Pharm Block 1 drugs

• Indirectly acting adrenergic agonist
• Competitively inhibits the dopamine transporter (DAT), goes in cell, and interferes with VMAT filling of dopamine
• Cytoplasmic increase in DA increases, refersing direction of DAT, pushing DA out of cell into cleft

• ADHD
• Narcolepsy

• Indirectly acting adrenergic agonist
• Inhibits DA tranpsorter (DAT), increasing synaptic cleft dopamine
• Inhibits NE transporter (NET) to increase NE

Weak amphetamine-like effects

• MAO-A inhibitor
• Metabolizes NE, epi, 5HT, DA, and tyramine, but not amphetamine

Wine & cheese reaction- HTN

• Severe HTN by interaction of MAO-A inhibitors and cheese-containing foods and adrenergic drugs
• Cheese has tyramine.
• Normally, tyramine is a wimpy transmitter but if there's too much (bc it's not getting broken down by MAO), then there's an increase in NE and thus increase in BP.

Block DA vesicle formation by blocking VMAT-mediated storage in granule

MAO-B inhibitor only present in the brain

• alpha1, beta1, and beta2 agonist
• alpha1: vasoconstriction, increase in BP
• beta1: increased HR
• beta2: vasodilation, decreased diastolic pressure

• Low/moderate dose: beta2 > alpha1, decreases resistance and decreases diastolic pressure
• High dose: alpha1 > beta2, increases diastolic pressure
• Bronchial asthma: beta2 dilates bronchioles (primatene?)

• alpha1 and beta1 agonist
• alpha1: increases diastolic pressure, vasoconstriction
• beta1: increases HR, (+) inotrope = increase pulse pressure
• Reflex bradycardia: NE has beta1 + vagal reflex thru ACh (ACh > NE)

Pressor agent used to increase BP in hypotensive state

• Low dose: DA-1 receptor (D1)- Increases cAMP in renal blood vessel = vasodilation
• Medium dose: beta1- inotropic and chronotropic
• Large dose: alpha1- vasoconstriction

Used in renal failure with shock

D1 agonist

Hypertensive crisis

• Mixed adrenergic agonist
• Acts directly on alpha and beta receptors
• Indirectly increases NE release, and blocks NE reuptake
• Resistant to MAO

• Bronchial asthma (beta2 bronchodilates)
• Hypotension after spinal anesthesia

• alpha1 agonist
• Constricts arterioles = increases diastolic pressure
• Reflex bradycardia due to carotid baroreceptors

• Hypotensive state
• Nasal decongestant
• Mydriatic effect (pupil dilation)

• alpha2 agonist
• Inhibits NE release
• Decreases BP

• HTN
• ADHD
• Given with amphetamines to downregulate alpha2 activity

• Sedation
• Bradycardia
• Rebound HTN

• alpha2 agonist
• Reduces formation of aqueous humor

Add-on choice for glaucoma tx

• alpha2 agonist
• Shuts down DA and NE synthesis by blocking dopa-decarboxylase
• Inhibits sympathetics and lowers BP

HTN with PREGNANCY

• beta1 agonist
• Milder
• Does not act on DA receptors
• Increases contraction of heart, but only weakly increases HR

• Acute heart failure
• Cardiogenic shock

• Non-selective beta1 and beta2 agonist
• beta1: Inotropic and chronotropic; tachycardia & sympathetic reflex
• beta2: dilates arterioles; peripheral resistance decreases; diastolic pressure decreases, causes reflex tachycardia

• Stimulate AV conduction (beta1)
• Dilate bronchioles (beta2)

Short acting beta2 agonist (SABA)

Acute asthma relief

Short acting beta2 agonist (SABA)

• Asthma relief
• Uterine smooth muscle relaxant

Long acting beta2 agonist (LABA)

• PREVENTION of asthma
• Not for acute bc slower onset of action
• Must be given with GLUCOCORTICOID bc long-term medication downregulates receptors and steroids increase their transcription

beta3 agonist

Overactive bladder

• Inhibition of eye radial fiber contraction (mydriasis) -> miosis
• Inhibition of vessel contraction -> decrease in peripheral resistance, vessel dilation, decreased BP, postural hypotension
• Nasal vessel dilation and increase in mucus gland secretion -> nasal congestion
• Inhibition of bladder trigone and sphincter contraction -> urinary outflow
• Inhibition of ejaculation

• Inhibition of decrease of NE release -> increase NE release
• Inhibition of decrease of insulin release -> increase insulin release
• Inhibition of increasing platelet aggregation -> inhibition of platelet aggregation

non-selective reversible alpha blocker

Pheochromocytoma

non-selective irreversible alpha blocker

Pheochromocytoma

selective reversible alpha1a blocker

• Benign prostatic hyperplasia (promotion of urinary outflow)
• Removes inhibitory action of sympathetics

selective reversible alpha1 blocker

• HTN
• Benign prostatic hyperplasia

• Inhibits increase in heart function -> decrease heart function
• Inhibits JG cells from releasing renin -> decrease in renin, decrease in BP

• Inhibition of vessel dilation -> vessel constriction
• Inhibition of uterus relaxation -> uterus contraction
• Inhibition of bronchi dilation -> bronchi constriction

• AV block and bradycardia
• bronchial asthma and COPD
• Cold extremities from little venous return and blood pooling
• Hyperlipidemia
• Sexual dysfunction

• cardio-selective beta1 blockers
• Atenolol
• Brisprolol
• Betaxolol
• Esmolol
• Acebtolol
• Metoprolol

• CAD
• Diabetes

• non-selective beta blocker and alpha1 blocker
• beta1 = beta2
• Better vasodilator bc blocks alpha1

• CHF
• HTN in pregnancy

• non-selective beta blocker
• beta1 blocker: (-) chronotropic action (decrease HR) and blocks reflex tachycardia; AV conduction is decreased
• beta2 blocker: (-) inotropic action (decrease pulse pressure)

• Hyperthyroidism
• Glaucoma- reduces aqueous humor production

• Can lead to bronchial asthma by blocking beta2 (causing bronchoconstriction)
• Caution for people with diabetes

beta1 and beta2 blocker

• Glaucoma- reduce formation of aqueous humor and possibly increase outflow
• But second choice for glaucoma, alternative to PGF2a

Can cause severe bronchospasm in asthmatics

N & M agonist

ACh-induced nitric oxide mediated vasodilation

• Cholinomimetic
• M agonist

• Non-obstructive urinary retention
• Atony of the GI tract and bladder
• Megacolon

• Resistant to hydrolysis by AChE
• Can cause cholinergic effects like sweating, salivation, flushing

• Cholinomimetic
• N & M agonist
• DOES cross BBB, so used in CNS

• Applied ot cornea for spasm of accomodation
• Choice for all glaucoma
• Sjogren's syndrome

• Cholinomimetic
• N & M agonist

Glaucoma

• Resistant to hydrolysis by AChE
• Can cause cholinergic effects like sweating, salivation, flushing

• Cholinomimetic
• M agonist

Bronchial hyperactivity

Susceptible to cholinesterase

• Reversible anticholinesterase
• Inhibits acetylcholinesterase: prolonged duration of ACh
• Short acting 5-15 mins

Tensilon TEST for myasthenia gravis (not treatment)

• Reversible anticholinesterase
• Does NOT cross BBB bc charged, so no CNS action

• TREATMENT of myasthenia gravis
• Directly stimulates receptor & also indirectly inhibits AChE- reverses NM blockade

• Reversible anticholinesterase
• DOES cross BBB, so CNS action

• Glaucoma
• Antidote in atropine poisoning
• Bladder atony

• Reversible anticholinesterase
• Does NOT cross BBB, so NO CNS action

• Myastenia gravis
• Prevention of nerve gas poison (soman)

• Reversible anticholinesterase
• Does NOT cross BBB, so NO CNS action

Alzheimer's and dementia

Reversible anticholinesterase

Open and closed angle glaucoma

• Irreversible anticholinesterase
• Organophosphate
• Binds covalently and permanently inactivates the enzyme

Aging occurs when ethyl group is released, so bond between drug and rest of enzyme is strengthened and can't be broken

• Miosis (induces mydriasis)- so will dilate the pupil
• Increases outflow of aqueous humor which decreases IOP
• Chronic open angle glaucoma
• Subacute or chonic angle closure glaucoma after iridectomy
• Or when surgery is contraindicated

• Irreversible anticholinesterase
• Organophosphates

• Cholinesterase reactivator
• Attaches to anionic site of AChE in presence of organophosphates and sets enzyme freeeee
• Used with ATROPINE

• Antidote for organophosphate poisoning (used with ATROPINE)
• Treat nerve gas poison (sarin, soman) which are irreversible anticholinesterases

Not recommended in oversdoses of stigmines

M antagonist

• Control bradycardia: increases HR and BP
• Induce mydriasis
• Cycloplegia (paralysis of accomodation)

• Overdose: hot as a hare, blind as a bat, dry as a bone, red as a beet, mad as a hatter
• Do not use in glaucoma or urinary retention

M antagonist

Motion sickness

• M3 antagonist (anticholinergic)
• Slower onset of action, sometimes given with LABA in baseline asthma

• COPD
• Asthma
• Alternative for people who cannot tolerate beta2 agonists
• Sometimes given with LABA in baseline asthma

• M antagonist
• Works in glands/heart

• Preanesthetic med
• Control bradycardia

• M antagonist
• Works on eyes

Fundoscopic exam (dilates eyes)

• M antagonist
• Works in urinary bladder

Overactive bladder

• M antagonist
• Works in CNS

Parkinson's disease

• Depolarizing NMJ blocker
• Excites so strongly -> desensitization
• Downregulates receptor so it can no longer release ACh

Paralytic

• Non-depolarizing NMJ blocker
• Blocks N1 receptors at the NMJ

Paralytic

• GANGLIONIC N2 blocker- blocks para and sym ganglia
• Non-depolarizing

• BLOCKS REFLEX bradycardia that occurs with phenylephrine
• Used to study direct effect of drug and not reflexes

• Non-depolarizing NMJ blocker
• Blocks NT release by degrading SNAP-25, required for vesicle fusion and ACh release
• Blocking ACh produces flaccid paralysis of skeletal muscle and diminished activity of cholinergic synapses

• Chronic migraine prophylaxis
• Blepharospasm
• Cervical dystonia
• Hyperhydrosis- stop sweating

• Blocks the NET and prevents NE reuptake
• Also has anticholinergic activity

Tricyclic antidepressant

Inhibits choline carrier so ACh cannot be synthesized

• PGF2a analog: Increases outflow of aqueous humor thru accessory uveoscleral outflow path, reduces IOP
• Eye drops

First choice for glaucoma by reducing IOP thru aqueous humor drainage

Increase iris pigmentation

• Carbonic anhydrase inhibitor
• Decreases aqueous humor PRODUCTION

Glaucoma

• M3 antagonist (antichoinergic)
• Slower onset of action

• Asthma
• COPD
• Bronchodilator
• Alternative for people who cannot tolerate beta2 agonists

• Glucocorticoid
• Bind to intracellular glucocorticoid receptors and modulate gene expression
• Increases levels of lipoprotein 1 which inhibits PLA2 = anti-inflammation

Chronic asthma

• Adrenal atrophy
• Peptic ulcer
• Oral candidiasis

• PDE inhibitor (PDE4 specifically for roflumilast)
• Inhibits breakdown of cAMP
• Increased cAMP maintains bronchodilation and blocks adenosine receptors

• Relieves asthma
• (and COPD?)

• Cardiac arrhythmias
• Caffeine-like adverse effects- N/V, headache, insomnia
• Persistent vomiting
• Intractable seizures which can be fatal

Lipoxygenase inhibitor: Prevents leukotriene synthesis

• Persistent asthma, allergic reactions, allergic asthma uncontrolled on low dose ihaled corticosteroids
• Causes bronchodilation

• Minimal
• Hepatotoxicity

• Leukotriene D4 receptor antagonist
• Blocks leukotriene receptors

• Persistent asthma, allergic reactions, allergic asthma uncontrolled on low dose ihaled corticosteroids
• Causes bronchodilation

Humanized anti-IgE monoconal Ab

3rd line drug for chronic severe asthma that is not controlled by anything else (like high dose inhaled corticosteroid & LABA)

• Expensive
• Anaphylaxis
• SQ q2-4 weeks

• Leukotriene D4 receptor antagonist
• Blocks leukotriene receptors

• Persistent asthma, allergic reactions, allergic asthma uncontrolled on low dose ihaled corticosteroids
• Causes bronchodilation

Mast cell stabilizers (cromones)

• Only send prophylactially for alleric rhinitis
• Do not relieve bronchospasm

• PPI
• Decreases acid secretion by irreversibly binding to H+/K+ ATPase

• Peptic ulcer disease & GERD
• Drug of choice for ZOLLINGER-ELLISON SYNDROME
• Treat NSAID ulcers

• Cyp450 inhibitor
• Do not use with clopidogrel or warfarin (blood thinners)

• PPI
• Decreases acid secretion by irreversibly binding to H+/K+ ATPase

• Peptic ulcer diseaes & GERD
• Drug of choice for ZOLLINGER-ELLISON SYNDROME
• Treat NSAID ulcers
• NOT a Cyp450 inhibitor so OKAY to use with clopidogrel and warfarin (blood thinners)

H2 receptor antagonist

• GERD
• Ulcers
• Zollinger-Ellison syndrome

• GYNECOMASTIA in men
• INFERTILITY
• GALACTORRHEA in women

H2 receptor antagonist

• GERD
• Ulcers
• SAFE IN PREGNANCY

H2 receptor antagonist

• GERD
• Ulcers

Antacids

Aluminum causes constipation

• Antacid
• Osmotic laxative: water retention by osmosis, increased CCK

Laxative

• Diarrhea
• Avoid in renal failure

They cancel out their adverse effects (constipation and diarrhea respectively)

Antacid

• Milk alkali syndrome: hypercalcemia, alkalosis
• Belching

Antacid

• PGE1 analog: cytoprotective, reduces acid production
• Enhances mucous secretion and blood flow

• PREVENTION & treatment of ulcers in patients on NSAIDs
• Induces ABORTION

Contraindicated in pregnancy bc induces abortion

• Forms physcial BARRIER to prevent further damage by stimulating prostaglandins
• Needs an acidic medium- DO NOT take with PPI

• GERD
• SAFE IN PREGNANCY- first line

Constipation

Bismuth salt binds pepsin & stimulates prostaglandins & mucous secretions

• Dyspepsia
• Traveler's diarrhea
• H. pylori

Black tongue

Everything is the same as bismuth subsailcylate

H1 receptor antagonist

• Motion sickness
• Allergies

H1 blocker

Motion sickness

H1 blocker

Motion sickness

• Dopamine D2 antagonist
• Blocks suppression of the release of ACh from the myenteric plexus (so increases ACh release)

• Constipation
• GERD
• Gastroparesis in diabetes

• Acute dystonias
• Parkinsonism
• Hyperprolactinoma

• 5-HT3 antagonist
• Vaginal inhibition

N/V post surgery or chemo

• Constipation
• QT interval prolongation
• Serotonin syndrome with SSRI

Substance P antagonist

• Delayed nausea
• Used in combo with corticosteroids & serotonin 5-HT3 antagonists for the prevention of acute & also delayed N/V with highly emetogenic chemo regimens

Avoid in those with QT prolongation

Hyperemesis gravidarum

Corticosteroid

Benzodiazepine

Anticipatory nausea

Cannabinoid agonist

• Stimulates appetite
• Used for anorexia in HIV/AIDS
• Prevention of chemo induced n/v (CIN/V)

• Paranoid reactions
• Abnormal thinking

THC analog

Prevention of refractory chemo induced n/v (CIN/V)

• Paranoid reactions
• Abnormal thinking

• Bulk forming laxatives
• SAFE FOR PREGNANCY

• Laxative
• SAFE FOR PREGNANCY

Bloating

• Stimulant laxative- act by inducing low grade inflammation
• Activates cAMP & cGMP pathways
• Inhibition of Na+/K+ ATPase

Short-term use in consultation

Avoid chronic use in pregnancy

Same as bisacodyl

• Avoid chronic use in pregnancy
• Melanosis coli

• Stool softener, anionic surfactants reduce surface tension of the stool to allow mixing of aqueous and fatty substances
• SAFE FOR PREGNANCY

• Laxative
• SAFE FOR PREGNANCY

Lipid pneumonitis

Osmotic laxative: water retention by osmosis, increased CCK

• Laxative
• Used before colonoscopy

Avoid in renal failure

• Osmotic laxative
• Disaccharide that resists intestinal metabolism of disaccharides, so they are hydrolyzed to short-chain fatty acids
• Stimulates propulsive motility by osmotic activity
• Acidifies the colonic contents which leads to the formation of NH4+ (non-absorbable) from NH3, and increases ammonium excretion

• Hepatic encephalopathy- forms NH4+ so that it can't cross BBB
• Constipation

Opioid agonist

Acute non-severe diarrhea (in elderly)

Chloride channel activator- increases cAMP to increase Cl- selection

• Chronic constipation
• IBS with constipation (IBS-C)
• Opioid induced constipation

Contraindicated in pregnancy

Chloride channel activator- agonist of gruanylyl cyclase that leads to activation of CFTR with stimulation of chloride rich secretion

• Constipation
• IBS-C

• Peripherally acting opioid receptor antagonist
• Blocks opioid receptors in the GI tract peripherally
• Does NOT cross BBB
• No limiting of analgesic action centrally

Opioid induced constipation

Azo-linked (5-ASA, 5-aminosalicylates)

#1 drug for IBS- preferred over sulfasalazine

• Azo-linked (5-ASA) to sulfapyridine
• DMARD

IBS

Causes bone marrow suppression & infertility so no longer used....

Decreases hepatic cholesterol secretion and reduces the cholesterol content of bile

• Oral bile acid dissolution therapy for gallstones
• But high risk of recurrence

• H1 receptor antagonist
• 2nd gen- lacks sedative properties

Prevents mast cells from releasing histamine

• H1 receptor antagonist
• 1st gen- some drowsiness
• 5-HT2a blocker
• No associated arrhythmia

• Motion sickness
• Allergy
• Sedative
• POSTGASTRECTOMY DUMPING SYNDROME

• H1 receptor antagonist
• 2nd gen- lacks sedative properties

• H1 receptor antagonist
• 2nd gen- lacks sedative properties

• H1 receptor antagonist
• 1st gen- some drowsiness

Motion sickness

H2 receptor antagonist

• H1 receptor antagonist
• 2nd gen- lacks sedative properties

SSRI inhibits 5-HT reputable

5-HT1B/1D agonist

Migraines

• Coronary vasospasms with resulting chest pain
• Contraindicated in pts with angina

5-HT1B/1D agonist

• Migraines
• Most rapid onset
• Co-administration with propanolol increases levels by 70%

• Coronary vasospasms with resulting chest pain
• Contraindicated in pts with angina

5-HT1B/1D agonist

Migraines

• Coronary vasospasms with resulting chest pain
• Contraindicated in pts with angina

5-HT2 (2A, 2B, 2C) antagonist

• Migraine PROPHYLAXIS
• Protective effect takes 1-2 days to develop

5-HT2C agonist

Appetite suppressant

• Irreversible non-selective COX1 & COX2 inhibitor
• Binds by acetylation
• Uncouples OXIDATIVE PHOSPHORYLATION- inhibits ATP dependent reaction

• Low doses (50-360mg): inhibits TXA2 - antiplatelet
• Medium doses: inhibits PGE2 - analgesic & antipyretic
• High doses: anti-inflammatory when given regularly for a long time (RHEUMATOID ARTHRITIS)

• Mild intoxication- respiratory alkalosis
• Severe OD- metabolic acidosis
• REYE'S SYNDROME: Children under 12 presenting with swollen brain and liver leading to death
• Gastric ulcers
• Contraindicated in gout- inhibits excretion of uric acid

• Reversible non-selective COX1 & COX2 inhibitor
• Same potency as aspirin but better tolerated

• Analgesic & antipyretic
• Anti-inflammatory- rheumatoid arthritis, osteoarthritis

Inhibits COX and may also inhibit lipoxygenase- will decrease PG, TX, & LTs

May be desirable for asthmatics or inflammation & allergic response bc LTs cause bronchospasm and constriction

Non-selective COX1 & COX2 inhibitor

• CLOSES PDA
• Gouty arthritis (#1 tx for acute gout)

More potent than aspirin but inferior at doses tolerated by RA pts

• Inactive pro-drug closely related to indomethacin
• Must be metabolized by hepatic microsomal enzymes to active form
• Long duration of action; half life ~8 hrs

Like indomethacin but adverse effects are less severe than NSAIDs

Non-selective COX1/COX2 inhbitor

• Potent anti-inflammatory but sefulness is limited by toxicity
• Chiefly short term therapy

Irreversible selective COX2 inhibitor

• Chronic arthritis
• NO GI irritation/ulceration
• Antipyretic & analgesic

• Controversy of increased risk of clotting & MI
• Increases level of lithium and warfarin

• COX3? inhibitor
• Weak inhibition of COX1 & COX2

Antipyretic & analgesic

• Small theraputic index
• Uses up liver GLUTATHIONE which leads to liver damage- fatal hepatotoxicity

N-acetylcysteine- brings GLUTATHIONE back

• PGE1 analog
• IV infusion
• Penile suppository

• MAINTAINS PDA
• Erectile dysfunction
• Vasodilator

• PGE2 analog
• Vaginal pessary

• Abortifacient & induction of labor
• Postpartum hemorrhage
• Promotes uterine contraction

Abortifacients

PGF2a analog

Abortifacient

• PGI2 analog
• IV infusion

• Pulmonary HTN
• Inhibits platelet aggregation, lowers BP

• Inhibits microtubule polymerization in PMNs
• Inhibits cell migration, adherance, degranulation
• Inhibits IL-8, ICAM, E-selectin, L-selectin, IL-1
• Anti-neutrophils
• Decreases lactic acid production by leukocytes- decrease in uric acid deposition
• Decrease phagocytosis- decrease in inflammatory response

• Abortive therapy in ACUTE GOUT- first 12 hrs
• Used as combination therapy with ALLOPURINOL & PROBENECID
• 2nd line in acute gout (indomethacin is 1st)

• CANNOT be used in pregnancy- may cross placenta & is found in breast milk
• Interacts with- cimetidine, terfenadine, EES, ketoconazole, diltazepam, nifedipine cyclosporin, statins
• Toxicity:<24 hrs = AP, N/V, diarrhea, dehydration skin irritation; 24-72 hrs = organ failure, anemia, lots of bad stuff

• Block action of PLA2
• Glucorticoid
• Ideally should be given at most every 3 months

• Acute gout- when NSAID+colchicine combo is contraindicated
• Effective short term pain relief, short term increase of joint strength
• Local anti-inflammatory

Intra-articular glucocorticoids

For gout pts unable to take oral meds, with only 1 or 2 inflamed joints, and infection is ruled out

• Mild flare of synovitis
• Low risk of infection
• Short term option
• Risk of cartilage damage with repeated use

• Bind to proximal convoluted tubule (PCT) to increase renal excretion of uric acid
• Uricosurics- promote excretion

• Gout with NORMAL uric acid secretion
• For PROPHYLAXIS in pts who have had recurrent attacks of acute gouty arthritis
• Tx of choice for CHRONIC gout

• Initiation of therapy may induce acute attack, caused by mobilization of urate from other sites to inflamed joints
• Prophylactic use of NSAIDs

• Xanthine oxidase inhibitor
• Results in decrease in synthesis of uric acid

• Chronic gout with EXCESS uric acid excretion, kidney failure, & stones
• NOT in acute gout

• Inhibits azathioprine metabolism
• Dose of azathioprine must be reduced to 1/4th of usual when pt is also taking allopurinol
• Can lead to severe & fatal rash, discontinue if develops

Xanthine oxidase inhibitor

Chronic gout in people who cannot use allopurinol

• Inhibits folate reductase- inhibits DNA synthesis
• Increases adenosine- modulates immune response
• Diseaes modifying anti-rheumatic drug (DMARD)

• DMARD of choice in rheumatoid arthritis
• Used when pts have not responded to NSAIDs

• Can lead to hepatotoxicity
• Give folic acid

• Inhibits dihydrooratate dehydrogenase- decrease activated T cells
• DMARD

• Rash, alopecia
• Diarrhea
• Bone marrow toxicity
• Hepatotoxicity

• Immunosuppressant
• Corticosteroid sparing
• DMARD

• Stabilizes lysosomes & decreases chemotaxis
• DMARD

Mild rheumatoid arthritis with methotrexate

Can cause hemolysis in people with G6PD

Anti-TNFa agents

Rheumatoid arthritis- 2nd choice & given with methotrexate

• TB
• Injection site reaction

IL-1 receptor antagonist

RA