Background PK/PD Flashcards
Why do older adults generally have less total body water than younger adults?
a. As functional cells die during the aging process, less water is needed.
b. The muscle mass of older adults is smaller than the muscle mass of younger adults.
c. Older adults have a smaller extracellular fluid to intracellular fluid ratio than younger adults.
d. The plasma volume of older adults is decreased to reduce the risk for excess fluid volume and heart failure.
Muscle cells are a large portion of the body and contain more water than many other types of cells. As a person ages, the size of muscle cells tends to decrease and the volume of total body water decreases in proportion to this loss of muscle cell mass.
Which adverse drug events in the elderly can be attributed to pharmacodynamic causes?
a. Constipation/confusion due to diphenhydramine and paroxetine.
b. Respiratory depression due to benzodiazepines.
c. AKI due to combination of ACE-I and NSAIDs.
Paroxetine class and indication
Class: Selective serotonin reuptake inhibitor (SSRI).
Treatment of
- Major depressive episode.
- Obsessive Compulsive Disorder (OCD).
- Panic disorder with and without agoraphobia.
- Social anxiety disorders/social phobia.
Diphenhydramine class and indication
Class: ethanolamine-derivative H1 receptor antihistamine. It is an antihistamine with anticholinergic.
Cough and colds: cough suppressant formulation
Seasonal allergies: in nasal decongestant formulation
Define frailty clinically
Frailty is described as a ‘reduced ability to withstand illness without loss of function’
What are the two changes in drug absorption seen with the elderly populations?
Changes to active transport. Thus reduced absorption of Vitamin B12, iron and calcium through active transport.
Reduced dopa decarboxylase in gastric mucosa. Increased Levodopa absorption.
How is first pass metabolism altered in the elderly population. And what are the potential effects?
Reduced liver mass and blood flow. Therefore increased bioavailability of the drugs with first pass metabolism and reduced activation of pro-drugs in the liver.
Name a drug that undergoes extensive first pass. Name is MAO, Class and indication.
Propranolol (highly lipophilic) non selective beta adrenergic receptor blocker. Used: Therapy of hypertension, cardiac arrhythmias, angina pectoris and hyperthyroidism
Labetalol: nonselective antagonist at beta-adrenoceptors and a competitive antagonist of postsynaptic alpha 1-adrenoceptors.
Name a prodrug and what is is converted to.
Give its MAO and indication
Enalapril is ACE-I used in management of hypertension and congestive heart failure. It is hydrolysed to release the active converting enzyme inhibitor enalaprilat.
How is drug distribution affected in the elderly population?
Relative reduction in total body water results in reduced volume distribution and increase serum concentration of water-soluble drugs.
Relative increase in adipose tissue. Therefore increased volume distribution and longer half life of lipid soluble drugs.
Name water soluble drug.
MAO and indication
Gentamicin is hydrophilic drug log S -1.6. It an aminoglycoside.
Digoxin Class 5 antiarrhythmic drugs( cardiac glycoside).
Name drug that is highly lipophilic
MAO and indication
Diazepam has log P 3.08 and it is a benzodiazepine.
How is drug clearance altered in elderly population ?
Reduction in glomerular filter action rate.
Reduction in liver mass and blood flow.
Name the classes of drugs that is cleared renally?
Water-soluble antibiotics
Diuretics
Digoxin
Lithium
Name a couple of drugs the have high hepatic extraction ratio
Clomethiazole
Glyceryl trinity ate
Propranolol
Draw the flowchart summarising the possible mechanism by which water homeostasis alteration can affect muscle function and promote frailty?
Drug A is weakly basic drug with a pKa of 7.8. If administered orally, at which of the following sites of absorption will the drug be able to readily pass through the membrane?
A. Mouth (pH 7.0)
B. Stomach (pH 2.5)
C. Duodenum (pH 6.1)
D. Jejunum (pH 8.0)
E. Ileum (pH 7.0)
D
NN610 is an investigational cholesterol-lowering agent. NN610 has a high molecular weight and is extensively bound to albumin. NN610 will have a _______ apparent volume of distribution (Vd)?
A. High
B. Low
C. Extremely high
D. Normal
B
Equation for Vd
Where F is the bioavailability: AUC IV/ AUC Drug from route administration.
Cp: peak plasma concentration.
Progonosis of CKD by GFR and albuminuria Categories
Common drugs renally excreted.
LMWH is 80% renally cleared.
a. True
b. False
True
UFH has variable pharmacokinetics due to it being mixture of fractionated and unfractionated and so requires continuous IV
a. True
b. False
True
SSRI and warfarin is what
a. Pharmacokinetic interaction
b. Pharmacodynamic interaction
B
Both increase the risk of bleeds.
Equation for loading dose
Equation for renal function.
Equation for half-life
Equation for Ke
What is the general reason that the ultimate desired maintenance dose of Carbamazepine is much higher than the beginning dose?
A) Pharmacodynamic drug tolerance
B) Disease progression
C) Metabolic enzyme autoinduction
D) Renal function increased
E) Carbamazepine is a high hepatic extraction drug
C) Metabolic enzyme autoinduction
M.T., 45-year-old, 65 kg female, is to be started on intravenous phenobarbital sodium (S=0.9). Calculate a loading dose (LD) to yield a phenobarbital concentration of 20 mg/L and the daily maintenance dose (MD) to maintain the phenobarbital concentration of 20 mg/L.
A) LD = 1400 mg, MD = 160 mg
B) LD = 700 mg, MD = 80 mg
C) LD = 1000 mg, MD = 140 mg
D) LD = 1500 mg, MD = 144 mg
E) LD=900g,MD=120g
C
Equation steady state concentration
Where R0= dose./Hr
- A 4 2 - y e a r - o l d m a n r e c e n t l y d ia g n o s e d w i t h g e n e r a l i z e d a nxiety disorder had started a treatm ent w ith sertraline, but the drug caused some sexual dysfunction, and the psychiatrist de-
cid ed to sw itch to a sh or t cou rse of alp razolam . W h ich of t h e
fo llo w in g m o le c u la r a c t io n s o n n e u r o n a l m e m b r a n e s m o s t
likely m e d iate d t h e t h e rap e u t ic e e ct of alp razolam in t h e
patient’s disorder?
A. De cr e a s e d o u t w a r d Na + cu r r e n t
B. In cr e a s e d in w a r d Cl − current
C. De cr e a s e d o u t w a r d K+ cu r r e n t
D. In cr e a s e d in w a r d Ca 2+ cu r r e n t
E. In cr e a s e d in w a r d H current
B Benzodiazepines binds to receptors located at the interface between alpha and gamma subunit of the GABAa receptor-chloride ion
A 6 3 - y e a r - o l d w o m a n w a s r e fe r r e d t o a p s y c h i a t r i s t b e c a u s e
o f e a sy fat igu e , w o r r y, ir r it a b ilit y, a n d d i cu lt y co n ce n t r at -
in g. Th ese sym p tom s h ad bee n p resen t alm ost con t in u ou sly
during the daytime since she retired from her job as a school-
teacher 1 m onth ago. She told the doctor that those symptom s
were unbearable and that she wanted to die. A preliminary
diagnosis of severe generalized anxiety disorder was m ade,
and a treatm ent w ith sertraline and diazepam was prescribed.
Which of the following adverse e ects were most likely to
occur during the rst days of therapy?
A. Ex c i t e m e n t a n d i r r i t a b i l i t y
B. Men tal con fusion an d an terograde am n esia
C. Ex c e s s iv e s e d a t i o n a n d d r o w s i n e s s
D. Re s p i r a t o r y d e p r e s s i o n a n d a p n e a
E. Dist u r b in g d r e a m s a n d e a r ly aw a ke n in g
C
A 4 4 - y e a r - o l d m a n c o m p l a i n e d t o h i s p h y s i c ia n o f b e i n g t i r e d ,
ir r it able, an d ten se, w it h frequ en t stom ach u p set an d d iar-
rhea. The m an denied past or present use of any illicit drugs
or alcohol. Past m edical history of the patient was signi cant
fo r p e p t ic u lce r, p r e s e n t ly t r e a t e d w it h o m e p r a z o le , a n d fo r
myasthenia gravis, presently treated with neostigmine. After
fu r t h e r clin ical assessm e n t , a d iagn osis of ge n e ralize d an xi-
ety disorder was m ade, and an appropriate therapy was pre-
scribed. Which of the follow ing drugs would be relatively
con t rain d icated for t h is p at ien t?
A. Ve n l a f a x i n e
B. Bu s p i r o n e
C. Pa r oxe t in e
D. Dia ze p a m
E. Se r t r a lin e
D Because of their m uscle relaxant properties, benzodiazepines are relatively contraindicated in myasthenia gravis.
A−C, E Al l o f t h e s e a g e n t s a r e r s t - o r s e c o n d - c h o i c e d r u g s in t reat in g ge n eralized an xiet y d isord er. Th ey lack m u scle relaxant activities and therefore are not contraindicated in myasthenic patients.
A 1 6 - y e a r - o l d g i r l b r o u g h t b y a m b u l a n c e t o t h e e m e r g e n c y
department was diagnosed with status epilepticus and was
given an in travenous injection of a drug that binds to the α
subunit of the GABA
low in g d r u gs w as m ost likely ad m in ist e re d ?
A. Lo r a z e p a m
B. Zo lp id e m
C. Flu m a z e n il
D. Ph e n yt o in
E. Va l p r o i c a c i d
Benzodiazepines (diazepam, lorazepam)
A 7 8 - y e a r - o l d m a n w a s a d m i t t e d t o t h e h o s p i t a l b e c a u s e o f
a broken leg. His w ife reported that he was walking in the
dining room when he suddenly lost his balance and fell down.
Th e m a n h a d b e e n s u e r in g fr o m a t r ia l b r illa t io n , in s o m -
n ia , h yp e r t e n sio n , a n d a n xiet y. Th e p at ie n t ’s m e d icat io n s o n
adm ission were atenolol, warfarin, diazepam , losartan, and
hydrochlorothiazide. Which of these drugs was m ost likely
to have contributed to the patient’s accident?
A. At e n o l o l
B. Warfarin
C. Dia ze p a m
D. Lo s a r t a n
E. Hyd roch lorot h iazid e
C Th e lin k b e t w e e n b e n z o d ia z e p in e u s e a n d fa lls is w e ll d o c-
umented and may result from balance impairment, seda-
tion, and muscle relaxant e ects. Although tolerance can
develop to these benzodiazepine actions, elderly people may
experience persistent impairm ent. The chronic use of ben-
zodiazepines is therefore relatively contraindicated in the
eld e r ly.
A, B, D, E Th e s e d r u g s d o n o t i n c r e a s e t h e r i s k o f fa l l- related fractures.
Define steady state concentration
A dynamic equilibrium in which drug concentrations consistently stay within therapeutic limits for long, potentially indefinite, periods.
A premature neonate who weighs 1.5kg and is 3 days old requires a HIGHER dose of benzylpenicillin on a mg/kg basis than an adult to achieve the same plasma concentration. Which ONE of the following statements explains why?
a Benzylpenicillin crosses the Blood Brain Barrier (BBB) more readily in neonates
b Neonates have a higher volume of distribution for water soluble drugs
c Benzylpenicillin is excreted from the kidney more slowly in neonates
d Protein binding of benzylpenicillin is lower in neonates.
(B) Highly water-soluble compounds, such as gentamicin, have larger volumes of distribution in neonates compared to adults
Which ONE of the following statements about breastfeeding is FALSE?
a Drugs that are highly protein bound should be avoided in breastfeeding
b Breastfeeding reduces the rate of ovarian cancer in the mother
c Breastfeeding reduces the risk of allergies in a baby
d Drugs with a short half life are preferred to those with a
long half life while breastfeeding
(A) less fee drug fraction so less drug will be found in the breastmilk.
Which ONE of the following drugs does NOT interact with warfarin?
a Erythromycin
b Aspirin
c Paracetamol
d Carbamazepine
(C)
Which ONE of the following interactions is NOT a pharmacokinetic interaction?
a Theophylline and erythromycin
b Rifampicin and warfarin
c Carbamazepine and prednisolone
d Diazepam and alcohol
(d)
Which ONE of the following drugs is NOT used in the acute treatment of stroke?
a Simvastatin
b Clopidogrel
c Aspirin
d Alteplase
(a)
Which ONE of the following is a normal resting respiration rate for an adult?
a 25 – 30 respirations /minute
b 5 – 10 respirations /minute
c 15 – 20 respirations / minute
d 10 – 15 respirations / minute
c 15 – 20 respirations / minute
A plasma digoxin level is taken and found to be extremely HIGH. Which ONE of the following statements is NOT a possible explanation for the result?
a The level may have been taken after steady state
b The patient may have taken an unintentional overdose
c The patients renal function may have deteriorated
d The patient may be taking another drug that reduces clearance of
digoxin
(a)
In therapeutic drug monitoring, it is important that drug levels are checked once steady state has been
reached. How many half lives (t1/2) does it take to reach steady state?
a 3
b 6
c 4.5
d 12
(c) 4.5
Which ONE of the following pharmacokinetic parameters is NOT required to calculate a loading
dose?
a Volume of distribution (Vd)
b Desired plasma concentration (Cp)
c Bioavailability (F)
d Clearance (Cl)
d
Atherosclerosis is BEST described as a pathological condition where:
a Cholesterol blocks arteries
b High pressure in arteries eventually thickens their walls
c Fat and fibrin become deposited within arterial walls
d Arteries rupture
(C) Atherosclerosis is a common condition that develops when a sticky substance called plaque builds up inside your artery.
Which ONE of the following sets of symptoms is NOT typical of heart failure?
a Fatigue and shortness of breath on exertion
b Weakness, shortness of breath and central chest pain
c Fatigue and shortness of breath when sleeping or lying
flat
d Shortness of breath and ankle swelling
(a) shortness of breath on exertion is typical of angina. CHF SOB is chronic.
Which ONE of the following medicines is used acutely to prevent arrhythmias in patients with hyperkalaemia?
a Calcium gluconate 10%
b Calcium resonium
c Insulin and dextrose
d Furosemide
A. Calcium gluconate
Equation for Cpss
Equation for Half life
Equation for elimination rate constant.
