drugs only module 12-14

Question 1

what are the classes of drugs to treat elevated blood lipids?

Answer 1

statins
bile acid sequestrants
nicotinic acid
cholesterol absorption ihibitors
fibric acid derivatives (fibrates)

Question 2

atorvastatin

Answer 2

low oral bioavailability (14%)
large fraction of absorbed does is extracted by the liver (site of action)
distrib primarily to liver but also to spleen, adrenal glands, & skeletal muscle
metabolized by CYP3A4
elminated in feces

Question 3

rosuvastatin

Answer 3

low oral bioavailability (20%)
large fraction of absorbed does is extracted by the liver (site of action)
distrib primarily to liver but also to skeletal muscle
not extensively metabolized
elminated in feces
*plasma concentrations approx. 2x higher in asian patients compared to caucasian - the initial dose should be 5mg and caution to be used when increasing dose

Question 4

adverse effects of statins

Answer 4

generally well-tolerated
myopathy (muscle injury)
rhabodomyolysis rare but serious - muscle lysis with severe muscle pain & diagnosed with high levels of creatine kinase. it’s also accompanied by high levels of potassium which can lead to kidney problems
hepatotoxicity - possible but low incidence
*teratogen as cholesterol required for synth of cell membranes & many hormones

Question 5

nicotinic acid

Answer 5

inhibits hepatic secretion of VLDL. Since, LDL is a by-product of VLDL degredation, this drug effectively reduces both
increases blood HDL levels
side effects: intense facial flushing, hepatotoxicity, hyperglycemia, skin rash, increased uric acid levels

Question 6

bile acid sequestrants

Answer 6

large + charged molecules that attract and bind bile acids (neg charged), preventing their absorption
causes increased demand for bile acid synth in liver which uses LDL cholesterol
liver increase # of LDL receptors, increasing uptake of LDL from blood
adverse effects: limited to GI tract - constipation and bloating
also, may decrease the absorption of some drugs that are neg. charged such as thiazide diuretics, digoxin, warfarin, and certain antibiotics

Question 7

ezetimibe (Zetia)

Answer 7

cholesterol absorption inhibitor
inhibits transport protein NPC1L1 which absorbs dietary cholesterol
lowers blood LDL cholesterol 15-20%
can produce a compensatory increase in hepatic cholesterol synth so usually an adjunct therapy used with a statin
*there is a combo pill called vytorin which contains a statin and ezetimibe (can reduce LDL cholesterol up to 60%)

Question 8

Fibric Acid Derivatives (Fibrates)

Answer 8

most effective class for lowering plasma triglyceride levels
they also increase HDL, no effect on LDL
bind to PPARalpha in liver
effects of activating PPAR alpha:
1.increased synth of enzyme lipoprotein lipase (gets rid of triglycerides)
2.decreased apolipoprotein C-III production (which normally inhibits lipoprotein lipase)
3. increased apolipoprotein A-I and apolipoprotein A-II levels - increases HDL levels

Question 9

adverse effects of fibrates

Answer 9

increased risk of gallstones
myopathy
hepatotoxicity
*fibrates & statins have some of the same adverse efects so pt.s on both need to be monitored for side effects

Question 10

Loop diuretics

Answer 10

antihypertensive
most effective diuretic
block sodium and chloride ion reabsorption in the thick ascending limb of the loop of henle
reserved for situations requiring rapid loss of fluid like edma, severe hypertension not responding to other diuretics, severe renal failure

Question 11

adverse effects of loop diuretics

Answer 11

hypokalemia (can cause fatal cardiac dysrhythmias)
hypoatremia
dehydration
hypotension

Question 12

thiazide diuretics

Answer 12

most common drug for HTN

2 mech: 1. block sodium and chloride ion reabsorption in distal tubule 2. decreasing vascular resistance

Question 13

adverse effects of thiazide diuretics

Answer 13

hypokalemia (can cause fatal cardiac dysrhythmias)
dehydration
hyponatremia

Question 14

potassium sparing diuretics/aldosterone atnagonists

Answer 14

minimal lowering of BP
inhibit aldosterone receptors in collecting duct
blocking these receptors causes increased sodium excretion and potassium retention
main use is in combo with loop or thiazide diuretics to counteract potential hypokalemia side effect
NOT to be used with ACE inhibitors or renin inhibitors as these drugs conserve potassium

Question 15

adverse effects of potassium sparing diuretics/aldosterone atnagonists

Answer 15

hyperkalemia (can cause fatal cardiac dysrhythmias)

Question 16

beta blockers

Answer 16

tx HTN
“olol”
antagonist
2 mech: 1.block cardiac beta 1 receptors - as blocks binding of catecholamines therefore decreasing CO 2.blocks beta 1 receptors juxtaglomerular cells -blocks renin release which decreases RAAS mediated vasoconstriction therefore decreasing peripheral resistance

Question 17

what is the difference between 1st and 2nd generation beta blockers?

Answer 17

1st gen - inhibit both beta 1 and beta 2 - beta 2 found in lung and can be problematic for those with lung issues
2nd gen- selective for beta 1 receptors

Question 18

adverse effects of beta blockers

Answer 18

selective beta 1: bradycardia, decreased CO, heart failure (rare), rebound hypertension if withdrawn abruptly
non-selective: bronchoconstriction, inhibition of hepatic and muscle glycogenolysis

Question 19

Angiotensin Converting Enzyme (ACE) inhibitors

Answer 19

tx HTN
“pril”
2 mech: 1.decreased production of angiotensin II therefore causing vasodilation and decreased blood vol therefore decrease CO and peripheral resistance 2.inhibit the breakdown of bradykinin - having more bradykinin causes vasodilation

Question 20

adverse effects of ACE inhibitors

Answer 20

generally well tolerated
side effects from decreased angiotensin II - first dose hypotension, hyperkalemia
side effects from increased bradykinin: persistent cough, angioedema
*use with certain NSAIDs may decrease effect of ACE inhibitors

Question 21

Angiotensin Receptor Blockers (ARBs)

Answer 21

tx HTN
“sartan”
block binding of angiotensin II to recptor AT1
cause vasodilation as blocking effect of angiotensin II
also decrease aldosterone release from adrenal cortex causing increase water and sodium excretion

Question 22

adverse effects of ARBs

Answer 22

not really any significant adverse effects

low risk of angioedema

Question 23

Direct Renin Inhibitors (DRIs)

Answer 23

bind to renin and block the conversion of angiotensinogen to angiotensin I
influences entire RAAS pathway
BP lowering effect similar to other HTN drugs

Question 24

adverse effects of DRIs

Answer 24

hyperkalemia - should not be taken with other drugs that may cause hyperkalemia and no potassium supplements
very low incidence of persisten cough and angioedema
diarrhea

Question 25

calcium channel blockers

Answer 25

tx HTN calcium essential for contraction blocks calcium from entering heart and smooth muscle cells, decreasing contraction 2 categories: dihydropyridine calcium channel blockers and non-dihydropyridine calcium channel blockers

Question 26

dihydropyridine calcium channel blockers

Answer 26

"dipine" significantly decrease calcium influx into cmooth muscle of arteries leads to relaxation of muscles = vasodilation -therapeutic doses don't act on heart

Question 27

adverse effects of dihydropyridine calcium channel blockers

Answer 27

flushing, dizziness, headache, peripheral edema, reflex tachycardia, rash

Question 28

non-dihydropyridine calcium channel blockers

Answer 28

block calcium influx in heart and smooth muscles of arteries | decrease peripheral resistance and CO

Question 29

adverse effects of non-dihydropyridine calcium channel blockers

Answer 29

``` constipation dizziness flushing headache edema may compromise cardiac function ```

Question 30

Centrally Acting Alpha 2 agonists

Answer 30

bind to and activate alpha 2 receptors in the brainstem decreases sympathetic outflow to heart and blood vessels inhibiting sympathetic outflow decreases peripheral resistance and CO

Question 31

adverse effects of Centrally Acting Alpha 2 agonists

Answer 31

drowsiness dry mouth rebound HTN if withdrawn abruptly

Question 32

Levodopa (L-Dopa)

Answer 32

tx of parkinson's disease dopamine replacement most effective drug for PD crosses BBB inactive until converted to dopamin in dopaminergic nerve terminals mediated by decarboxylase enzymes cofactor pyridoxine (vit B6) speeds up reaction *usually given with carbidopa which inhibits peripheral metabolism mediated by decarboxylase enzymes so more L-Dopa reaches the brain (10%)

Question 33

adverse effects of L-Dopa

Answer 33

``` nausea and vomiting dyskinesias cardiac dysrhythmias orthostatic hypotension psychosis ``` may experience 2 types of loss of effect: 1 - wearing off - gradual loss of effect 2. on-off - abrupt loss of effect

Question 34

dopamine agonist

Answer 34

tx PD directly activate dopamine receptors on post-synaptic cell membrane not as effective as L-Dopa but usually first line of tx for people with milder symptoms

Question 35

adverse effects of dopamine agonists

Answer 35

hallucinations daytime drowsiness orthostatic hypotension

Question 36

dopamine releaser

Answer 36

tx PD stim release of dopamine from neurons, blocks dopamine reuptake, blocks NMDA receptors (blockade of these decreases dyskinesia side effect of L-Dopa) *used in combo with L-Dopa or alone

Question 37

adverse effects of dopamine releaser

Answer 37

dizziness, nausea, vomiting, lethargy, and anticholinergic side effects

Question 38

Catecholamine-O-Methyltransferase Inhibitor (COMT inhibitor)

Answer 38

Tx PD COMT is exnyme that adds methyl group to dopamine and L-Dopa which inactivates them by inhibiting COMT, greater fraction of L-Dopa avail *often combined with L-Dopa

Question 39

adverse effects COMT inhibitor

Answer 39

nausea orthostatic hypotension vivid dreams hallucinations

Question 40

Monoamine oxidase-B (MAO-B) inhibitors

Answer 40

tx PD MAO-B is an enzyme that metabolizes dopamine and L-Dopa through oxidation, causing inactivation therefore, inhibiting MAO-B allows more L-Dopa to be converted and more dopamine to remain in nerve terminals *often combined with L-Dopa

Question 41

adverse effects of MAO-B inhibitors

Answer 41

insomnia, orthostatic hypotension, dizziness *at therapeutic doese MAO-B inhibitors used to tx PD don't inhibit MAO-A in the liver and so they don't cause hypertensive crisis when pt.s eat tyrosine containing foods

Question 42

aticholinergic drugs

Answer 42

tx PD block binding of acetylcholine to receptor may increase effectiveness of L-Dopa decrease incidence of diaphoresis, salivation, and incontinence (symptoms of relative excess of acetylcholine)

Question 43

adverse effects of aticholinergic drugs

Answer 43

dry mouth, blurred vision, urinary retention, constipation, tachycardia *elderly people may experience severe CNS effects such as hallucination, confusion, and delirium so usually these drugs not given to elderly

Question 44

cholinesterase inhibitors

Answer 44

tx AD inhibit metabolism of acteylcholine by enzyme acetylcholinesterase allows more acetylcholine to remain in synaptic cleft only able to enhance cholinergic transmission is remaining healthy neurons only effective in approx 25% of pt.s

Question 45

adverse effects of cholinesterase inhibitors

Answer 45

nausea and vomiting diarrhea insomnia

Question 46

NMDA receptor antagonists

Answer 46

tx AD in AD there is excess glutamate release so the NMDA receptor remains open allowing excess calcium into cells (excess calcium detrimental to learning/memory & causes degredation of neurons) NMDA receptor antagonists blocks calcium influx into the post-synaptic neuron

Question 47

adverse effects of NMDA receptor antagonists

Answer 47

well tolerated | side effects same incidence as placebo group in trials

Question 48

what are the two classes of drugs to treat schizophrenia?

Answer 48

conventional antipsychotics atypical antipsychotics *differ in mech of action and side effect profile

Question 49

conventional antipsychotics

Answer 49

block dopamine 2 (D2) receptors in the medolimbic area of the brain also block (to a lesser extent) acetylcholine, histamine, and norepinephrine more effective at treating + symptoms initial effects 1 or 2 days but improvement 2 to 4 weeks

Question 50

adverse effects of conventional antipsychotics and atypical

Answer 50

shared: anticholinergic effects, orthostatic hypotension, sedation Uniqe to conventional: extrapyramidal symptoms, sudden high fever, skin reactions Unique to atypical: weight gain, risk of devel type II diabetes

Question 51

what are extra pyramidal symptoms?

Answer 51

a.k.a. EPS movement disorders that resemble symptoms of PD d/t blockade of D2 & 4 types 1. acute dystonia - involuntary spasm face, tongue, neck, or back. occurs early in therapy 2. parkinsonism - same as symptoms of PD. may treat with anticholinergic to help relieve. L-Dopa must be avoided> 3. Akathesia - pacing, squirming, and a desire to continually be in motion. early in tx. 4. tardive dyskinesia - irreversible so early detection is important. includes involuntary twisting and writhing of face and tongue along with lipsmacking. should be switched to atypical antipsychotic

Question 52

atypical antipsychotics

Answer 52

block D2 and 5-HT1A and 5-HT2A receptors affinity for D2 is very low therapeutic action attributed to blocking of the 5-HT receptors

Question 53

compare and contrast conventional with atypical antipsychotics

Answer 53

comapred with conventional, atypical antipsychotics... 1. Same efficacy vs. + symptoms 2. greater efficacy vs. - symptoms 3. much lower risk of devel. extrapyramidal symptoms, esp. tardive dyskinesia. attributable to decreased D2 blocking

Question 54

what are the 4 mech of action that antiepileptic drugs (AEDs) work by?

Answer 54

blocking sodium channels blocking voltage-dependent calcium channels glutamate antagonists potentiating the actions of GABA

Question 55

Phenytoin

Answer 55

antiepileptic drug blocking sodium channels - prolong the inactivation state of the sodium channel and therefore don't allow neurons to fire at a high freq all seizures except absence metabolic capacity by liver limited, so easy to spike blood levels narrow therapeutic range

Question 56

adverse effects of phenytoin

Answer 56

sedation, gingival hyperplasia, skin rash | *teratogenic

Question 57

blocking voltage-gated calcium channels

Answer 57

inhibition of voltage-gated calcium channels suppresses neurotransmitter release

Question 58

glutamate antagonists

Answer 58

blocking glutamate decreases CNS excitation | -glutamate binds to NMDA and AMPA receptirs so the antagonists bind to these

Question 59

potentiating the actions of GAVA

Answer 59

increase inhibitory stimuli in the CNS and therefor suppress seizure activity - these drugs mediate their effects in 4 different ways: 1. enhancing binding of GABA to its receptor 2. stimulating GABA release 3. inhibiting GABA reuptake 4. inhibiting GABA metabolism

Question 60

talk about traditional vs. newer antiepileptic drugs

Answer 60

traditional - phenytoin, valproic acid newer - lamotigrine *newer = decreased side effects, decreased propensity to induce hepatic drug metabolizing enzymes

Question 61

classes of antidepressants

Answer 61

tricyclic antidepressents selective serotonin reuptake inhibitors (SSRIs) selective serotonin/norepinephrine reuptake inhibitors (SNRIs) monoamine oxidase inhibitors (MAOIs)

Question 62

tricyclic antidepressents (TCAs)

Answer 62

inhibit reuptake of serotonin and norepinephrine | tx major depression

Question 63

adverse effects of tricyclic antidepressents

Answer 63

``` anticholinergic effects sedation orthostatic hypotension decreased seizure threshold cardiac toxicity (rare but serious) weight gain sexual dysfunction ```

Question 64

selective serotonin reuptake inhibitors (SSRIs)

Answer 64

block serotonin reuptake less incidence of side effects than TCAs *most common tx and most commonly used in major depression

Question 65

adverse effects of selective serotonin reuptake inhibitors (SSRIs)

Answer 65

weight gain sexual dysfunction insomnia serotonin syndrome - increased serotonin can cause agitation, confusion, anxiety, hallucinations, incoordination *may appear within 3 days of therapy & stop when drug is stopped

Question 66

selective serotonin/norepinephrine reuptake inhibitors (SNRIs)

Answer 66

block reuptake of norepinephrine and serotonin tx major depression faster onset of action (than TCAs)

Question 67

adverse effects of selective serotonin/norepinephrine reuptake inhibitors (SNRIs)

Answer 67

nausea diastolic hypertension sexual dysfunction

Question 68

monoamine oxidase inhibitors (MAOIs)

Answer 68

MAO-A enzymes metabolize serotonin and norepinephrine MAO-B enzymes metabolize dopamine MAOIs inhibit both types of MAO enzymes tx atypical depression and dysrhythmia

Question 69

adverse effects of MAOIs

Answer 69

CNS excitation - anxiety, insomnia, agitation orthostatic hypotension **hypertensive crisis if taken with tyrosine containing foods

Question 70

three major groups of drugs to treat bipolar disorder

Answer 70

mood stabilizers antipsychotics antidepressants

Question 71

mood stabilizers

Answer 71

1.relieve symptoms during manic/depressive episodes 2.prevent recurrence of episodes 3. don't worsen the manic or depressive symptoms primary drugs: lithium and valproic acid

Question 72

lithium

Answer 72

mood stabilizer thought to alter release and uptake of glutamate and block the binding of serotonin narrow therapeutic range and plasma concentrations may be altered by sodium sodium loss from body may increase the plasma concentrations and cause toxicity

Question 73

antipsychotics for bipolar

Answer 73

used acutely for manic symptoms and long term to stabilize mood atypical antipsychotics are preferred over conventional antipsychotics d/t less risk of extrapyramidal sympoms

Question 74

antidepressants for bipolar

Answer 74

tx depressive episodes | always combined with mood stabilizer

Question 75

drugs treat anxiety

Answer 75

benzodiazepines (BDZs) buspirone antidepressants

Question 76

benzodiazepines (BDZs)

Answer 76

first line therapy potentiaing action of GABA they are not agonists - they bind to a different site on the receptor and cause increased binding of endogenous GABA causes CNS depression tx generalized anxiety disorder and social anxiety disorder

Question 77

adverse effects of benzodiazepines (BDZs)

Answer 77

``` CNS depression anterograde amneisa respiratory depression teratogenic tolerance withdrawal ```

Question 78

Buspirone

Answer 78

acts on serotonergic and/or dopaminergic neurons useful in tx clts who use alcohol (no CNS depression) tx generalized anxiety disorder its effect on anxiety if slow going so not good for immediate relief

Question 79

adverse effects of Buspirone

Answer 79

generally well-tolerated and non-sedating dizziness lightheadedness excitement

Question 80

which antidepressants are good for treating generalized anxiety disorder?

Answer 80

SSRIs and SNRIs

Question 81

which antidepressants are good for treating panic disorder/agoraphobia?

Answer 81

SSRIs, TCAs and MAO inhibitors | *SSRIs preferred as better tolerated

Question 82

which antidepressants are good for treating OCD?

Answer 82

SSRIs first line therapy | *also require behavioural therapy

Question 83

which antidepressants are good for treating social anxiety disorder?

Answer 83

SSRIs first line therapy although BDZs may also be used | *BDZs provide immediate relief while SSRIs take a while to kick in

Question 84

PTSD

Answer 84

no good evidence that any drug is effective in treating PTSD