DRUGS TO LOWER BLOOD CHOLESTEROL & TRIGLYCERIDES
Drug Category Mechanism of Action
HMG-CoA Reductase Inhibits hepatic synthesis of
Inhibitors (Statins) cholesterol by inhibiting HMG CoA
reductase (converts HMG CoA
mevalonic acid)
Causes upreg of hepatic LDL
receptors, lets liver remove more
chol from blood
Net effects:
o decreases in [LDL],
[triglycerides]
o increase in [HDL]
Nicotinic Acid Inhibits hepatic secretion of VLDL
(Niacin) Since LDL = byproduct of VLDL
degradation, nicotinic acid reduces
VLDL & LDL
Net effects:
o Decreases in [VLDL],
[LDL]
o Increase in [HDL]
Bile-Acid Large, positively charged molecules
Sequestrants Bind to bile acids (-ve charge),
prevent reabsorption (usually,
95%+ of bile acids absorbed)
Liver will need to synth more bile
acids using CYP7A1 mediated chol
metabolism, will take up more LDL
from blood to do so
Net effect: decreased plasma [LDL]
Cholesterol Inhibits NPC1L1: responsible for
Absorption intestinal uptake of majority of
dietary cholesterol
Inhibitors
Diseases/Conditions Treated
Primary prevention of coronary
heart disease (effective even in low
risk patients w/ no history)
Secondary prevention: prevent
recurrence of cardiovasc events
(effective for higher risk patients)
Side Effects Examples Additional Notes
Generally well tolerated Atorvastatin (Lipitor) Among highest prescribed drugs in
Myopathy (muscle injury) Low oral bioavail (14%) world
most common Largely extracted by liver
mild = muscle aches, weakness Metabolized by CYP3A4
Rhabodomyolysis Elim in feces, min renal excretion
Muscle lysis w severe pain
Rare but serious Rosuvastatin (Crestor)
Low incidence of hepatotoxicity: should Low oral bioavail (20%)
perform liver fxn tests before + during. Largely extracted by liver
Chol req’d for cell memb & horm synth: Distr mostly to liver, also to
statins should not be used in skeletal musc
pregnant/trying females Not extensively metabolized
Elim in feces, min renal excretion
Plasma conc approx 2x higher in
Asian patients cf Caucasian (for
Asians should be 5mg, use caution
when increasing dose)
Side effects limit use in many
patients
Intense facial flushing
Hepatotoxicity
Hyperglycemia
Skin rash
Increased uric acid levels
Not absorbed at all, therefore have
no systemic side effects
Predom side effects limited GI
tract: e.g. constipation, bloating
Since designed to bind to –vely
charged molecules, may decrease
absorption of thiazide diuretics,
digoxin, warfarin, certain
antibiotics
Ezetimibe (Zetia): decrease Often prescr along w statin,
intestinal chol absorption by 54%, because decr absorp can incr in
lower blood [LDL] by 15-20% hepatic chol synth
Combo pill: vytorin = statin +
ezetimibe
Fibric Acid Bind to & activate PPAR-α
Derivatives (peroxisome-proliferated activated
receptor-alpha): receptor in liver
(Fibrates)
Increases synth of lipoprotein
lipase: enhances clearance of
triglyceride-rich lipoproteins
Decreases apolipoprotein C-III
production: inhibitor of lipoprotein
lipase therefore, increased
lipoprotein lipase activity
Increases apolipoprotein A-I &
apolipoprotein A-II levels:
responsible for increased HDL lvls
assoc with fibrates
Net effect:
o Increase [HDL]
o Almost no effect on [LDL]
DRUGS FOR HYPERTENSION
Drug Category Mechanism of Action
Diuretics Block Na+/Cl- reabsorption in
nephron
Creates osmotic P within tubule,
prevents reabsorption of water,
promotes excretion of Na+/Cl- ions
Loop diuretics Block Na+/Cl- reabsorption in thick
ascending limb of loop of Henle
Thiazide diuretics Block Na+/Cl- reabsorption in distal
tubule
Decrease vascular resistance
Potassium Sparing Produce minimal lowering of BP
Diuretics/ Inhibit aldosterone receptors in
collecting duct: aldost normally
Aldosterone
causes Na+ reuptake, K+ secretion
Antagonists Blocking = incr Na+ excretion, K+
retention
Most effective class of drugs for
lowering plasma triglyceride levels
Diseases/Conditions Treated
Usually used for situations
requiring rapid loss of fluid:
Edema, severe hypertension not
responding to milder diuretics,
severe renal failure
Most commonly used class of drug
to treat hypertension
Mainly used in combo with
thiazide, loop diuretics, to
counteract hypokalemia
Increased risk of gallstones
Myopathy: fibrates alone can cause
myopathy in small fraction of
patients
o If combined with statin:
use a low dose, monitor
for signs of myopathy
hepatotoxicity
Side Effects Examples Additional Notes
3 main classes:
1. Loop diuretics
2. Thiazide diuretics
3. K+ sparing diuretics, aldosterone
antagonists
Hypokalemia: may cause fatal Most effective diuretics available
cardiac dysrhythmias
Hyponatremia
Dehydration
hypotension
Hypokalemia Max amt of diuresis (ie urine
Dehydration production) less than loop diuretics
hyponatremia For many hypertensive patients,
these alone enough to control BP
Should not be used with ACE
inhibitors or ARBs: these drugs also
conserve K+
Hyperkalemia: may result in fatal
dysrythmias
Beta Blockers Block cardiac beta 1 receptors
(“-olol”) Normally: catecholamines (ie epi,
norepi) bind to cardiac beta
receptors increased CO
If blocked: decrease CO
decrease BP
Block beta 1 receptors on
juxtaglomerular cells
Normally: juxtaglom cells release
renin activate RAAS pathway
vasoconstriction
1st generation beta Non-selective blockade of beta
blockers receptors
Inhibit both beta 1 (in heart &
juxtaglom cells) and beta 2 (in
lung) receptors
2nd generation beta Selective blockade of beta 1
blockers receptors
Angiotensin Net effect: decrease BP, using 2
Converting Enzyme mechs
1. Decr angiotensin II prodxn:
Inhibitors (ACEI)
potent vasoconstrictor, so will
(“-pril”) cause vasodilation. Will also
decrease total blood vol
reduce CO & periph resistance
2. Inhibit bradykinin breakdown:
elevated lvls cause
vasodilation
E.g. propanolol, metoprolol, etc.
st nd
Either 1 generation or 2
generation
nd
Same as 2 gen, and also:
Bronchoconstriction: due to
blockade of beta 2 receptors in
lung. Avoid use in patients w
asthma & other pulmon diseases
Inhibition of hepatic & musc
glycogenolysis: can be dangerous
in diabetics if take too much insulin
Bradycardia: slow heart rate
Decreased CO
Heart failure (rare)
Rebound hypertension/cardiac
excitation if withdrawn abruptly:
should slowly taper off dose over
10-14 days to prevent this
Generally well tolerated E.g. capopril, ramipril
Side effects of decr angiotensin II:
st st
1 dose hypotension: 1 few doses
should be low
Hyperkalemia: decr ang II decr
aldosterone release K+
retention. Avoid K+ supplements,
use of K+ sparing diuretics
Side effects of incr bradykinin
Persistent cough: 5-10% of patients
Angioedema: rare but could be
fatal
Effects can decrease if used with
certain NSAIDs
Angiotensin Like ACEIs in that they decrease Don’t inhibit bradykinin breakdown E.g. losartan, valsartan
Receptor Blockers ang II actions (but diff mech) as well as ACEIs, so don’t produce
Block ang II binding to its receptor persistent cough
(ARBs)
(AT1 receptor) Don’t cause hyperkalemia
(“-sartan”) Block ang II action on all arterioles Incidence of angioedema much
vasodilation lower than with ACEIs
Decrease aldosterone release from
adrenal cortex incr Na+/H20
excretion
Direct Renin Bind to renin, block conversion of Hyperkalemia: should not be used
Inhibitors (DRIs) angiotensinogen to angiotensin I in combo with other drugs that can
(which is rate limiting step) cause hyperkalemia (e.g. K+
Decrease plasma renin activity by sparing diuretics, ACEI) and K+
50-80% but BP lowering effect supplements
same as other classes of drugs V low incidence of persistent cough
& angioedema (much lower than
ACEI)
diarrhea
Calcium Channel Block Ca++ entry into heart & 2 categories:
Blockers smooth musc decr contraction 1. Dihydropyridine Ca++ channel
blockers
2. Non-dihydropyridine Ca++
channel blockers
Dihydropyridine Significantly decrease Ca++ influx Flushing E.g. nifedipine, felodipine
Ca++ channel into arteriolar smooth musc Dizziness
Relaxes musc around arteries Headache
blockers
vasodilation Peripheral edema
(“-dipine”) Do not act on heart at therapeutic Reflex tachycardia
doses Rash
Non- Block Ca++ channels in both heart Constipation
dihydropyridine and smooth musc of arteries Dizziness
Net effect: arteriolar vasodilation, Flushing
Ca++ channel
decrease CO Headache
blockers
Edema
May compromise cardiac fxn: use
caution in cardiac failure patients
Centrally acting Bind to & activate alpha 2 Drowsiness
Alpha 2 Agonists receptors in brainstem Dry mouth
Decreases sympathetic outflow to Rebound hypertension if
heart & BVs (would normally cause withdrawn abruptly
increased CO, vasoconstriction)
Net effect: decr CO & periph
resistance
CNS DRUGS
Drug Category Mechanism of Action
Levodopa (L-Dopa) Dopamine replacement
L-DOPA crosses BBB via active
transport
Inactive but converted into
dopamine in dopaminergic nerve
terminals, by decarboxylase
enzymes
Rxn sped up by cofactor pyridoxine
(vitamin B6)
Dopamine Agonist Directly activate dopamine
receptors on post-synaptic cell
memb
Dopamine Releaser Stimulates dopa release from
dopaminergic neurons
Blocks dopa reuptake into pre-
synaptic nerve terminals
Blocks NMDA receptors
Response usu develops rapidly: 2-3
days
Catecholamine-O- COMT adds methyl group to both
Methyltransferase dopa & L-DOPA, inactivates them
can’t activate dopa receptors
(COMT) Inhibitor
Inhibiting COMT means that more
L-DOPA can be converted into
dopa
Monoamine MAO-B oxidatively metabolizes
oxidase-B (MAO-B) dopa & L-DOPA inactivation
Found in periphery & brain
inhibitor
Inhibiting MAO-B allows more
conversion to dopa, lets dopa
remain in nerve terminals
Diseases/Conditions Treated
Parkinson’s Disease: most effective drug
Beneficial effects of L-DOPA
decrease over time as disease
progresses
Can’t just give dopamine because it:
Does not cross BBB
Has very short ½ life in blood
Parkinson’s Disease: not as effective as
st
L-DOPA but often used as 1 line
treatment for milder cases
Parkinson’s Disease
Not as effective as L-DOPA
Usu used in combo with L-DOPA,
or alone in mild cases
Parkinson’s Disease
Moderately effective
Often used in combo with L-DOPA
Parkinson’s Disease
Moderately effective
Often used in combo with L-DOPA
Side Effects
Nausea, vomiting: from dopa
mediated activation of
chemoreceptor trigger zone in
medulla
Dykinesias: abnormal, invol mov’ts
Cardiac dysrythmias: conversion of
L-DOPA to dopa in periphery can
activate cardiac beta 1 receptors
Orthostatic hypotension: rapid
drop in BP when stand up
Psychosis: 20% develop
hallucinations, vivid dreams/
nightmares, paranoid thoughts
Hallucinations
Daytime drowsiness
Orthostatic hypotension
Dizziness
Nausea
Vomiting
Lethargy
Anticholinergic side effects
Similar to L-DOPA
Nausea
Orthostatic hypotension
Vivid dreams
hallucinations
Insomnia
Orthostatic hypotension
dizziness
Examples
Alone, only 1% of L-DOPA dose will
reach brain: rest is metabolized in
peripheral tissue (mostly in
intestine) before reaching brain
L-DOPA almost always admin with
carbidopa: decarboxylase inhibitor,
inhibits periph L-DOPA metabolism
In combination: approx 10% L-
DOPA reaches brain
Allows lower dose of L-DOPA,
decreases cardiac dysrythmias,
nausea, vomiting
Additional Notes
Two Types of Loss of Effect
Wearing Off: gradual loss of effect
Usu at end of dosing interval,
indicates drug lvls may be low
Minimize by: shortening dosing
interval, giving drug inhibiting L-
DOPA metabolism (ie COMT
inhibitor), adding dopa agonist
On-Off: abrupt loss of effect
Can happen even when drug lvls
high
Minimize by: dividing meds into 3-
6 doses/day, using controlled
release formulation, move protein
containing meals to evening
At therapeutic doses, MAO-B
inhibitors used for Parkinson’s
don’t inhibit MAO-A in liver do
not cause hypertensive crisis when
patients eat foods containing Tyr
Anticholinergic Parkinson’s caused by too little Parkinson`s Disease Dry mouth Usually reserved for younger
Drugs (Cholinergic dopa, too much ACh Decrease side effects of too much Blurred vision patients only (elderly patients have
Drugs block Ach binding to Ach: diaphoresis (excess sweating), Urinary retention too many side effects)
Antagonists)
receptor salivation, incontinence Constipation
Can increase effectiveness of L- Tachycardia
DOPA Elderly patients can have severe
CNS side effects: hallucination,
confusion, delirium
Cholinesterase Inhibit metabolism of Ach by Alzheimer’s Disease Nausea, vomiting
inhibitors acetylcholinesterase --. Allows Minimal benefit on some measures Diarrhea
more Ach to remain in synaptic of memory Insomnia
cleft Only effective in approx 25% of
Can only enhance cholinergic patients
neurotransmission in remaining
healthy neurons
2+
NMDA receptor NMDA receptor: blocked by Mg at rest
2+
Alzheimer’s Disease Well tolerated
antagonists When glutamate binds, Mg
2+
Side effects in clinical trials = same
dissoc, allows Ca to enter incidence as placebo group
2+
Normal Ca influx important in
learning & memory
In Alzheimer’s: excess glut release
NMDA receptor remains open,
2+
allows Ca to enter cell
2+
Excess Ca detrimental:
1. Bad for learning & memory:
2+
overpowers norm Ca signal
2. Causes neural degradation:
toxic
2+
NMDA receptor antagonists: block Ca
influx into post-synaptic neuron

Conventional Block dopamine 2 (D2) receptors
antipsychotics primarily in mesolimbic area of
brain
Also block receptors for Ach,
histamine, norepi
Potency directly to ability to
inhibit D2 receptors
Atypical Block both D2 receptors and 5-
antipsychotics HT1A and 5-HT2A receptors
Blocks some D2 receptors (low
affinity), therapeutic action is from
blocking 5-HT receptors
Schizophrenia
More effective at treating positive
symptoms than negative
symptoms
Initial effects: as soon as 1-2 days
Substantial improvement in
symptoms: 2-4 weeks
Schizophrenia
Bipolar disorder (see “additional
notes” for conventional
antipsychotics)
Extrapyramidal symptoms (EPS)
Sudden high fever
Anticholinergic effects
Orthostatic hypotension
Sedation
Skin reactions
Sedation
Orthostatic hypotension
Weight gain (sometimes severe)
Type II diabetes risk
Anticholinergic effects
Antipsychotics can also be used in
bipolar disorder: control manic
symptoms, stabilize long term
mood. Atypical antipsychotics
preferred for this to lessen risk of
EPS.
Cf. Conventional antipsychotics: same
efficacy vs +ve symptoms, greater vs –
ve symptoms, lower risk for EPS (esp
tardiv dyskin, due to decr D2 receptor
blocking)
 +
Phenytoin Blocks Na channels: prolongs Epilepsy Teratogenic Also, newer AED: lamotrigine Liver can only metabolize
inactivation status of channels Most widely used AED Sedation phenytoin in a limited manner:
after an action potential, doesn’t (antiepileptic drug) Gingival hyperplasia displays non-linear kinetics (ie
allow neurons to fire at high Useful in treatment of all types of Skin rash small increase in dose can large
frequency epileptic seizures except absence increase in plasma conc)
seizures Narrow therapeutic range, often
undergoes therapeutic drug
monitoring
2+
Blocking voltage Ca influx through these channels Epilepsy Traditional: valproic acid
dependent Ca2+ promotes NT release from pre-
synaptic terminal
channels
Inhibition suppresses NT release
Glutamate Glut = excitatory CNS NT (binds to Epilepsy
antagonists NMDA receptor or AMPA receptor)
Blocking glut (by blocking both
receptors) decreases CNS
excitation
Drugs that GABA is inhibitory CNS NT: binding
-
Epilepsy
potentiate actions to receptor Cl rushes into cell
Increased –ve charge will make
of GABA
more difficult for AP threshold to
be reached
Drugs can:
1. Enhance GABA binding
2. Stimulate GABA release
3. Inhibit GABA reuptake
4. Inhibit GABA metabolism
Tricyclic Inhibit reuptake of serotonin and Major depression Anticholinergic effects Name comes from chemical
antidepressants norepi Panic disorder/agoraphobia: Sedation structure: three rings
effects take 6-12 wks to appear Orthostatic hypotension
(TCAs)
Decreased seizure threshold
Cardiac toxicity: rare but serious
Weight gain
Sexual dysfunction
Selective serotonin Block serotonin reuptake Most commonly used treatment of Weight gain Antidepressants can be used in
reuptake inhibitors depression, most commonly used Sexual dysfunction bipolar disorder to treat depressive
in major depression Insomnia episodes. Always combined with
(SSRIs)
Similar efficacy to TCAs, but side Serotonin syndrome: symptoms mood stabilizer (if used alone,
effects less common may appear within 3 days of initial could trigger manic episode). Don’t
Generalized anxiety: slow to therapy, disappear when drug is know which antidepressant works
generate effect stopped best for bipolar patients.
Panic disorder/agoraphobia:
effects take 6-12 wks to appear,
 preferred treatment because
better tolerated
OCD: also need behavioural
therapy
st
Social anxiety: 1 line therapy,
need time to have effect
Selective Block reuptake of both norepi & Major depression: effective Nausea
serotonin/ serotonin treatment Diastolic hypertension
Mechanism similar to TCAs, but do Generalized anxiety: slow to Sexual dysfunction
norepinephrine
not have three-ring structure generate effect
reuptake inhibitors Main advantage: Faster onset of
(SNRIs) action
Monoamine MAO inactivates monoamine NTs Atypical depression CNS excitation: anxiety, insomnia,
Oxidase Inhibitors o MAO-A: metabolizes Dysthymia agitation
serotonin & norepi Panic disorder/agoraphobia: Orthostatic hypotension
(MAOIs)
o MAO-B: metabolizes effects take 6-12 wks to appear Hypertensive crisis if taken with
dopamine foods containing tyramine
MAO inhibitors used to treat
depression are non-selective:
inhibit both MAO-A & MAO-B
Inhibit metabolism of monoamines
in pre-synaptic neuron
+
Mood stabilizers Relieve symptoms during manic/ Bipolar disorder Agents that increase Na loss form Primary drugs used:
depressive episodes body (ie diuretics) increase Li o Lithium: narrow
Prevent recurrence of manic/ concentrations, which may therapeutic range,
depressive episodes produce toxicity: plasma conc may be
+
Do not worsen symptoms of o GI upset altered by Na
mania/depression, do not alter o Tremor o Valproic acid:
rate of cycling o Sedation antiepileptic
Li: thought to alter uptake & o hypotension
release of glutamate, block
serotonin binding
Benzodiazepines Potentiate actions of GABA at Anxiety: BDZs are first line therapy CNS depression: drowsiness, Withdrawal: dose should be tapered off
(BDZs) receptor o Generalized anxiety difficulty concentrating slowly to avoid withdrawal
Not GABA agonists: bind to diff site o Social anxiety: immediate Anterograde amnesia
on GABA receptor, increases relief from symptoms Respiratory depression: rare, but
affinity for GABA Seizures more common in combo w alcohol
Amplify actions of endogenous Insomnia Teratogenic
GABA, so there is limit to how Alcohol withdrawal Tolerance: occurs to some effects
much they can depress CNS: makes Muscle spasm but not others. No tolerance to
them safer than GABA agonists (eg Diff dosages for diff effects: eg anxiolytic or sedative effects, but
barbiturates) higher dose used to treat insomnia tolerance does develop to effect
than anxiety on seizures
Buspirone Not CNS depressant: useful for
treating patients who use alcohol
Unclear mech: appears to involve
modulation of serotonergic and/or
dopaminergic neurotransmission
DRUGS TO TREAT DIABETES
Drug Category Mechanism of Action
Short duration rapid administered with meals to control
acting insulin postprandial (after eating) rise in
glu
subcut injection (or IV if needed)
Short duration Injected before meals to control
slower acting postprandial rises in glu, or infused
to provide basal control of blood
insulin
glu
(unmodified human Subcut injection (or rarely, IM)
insulin) o After subcut, insulin forms
dimers that slow absorption
Generalized anxiety disorder No signs of tolerance, physical major disadvantage: anxiolytic
Ineffective in other types of anxiety dependence effects develop slowly
(ie panic disorder, OCD) Well-tolerated, non-sedating ineffective at treating symptoms
Dizziness, light-headedness requiring immediate relief
excitement
Diseases/Conditions Treated Side Effects Examples Additional Notes
diabetes primary complication: Three types: All clear solutions
hypoglycemia (blood glu ≤ 3 1. Insulin lispro Can only be mixed with NPH insulin
mmol/L) 2. Insulin aspart (short acting insulin should be
rapid decr in blood glu activates 3. Insulin glulisine drawn into syringe first) stable
sympathetic nervous system: for 28 days
o tachycardia
o palpitations
o sweating
o nervousness
is blood glu decr more gradually:
o headache
o confusion
o drowsiness
o fatigue
severe hypoglycemia:
o coma
o convulsions
o death
diabetes ↑ as above Only type available is unmodified Clear solution
Management of hypoglycemia: human insulin Can only be mixed with NPH insulin
crucial to prevent irreversible brain (short acting insulin should be
damage drawn into syringe first) stable
if conscious: fast acting oral sugar for 28 days
(glu tablets, orange juice, corn
syrup, honey, pop [not diet])
unconscious: IV glu
diabetics recommended to keep
horm glucagon on hand
Intermediate Delayed onset of action: can’t use diabetes ↑ as above Two types: Mixtures stable for 28 days
duration insulin at mealtime to control 1. Neutral protamine hormone
postprandial blood glu rising (NPH) insulin: cloudy
Inject 1-2x daily to control blood suspension
glu between meals and in evening 2. Insulin detemir: clear solution
Why actions delayed?
o NPH: conjugated to
protamine (lg protein), makes
less soluble & decr absorption
o Detemir: bind strongly to
each other delays
absorption
Subcut injections
Long acting insulin Long duration due to low solubility diabetes ↑ as above Only type: insulin glargine Clear solution
(insulin glargine) @ physiological pH Mixtures stable for 28 days
Subcut inj once daily at bedtime
After injection, forms precipitates
that slowly dissolve (release sm
amts over extended time)
Glucagon Hormone produced by pancreas Hypoglycemia: often used when Ineffective in starving/
Converts glycogen to glu hypoglycemic patient is malnourished patients: don’t have
For unconscious patients: IV glu unconscious any glycogen stores to begin with
preferred to glucagon, but Once consciousness regained, oral
impractical outside of medical sugar solutions should be used
supervision
Biguanides Lower blood glu by: Often type of choice for Type II Nausea
1. Increasing sensitivity & # of diabetes Decreased appetite
insulin receptors Largely ineffective for Type I Diarrhea
2. Decreasing hepatic diabetes Decreased absorption of vit B12,
gluconeogenesis folic acid
3. Reducing intestinal glu Lactic acidosis rare but serious
absorption (50% mortality)
Maj advantage: don’t increase
insulin lvls no hypoglycemia risk
st nd
Sulfonylureas Stimulate release of insulin from Type II diabetes Hypoglycemia Two Classes: 1 & 2 generation
nd
pancreas Largely ineffective for Type I Prolonged use: pancreatic burnout o 2 : much more potent,
Inhibit glycogenolysis (breakdown diabetes (pancreas has reduced capacity to fewer drug interxns
of glycogen glu) synth insulin)
Meglitinides Same mech of action as Type II diabetes
sulfonylureas Largely ineffective for Type I
Differ in that they have short half diabetes
life: effective for treating
postprandial rises in glu
 Less likely to cause hypoglycemia &
pancreatic burnout
Thiazolidinediones ↑ insulin sensitivity in target Type II diabetes Fluid retention/edema
(glitazones) tissues: Activate PPARϒ receptor Largely ineffective for Type I Headache
(intracell receptor) ↑ # diabetes myalgia
receptors
Decrease hepatic gluconeogenesis
↑HDL, ↓triglycerides, via
activation of PPARα
Alpha-glucosidase Act @ intestine to delay carb Type II diabetes Side effects limited to intestine,
inhibitors absorption (need to be broken Largely ineffective for Type I since alpha-glucosidase inhibitors
down into monosacchs by alpha- diabetes poorly absorbed
glucosidase, to be absorbed) Flatulence
↓ in complex carb metabolism = Cramps
reduction in postprandial rise in glu Abdominal distention
Diarrhea
Decreased Fe absorption
Gliptins Inhibit dipeptidyl peptidase 4 (DPP- Type II diabetes No known major adverse effects
4), which breaks down incretin Largely ineffective for Type I
hormones GLP-1 & GIP diabetes
o GLP-1 & GIP released from GI
tract after meal, causing:
1. ↑insulin release
2. ↓glucagon release
Inhibiting DPP-4 allows more GLP-1
& GIP to reach pancreas: ↑insulin
release, ↓ glucagon release
Incretin mimetics Synthetic incretin analogs, mimic diabetes Hypoglycemia
actions of incretins: ↑insulin pancreatitis
release, ↓ glucagon release
Administered by subcut, used as
adjunctive therapy w biguanides,
sulfonylureas
Antibiotics
Drug Category Mechanism of Action
Penicillins Bacterial cell wall has
peptidoglycan layer
Penicillin binding proteins (PBPs)
Transpeptidases form cross-bridges
between peptidoglycan strands
(stability)
Autolysins degrade peptidoglycan
cell wall
Penicillins inhibit transpeptidases,
activate autolysins: disrupt cell wall
synth, promote destruction
bacteria take up excess water & die
Bactericidal, only effective against
bacteria that are actively growing
& dividing
Narrow spectrum Can be destroyed by gastric acid,
penicillins so must admin IV or IM
Narrow spectrum Altered side chain: not susceptible
penicillinase to inactivation by beta lactamase
enzymes
resistant penicillins
Broad spectrum Can penetrate outer memb of
penicillins gram –ve
Extended spectrum
penicillins
Cephalosporins Same mech as penicillins: inhibit
transpeptidases and activate
autolysins
st th
Bacteridal, 4 generations: 1 4 cephalosporins suitable alternative
Drugs tend to ↑ activity against
gram –ve, ↑ resistance against
beta lactamases, ↑ ability to
penetrate cerebrospinal fluid
Diseases/Conditions Treated
Much more effective against gram
+ve than gram –ve: gram+ don’t
have outer memb
Gram +ve bacteria
Pneumonia, meningitis
Effective in treating penicillinase-
producing staphylococci
Less effective against non-
penicillinase producing bacteria
Not effective in treating abscesses,
penetrating into bone
Gram +ve
Gram –ve
Gram +ve
Gram –ve
Pseudomonas aeruginosa (bacteria
resistant to all other penicillins)
Gram +ve
Gram –ve
Side Effects Examples Additional Notes
Resistance may be caused by: Classes of penicillins
1. Inability to reach target Narrow spectrum
2. Inactivation: by beta Narrow spectrum penicillinase
lactamases, which target beta resistant
lactam ring of penicillins, Broad spectrum
rendering inactive Extended spectrum
Now have beta
lactamase inhibitors to
help avoid resistance
3. Mutations in PBPs that make
them have low affinity for
penicillins (methicillin
resistant Staphylococcus
aureus, MRSA)
Generally safe
Primary side effect: drug allergy
Some bacteria are resistant: ie
MRSA
Readily inactivated by beta
lactamases
Susceptible to degradation by beta
lactamase enzymes
Most frequent: allergy
Cross-reactivity with penicillin
allergy is rare (<1%), so
for patients allergic to penicillins
Vancomycin Inhibits cell wall synth by binding Potentially toxic, only used to treat ototoxicity
to precursors of cell wall synth serious infections, including those rapid infusion may cause “red
blocks transglycosylation step in cause by MRSA: person syndrome”: flushing, rash,
cross-bridge synth Osteomyelitis itching, hypotension
Meningitis
Pneumonia
septicemia
Tetracyclines Protein synth inhibitors Typhus fever GI irritation
Bind to 30S ribosomal subunit Chlamydia Photosensitivity: patients must UV
(small subunit), prevent addition of cholera (A and B) light, always wear sun
AAs to peptide chain block outside
Broad spectrum antibiotics, Susceptible to superinfection
bacteriostatic
Macrolide Protein synth inhibitors GI upset
antibiotics Block 50S ribosomal subunit (large QT interval prolongation
subunit), prevent addition of AAs
to peptide chain
Broad spectrum, bacteriostatic
Oxazolodinones Bacteriostatic protein synth Gram +ve Reversible myelosuppression
inhibitors MRSA
Bind to specific region of 50S Vancomycin resistant enterococci
ribosomal subunit, inhibit protein (VRE)
synth Should only use for MRSA/VRE
Narrow spectrum, only work
against gram +ve bacteria
Aminoglycosides Bactericidal Gram –ve Irreversible ototoxicity
Protein synth inhibitor Reversible nephrotoxicity
Narrow spectrum: gram –ve
Rapidly lethal to bacteria: mech
unknown
Sulfonamides & Survival of bacteria dependent on Most common: UTIs Hypersensitivity rxns: fever,
trimethoprim synth of folic acid, incorporate into photosensitivity
DNA (humans can obtain from diet) Small risk of severe
Sulfonamides & trimethoprim act hypersensitivity rxn: Stevens-
at diff stages, block folic acid synth Johnson Syndrome
Often in combo bactericidal
Fluroquinolones Inhibit DNA replication UTIs GI symptoms: nausea, vomiting,
Inhibit DNA gyrase & Osteomyelitis diarrhea
topoisomerase IV Soft tissues infections
Bactericidal
Broad spectrum
Isoniazid Inhibits synth of mycolic acid: Tuberculosis Peripheral neuropathy
component unique to cell wall of Hepatotoxicity
TB bacteria
Only effective in treating TB

CANCER CHEMOTHERAPY DRUGS: cytotoxic agents & hormonal agents

Drug Category Mechanism of Action Diseases/Conditions Treated Side Effects Examples Additional Notes
Cytotoxic agents Either cell cycle phase specific or Types of cytotoxic anticancer drugs:
cell cycle phase non-specific Alkylating agents
o Cell cycle phase specific: only Platinum compounds
effective if cancer cell in specific Antimetabolites
phase of cycle Antitumour antibiotics
o Eg mitotic inhibitors only Mitotic inhibitors
effective during mitosis
o Only effective in cells that are
actively part of cell cycle,
ineffective for cells in G0
Cell cycle non-specific drugs: act
during any stage of cell cycle (incl
G0)
o More toxic to cells that are
proliferating than to cells in G0
Alkylating agents Highly reactive, act by transferring Hodgkin’s disease Most widely used:
alkyl group to cell components Solid tumours of head, neck, ovary, cyclophosphamide
(primarily DNA) breast Prodrug, converted to active form
Form cross-bridges between N by liver: onset of effect often
atoms on guanines in DNA delayed
End result: miscoding, DNA
breakage, possibly inhibition of
DNA replication
Cell-cycle phase non-specific
Platinum Have Pt in chem. Structure Metastatic ovarian & testicular Extremely nephrotoxic, ototoxic Most widely used: cisplatin
compounds Cross-link DNA via guanines, inhibit cancers (toxic to ear)
DNA replication Advanced bladder cancer Emetogenic: causes nausea,
Cell-cycle phase non-specific vomiting
Antimetabolites Structurally similar to natural 3 subclasses:
compounds body uses to synth 1. Folic acid analogs: block conversion
cellular constituents/ incorporate of folate to active form
into DNA 2. Purine analogs: inhibit synth of DNA
 Inhibit particular enzymes, prevent & RNA
DNA replication 3. Pyrimidine analogs: inhibit synth of
Phase-specific, most act during S- DNA & RNA
phase
Antitumour Intercalate DNA: move between Effective, widely used Anthracyclines: severe bone anthracyclines
antibiotics DNA bases & bind to DNA chemotherapeutic agents marrow suppression, cardiotoxic
molecule, causes change in
structure can’t use as template
by DNA polymerase DNA synth
inhibited
Very poorly absorbed, given via IV
Mitotic inhibitors Inhibit mitosis, prevent cell division 2 subclasses:
1. Vinca alkaloids: from periwinkle
plant. Block metaphase by binding
to tubulin disrupts MT
organization, leads to inappropriate
distr of chrs cell death
2. Taxanes: during late G2 phase, just
prior to mitosis. Stabilize MT
bundles, prevent cell division.
Glucocorticoids Used as adjunct to other chemo Cancer of lymphoid tissue Long-term use: osteoporosis,
agents in cancers derived from Can help manage complications of adrenal insufficiency, susceptibility
lymphoid tissue other chemos: reduction in to infection, GI ulceration,
Directly toxic to lymphoid tissue nausea/vomiting/pain, improved electrolyte disturbance, growth
appetite retardation
Drugs for prostate Prostate tissue (normal & Prostate cancer 2 routes:
cancer neoplastic) is androgen dependent 1. Gonadotropin releasing
GnRH causes release of hormone (GnRH)/ surgical
testosterone from testes castration
Testosterone “feeds” prostate 2. Androgen receptor
cancer cells but also acts by –ve antagonists
feedback to inhibit further GnRH
release
1° goal in treatment of prostate
cancer: androgen (ie testosterone)
deprivation
Gonadotropin transient ↓ in testosterone so prostate cancer
releasing hormone cancer symptoms may ↑ @ start
of therapy
(GnRH) agonists/
over time: ↓ GnRH activity
surgical castration through desensitization and –ve
feedback testosterone synth &
release ↓
Androgen receptor Used in combo with GnRH agonist Prostate cancer
antagonists or castration
Block androgen receptors in
tumour cells
Drugs for breast Estrogen makes breast tumour Breast cancer most common type 3 major classes:
cancer cells proliferate of cancer affecting women 1. Antiestrogens
1° goal: deprive cancer cells of Estrogen receptor antagonism 2. Aromatase inhibitors
estrogen used as adjunct to surgery, 3. trastuzumab
radiation therapy
Antiestrogens Block estrogen receptors Breast cancer tamoxifen
Most common is tamozifen: partial
estrogen receptor agonist:
minimally activates estrogen
receptor, blocks endogenous
estrogen from binding
Aromatase Aromatization: converting Breast cancer Do not block ovarian estrogen
inhibitors androgen precursors into estrogen synth: only useful in
Inhibiting this process: ↓ amt of postmenopausal women
estrogen available to cancer cells
Trastuzumab Some breast cancer patients have Breast cancer cardiotoxicity
↑ # of human epidermal growth
factor receptor 2 (HER2):
transmemb receptor helping
regulate cell growth
Tumours w ↑ HER2 have esp
aggressive tumour growth
Trastuzumab is monoclonal Ab:
binds to HER2, prevents prolifert’n
Is Ab so must admin IV: Abs
degraded in stomach, poorly
absorbed
Tyrosine kinase Protein kinases +P proteins on Chronic myelogenous leukemia Nausea Imatinib: prototype Tyr kinase
inhibitors specific AA residues (ie Tyr) (CML) Vomiting inhibitor
Activity can activate gene txn/DNA GI stromal tumours (GIST) Edema
synth Muscle cramps
↑activity of Tyr kinases observed
in many human cancers
Imatinib: binds to kinase domain of
bcr-abl so substrate cannot enter
complete inhibition of cell
prolif, causes apoptosis