pharm-d 2nd year previous question papers 2010,2011,2012,2013,2014(new)

pharmacology mnemonics

these are easy ways to remember mind-twisting pharmacology in you

RTI: drugs to treat viral respiratory infections "You'd get
a respiratory infection if you shoot an ARO (arrow) laced with 
viruses into the lungs":
ARO:
Amantadine
Rimantadine
Oseltamivir

Medication administration: short checklist TRAMP:
· Before dispensing medication, ensure have correct:
Time
Route
Amount
Medication
Patient

Opiates: overdose findings "Cool to the touch, unresponsive
to pain,
Hunger diminished, and scars over vein.
Pupils pinpointed, and blood pressure low,
Urine diminished, and breathing is slow."

Cocaine: cardiovascular effect COcaine causes blood
vessels to
COnstrict (unlike other local anesthetics which cause vasodilation).

Aminoglycosides: common characteristics AMINO:
Active Against Aerobic gram negative
Mechanism of resistance are Modifying enzymes
Inhibit protein synthesis by binding to 30S subunit
Nephrotoxic
Ototoxic

Sulfonamides: common characteristics SULFA:
Steven-Johnson syndrome/ Skin rash / Solubility low
Urine precipitation/ Useful for UTI
Large spectrum (gram positives and negatives)
Folic acids synthesis blocker (as well as synthesis of nucleic acids)
Analog of PABA

Diuretics: groups "Leak Over The CAN":
Loop diuretics
Osmotics
Thiazides
Carbonic anhydrase inhibitors
Aldosterone inhibitors
Na (sodium) channel blockers
· Note: "leak" is slang for urination and "can" is slang for a toilet.

Thalidomide: effect on cancer cells "Thalidomide
makes the blood vessels hide":
Use thalidomide to stop cancer cells from growing new blood vessels.

Tuberculosis: treatment If you forget your TB drugs, you'll
die and might need a PRIEST":
Pyrazinamide
Rifampin
Isoniazid (INH)
Ethambutol
STreptomycin

Warfarin: interactions ACADEMIC QACS:
Amiodarone
Cimetidine
Aspirin
Dapsone
Erythromycin
Metronidazole
Indomethacin
Clofibrates
Quinidine
Azapropazone
Ciprofloxacin
Statins

Patent ductus arteriosus: which prostaglandin keeps it open
kEEp opEn with prostaglandin E.

Carbamazepine (CBZ): use CBZ:
Cranial Nerve V (trigeminal) neuralgia
Bipolar disorder
Zeisures

Morphine: side-effects MORPHINE:
Myosis
Out of it (sedation)
Respiratory depression
Pneumonia (aspiration)
Hypotension
Infrequency (constipation, urinary retention)
Nausea
Emesis

Corticosteroids: adverse side effects CUSHINGS BAD MD:
Cataracts
Up all night (sleep disturbances)
Suppression of HPA axis
Hypertension/ buffalo Hump
Infections
Necrosis (avascular)
Gain weight
Striae
Bone loss (osteoporosis)
Acne
Diabetes
Myopathy, moon faces
Depression and emotional changes

Tricyclic antidipressents (TCA): side effects TCA'S:
Thrombocytopenia
Cardiac (arrhymia, MI, stroke)
Anticholinergic (tachycardia, urinary retention, etc)
Seizures

Bromocriptine [for USA gang members] The CRYPTS are
an LA street gang that likes to smoke DOPE.
BromoCRYPTine is a DOPamine agonist.

Beta blockers: members "The NEPAL Prime
Minister":
Timolol
Nadolol
Esmolol
Pindolol
Atenolol
Labetalol
Propranolol
Metoprolol

Microtubules: drugs that act on microtubules. "The 
MicroTubule Growth Voiding Chemicals":
Thiabendazole
Mebendazole
Taxol
Griseofulvin
Vincristine/ Vinblastine
Colchicine

Insulin: mixing regular insulin and NPH "Not Ready,
Ready Now":
Air into NPH
Air into Regular
Draw up Regular
Draw up NPH

Benzodiazepins: 3 members that undergo extrahepatic metabolism
"Outside The Liver":
Oxazepam
Temazepam
Lorazepam
These undergo extrahepatic metabolism and do not form active metabolites.

Guanethidine: mechanism GuaNEthidine prevents NE
(norepinephrine) release.

Parasympathetic vs. sympathetic neurotransmitters "No
sympathy for a Pair of Aces":
Norepinephren is secreted in by the Sympathetic nervous system
while Acetylcholine is secreted in the Parasympathetic nervous
system.

Adrenoceptors: vasomotor function of alpha vs. beta ABCD:
Alpha = Constrict.
Beta = Dilate.

Beta 1 selective blockers "BEAM ONE up, Scotty":
Beta 1 blockers:
Esmolol
Atenolol
Metropolol

Opiods: mu receptor effects "MD CARES":
Miosis
Dependency
Constipation
Analgesics
Respiratory depression
Euphoria
Sedation

Cancer drugs: time of action between DNA->mRNA ABCDEF:
Alkylating agents
Bleomycin
Cisplastin
Dactinomycin/ Doxorubicin
Etoposide
Flutamide and other steroids or their antagonists (eg tamoxifen,
leuprolide)

Busulfan: features ABCDEF:
Alkylating agent
Bone marrow suppression s/e
CML indication
Dark skin (hyperpigmentation) s/e
Endrocrine insufficiency (adrenal) s/e
Fibrosis (pulmonary) s/e

Tricyclic antidepressants: members worth knowing "I have to
hide, the CIA is after me":
Clomipramine
Imipramine
Amitrptyline
· If want the next 3 worth knowing, the DND is also after me:
Desipramine
Norrtriptyline
Doxepin

Asthma drugs: leukotriene inhibitor action zAfirlukast:
Antagonist of lipoxygenase
zIlueton: Inhibitor of LT receptor

Torsades de Pointes: drugs causing APACHE:
Amiodarone
Procainamide
Arsenium
Cisapride
Haloperidol
Eritromycin

Serotonin syndrome: components Causes HARM:
Hyperthermia
Autonomic instability (delirium)
Rigidity
Myoclonus

Beta blockers: B1 selective vs. B1-B2 non-selective A
through N: B1 selective: Acebutalol, Atenolol, Esmolol, Metoprolol.
O through Z: B1, B2 non-selective:Pindolol, Propanalol, Timolol.

HMG-CoA reductase inhibitors (statins): side effects,
contraindications, interactions HMG-CoA:
· Side effects:
Hepatotoxicity
Myositis [aka rhabdomyolysis]
· Contraindications:
Girl during pregnancy/ Growing children
· Interactions:
Coumarin/ Cyclosporine

Therapeutic index: formula TILE:
TI = LD50 / ED50

Antirheumatic agents (disease modifying): members CHAMP:

Cyclophosphamide
Hydroxycloroquine and choloroquinine
Auranofin and other gold compounds
Methotrexate
Penicillamine

Auranofin, aurothioglucose: category and indication Aurum
is latin for "gold" (gold's chemical symbol is Au).
Generic Aur- drugs (Auranofin, Aurothioglucose) are gold
compounds.
· If didn't learn yet that gold's indication is rheumatoid arthritis, AUR- Acts
Upon Rheumatoid.

Antiarrhythmics: class III members BIAS:
Bretylium
Ibutilide
Amiodarone
Sotalol

MAOIs: indications MAOI'S:
Melancholic [classic name for atypical depression]
Anxiety
Obesity disorders [anorexia, bulemia]
Imagined illnesses [hypochondria]
Social phobias
· Listed in decreasing order of importance.
· Note MAOI is inside MelAnchOlIc.

SIADH-inducing drugs ABCD:
Analgesics: opioids, NSAIDs
Barbiturates
Cyclophosphamide/ Chlorpromazine/ Carbamazepine
Diuretic (thiazide)

K+ increasing agents K-BANK:
K-sparing diuretic
Beta blocker
ACEI
NSAID
Ksupplement

Diuretics: thiazides: indications "CHIC to use
thiazides":
CHF
Hypertension
Insipidous
Calcium calculi

Ribavirin: indications RIBAvirin:
RSV
Influenza B
Arenaviruses (Lassa, Bolivian, etc.)

Parkinsonism: drugs SALAD:
Selegiline
Anticholinenergics (trihexyphenidyl, benzhexol, ophenadrine)
L-Dopa + peripheral decarboxylase inhibitor (carbidopa, benserazide)
Amantadine
Dopamine postsynaptic receptor agonists (bromocriptine, lisuride,
pergolide)

Morphine: effects at mu receptor PEAR:
Physical dependence
Euphoria
Analgesia
Respiratory depression

Thrombolytic agents USA:
Urokinase
Streptokinase
Alteplase (tPA)

Anticholinergic side effects "Know the ABCD'S of
anticholinergic side effects":
Anorexia
Blurry vision
Constipation/ Confusion
Dry Mouth
Sedation/ Stasis of urine

Teratogenic drugs "W/ TERATOgenic":
Warfarin
Thalidomide
Epileptic drugs: phenytoin, valproate, carbamazepine
Retinoid
ACE inhibitor
Third element: lithium
OCP and other hormones (eg danazol)

Antiarrhythmics: classification I to IV MBA College
· In order of class I to IV:
Membrane stabilizers (class I)
Beta blockers
Action potential widening agents
Calcium channel blockers

Epilepsy types, drugs of choice "Military General
Attacked Weary Fighters Pronouncing 'Veni
Vedi Veci' After Crushing Enemies":
· Epilepsy types:
Myoclonic
Grand mal
Atonic
West syndrome
Focal
Petit mal (absence)
· Respective drugsy:
Valproate
Valproate
Valproate
ACTH
Carbamazepine
Ethosuximide

Respiratory depression inducing drugs "STOP
breathing":
Sedatives and hypnotics
Trimethoprim
Opiates
Polymyxins

Pulmonary infiltrations inducing drugs "Go BAN Me!":
Gold
Bleomycin/ Busulphan/ BCNU
Amiodarone/ Acyclovir/ Azathioprine
Nitrofurantoin
Melphalan/ Methotrexate/ Methysergide

Migraine: prophylaxis drugs "Very Volatile 
Pharmacotherapeutic Agents For Migraine Prophylaxis":
Verpamil
Valproic acid
Pizotifen
Amitriptyline
Flunarizine
Methysergide
Propranolol
· Bare bones version [eg Lippincott's two], just Migraine Prophylaxis,
as above.

Benzodiazapines: ones not metabolized by the liver (safe to use in
liver failure) LOT:
Lorazepam
Oxazepam
Temazepam

Vigabatrin: mechanism Vi-GABA-Tr-In:
Via GABA Transferase Inhibition

TB: antibiotics used STRIPE:
STreptomycin
Rifampicin
Isoniazid
Pyrizinamide
Ethambutol

Propythiouracil (PTU): mechanism It inhibits PTU:
Peroxidase/ Peripheral deiodination
Tyrosine iodination
Union (coupling)

Enoxaprin (prototype low molecular weight heparin): action,
monitoring EnoXaprin only acts on factor Xa.
Monitor Xaconcentration, rather than APTT.

Beta-blockers: nonselective beta-blockers "Tim Pinches
His Nasal Problem" (because he has a runny nose...):
Timolol
Pindolol
Hismolol
Naldolol
Propranolol

Nicotinic effects MTWTF (days of week):
Mydriasis/ Muscle cramps
Tachycardia
Weakness
Twitching
Hypertension/ Hyperglycemia
Fasiculation

Muscarinic effects SLUG BAM:
Salivation/ Secretions/ Sweating
Lacrimation
Urination
Gastrointestinal upset
Bradycardia/ Bronchoconstriction/ Bowel movement
Abdominal cramps/ Anorexia
Miosis

Phenytoin: adverse effects PHENYTOIN:
P-450 interactions
Hirsutism
Enlarged gums
Nystagmus
Yellow-browning of skin
Teratogenicity
Osteomalacia
Interference with B12 metabolism (hence anemia)
Neuropathies: vertigo, ataxia, headache

Gynaecomastia-causing drugs DISCOS:
Digoxin
Isoniazid
Spironolactone
Cimetidine
Oestrogens
Stilboestrol

Hypertension: treatment ABCD:
ACE inhibitors/ AngII antagonists (sometimes Alpha agonists
also)
Beta blockers
Calcium antagonists
Diuretics (sometimes vasoDilators also)

Diuretics classification in order of site of action "COLT
Pee:"
· In their sequential site of action along the nephron:
Carbonic anhydrase inhibitors (at the proximal tubule)
Osmotic diuretics (at the Loop of Henle)
Loop diuretics (at the ascending loop)
Thiazides (at the distal tubule)
Potassium-sparing diuretics (at the collecting tubules)
· Diuretics make patient pee like a horse, hence "Colt Pee".

Aspirin: side effects ASPIRIN:
Asthma
Salicyalism
Peptic ulcer disease/ Phosphorylation-oxidation uncoupling/ PPH/
Platelet disaggregation/ Premature closure of PDA
Intestinal blood loss
Reye's syndrome
Idiosyncracy
Noise (tinnitus)

Clopidogrel: use CLOPIdogrel is a drug that prevents
CLots, an Oral Platelet Inhibitor (OPI).

Teratogenic drugs: major non-antibiotics TAP CAP:
Thalidomide
Androgens
Progestins
Corticosteroids
Aspirin & indomethacin
Phenytoin

Physostigmine vs. neostigmine LMNOP:
Lipid soluble
Miotic
Natural
Orally absorbed well
Physostigmine
· Neostigmine, on the contrary, is:
Water soluble
Used in myesthenia gravis
Synthetic
Poor oral absorption

Prazocin usage Prazocin sounds like an acronym of "praszz
zour urine".
Therefore Prazocin used for urinary retention in BPH.

Steroid side effects CUSHINGOID:
Cataracts
Ulcers
Skin: striae, thinning, bruising
Hypertension/ Hirsutism/ Hyperglycemia
Infections
Necrosis, avascular necrosis of the femoral head
Glycosuria
Osteoporosis, obesity
Immunosuppression
Diabetes

Beta blockers with CYP2D6 polymorphic metabolism "I Met
Tim Carver, the metabolic polymorph":
· The following beta blockers require dose adjustment due to CYP2D6 polymorphic
metabolism:
Metoprolol
Timolol
Carvedilol
(in patients with lower or higher than normal CYP2D6 activity)

Beta blockers with intrinsic sympathomimetic activity
Picture diabetic and asthmatic kids riding away on a cart
that rolls on pinwheels.
Pindolol and Carteolol have high and moderate ISA respectively,
making them acceptable for use in some diabetics or asthmatics despite the fact
that they are non-seletive beta blockers.

Amiodarone: action, side effects 6 P's:
Prolongs action potential duration
Photosensitivity
Pigmentation of skin
Peripheral neuropathy
Pulmonary alveolitis and fibrosis
Peripheral conversion of T4 to T3 is inhibited -> hypothyroidism

Morphine: effects MORPHINES:
Miosis
Orthostatic hypotension
Respiratory depression
Pain supression
Histamine release/ Hormonal alterations
Increased ICT
Nausea
Euphoria
Sedation

Monoamine oxidase inhibitors: members "PIT of
despair":
Phenelzine
Isocarboxazid
Tranylcypromine
· A pit of despair, since MAOs treat depression.

Antimuscarinics: members, action "Inhibits Parasympathetic
And Sweat":
Ipratropium
Pirenzepine
Atropine
Scopolamine
· Muscarinic receptors at all parasympathetic endings sweat glands in
sympathetic.

Patent ductus arteriosus: treatment "Come In and 
Close the door":
INdomethacin is used to ClosePDA.

Etoposide: action, indications, side effect "eTOPoside":
· Action:
Inhibits TOPoisomerase II
· Indications:
Testicular carcinoma
Oat cell carcinoma of lung
Prostate carcinoma
· Side effect:
Affects TOP of your head, causing alopecia

Antibiotics contraindicated during pregnancy MCAT:
Metronidazole
Chloramphenicol
Aminoglycoside
Tetracycline

Lithium: side effects LITHIUM:
Leukocytes Increased (leukocytosis)
Tremors
Hypothyroidism
Increased Urine
Moms beware (teratogenic)

Quinolones [and Fluoroquinolones]: mechanism "Topple
the Queen":
Quinolone interferes with Topoisomerase II.

MPTP: mechanism, effect MPTP:
Mitochondrial Parkinson's-Type Poison.
· A mitochondrial poison that elicits a Parkinson's-type effect.

Osmotic diuretics: members GUM:
Glycerol
Urea
Mannitol

Sulfonamide: major side effects · Sulfonamide side
effects:
Steven-Johnson syndrome
Skin rash
Solubility low (causes crystalluria)
Serum albumin displaced (causes newborn kernicterus and potentiation of
other serum albumin-binders like warfarin)

Benzodiazepenes: antidote "Ben is off with the
flu":
Benzodiazepine effects off with Flumazenil.

Narcotics: side effects "SCRAM if you see a drug
dealer":
Synergistic CNS depression with other drugs
Constipation
Respiratory depression
Addiction
Miosis

Sex hormone drugs: male "Feminine Males Need
Testosterone":
Fluoxymesterone
Methyltestosterone
Nandrolone
Testosterone

Ca++ channel blockers: uses CA++ MASH:
Cerebral vasospasm/ CHF
Angina
Migranes
Atrial flutter, fibrillation
Supraventricular tachycardia
Hypertension
· Alternatively: "CHASM":
Cererbral vasospasm / CHF
Hypertension
Angina
Suprventricular tachyarrhythmia
Migranes

Benzodiazepenes: drugs which decrease their metabolism "I'm
Overly Calm":
Isoniazid
Oral contraceptive pills
Cimetidine
· These drugs increase calming effect of BZDs by retarding metabolism.

Tetracycline: teratogenicity TEtracycline is a
TEratogen that causes staining of
TEeth in the newborn.

Warfarin: metabolism SLOW:
· Has a slow onset of action.
· A quicK Vitamin K antagonist, though.
Small lipid-soluble molecule
Liver: site of action
Oral route of administration.
Warfarin

Myasthenia gravis: edrophonium vs. pyridostigmine eDrophonium
is for Diagnosis.
pyRIDostigmine is to get RIDof symptoms.

Narcotic antagonists The Narcotic Antagonists
are NAloxone and NAltrexone.
· Important clinically to treat narcotic overdose.

Inhalation anesthetics SHINE:
Sevoflurane
Halothane
Isoflurane
Nitrous oxide
Enflurane
· If want the defunct Methoxyflurane too, make it MoonSHINE.

Therapeutic dosage: toxicity values for most commonly monitored
medications "The magic 2s":
Digitalis (.5-1.5) Toxicity = 2.
Lithium (.6-1.2) Toxicity = 2.
Theophylline (10-20) Toxicity = 20.
Dilantin (10-20) Toxicity = 20.
APAP (1-30) Toxicity = 200.

Opioids: effects BAD AMERICANS:
Bradycardia & hypotension
Anorexia
Diminished pupilary size
Analgesics
Miosis
Euphoria
Respiratory depression
Increased smooth muscle activity (biliary tract constriction)
Constipation
Ameliorate cough reflex
Nausea and vomiting
Sedations

Delerium-causing drugs ACUTE CHANGE IN MS:
Antibiotics (biaxin, penicillin, ciprofloxacin)
Cardiac drugs (digoxin, lidocaine)
Urinary incontinence drugs (anticholinergics)
Theophylline
Ethanol
Corticosteroids
H2 blockers
Antiparkinsonian drugs
Narcotics (esp. mepridine)
Geriatric psychiatric drugs
ENT drugs
Insomnia drugs
NSAIDs (eg indomethacin, naproxin)
Muscle relaxants
Seizure medicines

Disulfiram-like reaction inducing drugs "PM PMT" as
in Pre Medical Test in the PM:
Procarbazine
Metronidazole
Cefo (Perazone, Mandole, Tetan).

Zafirlukast, Montelukast, Cinalukast: mechanism, usage "Zafir-luk-ast,
Monte-luk-ast, Cina-luk-ast":
· Anti-Lukotrienes for Asthma.
· Dazzle your oral examiner: Zafirlukast antagonizes leukotriene-4.

4-Aminopyradine (4-AP) use "4-AP is For AP":
For AP (action potential) propagation in Multiple Sclerosis.

Direct sympathomimetic catecholamines DINED:
Dopamine
Isoproterenol
Norepinephrine
Epinephrine
Dobutamine

Vir-named drugs: use "-vir at start, middle or end
means for virus":
· Drugs: Abacavir, Acyclovir, Amprenavir, Cidofovir,
Denavir, Efavirenz, Indavir, Invirase, Famvir,
Ganciclovir, Norvir, Oseltamivir, Penciclovir,
Ritonavir, Saquinavir, Valacyclovir, Viracept, 
Viramune, Zanamivir, Zovirax.

Nitrofurantoin: major side effects NitroFurAntoin:
Neuropathy (peripheral neuropathy)
Fibrosis (pulmonary fibrosis)
Anemia (hemolytic anemia)

Steroids: side effects BECLOMETHASONE:
Buffalo hump
Easy bruising
Cataracts
Larger appetite
Obesity
Moonface
Euphoria
Thin arms & legs
Hypertension/ Hyperglycaemia
Avascular necrosis of femoral head
Skin thinning
Osteoporosis
Negative nitrogen balance
Emotional liability

Methyldopa: side effects METHYLDOPA:
Mental retardation
Electrolyte imbalance
Tolerance
Headache/ Hepatotoxicity
psYcological upset
Lactation in female
Dry mouth
Oedema
Parkinsonism
Anaemia (haemolytic)

Sodium valproate: side effects VALPROATE:
Vomiting
Alopecia
Liver toxicity
Pancreatitis/ Pancytopenia
Retention of fats (weight gain)
Oedema (peripheral oedema)
Appetite increase
Tremor
Enzyme inducer (liver)

Captopril (an ACE inhibitor): side effects CAPTOPRIL:
Cough
Angioedema/ Agranulocystosis
Proteinuria/ Potassium excess
Taste changes
Orthostatic hypotension
Pregnancy contraindication/ Pancreatitis/ Pressure drop
(first dose hypertension)
Renal failure (and renal artery stenosis contraindication)/ Rash
Indomethacin inhibition
Leukopenia/ Liver toxicity

Lead poisoning: presentation ABCDEFG:
Anemia
Basophilic stripping
Colicky pain
Diarrhea
Encephalopathy
Foot drop
Gum (lead line)

Beta-blockers: main contraindications, cautions ABCDE:
Asthma
Block (heart block)
COPD
Diabetes mellitus
Electrolyte (hyperkalemia)

Lupus: drugs inducing it HIP:
Hydralazine
INH
Procanimide

Lithium: side effects LITH:
Leukocytosis
Insipidus [diabetes insipidus, tied to polyuria]
Tremor/ Teratogenesis
Hypothyroidism

SSRIs: side effects SSRI:
Serotonin syndrome
Stimulate CNS
Reproductive disfunctions in male
Insomnia

Metabolism enzyme inducers "Randy's Black Car
Goes Putt Putt and Smokes":
Rifampin
Barbiturates
Carbamazepine
Grisoefulvin
Phenytoin
Phenobarb
Smokingcigarettes

Phenobarbitone: side effects Children are annoying (hyperkinesia,
irritability, insomnia, aggression).
Adults are dosy (sedation, dizziness, drowsiness).

Cholinergics (eg organophosphates): effects If you know
these, you will be "LESS DUMB":
Lacrimation
Excitation of nicotinic synapses
Salivation
Sweating
Diarrhea
Urination
Micturition
Bronchoconstriction

Routes of entry: most rapid ways meds/toxins enter body "Stick
it, Sniff it, Suck it, Soak it":
Stick = Injection
Sniff = inhalation
Suck = ingestion
Soak = absorption

Depression: 5 drugs causing it PROMS:
Propranolol
Reserpine
Oral contraceptives
Methyldopa
Steroids

Hepatic necrosis: drugs causing focal to massive necrosis "Very
Angry Hepatocytes":
Valproic acid
Acetaminophen
Halothane

Warfarin: action, monitoring WePT:
Warfarin works on the extrinsic pathway and is monitored by PT.

Beta-blockers: side effects "BBC Loses Viewers
In Rochedale":
Bradycardia
Bronchoconstriction
Claudication
Lipids
Vivid dreams & nightmares
-ve Inotropic action
Reduced sensitivity to hypoglycaemia

Zero order kinetics drugs (most common ones) "PEAZ
(sounds like pees) out a constant amount":
Phenytoin
Ethanol
Aspirin
Zero order
· Someone that pees out a constant amount describes zero order kinetics (always
the same amount out)

Benzodiazepines: actions "Ben SCAMs Pam into
seduction not by brain but by muscle":
Sedation
anti-Convulsant
anti-Anxiety
Muscle relaxant
Not by brain: No antipsychotic activity.

Beta-1 vs Beta-2 receptor location "You have 1 heart
and 2 lungs":
Beta-1 are therefore primarily on heart.
Beta-2 primarily on lungs.

Cisplatin: major side effect, action "Ci-Splat-In":
Major side effect: Splat (vomiting sound)--vomiting so severe that
anti-nausea drug needed.
Action: Goes Into the DNA strand.

Pupils in overdose: morphine vs. amphetamine "MorPHINE:
Fine. AmPHETamine: Fat":
Morphine overdose: pupils constricted (fine).
Amphetamine overdose: pupils dilated (fat).

Atropine use: tachycardia or bradycardia "A goes with
B":
Atropine used clinically to treat Bradycardia.

Reserpine action Reserpine depletes the 
Reserves of catecholamines [and serotonin].

Botulism toxin: action, related bungarotoxin Action: "Botulism
Bottles up the Ach so it can't be the released":
Related bungarotoxin: "Botulism is related to Beta Bungarotoxin
(beta-, not alpha-bungarotoxin--alpha has different mechanism).

Ipratropium: action Atropine is buried in the middle:
iprAtropium, so it behaves like Atropine.

Bleomycin: action "Bleo-Mycin Blows 
My DNA to bits":
Bleomycin works by fragmenting DNA (blowing it to bits).
MyDNA signals that its used for cancer (targeting self cells).

Propranolol and related '-olol' drugs: usage "olol"
is just two backwards lower case b's.
Backward b's stand for "beta blocker".
· Beta blockers include acebutolol, betaxolol, bisoprolol,
oxprenolol, propranolol.

Succinylcholine: action, use Succinylcholine gets 
Stuck to Ach receptor, then Sucks ions in through open pore.
You Suck stuff in through a mouth-tube, and drug is used for intubation

BASICS OF PHARMACOLOGY

BASIC OF PHARMACOLOGY

 Pharmacokinetics

The goal of drug therapy is to prevent, cure, or control various disease states. To achieve this goal, adequate drug doses must be delivered to the target tissues so that therapeutic yet nontoxic levels are obtained. Pharmacokinetics examines the movement of a drug over time through the body. Pharmacological as well as toxicological actions of drugs are primarily related to the plasma concentrations of drugs. Thus, the clinician must recognize that the speed of onset of drug action, the intensity of the drug's effect, and the duration of drug action are controlled by four fundamental pathways of drug movement and modification in the body 

First, drug absorption from the site of administration (Absorption) permits entry of the therapeutic agent (either directly or indirectly) into plasma. 

Second, the drug may then reversibly leave the bloodstream and distribute into the interstitial and intracellular fluids (Distribution). 

Third, the drug may be metabolized by the liver, kidney, or other tissues (Metabolism). Finally, the drug and its metabolites are removed from the body in urine, bile, or feces (Elimination). This chapter describes how knowledge of these four processes (Absorption, Distribution, Metabolism, and Elimination) influences the clinician's decision of the route of administration for a specific drug, the amount and frequency of each dose, and the dosing intervals.

 Drug–Receptor Interactions and Pharmacodynamics

Most drugs exert their effects, both beneficial and harmful, by interacting with receptors—that is, specialized target macromolecules—present on the cell surface or intracellularly. Receptors bind drugs and initiate events leading to alterations in biochemical and/or biophysical activity of a cell, and consequently, the function of an organ

Drugs may interact with receptors in many different ways. Drugs may bind to enzymes (for example, inhibition of dihydrofolate reductase by trimethoprim), nucleic acids (for example, blockade of transcription by dactinomycin), or membrane receptors (for example, alteration of membrane permeability by pilocarpine). 

In each case, the formation of the drug–receptor complex leads to a biologic response. Most receptors are named to indicate the type of drug/chemical that interacts best with it; for example, the receptor for histamine is called a histamine receptor. Cells may have tens of thousands of receptors for certain ligands (drugs). Cells may also have different types of receptors, each of which is specific for a particular ligand. On the heart, for example, there are β receptors for norepinephrine, and muscarinic receptors for acetylcholine. These receptors dynamically interact to control vital functions of the heart. The magnitude of the response is proportional to the number of drug–receptor complexes.

This concept is closely related to the formation of complexes between enzyme and substrate,1 or antigen and antibody; these interactions have many common features, perhaps the most noteworthy being specificity of the receptor for a given ligand. However, the receptor not only has the ability to recognize a ligand, but can also couple or transduce this binding into a response by causing a conformational change or a biochemical effect. 

Although much of this chapter will be centered on the interaction of drugs with specific receptors, it is important to be aware that not all drugs exert their effects by interacting with a receptor; for example, antacids chemically neutralize excess gastric acid, reducing the symptoms of “heartburn.” This chapter introduces the study of pharmacodynamics—the influence of drug concentrations on the magnitude of the response. It deals with the interaction of drugs with receptors, the molecular consequences of these interactions, and their effects in the patient. A fundamental principle of pharmacodynamics is that drugs only modify underlying biochemical and physiological processes; they do not create effects de novo.

Drugs affecting the ANS

• The AutonomicNervous System

The autonomic nervous system, along with the endocrine system, coordinates the regulation and integration of bodily functions. The endocrine system sends signals to target tissues by varying the levels of blood-borne hormones. In contrast, the nervous system exerts its influence by the rapid transmission of electrical impulses over nerve fibers that terminate at effector cells, which specifically respond to the release of neuromediator substances. Drugs that produce their primary therapeutic effect by mimicking or altering the functions of the autonomic nervous system are called autonomic drugs and are discussed in the following four chapters. These autonomic agents act either by stimulating portions of the autonomic nervous system or by blocking the action of the autonomic nerves. This chapter outlines the fundamental physiology of the autonomic nervous system, and it describes the role of neurotransmitters in the communication between extracellular events and chemical changes within the cell.

• Cholinergic Agonists

Drugs affecting the autonomic nervous system are divided into two groups according to the type of neuron involved in their mechanism of action. The cholinergic drugs, which are described in this and the following chapter, act on receptors that are activated by acetylcholine. The second group act on receptors that are stimulated by norepinephrine or epinephrine. Cholinergic and adrenergic drugs both act by either stimulating or blocking receptors of the autonomic nervous system. 

• Cholinergic Antagonists

The cholinergic antagonists (also called cholinergic blockers, parasympatholytics or anticholinergic drugs) bind to cholinoceptors, but they do not trigger the usual receptor-mediated intracellular effects. The most useful of these agents selectively block muscarinic synapses of the parasympathetic nerves. The effects of parasympathetic innervation are thus interrupted, and the actions of sympathetic stimulation are left unopposed. A second group of drugs, the ganglionic blockers, show a preference for the nicotinic receptors of the sympathetic and parasympathetic ganglia. Clinically, they are the least important of the anticholinergic drugs. A third family of compounds, the neuromuscular blocking agents, interfere with transmission of efferent impulses to skeletal muscles. These agent are used as adjuvants in anesthesia during surgery.

• Adrenergic Agonists 

The adrenergic drugs affect receptors that are stimulated by norepinephrine or epinephrine. Some adrenergic drugs act directly on the adrenergic receptor (adrenoceptor) by activating it and are said to be sympathomimetic.  block the action of the neurotransmitters at the receptors (sympatholytics), whereas still other drugs affect adrenergic function by interrupting the release of norepinephrine from adrenergic neurons. This chapter describes agents that either directly or indirectly stimulate adrenoceptors .

• Adrenergic Antagonists 

The adrenergic antagonists (also called blockers or sympatholytic agents) bind to adrenoceptors but do not trigger the usual receptor-mediated intracellular effects. These drugs act by either reversibly or irreversibly attaching to the receptor, thus preventing its activation by endogenous catecholamines. Like the agonists, the adrenergic antagonists are classified according to their relative affinities for α or β receptors in the peripheral nervous system. [Note: Antagonists that block dopamine receptors are most important in the central nervous system (CNS) and are therefore considered in that section

major receptor family

Pharmacology defines a receptor as any biologic molecule to which a drug binds and produces a measurable response. Thus, enzymes and structural proteins can be considered to be pharmacologic receptors. However, the richest sources of therapeutically exploitable pharmacologic receptors are proteins that are responsible for transducing extracellular signals into intracellular responses. These receptors may be divided into four families: 

1) ligand-gated ion channels, 

2) G proteincoupled receptors,

3) enzyme-linked receptors, and
4) intracellular receptors

Figure 2.2 Transmembrane signaling mechanisms. A. Ligand binds to the extracellular domain of a ligand-gated channel. B. Ligand binds to a domain of a serpentine receptor, which is coupled to a G protein. C. Ligand binds to the extracellular domain of a receptor that activates a kinase enzyme. D. Lipid-soluble ligand diffuses across the membrane to interact with its intracellular receptor.

The type of receptor a ligand will interact with depends on the nature of the ligand. Hydrophobic ligands interact with receptors that are found on the cell surface (families 1, 2, and 3). In contrast, hydrophobic ligands can enter cells through the lipid bilayers of the cell membrane to interact with receptors found inside cells (family 4)

A. Ligand-gated ion channels

The first receptor family comprises ligand-gated ion channels that are responsible for regulation of the flow of ions across cell membranes (see Figure above A).

The activity of these channels is regulated by the binding of a ligand to the channel. Response to these receptors is very rapid, having durations of a few milliseconds. The nicotinic receptor and the γaminobutyric acid (GABA) receptor are important examples of ligand-gated receptors, the functions of which are modified by numerous drugs. Stimulation of the nicotinic receptor by acetylcholine results in sodium influx, generation of an action potential, and activation of contraction in skeletal muscle. Benzodiazepines, on the other hand, enhance the stimulation of the GABA receptor by GABA, resulting in increased chloride influx and hyperpolarization of the respective cell. Although not ligand-gated, ion channels, such as the voltage-gated sodium channel, are important drug receptors for several drug classes, including local anesthetics. 

B. G protein–coupled receptors

A second family of receptors consists of G protein–coupled receptors. These receptors are comprised of a single peptide that has seven membrane-spanning regions, and these receptors are linked to a G protein (Gs and others) having three subunits, an α subunit that binds guanosine triphosphate (GTP) and a βγ subunit.

Figure : The recognition of chemical signals by G protein-coupled membrane receptors triggers an increase (or, less often, a decrease) in the activity of adenylyl cyclase.

 Binding of the appropriate ligand to the extracellular region of the receptor activates the G protein so that GTP replaces guanosine diphosphate (GDP) on the α subunit. Dissociation of the G protein occurs, and both the α-GTP subunit and the βγ subunit subsequently interact with other cellular effectors, usually an enzyme or ion channel. These effectors then change the concentrations of second messengers that are responsible for further actions within the cell. Stimulation of these receptors results in responses that last several seconds to minutes. 

-Second messengers: These are essential in conducting and amplifying signals coming from G protein–coupled receptors. A common pathway turned on by Gs, and other types of G proteins, is the activation of adenylyl cyclase by α-GTP subunits, which results in the production of cyclic adenosine monophosphate (cAMP)—a second messenger that regulates protein phosphorylation. G proteins also activate phospholipase C, which is responsible for the generation of two other second messengers, namely inositol-1,4,5-trisphosphate and diacylglycerol. These effectors are responsible for the regulation of intracellular free calcium concentrations, and of other proteins as well. This family of receptors transduces signals derived from odors, light, and numerous neurotransmitters, including norepinephrine, dopa-mine, serotonin, and acetylcholine. G protein–coupled receptors also activate guanylyl cyclase, which converts (GTP) to cyclic guanosine monophosphate (cGMP), a fourth second messenger that stimulates cGMP-dependent protein kinase. cGMP signaling is important in only a few cells, for example, intestinal mucosa and vascular smooth muscle, where it causes relaxation of vascular smooth muscle cells. Some drugs such as sildenafil produce vasodilation by interfering with specific phosphodiesterases, the enzymes that metabolically break down cGMP. 

C. Enzyme-linked receptors

A third major family of receptors consists of those having cytosolic enzyme activity as an integral component of their structure or function (see Figure  above C).

Binding of a ligand to an extracellular domain activates or inhibits this cytosolic enzyme activity. Duration of responses to stimulation of these receptors is on the order of minutes to hours. The most common enzyme-linked receptors (epidermal growth factor, platelet-derived growth factor, atrial natriuretic peptide, insulin, and others) are those that have a tyrosine kinase activity as part of their structure. Typically, upon binding of the ligand to receptor subunits, the receptor undergoes conformational changes, converting from its inactive form to an active kinase form. The activated receptor autophosphorylates, and phosphorylates tyrosine residues on specific proteins. The addition of a phosphate group can substantially modify the three-dimensional structure of the target protein, thereby acting as a molecular switch. For example, when the peptide hormone insulin binds to two of its receptor subunits, their intrinsic tyrosine kinase activity causes autophosphorylation of the receptor itself. In turn, the phosphorylated receptor phosphorylates target molecules—insulin-receptor substrate peptides—that subsequently activate other important cellular signals such as IP3 and the mitogen-activated protein kinase system. This cascade of activations results in a multiplication of the initial signal, much like that which occurs with G protein–coupled receptors

D. Intracellular receptors

The fourth family of receptors differs considerably from the other three in that the receptor is entirely intracellular and, therefore, the ligand must diffuse into the cell to interact with the receptor 

Figure  Mechanism of intracellular receptors.

This places constraints on the physical and chemical properties of the ligand in that it must have sufficient lipid solubility to be able to move across the target cell membrane. Because these receptor ligands are lipid soluble, they are transported in the body attached to plasma proteins, such as albumin. For example, steroid hormones exert their action on target cells via this receptor mechanism. Binding of the ligand with its receptor follows a general pattern in which the receptor becomes activated because of the dissociation of a small repressor peptide. The activated ligand–receptor complex migrates to the nucleus, where it binds to specific DNA sequences, resulting in the regulation of gene expression.

 The time course of activation and response of these receptors is much longer than that of the other mechanisms described above. Because gene expression and, therefore, protein synthesis is modified, cellular responses are not observed until considerable time has elapsed (thirty minutes or more), and the duration of the response (hours to days) is much greater than that of other receptor families.

Drug Distribution

Drug distribution is the process by which a drug reversibly leaves the bloodstream and enters the interstitium (extracellular fluid) and/or the cells of the tissues. The delivery of a drug from the plasma to the interstitium primarily depends on blood flow, capillary permeability, the degree of binding of the drug to plasma and tissue proteins, and the relative hydrophobicity

A. Blood flow 

The rate of blood flow to the tissue capillaries varies widely as a result of the unequal distribution of cardiac output to the various organs. Blood flow to the brain, liver, and kidney is greater than that to the skeletal muscles; adipose tissue has a still lower rate of blood flow. This differential blood flow partly explains the short duration of hypnosis produced by a bolus IV injection of thiopental . 

The high blood flow, together with the superior lipid solubility of thiopental, permit it to rapidly move into the central nervous system (CNS) and produce anesthesia. Slower distribution to skeletal muscle and adipose tissue lowers the plasma concentration sufficiently so that the higher concentrations within the CNS decrease, and consciousness is regained. Although this phenomenon occurs with all drugs to some extent, redistribution accounts for the extremely short duration of action of thiopental and compounds of similar chemical and pharmacologic properties.

 B. Capillary permeability 

Capillary permeability is determined by capillary structure and by the chemical nature of the drug.

 1. Capillary structure: Capillary structure varies widely in terms of the fraction of the basement membrane that is exposed by slit junctions between endothelial cells. In the brain, the capillary structure is continuous, and there are no slit junctions.

(Figure Cross-section of liver and brain capillaries.)

 This contrasts with the liver and spleen, where a large part of the basement membrane is exposed due to large, discontinuous capillaries through which large plasma proteins can pass. a. Blood-brain barrier: To enter the brain, drugs must pass through the endothelial cells of the capillaries of the CNS or be actively transported. For example, a specific transporter for the large neutral amino acid transporter carries levodopa into the brain. By contrast, lipid-soluble drugs readily penetrate into the CNS because they can dissolve in the membrane of the endothelial cells. Ionized or polar drugs generally fail to enter the CNS because they are unable to pass through the endothelial cells of the CNS, which have no slit junctions. These tightly juxtaposed cells form tight junctions that constitute the so-called blood-brain barrier.

 2. Drug structure: The chemical nature of a drug strongly influences its ability to cross cell membranes. Hydrophobic drugs, which have a uniform distribution of electrons and no net charge, readily move across most biologic membranes. These drugs can dissolve in the lipid membranes and, therefore, permeate the entire cell's surface. The major factor influencing the hydrophobic drug's distribution is the blood flow to the area. By contrast, hydrophilic drugs, which have either a nonuniform distribution of electrons or a positive or negative charge, do not readily penetrate cell membranes, and therefore, must go through the slit junctions. 

C. Binding of drugs to plasma proteins 

Reversible binding to plasma proteins sequesters drugs in a nondiffusible form and slows their transfer out of the vascular compartment. Binding is relatively nonselective as to chemical structure and takes place at sites on the protein to which endogenous compounds, such as bilirubin, normally attach. Plasma albumin is the major drug-binding protein and may act as a drug reservoir; that is, as the concentration of the free drug decreases due to elimination by metabolism or excretion, the bound drug dissociates from the protein. This maintains the free-drug concentration as a constant fraction of the total drug in the plasma.