between dose & response (graph)?
Plotting drug dose against response produces signmodial dose-response curve.
Increase in drug dose (which is proportional to plasma drug conc) produce increasing response but only w/in narrow range of dose
- further increase in dose beyond this range produces little effect.
Full agnostic produces maximum response that receptor is capable of
- partial agonist at same receptor will have lower efficacy
More potent drugs produce biological effects at lower doses- have lower ED50
- lessphortent drug can still have same efficacy if given at higher dose.
Definition of desensitisation?
When biological response to a drug diminishes when given continuously or repeatedly
- possible to restore response by increasing the dose of drug
Definition of Tachyphylaxis
desensitisation that occurs rapidly, sometimes w/ initial dose, Implies depletion of chemicals that may be necessary for pharmacological actions of drug or receptor phosphorylation.
