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
