Pharmaceutical Priniciples Flashcards
Define pharmacokinetics
Study of time course of drug concentration in body
What body dues to drag
Name the 6 aspects of pharmacokinetics
Lad-met Liberation Absorption! (Bioavailability) Distribution! Vd Metabolism! (Half life) Excretion! (Clearance) Toxicity
Bioavailability formula?
Auc oral / AUC IV
Name 3 important factors that influence bioavailability
- Absorption: how much reaches target site. Poor absorption = low bioavailability
- first pass metabolism: metabolism of drug prior to reaching systemic circulation by gut wall, intestinal flora and liver. Highly metabolised. = low bioavailability
- Food interactions: May influence absorption or metabolism
Define steady state
Drug absorption = elimination and Cp (plasma conc) plateaus
How many t1/2 take to reach steady state for first order kinetic drugs?
4-5
Volume of distribution formula?
Vd = total amount drug in body (mg) / drug Cp (mg/l)
Define low Vd (4)
<15 l. Mostly confined to systemic circulation Higher Cp Faster metabolism/ elimination Eg penicillin
Define high Vd (5)
>40 L Spread throughout body Lower Cp Slower metabolism /elimination Eg tricyclic antidepressants
Importance of volume of distribution?
Determine loading dose.
Define half life
Time necessary for Cp of drug to decrease by half
Why is half Life important?
Used to determine steady state (time course of drug accumulation and elimination ) and dosing interval
How calculate loading dose from volume of distribution?
Vd x cp
Name 3 important factors that influence half life
- Elimination rate - high clearance reduce half life
- volume of distribution- direct relationship
- patient factors- genetics, food or drug interactions
How does a short half life affect duration of action, dosing frequency, compliance, steady state and side effects?
- Short duration
- increased dosing
- lower compliance
- steady state reached earlier
- side effects disappear faster: short washout
How does a long half life affect duration of action, dosing frequency, compliance, steady state and side effects?
- Longer duration
- decreased dosing
- higher compliance
- steady state reached later
- side effects disappear slower:long washout
Define first order kinetics and how t1/2 , concentration and decline applies
Constant fraction of drug eliminated per unit of time
• T1/2 constant
• Concentration independent
• doubling dose doubles Cp
• undergoes exponential decline - will not accumulate, predictable, never completely disappear but reach clinically insignificant conc
• most drugs
Define zero order kinetics and how t1/2 , concentration and decline applies
Constant amount of drug eliminated per unit time
. T 1/2 variable
• concentration dependant due to saturable kinetics.
• high Cp require more time to clear thus T1/2 increase
• linear decline - saturable parameters, ADME are rate limiting factors, will eventually completely disappear
• only few drugs eg phenytoin, alcohol
name 3 examples of drugs that follow zero order kinetics
- Phenytoin
- alcohol
- Aspirin
Formula for clearance?
Cl (L /h) = rate of elimination (mg/h) / drug cp (mg/l)
What is the relationship of clearance to vd and T1/2
Cl (L/h) = (0,693 x Vd ) / t1/2
How calculate clearance of Iv drugs?
Cl (L/h) = dose / area under curve
How calculate clearance of oral drugs?
Cl (L/h) = (bioavailability x dose ) / area under curve
Why is clearance important?
Determine maintenance dose at steady state and indicate route of elimination when compare hepatic and renal blood flow
Maintenance dose rate formula?
Maintenance dose rate (mg /h ) = cl (L /h) x CSS (conc steady state) (mg /L)
How’s total elimination or clearance calculated?
Cl (total) = cl (hepatic) + cl (renal) + cl (other)
Name 6 inducers of CYP 450
P Crabs Phenytoin Carbamazepine Rifampicin Alcohol (chronic) Barbiturates St John's wort
Name 7 inhibitors of CYP 450
GV pacman Grapefruit Valproate ' Protease inhibitors Azole antifungals Cimetidine Macrolide's except azithromycin Amiodarone Non-DHP CCBs : diltiazem and verapamil
Which drugs types are most susceptible to drug drug interactions? (3)
• Narrow therapeutic index
. High first pass metabolism
• single route of elimination
Define pharmacodynamic drug interactions
Alternations to drug’s effect in body by additive, synergistic or antagonistic interactions
Define additive pharmacodynamic interaction
Both drugs exert similar effect and the sum of these 2 drugs is the result
Define synergist pharmacodynamic interaction
Both drugs exert similar effect and result in activity greater than the sum of both drugs.
Define pharmacokinetic drug interactions
Alteration to drug’s concentration in body by ADME
Name 6 factors that may affect absorption and result in pharmacokinetic drug interactions
• Adsorption (drug solubility)
• gut flora - alter bioavailability
• protein carriers
• gut ph _ influence ionisation of compounds (uncharged cross easier than ionised)
. Gastric motility
• Transporter function - p-gp transporters
Define adsorption
Binding or adsorption agent in gut binds or entraps agent in structure and doesn’t release it easily, forming insoluble complexes
What is p-glycoprotein and what is its function?
Protective measure to efflux cytotoxins from intracellular compartment back into extra cellular space or gastric lumen but also efflux drugs
Therefore p-gp blockers cause higher accumulation and bio availability leadin to adverse effects, while modulation reduce bioavailability and may lead to therapeutic failure
Name 3 factors that may affect drug distribution and result in a drug drug reaction
- 2 plasma proteins- albumin (binds mostly acidic drugs, but also basic ) and alpha acid glycoprotein (bind basic drugs)
- plasma bound drugs- pharmacologically inert and can’t be filtered through kidney
- free-fraction of drug- bioactive, may be metabolised and removed
Name 2 important factors that may effect drug metabolism and cause pharmacokinetic drug interaction
- Enzyme induction: treatment failure due to decreased drug plasma concentrations of active drugs or increased pro- drug or toxic metabolite formation causing adverse effects
- enzyme inhibition: by blockage (acute) or down - regulation (chronic) -higher plasma concentrations leading to Ae or decreased active metabolites leading to treatment failure.
Name 4 renal factors that may affect drug excretion and cause pharmacokinetic drug interaction.
• Urinary ph : ionisation - acidic urine excrete weak bases more and vice verse
• competition for transporters
• renal blood flow
. Active tubular secretion - competition for elimination in kidney tubules
Name the 3 roles of CYP450
- Formation steroids, cholesterol, arachidonic acid metabolites
- metabolism and detox of many compounds After ingestion (xenobiotics)
- Drug metabolism = new and secondary role
Name pharmacogenetic differences in CYP2D6
5-10% Caucasians poor metabolisers
> 25% East Africans ultrapid
Name the 2 criteria for selection of candidate gene for pharmacogenetic analysis
- Genotype predictive of phenotype → minimal effect of environmental factors
- multiple genotype variations leading to variations in phenotype (enzyme activity) - highly polymorphic
Name the 4 metaboliser statuses and describe
- Poor metaboliser: more toxicity and side effects of active drugs, and therapeutic failure of pro-drugs
- intermediate
- extensive
- ultra fast therapeutic failure of active drugs, more toxicity and adverse effects of prodrugs
Name 6 drugs metabolised by CYP2D6
- Antidepressants: tricyclics and ssri
- analgesics: codeine (prodrug metabolised to morphine).
- antipsychotics including risperidone
- antiarrhythmics
- anti-emetics
- beta blockers
Name 3 drugs metabolised by CYP2C19
- Proguanil (prodrug metabolized to cycloguanil) (malaria prophylactic)
- clopidogrel (prodrug- active inhibit. platelet aggregation)
- PPI
Name a drug metabolised by CYP2C9
Warfarin
Which CYP450 enzyme is most abundant?
CYP3A4
Name, in sequence, the steps of drug discovery and development. (8)
- Early exploratory discovery
- lead identification ( identify hits first)
- lead optimisation
- preclinical transition
- phase 1 clinical development
- phase 2
- phase 3
- Registration
What are the national core standards NCS (5)
• Tell us what to do to achieve good basic services
• require managers and staff of all public hospitals and clinics to take immediate action
• NHC resolved that NCS must be followed in every province, health district, public health facility. Private encouraged
• can achieve by better teamwork , clearer direction and stronger management. District and provincial help or funding may be needed for some.
. Good standard of basic health care anywhere in country.
What is the scope of the National core standards? (7)
93 individual standards grouped into 7 main categories or domains.
- Patient rights
- Clinical governance and care.
- Clinical support services
- Health promotion and disease prevention
- Leadership and governance.
- Operational management
- Facilities and infrastructure
Name 4 factors that influence rational drug prescribing.
- Diagnosis and prognosis
- Drug factors: pharmacokinetic, pharmacodynamic, safety, cost.
- Prescriber factors: knowledge of disease and drugs, experience, follow up
4 patient factors: comorbidities, allergies etc
Name the 5 “rights” of rational drug prescribing
- Right drug
- right patient
- right dose
- right time
- right route
Name 6 steps in rational dispensing
- Receive and validate prescription
- understand interpretation: symbols, dose, potential interactions
- prepare and label items for use
- make final check
- record maintenance
- issuance, counselling and follow ups
Name 6 drug interactions with grapefruit juice
All due to inhibit cyp3a4 and reduced mRNA expression • amiodarone: arrhythmia . Cyclosporine: immunosuppression . Diazepam: increased sedation • Quitapine: hallucinations, hypotension . Loperamide: severe git pain • oxycodone: bradycardia, hallucinations
Name 6 drug interactions with St John’s wort
• Warfarin: induce cyp3a4 and cyp2c19 - increased coagulation treat fail
. Cyclosporine: induce cyp3a4 and cyp2c19 - treat fail organ reject
. Contraceptives fail: induce cyp3a4 and cyp2c19
• antiretrovirals fail: induce cyp3a4 and cyp2c19
• ssri:increased plasma serotonin- serotonin syndrome
• aminolevulinic acid: increased photosensitive- skin irritation
Name 5 drugs metabolised by n-acetyltransferase
- Nydrazid, isoniazid ( anti tb)
- sulfonamides antibiotics
- procainamide (anti-arrhythmic)
- hydralazine (antihypertensive)
- caffeine
What makes a prescription different for schedule 6 drug? (3)
• prescription may not be repeated
. Abbreviations and Latin terms must be followed by official language in written format
• dosage and quantity must be written in words
If you do not report forgery of sick note, what can hpcsa do? (4)
• Caution •Reprimandmants • guilty of unprofessional conduct • fines up to 15000 According to section 23 of basic conditions of employment act 75 of 1997 and rule 16 of hpcsa ethical rules of conduct
Which act addresses registration of medicines and medical devices, scheduling, control manufacturers wholesalers distributors and persons compounding and dispensing medicines?
Medicines and related substances act 101 of 1965
Name 4 factors that medicine scheduling depends on
• Dosage • dosage form eg oral vs inject . Pack size (amout tablets) • amount active ingredients To prevent abuse
How old must person be to purchase schedule 1 drug unless prescribed?
14
Name 3 purposes of drug scheduling
- Limit and control use by medical professionals
- prevent misuse or wrongful use
- prevent drug abuse
Name 3 drugs that may be prescribed by nurse
- schedule 0: aspirin, paracetamol (any can prescribe)
- Schedule 1: antimalaria prophylax (any )
- Schedule 2: antihistamines, low strength cortisone cream, combined analgesia, cough medicines
- schedule 3: oc, oral hypoglycaemic, antihypertensives, insulin, inhalation preparations
- schedule 4 limited in some circumstances: antibiotics , hrT, steroid creams
Which drugs. may only be prescribed by doctors? (2)
- Schedule 5: testosterone replacements, antidepressants, tranquilizers, some narcotics and hypnotics
- schedule 6 : morphine, pethidine, hypnotics (flunitrazepam), methylphenidate
